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Circulation
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e1
Circulation is available at www.ahajournals.org/journal/circ
*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for
detailed information. †AMSSM representative. ‡HRS representative. §Lay stakeholder representative. ‖AHA/ACC Joint Committee on Clinical Practice Guidelines liaison.
¶SCMR representative. #ACC/AHA Joint Committee on Performance Measures representative. **PACES representative. ††ACC/AHA Joint Committee on Clinical Data
Standards representative. ‡‡Joint ACC/AHA staff representative. §§Former Joint Committee on Clinical Practice Guidelines member; current member during the writing effort.
Peer Review Committee Members and AHA/ACC Joint Committee on Clinical Practice Guidelines Members, see page __.
The American Heart Association requests that this document be cited as follows: Ommen SR, Ho CY, Asif IM, Balaji S, Burke MA, Day SM, Dearani JA, Epps-Anderson
KC, Evanovich L, Ferrari VA, Joglar JA, Khan SS, Kim JJ, Kittleson MM, Krittanawong C, Martinez MW, Mital S, Naidu SS, Saberi S, Semsarian C, Times S, Waldman CB.
2024 AHA/ACC/AMSSM/ HRS/PACES/SCMR guideline for the management of hypertrophic cardiomyopathy: a report of the American Heart Association/American
College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. Published online May 8, 2024. doi:10.1161/CIR.0000000000001250
© 2024 by the American Heart Association, Inc., and the American College of Cardiology Foundation.
CLINICAL PRACTICE GUIDELINES
2024 AHA/ACC/AMSSM/HRS/PACES/SCMR
Guideline for the Management of Hypertrophic
Cardiomyopathy: A Report of the American Heart
Association/American College of Cardiology
Joint Committee on Clinical Practice Guidelines
Developed in Collaboration With and Endorsed by the American Medical Society for Sports Medicine, the Heart Rhythm Society,
Pediatric & Congenital Electrophysiology Society, and the Society for Cardiovascular Magnetic Resonance
Writing Committee Members*
Steve R. Ommen, MD, FACC, FAHA, Chair; Carolyn Y. Ho, MD, FAHA, Vice Chair; Irfan M. Asif, MD, FAMSSM†;
Seshadri Balaji, MBBS, MRCP(UK), PhD, FHRS‡; Michael A. Burke, MD; Sharlene M. Day, MD, FAHA;
Joseph A. Dearani, MD, FACC; Kelly C. Epps, MD, FACC; Lauren Evanovich, PhD§; Victor A. Ferrari, MD, FACC, FAHA, MSCMR‖¶;
José A. Joglar, MD, FACC, FAHA, FHRS; Sadiya S. Khan, MD, MSc, FACC, FAHA#; Jeffrey J. Kim, MD, FACC, FHRS**;
Michelle M. Kittleson, MD, PhD, FAHA, FACC‖; Chayakrit Krittanawong, MD††; Matthew W. Martinez, MD, FACC;
Seema Mital, MD, FACC, FAHA; Srihari S. Naidu, MD, FACC, FAHA; Sara Saberi, MD, MS;
Christopher Semsarian, MBBS, PhD, MPH, FHRS, FAHA; Sabrina Times, DHSC, MPH‡‡; Cynthia Burstein Waldman, JD§
AIM: The “2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy”
provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy.
METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing
studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane
Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional
relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing
committee and added to the evidence tables, where appropriate.
STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally.
Recommendations from the “2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic
Cardiomyopathy” have been updated with new evidence to guide clinicians.
Key Words: AHA Scientific Statements ◼ athlete ◼ atrial fibrillation ◼ cardiac myosin inhibitors ◼ cardiovascular magnetic resonance imaging
◼ diastolic dysfunction ◼ echocardiography ◼ exercise, exercise stress testing ◼ family screening ◼ genetics ◼ hypertrophic cardiomyopathy
◼ implantable cardioverter defibrillator ◼ left ventricular outflow tract obstruction ◼ occupation ◼ physical activity ◼ pregnancy
◼ rhythm monitoring ◼ risk stratification ◼ sarcomeric genes ◼ septal alcohol ablation ◼ septal reduction therapy ◼ shared decision-making
◼ sports, sudden cardiac death ◼ surgical myectomy ◼ systolic dysfunction ◼ ventricular arrhythmias
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CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e2
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
TABLE OF CONTENTS
What Is New ...................................eXXX
Top 10 Take-Home Messages ...................eXXX
Preamble ......................................eXXX
1. Introduction ................................eXXX
1.1. Methodology and Evidence Review ....eXXX
1.2. Composition of the Writing
Committee ...........................eXXX
1.3. Document Review and Approval .......eXXX
1.4. Scope of the Guideline ................eXXX
1.5. Class of Recommendations and
Level of Evidence .....................eXXX
1.6. Abbreviations .........................eXXX
2. Definition, Etiology, Clinical Course, and
Natural History .............................eXXX
2.1. Prevalence ...........................eXXX
2.2. Nomenclature/Differential
Diagnosis ............................eXXX
2.3. Definition, Clinical Diagnosis, and
Phenotype ...........................eXXX
2.4. Etiology ..............................eXXX
2.5. Natural History/Clinical Course ........eXXX
3. Pathophysiology ............................eXXX
3.1. Left Ventricular Outflow Tract
Obstruction ..........................eXXX
3.2. Diastolic Dysfunction .................eXXX
3.3. Mitral Regurgitation ...................eXXX
3.4. Myocardial Ischemia ..................eXXX
3.5. Autonomic Dysfunction ...............eXXX
4. Shared Decision-Making ....................eXXX
5. Multidisciplinary HCM Centers ..............eXXX
6. Diagnosis, Initial Evaluation, and
Follow-Up ..................................eXXX
6.1. Clinical Diagnosis .....................eXXX
6.2. Echocardiography ....................eXXX
6.3. CMR Imaging ........................eXXX
6.4. Cardiac CT ...........................eXXX
6.5. Heart Rhythm Assessment ............eXXX
6.6. Angiography and Invasive
Hemodynamic Assessment ............eXXX
6.7. Exercise Stress Testing ...............eXXX
6.8. Genetics and Family Screening ........eXXX
6.9. Individuals Who Are Genotype-Positive,
Phenotype-Negative ..................eXXX
7. SCD Risk Assessment and Prevention .......eXXX
7.1. SCD Risk Assessment ................eXXX
7.1.1. SCD Risk Assessment in
Adults With HCM ..............eXXX
7.1.2. SCD Risk Assessment in
Children and Adolescents
With HCM ....................eXXX
7.2. Patient Selection for ICD Placement ...eXXX
7.3. Device Selection Considerations .......eXXX
8. Management of HCM .......................eXXX
8.1. Management of Symptomatic
Patients With Obstructive HCM ........eXXX
8.1.1. Pharmacological Management
of Symptomatic Patients With
Obstructive HCM ..............eXXX
8.1.2. Invasive Treatment of
Symptomatic Patients With
Obstructive HCM ..............eXXX
8.2. Management of Patients with
Nonobstructive HCM With
Preserved EF .........................eXXX
8.3. Management of Patients With HCM
and Advanced HF ....................eXXX
8.4. Management of Patients With
HCM and AF .........................eXXX
8.5. Management of Patients With
HCM and Ventricular Arrhythmias ......eXXX
9. Lifestyle Considerations for Patients
With HCM .................................eXXX
9.1. Recreational Physical Activity and
Competitive Sports ...................eXXX
9.2. Occupation in Patients With HCM .....eXXX
9.3. Pregnancy in Patients With HCM ......eXXX
9.4. Patients With Comorbidities ...........eXXX
10. Evidence Gaps and Future Directions ........eXXX
10.1. Refining the Diagnosis of HCM ........eXXX
10.2. Developing Therapies to Attenuate
or Prevent Disease Progression .......eXXX
10.3. Improving Care for Nonobstructive
HCM ................................eXXX
10.4. Improving and Expanding Risk
Stratification .........................eXXX
10.5. Arrhythmia Management ..............eXXX
10.6. Expanding Understanding of the
Genetic Architecture of HCM ..........eXXX
References .....................................eXXX
Appendix 1
Author Relationships With Industry and
Other Entities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .eXXX
Appendix 2
Reviewer Relationships With Industry and
Other Entities (Comprehensive) . . . . . . . . . . . . . . eXXX
WHAT IS NEW
Table 1 reflects recommendations that are substantially
revised from the 2020 Hypertrophic Cardiomyopathy
Guidelines or were drafted as new recommendations in
the 2024 Hypertrophic Cardiomyopathy Guidelines.
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CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e3
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
Table 1. What Is New: New and Substantially Revised Recommendations in the 2024 HCM Guideline*
New or
Revised
2024
Section Title Recommendation in 2020 HCM Guideline
COR in 2020
Guideline Recommendation in 2024 HCM Guideline
COR in 2024
Guideline
Revised 6.5 Heart Rhythm
Assessment
In patients with HCM who have additional
risk factors for AF, such as left atrial dilatation,
advanced age, and NYHA functional class III
to class IV HF, and who are eligible for
anticoagulation, extended ambulatory
monitoring is reasonable to screen for AF as
part of initial evaluation and periodic follow-up.
2a In patients with HCM who are deemed to be
at high risk for developing AF based on the
presence of risk factors or as determined by
a validated risk score, and who are eligible for
anticoagulation, extended ambulatory
monitoring is recommended to screen for AF as
part of initial evaluation and annual follow-up.
1
New 6.7 Exercise
Stress Testing
N/A N/A In pediatric patients with HCM, regardless
of symptom status, exercise stress testing is
recommended to determine functional
capacity and to provide prognostic information.
1
Revised 7.2 Patient
Selection for ICD
Placement
For patients ≥16 years of age with HCM and
with ≥1 major SCD risk factors, discussion
of the estimated 5-year sudden death risk
and mortality rates can be useful during the
shared decision-making process for ICD
placement.
2a For patients with HCM with ≥1 major SCD
risk factor, discussion of the estimated 5-year
sudden death risk and mortality rates can
be useful during the shared decision-making
process for ICD placement.
2a
Revised 8.1.1
Pharmacological
Management of
Symptomatic
Patients with
Obstructive HCM
For patients with obstructive HCM who have
persistent severe symptoms attributable
to LVOTO despite beta blockers or
nondihydropyridine calcium channel blockers,
either adding disopyramide in combination
with 1 of the other drugs, or SRT performed
at experienced centers, is recommended.
1 For patients with obstructive HCM who have
persistent symptoms attributable to LVOTO
despite beta blockers or nondihydropyridine
calcium channel blockers, adding a
myosin inhibitor (adult patients only), or
disopyramide (in combination with an
atrioventricular nodal blocking agent), or
SRT performed at experienced centers, is
recommended.
1
New 8.2 Management
of Patients With
Nonobstructive
HCM With
Preserved EF
N/A N/A For younger (eg, ≤45 years of age) patients
with nonobstructive HCM due to a
pathogenic or likely pathogenic cardiac
sarcomere genetic variant, and a mild
phenotype, valsartan may be beneficial to
slow adverse cardiac remodeling.
2b
New 8.3 Management
of Patients With
HCM and Ad-
vanced HF
N/A N/A In patients with HCM who develop persistent
systolic dysfunction (LVEF <50%), cardiac
myosin inhibitors should be discontinued.
1
Revised 9.1 Recreational
Physical Activity
and Competitive
Sports
For patients with HCM, participation in
high-intensity recreational activities or
moderate- to high-intensity competitive sports
activities may be considered after a
comprehensive evaluation and shared
discussion, repeated annually with an expert
provider who conveys that the risk of sudden
death and ICD shocks may be increased, and
with the understanding that eligibility
decisions for competitive sports participation
often involve third parties (eg, team
physicians, consultants, and other institutional
leadership) acting on behalf of the schools
or teams.
2b For patients with HCM, participation in
vigorous recreational activities is reasonable
after an annual comprehensive evaluation and
shared decision-making with an expert
professional who balances potential benefits
and risks.
2a
For patients with HCM who are capable of
a high level of physical performance,
participation in competitive sports may be
considered after review by an expert
provider with experience managing athletes
with HCM who conducts an annual
comprehensive evaluation and shared
decision-making that balances potential ben-
efits and risks.
2b
New 9.1 Recreational
Physical Activity
and Competitive
Sports
N/A N/A For most patients with HCM, universal
restriction from vigorous physical activity or
competitive sports is not indicated.
3: No Benefit
New 9.3 Pregnancy
in Patients With
HCM
N/A N/A In pregnant women, use of mavacamten is
contraindicated due to potential teratogenic
effects.
3: Harm
*Table 1 highlights new and substantially revised practice-changing recommendations since 2020 and is not a comprehensive list of all updates in this guideline.
AF indicates atrial fibrillation; COR, Class of Recommendation; EF, ejection fraction; HCM, hypertrophic cardiomyopathy; HF, heart failure; ICD, implantable cardioverter-
defibrillator; LVEF, left ventricular ejection fraction; LVOTO, left ventricular outflow tract obstruction; N/A, not applicable; NYHA, New York Heart Association; SCD,
sudden cardiac death; and SRT, septal reduction therapy.
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CLINICAL STATEMENTS
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TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e4
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
TOP 10 TAKE-HOME MESSAGES
1. Shared decision-making is essential to provide the
best clinical care. This involves thoughtful dialogue
among patients, families, and their care team in
which health care professionals present all avail-
able testing and treatment options; discuss the
risks, benefits, and applicability of those options
to the individual patient; and ensure the patient
expresses their personal preferences and goals to
develop their treatment plan.
2. Although the primary cardiology team can initiate
evaluation, treatment, and longitudinal care, refer-
ral to multidisciplinary hypertrophic cardiomyopa-
thy (HCM) centers with appropriate expertise can
be important to optimizing care for patients with
HCM. Challenging treatment decisions—where
reasonable alternatives exist, where the strength of
recommendation is weak (eg, any decision relying
on a Class of Recommendation 2b) or is particu-
larly nuanced (eg, interpretation of genetic testing;
primary prevention implantable cardioverter-
defibrillator decision-making), and for HCM-
specific invasive procedures—may critically benefit
from involving specialized HCM centers.
3. Careful ascertainment of family history, counseling
patients with HCM about the potential for genetic
transmission of HCM, and options for genetic
testing are cornerstones of care. Screening first-
degree family members of patients with HCM,
using either genetic testing, serial imaging, or elec-
trocardiographic surveillance as appropriate, can
begin at any age and can be influenced by spe-
cifics of the patient and family history and family
preference. Because screening recommendations
for family members hinge on the pathogenicity of
any detected variants, the reported pathogenic-
ity should be reconfirmed every 2 to 3 years, and
input from specialized HCM centers with genetics
expertise may be valuable.
4. Assessing a patient’s risk for sudden cardiac
death is an important component of management.
Integrating the presence or absence of established
risk markers with tools to estimate individual risk
score will facilitate the patient’s ability to par-
ticipate in decision-making regarding implantable
cardioverter-defibrillator placement. These discus-
sions should incorporate a patient’s personal level
of risk tolerance and their specific treatment goals.
5. The risk factors for sudden cardiac death in children
with HCM carry different weights and components
than those used in adult patients. Pediatric risk
stratification also varies with age and must account
for different body sizes. Coupled with the complex-
ity of placing implantable cardioverter-defibrillators
in young patients with anticipated growth and a
higher risk of device complications, the threshold
for implantable cardioverter-defibrillator implan-
tation in children often differs from adults. These
differences are best addressed at comprehensive
HCM centers with expertise in caring for children
with HCM. New risk calculators, specific to chil-
dren and adolescents, have been validated and can
help young patients and their families contextualize
their estimated risk of sudden cardiac death.
6. Cardiac myosin inhibitors are now available to
treat patients with symptomatic obstructive HCM.
This new class of medication inhibits actin-myosin
interaction, thus decreasing cardiac contractility
and reducing left ventricular outflow tract obstruc-
tion. Mavacamten is currently the only US Food
and Drug Administration–approved agent. These
agents can be beneficial for patients with obstruc-
tive HCM who do not derive adequate symptomatic
relief from first-line drug therapy.
7. Invasive septal reduction therapies (surgical septal
myectomy and alcohol septal ablation), when per-
formed by experienced HCM teams at dedicated
centers, can provide safe and effective symp-
tomatic relief for patients with drug-refractory or
severe outflow tract obstruction. Given the data on
the significantly improved outcomes at compre-
hensive HCM centers, these decisions represent
an optimal opportunity for referral.
8. Patients with HCM and persistent or paroxysmal
atrial fibrillation have a sufficiently increased risk
of stroke such that oral anticoagulation with direct-
acting oral anticoagulants (or alternatively warfarin)
should be considered the default treatment option
irrespective of the CHA2DS2-VASc score. New tools
to stratify risk for incident atrial fibrillation have been
developed and may assist in determining the fre-
quency of screening patients with ambulatory telem-
etry. Because rapid atrial fibrillation is often poorly
tolerated in patients with HCM, maintenance of sinus
rhythm and rate control are key treatment goals.
9. Exercise stress testing is particularly helpful in
determining overall exercise tolerance and for
latent exercise provoked left ventricular out-
flow tract obstruction. Because children may not
describe symptoms readily, routine exercise testing
can be particularly important for young patients.
10. Increasingly, data affirm that the beneficial effects
of exercise on general health are extended to
patients with HCM. Healthy recreational exercise
(light [<3 metabolic equivalents], moderate [3-6
metabolic equivalents], and vigorous [>6 metabolic
equivalents] intensity levels) has not been associ-
ated with increased risk of ventricular arrhythmia
events in short-term studies. If patients pursue rig-
orous exercise training for the purpose of perfor-
mance or competition, it is important to engage in
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CLINICAL STATEMENTS
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
a comprehensive discussion and seek input from
expert HCM professionals regarding the poten-
tial risks and benefits, to develop an individualized
training plan, and to establish a regular schedule
for reevaluation.
PREAMBLE
Since 1980, the American College of Cardiology (ACC)
and American Heart Association (AHA) have translated
scientific evidence into clinical practice guidelines with
recommendations to improve cardiovascular health.
These guidelines, which are based on systematic meth-
ods to evaluate and classify evidence, provide a founda-
tion for the delivery of quality cardiovascular care. The
ACC and AHA sponsor the development and publication
of clinical practice guidelines without commercial sup-
port, and members volunteer their time to the writing and
review efforts. Guidelines are the official policy of the
ACC and AHA. For some guidelines, the ACC and AHA
partner with other organizations.
Intended Use
Clinical practice guidelines provide recommendations
applicable to patients with or at risk of developing car-
diovascular disease. The focus is on medical practice in
the United States, but these guidelines are relevant to
patients throughout the world. Although guidelines may
be used to inform regulatory or payer decisions, the in-
tent is to improve quality of care and align with patients’
interests. Guidelines are intended to define practices
meeting the needs of patients in most, but not all, cir-
cumstances and should not replace clinical judgment.
Clinical Implementation
Management, in accordance with guideline recommenda-
tions, is effective only when followed by both practition-
ers and patients. Adherence to recommendations can be
enhanced by shared decision-making between clinicians
and patients, with patient engagement in selecting inter-
ventions on the basis of individual values, preferences,
and associated conditions and comorbidities.
The ACC/AHA Joint Committee on Clinical Prac-
tice Guidelines (Joint Committee) continuously reviews,
updates, and modifies guideline methodology on the
basis of published standards from organizations, includ-
ing the Institute of Medicine,1,2 and on the basis of inter-
nal reevaluation. Similarly, presentation and delivery of
guidelines are reevaluated and modified in response to
evolving technologies and other factors to optimally facil-
itate dissemination of information to health care profes-
sionals at the point of care.
Numerous modifications to the guidelines have been
implemented to make them shorter and enhance “user
friendliness.” Guidelines are written and presented in a
modular, “knowledge chunk” format, in which each chunk
includes a table of recommendations, a brief synopsis,
recommendation-specific supportive text, and, when
appropriate, flow diagrams or additional tables. Hyper-
linked references are provided for each modular knowl-
edge chunk to facilitate quick access and review.
In recognition of the importance of cost–value con-
siderations, in certain guidelines, when appropriate and
feasible, an analysis of value for a drug, device, or inter-
vention may be performed in accordance with the ACC/
AHA methodology.3
To ensure that guideline recommendations remain cur-
rent, new data will be reviewed on an ongoing basis by
the writing committee and staff. Going forward, targeted
sections/knowledge chunks will be revised dynamically
after publication and timely peer review of potentially
practice-changing science. The previous designations of
“full revision” and “focused update” will be phased out.
For additional information and policies on guideline devel-
opment, readers may consult the ACC/AHA guideline
methodology manual4 and other methodology articles.5–7
Selection of Writing Committee Members
The Joint Committee strives to ensure that the guide-
line writing committee contains requisite content exper-
tise and is representative of the broader cardiovascular
community by selection of experts across a spectrum of
backgrounds, representing different geographic regions,
sexes, races, ethnicities, intellectual perspectives/biases,
and clinical practice settings. Organizations and profes-
sional societies with related interests and expertise are
invited to participate as collaborators.
Relationships With Industry and Other Entities
The ACC and AHA have rigorous policies and methods
to ensure that documents are developed without bias or
improper influence. The complete policy on relationships
with industry and other entities (RWI) can be found online.
Appendix 1 of the guideline lists writing committee mem-
bers’ comprehensive and relevant RWI; for the purposes
of full transparency, comprehensive and relevant disclosure
information for the Joint Committee is also available online.
Evidence Review and Evidence Review
Committees
In developing recommendations, the writing commit-
tee uses evidence-based methodologies that are based
on all available data.4,5 Literature searches focus on
randomized controlled trials (RCTs) but also include reg-
istries, nonrandomized comparative and descriptive stud-
ies, case series, cohort studies, systematic reviews, and
expert opinion. Only key references are cited.
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CLINICAL STATEMENTS
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
An independent evidence review committee is com-
missioned when there are ≥1 questions deemed of
utmost clinical importance and merit formal systematic
review to determine which patients are most likely to ben-
efit from a drug, device, or treatment strategy and to what
degree. Criteria for commissioning an evidence review
committee and formal systematic review include absence
of a current authoritative systematic review, feasibility of
defining the benefit and risk in a time frame consistent
with the writing of a guideline, relevance to a substantial
number of patients, and likelihood that the findings can
be translated into actionable recommendations. Evidence
review committee members may include methodologists,
epidemiologists, clinicians, and biostatisticians. Recom-
mendations developed by the writing committee on the
basis of the systematic review are marked “SR”.
Guideline-Directed Management and Therapy
The term guideline-directed management and therapy
(GDMT) encompasses clinical evaluation, diagnostic
testing, and both pharmacological and procedural treat-
ments. For these and all recommended drug treatment
regimens, the reader should confirm dosage with prod-
uct insert material and evaluate for contraindications
and interactions. Recommendations are limited to drugs,
devices, and treatments approved for clinical use in the
United States.
Joshua A. Beckman, MD, MS, FAHA, FACC
Chair, ACC/AHA Joint Committee on
Clinical Practice Guidelines
1. INTRODUCTION
1.1. Methodology and Evidence Review
The recommendations listed in this guideline are,
whenever possible, evidence based. An initial extensive
evidence review, which included literature derived from
research involving human subjects, published in English,
and indexed in MEDLINE (through PubMed), EMBASE,
the Cochrane Library, the Agency for Healthcare Re-
search and Quality, and other selected databases rel-
evant to this guideline, was conducted from September
14, 2022, to November 2022, and included literature
published between 2013 and 2022. Various published
search hedges were used to eliminate animal studies
and to locate relevant material that may not have been
retrievable using existing database study type filters at
the time the searches were performed.1–6 Key search
words included but were not limited to the following:
hypertrophic cardiomyopathy, coronary, ischemia, sys-
tole, atrial fibrillation, exercise, stroke volume, transplant,
magnetic resonance imaging, sudden death, left ven-
tricular hypertrophy, subvalvular stenosis, echocardiog-
raphy, nuclear magnetic resonance imaging, computed
tomographic angiography, genetic testing, and diagnostic
imaging. Additional relevant studies, published through
May 23, 2023, during the guideline writing process, were
also considered by the writing committee and added to
the evidence tables when appropriate. The final evidence
tables are included in the Online Data Supplement and
summarize the evidence used by the writing committee
to formulate recommendations. References selected and
published in the present document are representative
and not all-inclusive.
1.2. Composition of the Writing Committee
The writing committee consisted of clinicians, adult car-
diologists, pediatric cardiologists, interventionalists, a
cardiac surgeon, and 2 lay/patient representatives. The
writing committee included representatives from the
ACC, AHA, American Medical Society for Sports Medi-
cine, Heart Rhythm Society, Pediatric & Congenital Elec-
trophysiology Society, and Society for Cardiovascular
Magnetic Resonance. Appendix 1 of the current docu-
ment lists writing committee members’ comprehensive
and relevant RWI.
1.3. Document Review and Approval
The Joint Committee appointed a peer review commit-
tee to review the document. The peer review committee
was composed of individuals nominated by ACC, AHA,
and the collaborating organizations. Reviewers’ RWI in-
formation was distributed to the writing committee and is
published in Appendix 2.
This document was approved for publication by the
governing bodies of the ACC and the AHA and was
endorsed by American Medical Society for Sports Medi-
cine, Heart Rhythm Society, Pediatric & Congenital Elec-
trophysiology Society, and Society for Cardiovascular
Magnetic Resonance.
1.4. Scope of the Guideline
In developing the “2024 AHA/ACC/AMSSM/HRS/
PACES/SCMR Guideline for the Management of Hy-
pertrophic Cardiomyopathy” (2024 HCM guideline), the
writing committee reviewed previously published guide-
lines. Table 2 contains a list of these publications and
statements deemed pertinent to this writing effort and is
intended for use as a resource, thus obviating the need
to repeat existing guideline recommendations.
1.5. Class of Recommendations and Level of
Evidence
The Class of Recommendation (COR) indicates the
strength of recommendation, encompassing the estimat-
ed magnitude and certainty of benefit in proportion to
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
risk. The Level of Evidence (LOE) rates the quality of sci-
entific evidence supporting the intervention on the basis
of the type, quantity, and consistency of data from clinical
trials and other sources (Table 3).
1.6. Abbreviations
Abbreviation Meaning/Phrase
AF atrial fibrillation
CAD coronary artery disease
CMR cardiovascular magnetic resonance
CPET cardiopulmonary exercise test
CRT cardiac resynchronization therapy
Abbreviation Meaning/Phrase
DOAC direct-acting oral anticoagulants
EF ejection fraction
ESM extended septal myectomy
GDMT guideline-directed management and therapy
HCM hypertrophic cardiomyopathy
HF heart failure
ICD implantable cardioverter-defibrillator
LBBB left bundle branch block
LGE late gadolinium enhancement
LV left ventricular
LVA D left ventricular assist device
LV E F left ventricular ejection fraction
LVH left ventricular hypertrophy
LVO T left ventricular outflow tract
LVO TO left ventricular outflow tract obstruction
MET metabolic equivalent
MR mitral regurgitation
NSVT nonsustained ventricular tachycardia
NYHA New York Heart Association
RCT randomized controlled trial
RV right ventricular
SAM systolic anterior motion
SCAF subclinical atrial fibrillation
SCD sudden cardiac death
SRT septal reduction therapy
TEE transesophageal echocardiogram
TTE transthoracic echocardiogram
VF ventricular fibrillation
VT ventricular tachycardia
VUS variant of uncertain significance
2. DEFINITION, ETIOLOGY, CLINICAL
COURSE, AND NATURAL HISTORY
2.1. Prevalence
HCM is a common inherited heart disease reported in
populations globally. The estimated prevalence of HCM
varies depending on whether subclinical or clinically
evident cases are being considered, how or if the di-
agnosis is adjudicated, and age of the sample studied.1
The prevalence of unexplained asymptomatic hyper-
trophy in young adults in the United States has been
reported in the range of 1:500.2 Symptomatic hypertro-
phy based on medical claims data has been estimated
at <1:3000 adults in the United States; however, the
true burden is much higher when unrecognized dis-
ease in the general population is considered.3 HCM
is often inherited in an autosomal dominant pattern
but does not require a family history of HCM. There
Table 2. Associated Guidelines and Statements
Title Organization
Publication Year
(Reference)
Guidelines
Hypertrophic cardiomyopathy ACC/AHA
ESC
20111
20142
20203
Atrial fibrillation AHA/ACC 20144
20195
20236
Heart failure ACC/AHA 20137
20168
20229
Primary prevention AHA/ACC 201910
Management of overweight and
obesity in adults
AHA/ACC/TOS 201411
Device-based therapy for cardiac
rhythm abnormalities
ACC/AHA/HRS 201312
Ventricular arrhythmias and sudden
cardiac death
AHA/ACC/HRS 201713
Bradycardia ACC/AHA/HRS 201814
Prevention of cardiovascular disease
in women
AHA/ACC 201115
Secondary prevention and risk
reduction therapy for patients with
coronary and other atherosclerotic
vascular disease
AHA/ACC 201116
Assessment of cardiovascular risk in
asymptomatic adults
ACC/AHA 201017
Seventh Report of the Joint National
Committee on Prevention, Detec-
tion, Evaluation, and Treatment of
High Blood Pressure
NHLBI 200318
VHD statement on comprehensive
centers
AATS/ACC/
ASE/SCAI/STS
201919
AATS indicates American Association for Thoracic Surgery; ACC, American
College of Cardiology; AHA, American Heart Association; ASE, American Society
of Echocardiography; ESC, European Society of Cardiology; HRS, Heart Rhythm
Society; NHLBI, National Heart, Lung, and Blood Institute; SCAI, Society for Car-
diovascular Angiography and Interventions; STS, Society of Thoracic Surgeons;
TOS, The Obesity Society; and VHD, valvular heart disease.
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is equal distribution of HCM by sex, although women
are diagnosed less commonly than men. Differences
in prevalence have been reported by race and ethnic-
ity. Whether this difference is due to social disparities
resulting in less access to specialists for diagnosis is
unclear. As a result, these differences likely reflect un-
derlying differences in social determinants of health,
such as structural inequities in access to care leading
to differences in diagnosis and awareness. Patients
who self-identified as Black individuals (8.3%, N=205)
compared with White individuals had a younger mean
age at diagnosis (40 years versus 45.5 years), were
more likely to have symptomatic heart failure (HF), and
were less likely to undergo genetic testing.4 Epidemio-
logic studies of diverse samples are needed to better
understand the interplay between genetic and social
factors in the prevalence of HCM.
2.2. Nomenclature and Differential Diagnosis
Since the original clinical description of HCM was pre-
sented >60 years ago, various names have been used to
describe this disease, including idiopathic hypertrophic
subaortic stenosis and hypertrophic obstructive cardio-
myopathy. Because left ventricular (LV) outflow tract ob-
struction (LVOTO) is not invariably present, the writing
committee recommends the term HCM (with or without
outflow tract obstruction).
Table 3. Applying American College of Cardiology/American Heart Association Class of Recommendation and Level of
Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated May 2019)
CLASS (STRENGTH) OF RECOMMENDATION
CLASS 1 (STRONG)
Suggested phrases for writing recommendations:
• Is recommended
•
• Should be performed/administered/other
• Comparative-Effectiveness Phrases†:
–Treatment/strategy A is recommended/indicated in preference to
treatment B
–Treatment A should be chosen over treatment B
CLASS 2a (MODERATE)
Suggested phrases for writing recommendations:
• Is reasonable
•
• Comparative-Effectiveness Phrases†:
–Treatment/strategy A is probably recommended/indicated in
preference to treatment B
– It is reasonable to choose treatment A over treatment B
CLASS 2b (WEAK)
Suggested phrases for writing recommendations:
• May/might be reasonable
• May/might be considered
• Usefulness/effectiveness is unknown/unclear/uncertain or not well-
established
(Generally, LOE A or B use only)
Suggested phrases for writing recommendations:
• Is not recommended
•
• Should not be performed/administered/other
Class 3: Harm (STRONG)
Suggested phrases for writing recommendations:
• Potentially harmful
• Causes harm
• Associated with excess morbidity/mortality
• Should not be performed/administered/other
LEVEL (QUALITY) OF EVIDENCE‡
LEVEL A
• High-quality evidence‡ from more than 1 RCT
• Meta-analyses of high-quality RCTs
• One or more RCTs corroborated by high-quality registry studies
LEVEL B-R (Randomized)
• Moderate-quality evidence‡ from 1 or more RCTs
• Meta-analyses of moderate-quality RCTs
LEVEL B-NR (Nonrandomized)
• Moderate-quality evidence‡ from 1 or more well-designed, well-
executed nonrandomized studies, observational studies, or registry
studies
• Meta-analyses of such studies
LEVEL C-LD (Limited Data)
• Randomized or nonrandomized observational or registry studies with
limitations of design or execution
• Meta-analyses of such studies
• Physiological or mechanistic studies in human subjects
LEVEL C-EO (Expert Opinion)
• Consensus of expert opinion based on clinical experience
COR and LOE are determined independently (any COR may be paired with any LOE).
A recommendation with LOE C does not imply that the recommendation is weak. Many
important clinical questions addressed in guidelines do not lend themselves to clinical
trials. Although RCTs are unavailable, there may be a very clear clinical consensus that a
particular test or therapy is useful or effective.
*
outcome or increased diagnostic accuracy or incremental prognostic information).
† For comparative-effectiveness recommendations (COR 1 and 2a; LOE A and B only),
studies that support the use of comparator verbs should involve direct comparisons
of the treatments or strategies being evaluated.
‡ The method of assessing quality is evolving, including the application of stan-
dardized, widely-used, and preferably validated evidence grading tools; and for
systematic reviews, the incorporation of an Evidence Review Committee.
COR indicates Class of Recommendation; EO, expert opinion; LD, limited data; LOE,
Level
of Evidence; NR, nonrandomized; R, randomized; and RCT, randomized controlled trial.
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In some areas, the use of HCM to describe the
increased LV wall thickness associated with systemic
disorders or secondary causes of LV hypertrophy (LVH)
can lead to confusion. Systemic disorders include
various metabolic and multiorgan syndromes such
as RASopathies (variants in several genes involved in
RAS-MAPK signaling); mitochondrial myopathies; gly-
cogen and lysosomal storage diseases in children; and
Fabry, amyloid, sarcoid, and Danon cardiomyopathies.
In these syndromic or infiltrative diseases, although the
magnitude and distribution of increased LV wall thick-
ness can be similar to that of HCM, the pathophysiologic
mechanisms responsible for hypertrophy, natural history,
and treatment strategies are not the same.1–5 For these
reasons, other cardiac or systemic diseases capable of
producing LVH (ie, HCM mimics) will not be addressed
in this document.
In addition, other scenarios can arise that pre sent
diagnostic challenges. These include conditions that
produce secondary LVH, which can also overlap phe-
notypically with HCM, including remodeling second-
ary to athletic training (ie, “athlete’s heart”) as well as
morphologic changes related to long-standing sys-
temic hypertension (ie, hypertensive cardiomyopathy).
Similarly, hemodynamic obstruction caused by left-sided
obstructive lesions (valvular or subvalvular stenosis) or
obstruction after antero-apical infarction and stress car-
diomyopathy can cause diagnostic dilemmas.6,7 Although
HCM cannot be definitely excluded in such situations, a
number of clinical markers and testing strategies can be
used to help differentiate between HCM and conditions
of physiologic LVH.
2.3. Definition, Clinical Diagnosis, and
Phenotype
For the purposes of this guideline, the clinical definition
of HCM is considered a disease state in which mor-
phologic expression is confined solely to the heart. It is
characterized predominantly by LVH in the absence of
another cardiac, systemic, or metabolic disease capable
of producing the magnitude of hypertrophy evident in a
given patient and for which a disease-causing sarcomere
(or sarcomere-related) variant is identified or genetic eti-
ology remains unresolved. A clinical diagnosis of HCM
in adult patients can therefore be established by imag-
ing (see Section 6.1, “Clinical Diagnosis”), typically
with 2D echocardiography or cardiovascular magnetic
resonance (CMR) showing a maximal end-diastolic wall
thickness of ≥15 mm anywhere in the left ventricle, in
the absence of another cause of hypertrophy in adults.1–4
More limited hypertrophy (13-14 mm) can be diagnostic
when present in family members of a patient with HCM
or in conjunction with a positive genetic test identifying
a pathogenic or likely pathogenic variant often in a sar-
comere gene.
For children, the diagnostic criteria are confounded
by needing to adjust for body size and growth. Tradi-
tionally, a body surface area adjusted z-score of ≥2
standard deviations above the mean has been used.
This cut-off represents a significantly lower threshold
than the 15-mm absolute value used in adults. For ref-
erence, 15 mm represents a z-score of approximately
6 standard deviations above the mean in adults. We
propose that the diagnosis of HCM in children should
therefore consider the circumstances of screening
and the pretest probability of disease: a threshold of
a z-score >2.5 may be appropriate to identify early
HCM in asymptomatic children with no family his-
tory, whereas for children with a definitive family his-
tory or a positive genetic test, a threshold of a z-score
>2 may suffice for early diagnosis. The emergence of
the HCM phenotype in younger family members who
carry a pathogenic or likely pathogenic variant with-
out previously evident LVH at initial screening (ie,
genotype-positive/previously phenotype-negative) is
well recognized and underscores the principle that, as
the disease manifests, normal or mildly increased LV
wall thicknesses will be encountered in individuals with
genetically affected status. In the absence of increased
wall thickness, such individuals should be considered
at risk for subsequent development of, but not yet hav-
ing, clinically evident HCM.
Nearly any pattern and distribution of LV wall thick-
ening can be observed in HCM, with the basal anterior
septum in continuity with the anterior free wall the most
common location for LVH. In a subset of patients, hyper-
trophy can be limited and focal, confined to only 1 or 2
LV segments with normal LV mass. Although common in
HCM, systolic anterior motion (SAM) of the mitral valve
and hyperdynamic LV function are not pathognomonic
and are not required for a clinical diagnosis. Several other
morphologic abnormalities are also not diagnostic of
HCM but can be part of the phenotypic expression of the
disease, including hypertrophied and apically displaced
papillary muscles, myocardial crypts, anomalous insertion
of the papillary muscle directly in the anterior leaflet of
the mitral valve (in the absence of chordae tendineae),
elongated mitral valve leaflets, myocardial bridging, and
right ventricular (RV) hypertrophy.
2.4. Etiology
In the early 1990s, the DNA sequencing from families
with HCM led to the discovery that damaging variants
in genes coding for sarcomere proteins segregated
(or were coinherited) with LVH identified by echocar-
diographic assessment, abnormal electrocardiograms
(ECGs), and physical findings. HCM thereby became
regarded as a potentially monogenic disease, helping
to consolidate a clinically heterogeneous disease into a
single entity based on genetic substrate.1
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Currently, variants in 1 of ≥8 genes encoding pro-
teins of the cardiac sarcomere (or sarcomere-related
structures) have been implicated in causing LVH, the
sine qua non of HCM. Among patients with HCM,
approximately 30% to 60% have an identifiable patho-
genic or likely pathogenic genetic variant. A substantial
proportion of patients with HCM are currently without
any evidence of a genetic etiology to their disease,
including a subgroup (up to 40% of patients in 1 study)
who also have no other affected family members (ie,
“nonfamilial” HCM).2 These observations suggest that
other novel pathophysiologic mechanisms may be
responsible for, or contribute to, phenotypic expres-
sion in these affected patients with HCM. Although
HCM appears to be a monogenic disease in some
cases, common genetic variants have also been iden-
tified as genetic modifiers of disease penetrance and
-associated with risk for LVH and HCM, which suggests
both monogenic and polygenic susceptibility.3
Among patients with HCM and a pathogenic sarco-
meric gene variant, the 2 most common genes are beta
myosin heavy chain 7 (MYH7) and myosin-binding protein
C3 (MYBPC3), identified in most patients who are vari-
ant positive, while other genes (TNNI3, TNNT2, TPM1,
MYL2, MYL3, ACTC1) each account for a small propor-
tion of patients (1%-5%). Within these genes, most rare
variants identified are “private” (unique to the individual
family). Each offspring of an affected family member
has a 50% chance of inheriting the variant.4 Although
the likelihood of developing clinical HCM is high in fam-
ily members with a pathogenic variant, the age at which
disease expression occurs in a given individual as well as
the degree of expression is variable.
The precise mechanisms by which sarcomere variants
result in the clinical phenotype have not been fully eluci-
dated. Alterations in the sarcomere gene trigger myocar-
dial changes, leading to hypertrophy and fibrosis, which
ultimately results in a small, stiff ventricle with impaired
systolic and diastolic performance despite a preserved
left ventricular ejection fraction (LVEF). Similarly, abnor-
mal sarcomeric proteins may not be solely responsible
for all of the clinical characteristics observed in patients
with HCM. Diverse disease features including abnormal
intramural coronary arteries responsible for small vessel
ischemia, elongated mitral valve leaflets, and congenital
anomalies of the submitral valve apparatus, which are
widely recognized components of the HCM phenotype,
appear to have no known direct association with sarco-
mere variants.
2.5. Natural History and Clinical Course
Although HCM can be compatible with normal life ex-
pectancy without limiting symptoms or the need for
major treatments in most patients, many patients can
experience significant consequences that are attribut-
able to the disease. To this point, there is increasing
recognition of patients with HCM identified clinically
at >60 years of age with little to no disability. Yet, a
multicenter registry report has suggested that the life-
long risk of adverse events (eg, mortality, HF, stroke,
ventricular arrhythmia, atrial fibrillation [AF]) caused by
HCM may be greater among patients with pathogenic
or likely pathogenic sarcomeric gene variants or those
diagnosed early in life.1 The large number and diver-
sity of the HCM-associated variants do not allow the
specific genotype to be used to inform the anticipated
outcomes in individual patients.
Among referral-based cohorts of patients with HCM,
many will experience adverse events, including: (1)
sudden death events; (2) progressive limiting symp-
toms because of LVOTO or diastolic dysfunction; (3)
HF symptoms associated with systolic dysfunction; and
(4) AF with risk of thromboembolic stroke. Neverthe-
less, studies reporting relatively long-term outcomes in
patients with HCM have demonstrated that for patients
at risk for, or who develop one of these disease-related
complications, the application of contemporary cardio-
vascular therapies and interventions has significantly
lowered HCM mortality rates.2,3 One of the major treat-
ment initiatives responsible for lowering the mortality
rate has been the evolution of sudden cardiac death
(SCD) risk stratification strategies based on several
major noninvasive risk markers that can identify adult
patients with HCM at greatest risk for sudden death
who are then candidates for implantable cardioverter-
defibrillator (ICD) placement. The decrease in sudden
death rates in HCM appears now to have shifted focus
to HF and complications of AF as the predominant
cause of disease-related morbidity and mortality and,
therefore, the greatest unmet treatment need in adults.
Risk for adverse events in HCM, particularly for HF,
are likely due to the complex interplay of genetics with
environmental factors, such as obesity, hypertension,
sleep apnea, and diabetes.4 Among patients with HCM,
cardiometabolic risk factors (eg, obesity, hypertension,
diabetes, obstructive sleep apnea) are highly prevalent
and are associated with poorer prognosis, highlighting
the importance of intensive risk factor modification of
traditional risk factors.
3. PATHOPHYSIOLOGY
The pathophysiology of HCM consists of dynamic
LVOTO, mitral regurgitation (MR), diastolic dysfunc-
tion, myocardial ischemia, arrhythmias, metabolic and
energetic abnormalities, and potentially autonomic
dysfunction. For a given patient with HCM, the clinical
outcome may be dominated by one of these compo-
nents or may be the result of a complex interplay. Thus,
the potential presence of such abnormalities should
be considered with comprehensive clinical evaluation
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and their impact addressed in the management of
these patients.
3.1. Left Ventricular Outflow Tract Obstruction
LVOTO, either at rest or with provocation, is present in
a significant proportion of patients with HCM1 and pri-
marily caused by SAM of the mitral valve. Obstruction is
considered present if peak LVOT gradient is ≥30 mm Hg.
Resting or provoked gradients ≥50 mm Hg are generally
considered capable of causing symptoms and, therefore,
are the threshold for contemplating advanced pharmaco-
logical or invasive therapies if symptoms are refractory to
standard management.
LVOTO in HCM is dynamic and sensitive to ventricu-
lar preload, afterload, and contractility.2 Thus, gradients
vary with heart rate, blood pressure, volume status, activ-
ity, medications, food, and alcohol intake.3,4 Provocative
maneuvers are recommended if minimal gradients (ie,
<30 mm Hg) are observed at rest. Maneuvers include
standing, Valsalva strain, or exercise with simultaneous
auscultation or echocardiography.5–9 Using dobutamine
to identify latent LVOTO and eligibility for advanced ther-
apies is not advised due to lack of specificity.10
The site and characteristics of obstruction should
be identified. Management will change depending
on whether the obstruction is deemed to be valvular,
dynamic LVOTO, fixed subvalvular, or midcavitary due
to hypertrophied/anomalous papillary muscles and/or
hyperdynamic LV function with systolic cavity oblitera-
tion. If clinical and echocardiographic findings are discor-
dant, invasive assessment for LVOTO may be helpful.11
3.2. Diastolic Dysfunction
Altered ventricular load with high intracavitary pres-
sures, impaired LV compliance from hypertrophy and
fibrosis, altered energetics, microvascular ischemia,
and delayed inactivation from abnormal intracellular
calcium reuptake are features of HCM that contribute
to diastolic dysfunction.1–3 Additionally, impaired relax-
ation can be identified in young sarcomere gene variant
carriers with normal LV wall thickness, suggesting that
diastolic abnormalities can be an early manifestation of
pathogenic sarcomere variants.4 In some patients, in-
creased stiffness and severe hypertrophy significantly
compromise ventricular cavity size and stroke volume
and may result in restrictive physiology. Diastolic dys-
function can contribute to decreased exercise capacity
and adverse prognosis independent of LVOTO.2,5,6 De-
termining if exercise intolerance or symptoms are due
to diastolic dysfunction may require invasive testing.
With impaired ventricular myocardial relaxation, greater
dependency on the atrial systole for ventricular filling
may occur, leading to poor tolerance of AF or similar
arrhythmias in some patients.
3.3. Mitral Regurgitation
MR can occur secondarily from SAM or primarily from
leaflet abnormalities and, regardless of etiology, can
contribute to symptom burden. Common primary abnor-
malities of the mitral valve in patients with HCM include
excessive leaflet length, anomalous papillary muscle in-
sertion, and anteriorly displaced papillary muscles.1–3 MR
jet characteristics can provide insight to etiology as MR
caused by SAM is typically mid-to-late systolic in timing
and posterior or lateral in orientation, owing to the ante-
rior distortion of the mitral valve and compromised leaflet
coaptation.4 However, central and anterior jets may also
result from SAM of the mitral valve. For patients in whom
invasive septal reduction therapy (SRT) is being contem-
plated, close examination of the mitral valve is required
to determine the optimal invasive approach and potential
need for concomitant mitral valve intervention.5,6
Factors that affect the severity of LVOTO may also
affect the degree of MR, thus imaging should be per-
formed at rest and with provocation. Additionally, variation
in the degree of MR may underlie some of the variation in
symptoms reported by patients.
3.4. Myocardial Ischemia
Patients with HCM may be susceptible to myocardial
ischemia due to potential mismatch between myocardial
oxygen supply and demand. Myocardial hypertrophy, mi-
crovascular dysfunction with impaired coronary flow re-
serve, and medial hypertrophy and reduced density of the
intramural arterioles are common findings in HCM.1,2 These
abnormalities may be exacerbated by the presence of hy-
perdynamic systolic function and LVOTO with high intra-
cavitary pressures.3,4 Blunted coronary flow reserve occurs
even without epicardial stenosis, although the presence of
concomitant severe coronary atherosclerosis exacerbates
mismatch and is associated with a poorer prognosis.5 Api-
cal myocardial ischemia and injury (with or without midven-
tricular obstruction) may be one of the mechanisms that
contributes to the development of LV apical aneurysms,
which may carry increased risk of HF, stroke, and ven-
tricular arrhythmias.6,7 Myocardial bridging, a congenital
anomaly whereby a bridge of overlying myocardium causes
systolic compression of an epicardial coronary artery that
can persist into diastole, may impair blood flow and may
rarely cause myocardial ischemia in a subset of patients.8–12
3.5. Autonomic Dysfunction
Patients with HCM may have autonomic dysfunction,
with impaired heart rate recovery and inappropriate
vasodilatation.1–4 The prevalence of autonomic dysfunc-
tion in HCM is uncertain, although studies have described
an abnormal blood pressure response to exercise in ap-
proximately 25% of patients.2–4 Whether these findings
were due to pure autonomic dysfunction, LVOTO, or other
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conditions is unclear. Currently, no specific recommen-
dations exist for assessment or treatment of autonomic
dysfunction in patients with HCM.
4. SHARED DECISION-MAKING
Recommendation for Shared Decision-Making
Referenced studies that support the recommendation are
summarized in the Online Data Supplement.
COR LOE Recommendation
1 B-NR
1. For patients with HCM or at risk for HCM, shared
decision-making is recommended in developing a
plan of care (including, but not limited to, decisions
regarding genetic evaluation, activity, lifestyle, and
therapy choices) that includes a full disclosure of the
risks, benefits, and anticipated outcomes of all
options, as well the opportunity for the patient and
caregivers to express their goals and concerns.1–5
Synopsis
Shared decision-making is a dialogue that allows pa-
tients, families, and health care professionals to work
together to select options that fully consider the input,
values, and preferences for the patient. This approach
has been shown to improve confidence in clinical deci-
sions and improved health outcomes.6 Although shared
decision-making discussions should be the default in-
teraction between patients (or their families in the case
of an affected minor) and their care teams, the biggest
opportunities are those areas where there are complex
pathways that vary by the individual patient.
Recommendation-Specific Supportive Text
1. In the management of HCM, decisions around
genetic testing, ICD implantation, advanced thera-
pies for relief of LVOTO, and participation in com-
petitive or high-intensity exercise are particularly
critical for these crucial dialogues. Some of these
discussions and decisions could also represent
opportunities where referral to centers with more
comprehensive experience are most appropri-
ate and highly impactful (as described in detail in
Section 5, “Multidisciplinary HCM Centers”).
5. MULTIDISCIPLINARY HCM CENTERS
Recommendations for Multidisciplinary HCM Centers
COR LOE Recommendations
1 C-LD
1. In patients with HCM in whom SRT is indicated, the
procedure should be performed at experienced
centers (comprehensive or primary HCM centers)
with demonstrated excellence in clinical outcomes
for these procedures (Tables 4 and 5).1–3
2a C-LD
2. In patients with HCM, consultation with or referral
to a comprehensive or primary HCM center is
reasonable to aid in complex disease-related
management decisions (Table 4).4–14
Synopsis
The specialized needs, complex and evolving clini-
cal management, and the relatively uncommon preva-
lence of HCM in many clinical practices have created a
greater demand and need for clinical HCM centers with
HCM-specific competencies similar to that proposed
for the management of patients with valvular heart
disease.5–7,15 The main goal of the HCM centers’ frame-
work is to optimize care and counseling of patients with
HCM and their families. The proposed approach recog-
nizes that a spectrum of expertise exists and is inclusive
of roles for cardiologists working outside of HCM cen-
ters, those working in primary HCM centers, and those
working at fully comprehensive HCM centers. Cardiolo-
gists practicing outside of HCM centers have a critical
role in many aspects of HCM management (Table 4)
including, but not limited to, providing ready access for
initial and surveillance testing, treatment recommenda-
tions, and availability for rapid assessment when a pa-
tient’s disease course changes.
Referral to HCM centers can help to confirm diag-
nosis, provide genetic counseling and testing, advise
regarding more advanced treatment decisions, and pro-
vide patients with access to the highest level of longitu-
dinal care possible for their disease.7
Recommendation-Specific Supportive Text
1. When performed in centers with limited experi-
ence and low procedural volume, invasive SRTs
for relief of LVOTO are associated with increased
mortality and morbidity rates, as well as mitral
valve replacement.1–3,16,17 Strong consideration
should therefore be given to referral of patients
with obstructive HCM who are candidates for
invasive SRTs to established high-volume primary
or comprehensive HCM centers, which can per-
form these procedures with optimal safety and
benefit outcomes. Primary HCM centers that
perform invasive SRTs should ensure outcomes
for safety and benefit, commensurate with that
reported from comprehensive HCM centers
(Tables 4 and 5). If only one of the invasive SRT
options is available at a given center, patients
should be fully informed of alternative options,
including the pros and cons of both procedures
and the possibility for referral to a comprehen-
sive HCM center that offers all treatment options
to ensure appropriate patient participation in the
decision-making.
2. Given the unique needs of patients with HCM in
clinical cardiovascular practice, as well as the
specialized training and interpretation associ-
ated with many of the procedures and testing for
this complex condition, challenging management
decision-making can arise for which referral to or
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consultation with an HCM center would be rea-
sonable.4–13 Referral to a comprehensive HCM
center should specifically be considered for
those patients with HCM who are candidates for
any procedure that requires specialized exper-
tise, including complex invasive SRTs,3,8,9 cath-
eter ablation for ventricular and complex atrial
tachyarrhythmias,10,11 and advanced HF thera-
pies, including transplant.12,13 In addition, refer-
ral to a comprehensive HCM center can aid in
complex disease-related management decisions
including, but not limited to, genetic counseling,
challenging primary prevention ICD decision-
making, as well as counseling patients with HCM
on sports participation.4
6. DIAGNOSIS, INITIAL EVALUATION, AND
FOLLOW-UP
6.1. Clinical Diagnosis
Recommendation for Clinical Diagnosis
Referenced studies that support the recommendation are
summarized in the Online Data Supplement.
COR LOE Recommendation
1 B-NR
1. In patients with suspected HCM, comprehensive
physical examination and complete medical and
3-generation family history is recommended as
part of the initial diagnostic assessment
(Tables 6 and 7).1–6
Synopsis
Clinical evaluation for HCM may be triggered by the
identification of a family history of HCM; by symptoms
including a cardiac event; by detection of a heart murmur
Table 4. Suggested Competencies of Comprehensive and
Primary HCM Centers
Potential HCM Care Delivery
Competencies
Comprehensive
HCM Center
Primary
HCM
Center
Referring
Centers and
Physicians
Diagnosis X X X
Initial and surveillance TTE X X X
Advanced echocardiographic
imaging to detect latent LVOTO
X X
Echocardiography to guide SRT X *
CMR imaging for diagnosis
and risk stratification
X X
Invasive evaluation for LVOTO X * *
Coronary angiography X X X
Stress testing for elicitation
of LVOTO or consideration of
advanced HF therapies and
transplant
X X
Counseling and performing
family screening (imaging and
genetic)
X X X
Genetic testing and counseling X X *
SCD risk assessment X X X
COR 1 and COR 2a ICD
decision-making with adult
patients
X X X
COR 2b ICD decision-making
with adult patients
X
ICD implantation (adults) X X *
ICD decision-making and
implantation with children and
adolescents and their parents
and caregivers
X *
Initial AF management and
stroke prevention
X X X
AF catheter ablation X X *
Initial management of HFrEF
and HFpEF
X X X
Advanced HF management
(eg, transplantation, CRT)
X *
Pharmacological therapy for HCM X X X
Invasive management of
symptomatic obstructive HCM
X †
Counseling occupational and
healthy living choices other
than high-intensity or
competitive activities
X X X
Counseling options on
participation in high-intensity or
competitive athletics
X
Managing women with HCM
through pregnancy
X *
Management of comorbidities X X X
*Optional depending on the core competencies of the institution.
†If these procedures are performed, adequate quality assurance should be in
place to demonstrate outcomes consistent with that achieved by comprehensive
centers.
AF indicates atrial fibrillation; CMR, cardiovascular magnetic resonance;
COR, Class of Recommendation; CRT, cardiac resynchronization therapy; HCM,
hypertrophic cardiomyopathy; HF, heart failure; HFpEF, heart failure with pre-
served ejection fraction; HFrEF, heart failure with reduced ejection fraction;
ICD, implantable cardioverter-defibrillator; LVOTO, left ventricular outflow tract
obstruction; SCD, sudden cardiac death; SRT, septal reduction therapy; and
TTE, transthoracic echocardiography.
Table 5. Targets for Invasive Septal Reduction Therapies
Outcomes
Rate (%)
Myectomy
Alcohol
Septal
Ablation
30-d mortality ≤1≤1
30-d adverse complications (tamponade, LAD
dissection, infection, major bleeding)
≤5≤5
30-d complete heart block resulting in need for
permanent pacemaker
≤5≤10
Mitral valve replacement within 1 y ≤5
More than moderate residual mitral regurgitation ≤5≤5
Repeat procedure rate ≤3≤10
Symptomatic improvement (eg, ≥1 NYHA
functional class)
>90 >90
Rest and provoked LVOT gradient <50 mm Hg >90 >90
LAD indicates left anterior descending; LVOT, left ventricular outflow tract; and
NYHA, New York Heart Association.
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during physical examination; during an echocardio-
graphic examination performed for other indications; or
by abnormal results on a 12-lead ECG. A proper clinical
evaluation should begin with a comprehensive cardiac
history, a family history including 3 generations, and a
comprehensive physical examination (including maneu-
vers such as Valsalva, squat-to-stand, passive leg rais-
ing, or walking). This should be followed by an ECG and
cardiac imaging to identify LVH when clinical findings are
suggestive.
Recommendation-Specific Supportive Text
1. Many patients with HCM are asymptomatic and
are identified incidentally or as a result of
screening. Clinical history includes a detailed
cardiac history and family history (3 genera-
tions) to identify relatives with HCM or unex-
pected or sudden death. Assessment of overall
fitness and functional capacity, and symptoms
in response to exertion—chest pain, dyspnea,
palpitations, and syncope—should also be per-
formed. Associated syndromic or systemic and
extracardiac symptoms or organ involvement
are also documented. Alternative etiologies
should be excluded, including athletic remod-
eling, uncontrolled hypertension, renal disease,
or infiltrative diseases. In neonates, a history of
maternal gestational diabetes should be consid-
ered and, in infants <1 year of age, exclude sys-
temic disease (Table 6).
Classically, patients with HCM have a harsh
crescendo-decrescendo systolic murmur often due
to SAM of the mitral valve with LVOTO, prominent
apical point of maximal impulse, abnormal carotid
pulse, and a fourth heart sound. Presence of out-
flow tract obstruction should be sought at rest
and with provocative maneuvers when possible
(Valsalva maneuver, standing from the squatting
position). SAM related to an elongated anterior
mitral valve leaflet and papillary muscle abnormali-
ties may result in leaflet separation or poor coap-
tation with posteriorly directed MR in late systole
over the mitral position. Those without LVOTO
(provocable or resting) may have a normal physical
examination.1–6
Table 6. Clinical Features in Patients With HCM Phenocopies (Mimics)
Typical Presentation Age Systemic Features Possible Etiology Diagnostic Approach
Infants (0-12 mo) and toddlers Dysmorphic features, failure to
thrive, metabolic acidosis
RASopathies
Glycogen storage diseases, other meta-
bolic or mitochondrial diseases
Infant of a mother with diabetes
Geneticist assessment
Newborn metabolic screening
Specific metabolic assays
Genetic testing
Early childhood Delayed or abnormal cognitive
development, visual or hearing
impairment
RASopathies
Mitochondrial diseases
Biochemical screening
Genetic testing
Youth and adolescence Skeletal muscle weakness or
movement disorder
Friedreich’s ataxia
Danon disease
Mitochondrial disease
Biochemical screening
Neuromuscular assessment
Genetic testing
Adulthood Movement disorder, peripheral
neuropathy, renal dysfunction
Anderson-Fabry disease
Friedreich’s ataxia
infiltrative disorders (eg, amyloidosis)
Glycogen storage diseases
Mitochondrial disease
Biochemical screening
Neuromuscular assessment
Genetic testing
HCM indicates hypertrophic cardiomyopathy.
Table 7. Screening With Electrocardiography and 2D Echo-
cardiography in Asymptomatic Family Members*
Age of First-Degree
Relative Initiation of Screening
Repeat
ECG, Echo
Pediatric
Children and
adolescents from
genotype-positive
families, and families
with early onset
disease
At the time HCM is diag-
nosed in another family
member
Every 1-2 y
All other children
and adolescents
At any time after HCM
is diagnosed in a family
member but no later than
puberty
Every 2-3 y
Adults At the time HCM is diag-
nosed in another family
member
Every 3-5 y
*Includes all asymptomatic, phenotype-negative, first-degree relatives deemed
to be at risk for developing HCM based on family history or genotype status
and may sometimes include more distant relatives based on clinical judgment.
Screening interval may be modified (eg, at onset of new symptoms or in families
with a malignant clinical course or late-onset HCM).
ECG indicates electrocardiogram; Echo, echocardiogram; and HCM, hypertro-
phic cardiomyopathy.
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6.2. Echocardiography
Recommendations for Echocardiography
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with suspected HCM, a transthoracic
echocardiogram (TTE) is recommended in the
initial evaluation.1–6
1
B-NR
(children)
2. In patients with HCM who have no change in
clinical status or events, repeat TTE is
recommended every 1 to 2 years to assess the
degree of myocardial hypertrophy, dynamic LVOTO,
MR, and myocardial function (Figure 1).7–14
C-LD
(adults)
1 B-NR
3. For patients with HCM who experience a change
in clinical status or a new clinical event, repeat
TTE is recommended.9,14–17
1 B-NR
4. For patients with HCM and resting peak LVOT
gradient <50 mm Hg, a TTE with provocative
maneuvers is recommended.18–21
1 B-NR
5. For symptomatic patients with HCM who do not
have a resting or provocable outflow tract peak
gradient ≥50 mm Hg on TTE, exercise TTE is
recommended for the detection and
quantification of dynamic LVOTO.20–25
1 B-NR
6. For patients with HCM who are undergoing
surgical septal myectomy, intraoperative
transesophageal echocardiogram (TEE) is
recommended to assess mitral valve anatomy and
function and adequacy of septal myectomy.26–29
1 B-NR
7. For patients with HCM who are undergoing
alcohol septal ablation, TTE or intraoperative TEE
with intracoronary ultrasound-enhancing contrast
injection of the candidate’s septal perforator(s) is
recommended.30–34
1 B-NR
8. For patients with HCM who have undergone
SRT, TTE within 3 to 6 months after the
procedure is recommended to evaluate the
procedural results.35–38
1 B-NR
9. Screening: In first-degree relatives of patients
with HCM, a TTE is recommended as part of
initial family screening and periodic follow-up
(Figure 1, Table 7).3–5,7,14,32
1 B-NR
10. Screening: In individuals who are genotype-
positive, phenotype-negative, echocardiography is
recommended at periodic intervals depending on
age (1-2 years in children and adolescents, 3-5
years in adults) and change in clinical status
(Figure 1, Table 7).39–43
2a C-LD
11. For patients with HCM, TEE can be useful if TTE
is inconclusive in clinical decision-making
regarding medical therapy, and in situations
such as planning for myectomy, exclusion of
subaortic membrane or MR secondary to
structural abnormalities of the mitral valve
apparatus, or in the assessment of the feasibility of
alcohol septal ablation.26–29
2a B-NR
12. For patients with HCM in whom the diagnosis of
apical HCM, apical aneurysm, or atypical patterns
of hypertrophy is inconclusive on TTE, the use of an
intravenous ultrasound-enhancing agent is reason-
able, particularly if other imaging modalities such
as CMR are not readily available or are contraindi-
cated.44,45
2a C-LD
13. For asymptomatic patients with HCM who do not
have a resting or provocable outflow tract peak
gradient ≥50 mm Hg on standard TTE, exercise
TTE is reasonable for the detection and
quantification of dynamic LVOTO.15,19,20,22–25
Synopsis
Cardiac imaging has an essential role in the diagnosis
and clinical decision-making for patients with HCM.
Echocardiography is the primary imaging modality in
most patients, with CMR imaging offering complemen-
tary information and as an alternative to echocardiogra-
phy for selected patients in whom the echocardiogram
is inconclusive. Important information to be gained from
imaging includes establishing the diagnosis (or exclud-
ing alternative diagnoses), evaluating the severity of
the phenotype, and evaluating for concomitant struc-
tural and functional cardiac abnormalities (eg, systolic,
diastolic, valvular function). Characterization of dynamic
LVOTO, including the integral role of the mitral valve, is
a key strength of echocardiography. Documentation of
the maximal wall thickness, cardiac chamber dimensions,
systolic function, and the presence of LV apical aneurysm
all inform phenotype severity and SCD risk stratification.
Recommendation-Specific Supportive Text
1. Comprehensive 2D echocardiography has a pri-
mary role in establishing the diagnosis of HCM,
determining hypertrophy pattern, presence of LV
apical aneurysms, LV systolic and diastolic function,
mitral valve function, and presence and severity of
LVOTO.1–6
2. Routine follow-up of patients with HCM is an impor-
tant part of optimal care. In asymptomatic patients,
serial TTE, performed every 1 to 2 years, can help
assess for changes in LV systolic and diastolic
function, wall thickness, chamber size, LVOTO, and
concomitant valvular disease. This interval may be
extended in patients who remain clinically stable
after multiple evaluations.7–14
3. Changes in signs or symptoms in patients with
HCM are often attributable to progression of the
hemodynamics of HCM, or the development of new
concomitant cardiovascular abnormalities, such as
valvular heart disease. Echocardiography is the pri-
mary imaging modality to assess these changes in
patients with new or worsening symptoms.9,14–17
4. LVOT gradients are dynamic, influenced by loading
conditions, and recumbent resting echocardiog-
raphy tends to underestimate the presence and
severity of ambulatory LVOTO, with up to 50% of
patients with obstructive physiology being iden-
tified on resting echocardiography. If the resting
gradient is <50 mm Hg, it is essential to perform
provocative maneuvers such as sustained Valsalva
or squat-to-stand (or simply standing) maneuvers
to uncover the presence of LVOTO, which may
inform the care of the individual.15,18–21 Provocative
maneuvers may not be as helpful in children, who
often cannot cooperate with these maneuvers.
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5. In general, to attribute effort-related symptoms to
LVOTO, the resting or provoked gradient would
need to be >50 mm Hg. LVOT gradients can be
dynamic and can be missed on resting echocar-
diography in up to 50% of patients with obstruc-
tive physiology.16 Maneuvers performed during
a resting TTE to provoke an LVOT gradient (eg,
Valsalva) can be variable because of inconsis-
tencies in instruction and patient effort. Stress
echocardiography (focusing on LVOTO rather
than regional wall motion), representing the most
physiologic form of provocation, can be most
helpful for those patients where the presence or
severity of LVOTO is uncertain after the baseline
echocardiogram.20,22–25 Postprandial exercise may
also be useful, particularly if the patient expresses
increased symptoms after meals.46 Exercise test-
ing is only useful in older children, typically >7 to 8
years of age, or when the child is able to cooper-
ate with testing, because young children are often
unable to cooperate with exercise testing.
6. Intraoperative TEE is a standard part of surgical
myectomy and adjunctive repairs for patients with
HCM. TEE can assess mitral valve abnormalities
and MR and extent of septal hypertrophy, as well as
provide assessment of residual SAM of the mitral
valve and LVOTO and occurrence of a ventricular
septal defect or new aortic insufficiency.26–29
7. TTE or TEE imaging helps guide alcohol septal
ablation, particularly in localizing the appropriate left
anterior descending septal perforator by intracoro-
nary contrast injection as well as monitoring of LVOT
gradient reduction during the procedure. The use of
transthoracic guidance with ultrasound-enhancing
agents has resulted in greater procedural success,
decreased intervention time, smaller infarct size,
and lower heart block rates.6,30–34 In cases where
transthoracic image quality is suboptimal, intrapro-
cedural TEE with ultrasound-enhancing agents can
be used to guide septal ablation therapy.6,34
8. Following SRT, efficacy of therapy, particularly
evidence of septal thinning and LVOT gradient
decrease, should be assessed. Residual SAM of the
mitral valve and MR, aortic insufficiency, LV systolic
and diastolic function, and ventricular septal defect
should also be assessed. Although these results are
usually apparent immediately after surgical septal
myectomy, changes in LVOTO and formation of a
myocardial septal scar may evolve over time (typi-
cally complete in 3 months but in some patients may
persist for a year) after septal ablation.35,37,38,47,48
9. When a diagnosis of HCM is made in a proband,
echocardiographic screening of first-degree rela-
tives is offered to identify affected relatives. In 2
large pediatric studies, yield on echocardiographic
screening for clinical HCM in first-degree relatives
was 10% to 15% throughout childhood and ado-
lescence with similar disease rates of penetrance
across age range.12,39,40 The median age at HCM
onset was 8.9 (4.7-13.4) years, with earlier onset in
male individuals, those with family history of SCD, and
pathogenic variants in MYH7/MYBPC3.39 Likewise,
the median time from HCM onset to a major cardiac
event, including death, SCD, or cardiac intervention
(eg, myectomy, ICD), was 1.5 years.39,40,49 Taken
together, these data support family screening initi-
ated in childhood and repeated on a periodic basis in
children and adults (Table 7). Changes in LV systolic
strain and diastolic function can precede definitive
hypertrophy.50–52 Family members with these abnor-
malities likely warrant closer follow-up.
10. The ongoing screening of genotype-positive,
phenotype-negative family members of all ages
is important. Previous small studies reported
onset of clinical HCM in adolescence or young
adulthood for most genotype-positive cases.2,53
However, large studies suggest that clinical HCM
can develop in younger family members, with 5%
to 10% being phenotype-positive at first screen-
ing and another 3% to 5% before 18 years of
age. Phenotype conversion can occur in young
adults; therefore, continued screening into adult-
hood is warranted, although frequency of screen-
ing can be lowered because the penetrance
rate is lower in individuals who are >18 years of
age.39–43 Although an absence of systematic evi-
dence is observed, most physicians continue clini-
cal screening until midlife (approximately 50 years
of age) because disease can manifest in adults,
albeit at a lower frequency.
11. TEE can be particularly useful if there is uncer-
tainty regarding mitral valve structural abnormali-
ties, mechanism of MR, or suspicion of alternate
causes of outflow obstruction (discrete subaortic
stenosis, valvular stenosis) on TTE or suspected or
by other clinical parameters.29
12. In patients with HCM, LVH can be localized to any
segment of the LV wall, and care should be taken
to completely image all LV wall segments. In cases
where the LV apex is suboptimally visualized, use
of an ultrasound-enhancing agent or CMR imaging
can aid in detection of apical hypertrophy, aneu-
rysm, and thrombus.44,45
13. In patients who are asymptomatic, understand-
ing whether they have LVOTO at rest or provoca-
tion is important in understanding the potential
pathophysiology. Even in asymptomatic patients,
knowing that they have provocable obstruction
can influence health advice (eg, regarding hydra-
tion) or choice of therapies for concomitant condi-
tions (eg, diuretics or vasodilators for patients with
hypertension).20,22–25
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6.3. CMR Imaging
Recommendations for CMR Imaging
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. For patients suspected of having HCM in whom
echocardiography is inconclusive, CMR imaging is
indicated for diagnostic clarification.1–7
1 B-NR
2. For patients with LVH in whom there is a suspicion
of alternative diagnoses, including infiltrative or stor-
age disease as well as athlete’s heart, CMR imaging
is useful (Figure 1).1–7
1 B-NR
3. For patients with HCM who are not otherwise
identified as high risk for SCD, or in whom a deci-
sion to proceed with ICD remains uncertain after
clinical assessment that includes personal or family
history, echocardiography, and ambulatory electrocar-
diographic monitoring, CMR imaging is beneficial to
assess for maximum LV wall thickness, EF, LV apical
aneurysm, and extent of myocardial replacement
fibrosis with late gadolinium enhancement (LGE).1–15
1 B-NR
4. For patients with obstructive HCM in whom the ana-
tomic mechanism of obstruction is inconclusive on
echocardiography, CMR imaging is indicated to inform
the selection and planning of SRT.16–20
2b C-EO
5. For patients with HCM, repeat contrast-enhanced
CMR imaging on a periodic basis (every 3-5 years)
for the purpose of SCD risk stratification may be
considered to evaluate changes in LGE and other
morphologic changes, including EF, development of
apical aneurysm, or LV wall thickness (Figure 1,
Table 8).
Synopsis
CMR imaging provides high spatial resolution and
tomographic imaging of the heart and assessment of
myocardial replacement fibrosis (LGE) after contrast
administration.1,2 These attributes make CMR imaging
well-suited for characterizing the diverse phenotypic
expressions of HCM. CMR imaging is therefore a com-
plementary imaging technique in the evaluation of HCM
patients for diagnosis, risk prediction, and preprocedural
planning for SRT.1,7
CMR imaging produces images with sharp contrast
between the blood pool and myocardium. This allows
for accurate LV wall thickness measurements, quan-
tification of LV and RV chamber size, LV mass, systolic
function, and identification of LVH not well visualized by
echocardiography.1–7 In addition, optimal images of LV
apical aneurysms and structural abnormalities of the
mitral valve and subvalvular apparatus that contribute to
LVOTO are produced, which may impact management
strategies.7–9,16–19 Extensive LGE (ie, myocardial replace-
ment fibrosis) represents a noninvasive marker for
increased risk for potentially life-threatening ventricu-
lar tachyarrhythmias and progression to systolic dys-
function.11–14 CMR imaging may not be feasible in
certain patients because of availability, cost, contraindi-
cations attributable to pacemakers or ICDs, severe renal
insufficiency, and patient factors (pediatric age and a
requirement for general anesthesia, or sedation, claus-
trophobia, or body habitus).
Recommendation-Specific Supportive Text
1. For patients in whom HCM is suspected based
on cardiac symptoms, an abnormal 12-lead ECG,
or family history of inherited heart disease, and in
whom echocardiographic examination is nondiag-
nostic or inconclusive, CMR imaging is an impor-
tant adjunctive test to clarify diagnosis.1–7 In such
clinical situations, CMR imaging can identify focal
areas of LVH, particularly when hypertrophy is con-
fined to certain regions of the LV wall, including
the anterolateral wall, posterior septum, and apex.
This increased sensitivity in detecting LVH by CMR
imaging is attributable to high spatial resolution
and the fact that CMR imaging is not encumbered
by poor acoustic windows caused by pulmonary or
thoracic parenchyma.4–6
2. Important differences in the pattern and location of
LVH, cavity dimensions, and the pattern and distri-
bution of LGE can aid in the differentiation of HCM
from other cardiovascular diseases associated
with LVH, including other inherited cardiomyopa-
thies (eg, lysosomal or glycogen storage diseases),
infiltrative cardiomyopathies (eg, amyloid), or con-
ditions with secondary hypertrophy attributable
to pressure overload (eg, hypertension or athletic
conditioning).7
3. Maximal LV wall thickness measurements can be
underestimated (or overestimated) with echocar-
diography compared with CMR imaging.1–7 This
can have direct management implications for
diagnosis and SCD risk assessment, because LV
wall thickness is a major risk marker for SCD.4–6,10
In addition, apical aneurysms may not always be
detected by echocardiography.8,9 Extensive LGE,
often occupying multiple LV segments, is associ-
ated with increased risk for life-threatening ven-
tricular arrhythmias, independent of location or
pattern within the LV wall.11–13 Studies have pro-
moted a threshold for extensive LGE of ≥15% of
the LV mass as representing a significant (2-fold)
increase in SCD risk.12 However, no consensus
on the optimal quantification technique(s) has
been determined. LGE can serve as an arbiter in
decision-making on whether to pursue ICD place-
ment when risk remains ambiguous after standard
risk stratification.12 Patients with HCM and systolic
dysfunction (EF <50%), adverse LV remodeling
with ventricular cavity enlargement and wall thin-
ning because of scarring, are at increased risk for
lethal ventricular tachyarrhythmias and increased
HF symptoms.14,15 CMR can provide quantitative
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EF assessment in whom determination of systolic
function remains uncertain with echocardiography.
Absence of (or minimal) LGE is associated with
lower risk of SCD.12,13,21
4. Because of specific anatomic features of the LVOT,
some patients with HCM will be more suitable can-
didates for septal myectomy than for percutane-
ous alcohol ablation.16–20 CMR imaging can reliably
characterize specific features of the LVOT anatomy
that may be contributing to SAM-septal contact
and obstructive physiology and, therefore, are rel-
evant to strategic planning for septal reduction
procedures, including precise distribution of septal
hypertrophy, abnormalities of the mitral valve and
subvalvular apparatus, including abnormally posi-
tioned papillary muscles, anomalous papillary mus-
cle insertion directly into mitral valve, accessory
muscle bundles, and abnormal chordal connec-
tions, particularly if these morphologic features are
not clearly identified with echocardiography.16–20
5. The progression of high-risk morphologic features,
including apical aneurysm, extensive LGE, systolic
dysfunction, and massive LVH, is not well-defined.
Nevertheless, given the importance of these in
management considerations, including SCD pre-
vention with ICD therapy, periodic longitudinal
evaluation with CMR imaging to detect develop-
ment or progression in ≥1 of these issues may be
informative.8,10,15,22,23
6.4. Cardiac CT
Recommendation for Cardiac CT
COR LOE Recommendation
2b C-LD
1. In adult patients with suspected HCM, cardiac
CT may be considered for diagnosis if the
echocardiogram is not diagnostic and CMR
imaging is unavailable.1–3
Synopsis
Cardiac CT provides excellent spatial resolution that al-
lows for clear definition of LV structure (including hyper-
trophy pattern, wall thickness measurement, detection
of subaortic membrane, and intracardiac thrombus) and
function. Small studies have demonstrated the ability of
CT to assess myocardial fibrosis, although this adds fur-
ther radiation exposure and needs further validation.2,3
In addition to myocardial structure, CT can provide an
assessment of coronary anatomy, including stenosis
and anomalous origin of coronary arteries. Disadvan-
tages of CT are the use of radiation and radioiodine
contrast and inferior temporal resolution compared with
echocardiography. CT angiography is discussed in Sec-
tion 6.6 (“Angiography and Invasive Hemodynamic
Assessment”).
Recommendation-Specific Supportive Text
1. Although not commonly used, CT can provide
important insights when echocardiography is tech-
nically limited and CMR imaging is contraindicated
or unavailable and is one of the tools that can be
used to define coronary anatomy.1–3
6.5. Heart Rhythm Assessment
Recommendations for Heart Rhythm Assessment
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with HCM, a 12-lead ECG is
recommended in the initial evaluation and as part of
periodic follow-up (every 1-2 years) (Figure 1, Table
7).1–3
1 B-NR
2. In patients with HCM, 24- to 48-hour ambulatory
electrocardiographic monitoring is recommended in
the initial evaluation and as part of periodic follow-up
(every 1-2 years) to identify patients who are at risk
for SCD and to guide management of arrhythmias
(Figure 1).4–6
1 B-NR
3. In patients with HCM who develop palpitations
or lightheadedness, extended (>24 hours) elec-
trocardiographic monitoring or event recording is
recommended for arrhythmia diagnosis and clinical
correlation.6
1 B-NR
4. In first-degree relatives of patients with HCM, a
12-lead ECG is recommended as a component of
the screening algorithm (Figure 1, Table 7).1–3
1 B-NR
5. In patients with HCM who are deemed to be at high
risk for developing AF based on the presence of risk
factors or as determined by a validated risk score,
and who are eligible for anticoagulation, extended
ambulatory monitoring is recommended to screen for
AF as part of initial evaluation and annual follow-up
(Figure 1).7–12
2b B-NR
6. In adult patients with HCM without risk factors
for AF and who are eligible for anticoagulation,
extended ambulatory monitoring may be considered
to assess for asymptomatic paroxysmal AF as part
of initial evaluation and periodic follow-up (every 1-2
years).7–12
Synopsis
Both 12-lead electrocardiographic and ambulatory moni-
toring are necessary for patients with HCM. A 12-lead
ECG can convey information about LVH and repolariza-
tion abnormalities as well as arrhythmias, including bra-
dycardia and tachycardia. It also provides information
about conduction abnormalities that may be present at
initial evaluation or in follow-up. Ambulatory monitoring is
necessary in the evaluation of SCD risk. Historically, this
has been 24 to 48 hours. Extended monitoring is most
useful for the determination of the cause of symptoms
or to diagnose AF. In patients with additional risk factors,
periodic screening of AF may be necessary in order to
intervene promptly.
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Recommendation-Specific Supportive Text
1. The 12-lead ECG is abnormal in 75% to 95% of
patients with phenotypic HCM, including, but not lim-
ited to, evidence for LVH and repolarization changes.
However, these abnormalities do not reliably corre-
late with the severity or pattern of hypertrophy.13 The
12-lead ECG is also useful in identifying other abnor-
malities, such as Wolff-Parkinson-White pattern,
which may suggest certain phenocopies of HCM.1–3
Alternative diagnoses may also be suggested, such
as amyloidosis in the presence of low-voltage and
conduction delays. In addition, a pseudo–myocardial
infarction pattern may be present in young individu-
als before there is manifest evidence of wall thick-
ening on echocardiography.13 A12-lead ECG is
commonly used in the screening for HCM, including
family members without LVH.1–3 There is consider-
able debate regarding the utilization of the 12-lead
ECG in screening healthy adolescents for HCM as
part of preparticipation athletic screening.14
2. Ambulatory electrocardiographic monitoring for
detection of ventricular tachyarrhythmias has his-
torically played an important role in risk stratification
of patients with HCM. Episodes of nonsustained
ventricular tachycardia (NSVT) may identify patients
at significantly higher risk of subsequent SCD.4–6
There is increasing evidence that NSVT in young
patients with HCM is more prognostic for SCD than
in patients >35 years of age, and also that longer
and faster NSVT is associated with greater inci-
dence of ICD-treated arrhythmias.15 There is also
evidence that longer periods of monitoring will diag-
nose more episodes of NSVT16; however, NSVT as
a risk factor for SCD has historically been based on
a 24- to 48-hour monitor. The optimal time frame of
monitoring is not yet established and, thus, at this
time, it is reasonable to perform serial ambulatory
electrocardiographic monitoring every 1 to 2 years
in patients who do not have ICDs.
3. In the presence of symptoms, ambulatory elec-
trocardiographic monitoring should be continued
until a patient has symptoms while wearing the
monitor, such that the proper diagnosis is made.
Clinical studies have shown a broad spectrum of
arrhythmias in patients with HCM, most of them
not lethal; thus, clinical correlation of symptoms
with monitor findings is essential.6 In some patients
with infrequent symptoms, portable event monitors
or implantable monitors may be warranted.
4. ECGs are considered to be a standard part of the
initial screening of relatives of patients with HCM.1–3
Electrocardiographic abnormalities may precede
the development of LVH in children who are gene
carriers; thus, ECG is considered more sensitive
than echocardiography as a screening tool in fami-
lies with HCM.13
5. AF is associated with adverse outcomes (including
stroke) in patients with HCM. Although several stud-
ies show that asymptomatic AF is present in up to
50% of patients,7–11 it is unclear that asymptomatic
episodes, especially if short in duration (<30 sec-
onds) and low burden (<1%), contribute to adverse
outcomes. Predictors of clinically important AF include
left atrial dilatation, increasing age, duration of disease,
and NYHA functional class III to IV HF. Thus, patients
with these characteristics should be assessed more
frequently and possibly including extended (duration
determined by clinical circumstances) ambulatory
electrocardiographic screening to provide prompt
intervention when AF is detected. To facilitate identify-
ing patients who would benefit the most from screen-
ing, a risk score (the HCM-AF score) was developed
that includes the aforementioned risk factors and
allows prognostic estimation of the risk of develop-
ing AF. The model was developed from a cohort of
1900 patients with HCM and subsequently validated;
in the development cohort, 17.2% of high-risk patients
developed AF (rate 3.4% per year), whereas in the
external validation cohort, 13.3% of high-risk patients
developed AF (rate 2.7% per year).12 In the HCM-AF
score study, AF was defined as ≥1 clinically overt
episodes documented by ECG or telemetry, requir-
ing medical attention and consideration for treatment
within 10 years of initial visit.12
6. AF is associated with adverse outcomes (including
stroke) in patients with HCM. Although several stud-
ies show that asymptomatic AF is present in up to
50% of patients,7–11 it is unclear whether asymptom-
atic episodes, especially if short in duration, contrib-
ute to adverse outcomes. Predictors of AF include
left atrial dilatation, advanced age, and NYHA func-
tional class III to class IV HF. Yet, in patients with-
out risk factors, the risk of developing AF is low,
although not zero: approximately 3.3% at 5 years.12
6.6. Angiography and Invasive Hemodynamic
Assessment
Recommendations for Angiography and Invasive Hemodynamic
Assessment
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. For patients with symptomatic HCM for whom there
is uncertainty regarding the presence or severity
of LVOTO on noninvasive imaging studies, invasive
hemodynamic assessment with cardiac
catheterization is recommended.1–4
1 B-NR
2. In patients with HCM who have symptoms or
evidence of myocardial ischemia, coronary
angiography (CT or invasive) is recommended.5
1 B-NR
3. In patients with HCM who are at risk of coronary
atherosclerosis, coronary angiography (CT or
invasive) is recommended before surgical myectomy.6
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Synopsis
Echocardiography remains the gold standard for the re-
liable, noninvasive assessment of dynamic outflow tract
obstruction in HCM. Invasive hemodynamic assessment
should be undertaken only when the diagnostic informa-
tion cannot be obtained from the clinical and noninvasive
imaging examinations and when such information will
alter patient management. In addition, invasive hemody-
namic assessment can be useful to guide management in
carefully selected patients with HCM who have persistent
symptoms despite optimal medical therapy to more fully
characterize the hemodynamic profile, presence or ab-
sence of LVOTO, and contribution of other disease states,
such as chronic primary or secondary pulmonary hyperten-
sion or concomitant valve disease. It is crucial that the op-
erator performing the assessment be experienced in such
cases and use appropriate catheters (eg, end-hole pigtail,
halo), while avoiding pitfalls such as catheter entrapment.
Recommendation-Specific Supportive Text
1. In patients with a clinical history of significant, limit-
ing HF symptoms (NYHA functional class II to IV)
but in whom there is ambiguity regarding presence
or magnitude of an LVOT gradient on cardiac imag-
ing, invasive hemodynamic studies can clarify the
presence of resting or latent outflow tract obstruc-
tion as well as provide information on cardiac out-
put and filling pressures.1,2 Such circumstances
may arise if the reliability of echocardiographic
imaging is limited by poor acoustic windows or if
the Doppler profile cannot be reliably distinguished
between increased velocity from outflow tract
obstruction versus contamination of the profile by
MR. Outflow gradients can be extremely dynamic,
with spontaneous variability influenced by altered
myocardial contractility and loading conditions at
the time of cardiac imaging testing.2 Several pro-
vocative maneuvers have been used in the cath-
eterization laboratory to identify the presence of a
latent gradient, including Valsalva maneuver, induc-
ing a premature ventricular contraction to assess
for the Brockenbrough-Braunwald-Morrow sign
(post-extrasystolic augmentation in LVOT gradient
and reduction in aortic pulse pressure), or upper or
lower extremity exercise.3,4 Documentation of the
LVOT gradient at rest and, if not severe (≥50 mm Hg),
after provocative maneuvers helps guide clinical
care.
2. Chest discomfort is a common symptom in patients
with HCM. For those patients with atherosclerotic
coronary risk factors or in whom chest pain does
not respond to medical therapy, the possibility of
epicardial coronary artery disease (CAD) needs
to be considered. Epicardial CAD may also be
suspected based on noninvasive testing, although
high false-positive and false-negative rates are
associated with nuclear and echocardiographic
stress testing. Coronary angiography is useful in
patients with HCM when findings of CAD could aid
in patient management.6
3. Coronary angiography is usually performed in
patients who are scheduled for surgical myectomy
and have risk factors for coronary atherosclero-
sis and significant myocardial bridging. Findings
of extensive CAD would inform decision-making
regarding altering the strategy to surgical myec-
tomy combined with coronary bypass surgery.6
Coronary angiography is a requisite component of
alcohol septal ablation, to assess septal anatomy,
and for the presence of CAD that can be addressed
at the time of septal ablation.
6.7. Exercise Stress Testing
Recommendations for Exercise Stress Testing
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. For symptomatic patients with HCM who do not have
resting or provocable outflow tract peak gradient
≥50 mm Hg on TTE, exercise TTE is recommended
for the detection and quantification of dynamic
LVOTO.1–6
1 B-NR
2. In patients with nonobstructive HCM and advanced
HF (NYHA functional class III to class IV), cardiopul-
monary exercise stress testing should be performed
to quantify the degree of functional limitation and aid
in selection of patients for heart transplantation or
mechanical circulatory support.7–9
1 B-NR
3. In pediatric patients with HCM, regardless of
symptom status, exercise stress testing is recom-
mended to determine functional capacity and to
provide prognostic information.10
2a B-NR
4. In adult patients with HCM, exercise stress testing is
reasonable to determine functional capacity and to
provide prognostic information as part of initial
evaluation.9,11,12
2a C-LD
5. For asymptomatic patients with HCM who do not
have a resting or provocable outflow tract peak
gradient ≥50 mm Hg on standard TTE, exercise TTE
is reasonable for the detection and quantification of
dynamic LVOTO.1,3–6,13,14
2b C-LD
6. In patients with obstructive HCM and ambiguous
functional capacity, exercise stress testing may be
reasonable to guide therapy (Figure 1).15,16
2b C-EO
7. In patients with HCM for whom it is unclear if their
functional capacity has declined, exercise stress
testing may be considered every 2 to 3 years
(Figure 1).
Synopsis
In patients with HCM, exercise stress testing is safe and
provides information on the severity and mechanism of
functional limitation. Particularly when combined with
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simultaneous analysis of respiratory gases (ie, cardiopul-
monary exercise test [CPET]), lower exercise capacity is
strongly prognostic of adverse events, including death,
HF, and ventricular arrhythmias in both adults and chil-
dren. The accuracy of exercise testing in assessing myo-
cardial ischemia can be limited if there are resting ECG
and/or wall motion abnormalities. Conversely, myocardial
perfusion imaging using single-photon or positron emis-
sion tomography has a high rate of false-positive find-
ings for epicardial CAD, with perfusion abnormalities
detectable in >50% of patients, most of whom have no
significant epicardial CAD. In patients with HCM with a
high clinical suspicion for myocardial ischemia, coronary
angiography (CT or invasive) should be considered. Do-
butamine is not recommended because diagnostic accu-
racy for ischemia is limited and induction of intracavitary
gradients is nonphysiologic. This section focuses only on
the modality of exercise stress testing for its utility in de-
tecting latent LVOT obstruction and exercise capacity as
it relates to prognosis and treatment recommendations.
Recommendation-Specific Supportive Text
1. In general, to attribute effort-related symptoms to
LVOTO, the resting or provoked gradient would
need to be >50 mm Hg. LVOT gradients can be
dynamic and can be missed on resting echocar-
diography in up to 50% of patients with obstruc-
tive physiology,17 and maneuvers performed during
a resting TTE to provoke an LVOT gradient (eg,
Valsalva) can be variable because of inconsisten-
cies in instruction and patient effort. Stress echo-
cardiography, representing the most physiologic
form of provocation, can be most helpful for those
patients where the presence or severity of LVOTO
is uncertain after the baseline echocardiogram.1,3–6
Postprandial exercise may also be useful, particu-
larly if the patient expresses increased symptoms
after meals.18 Exercise testing is only useful in
older children, typically >7 to 8 years of age, or
when able to cooperate with the testing protocol.
2. CPET is a standard part of the evaluation for
patients with severe symptoms, including those
being considered for cardiac transplantation.7–9
3. In pediatric patients with HCM, there is a strong
association of exercise-induced ischemic electro-
cardiographic changes and abnormal blood pres-
sure response with lower transplant-free survival.10
Exercise-induced ischemia in pediatric patients is
also independently associated with a higher risk of
SCD. Exercise testing is only useful in older chil-
dren, typically >7 to 8 years of age, or when able to
cooperate with the testing protocol.
4. Exercise stress testing provides information on
the severity and mechanism of functional limitation
(eg, provocable LVOTO, abnormal blood pressure
response, chronotropic incompetence, arrhythmias,
ischemia, and/or reduced heart rate reserve). When
available, the use of CPET, with simultaneous mea-
surement of respiratory gases, is preferred. Data
from >9000 patients show that reduced peak oxy-
gen consumption and submaximal exercise param-
eters, such as ventilatory efficiency and anaerobic
threshold, are associated with a higher rate of ven-
tricular arrhythmias, progression to advanced HF,
and higher all-cause mortality.9,11,12
5. In patients who are asymptomatic, understand-
ing whether they have LVOTO at rest or provoca-
tion is important in understanding the potential
pathophysiology. Even in asymptomatic patients,
knowing that they have provocable obstruction
can influence health advice (eg, regarding hydra-
tion) or choice of therapies for concomitant condi-
tions (eg, diuretics or vasodilators for patients with
hypertension).1,3–6
6. In patients with symptomatic LVOTO who are under-
going septal myectomy, lower preoperative peak
VO2 and lack of improvement in peak VO2 postoper-
atively despite resolution of LVOTO are associated
with higher mortality.15,16 Therefore, significantly
reduced exercise capacity measured with or with-
out use of CPET compared with the norm for the
patient’s age and sex may prompt earlier consider-
ation for advanced therapies to alleviate LVOTO.
7. A decline in exercise capacity relative to the norm
for a patient’s age and sex can impact decisions
on whether to escalate therapies, particularly if the
patient’s functional capacity is ambiguous based
on their clinical history.
6.8. Genetics and Family Screening
Recommendations for Genetics and Family Screening
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with HCM, evaluation of familial
inheritance, including a 3-generation family history,
is recommended as part of the initial assessment.1–7
1 B-NR
2. In patients with HCM, genetic testing is beneficial
to elucidate the genetic basis to facilitate the
identification of family members at risk for
developing HCM (cascade testing).8–11
1 B-NR
3. In patients with an atypical clinical presentation of
HCM or when another genetic condition is suspected
to be the cause, a workup including genetic testing
for HCM and other genetic causes of unexplained
cardiac hypertrophy (“HCM phenocopies”)
is recommended.12–14
1 B-NR
4. In patients with HCM, genetic counseling by an
expert in the genetics of cardiovascular disease is
recommended so that risks, benefits, test results,
and their clinical significance can be reviewed
and discussed with the patient in a shared
decision-making process.1–3,15
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1 B-NR
5. When performing genetic testing in a proband with
HCM, the initial tier of genes tested should include
genes with strong evidence to be disease-causing
in HCM.*8,11,16,17
1 B-NR
6. In first-degree relatives of patients with HCM, both
clinical screening (ECG and 2D echocardiogram)
and cascade genetic testing (when a pathogenic/
likely pathogenic variant has been identified in the
proband) should be offered.3,7,12,18–20
1 B-NR
7. In families where a sudden unexplained death has
occurred with a postmortem diagnosis of HCM,
postmortem genetic testing is beneficial to facilitate
cascade genetic testing and clinical screening in
first-degree relatives.21,22
1 B-NR
8. In patients with HCM who have undergone genetic
testing, serial reevaluation of the clinical significance
of the variant(s) identified is recommended to
assess for variant reclassification, which may impact
diagnosis and cascade genetic testing in family
members23–25 (Figures 1 and 2).
1 B-NR
9. In affected families with HCM, preconception and
prenatal reproductive and genetic counseling should
be offered.1–3,15
2b B-NR
10. In adult patients with HCM, the usefulness of
genetic testing in the assessment of risk of SCD is
uncertain.10,25–27
2b B-NR
11. In patients with HCM who have a variant of
uncertain significance (VUS), the usefulness of
clinical genetic testing of phenotype-negative
relatives for the purpose of variant reclassification
is uncertain.4,7,8,28
3: No
benefit B-NR
12. For patients with HCM who have undergone
genetic testing and were found to have no
pathogenic variants (ie, harbor only benign or likely
benign variants), cascade genetic testing of the
family is not useful.4,8–10
3: No
benefit B-NR
13. Ongoing clinical screening is not indicated in
genotype-negative relatives in families with
genotype-positive HCM, unless the disease-
causing variant is downgraded to a VUS, likely
benign, or benign variant during follow-up.23,29–32
*Strong evidence HCM genes include, at the time of this publication: MYH7,
MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1.
Synopsis
Genetic testing has an important role in the diagnosis
and management of HCM in patients and their families.
HCM is inherited as an autosomal dominant trait in most
cases, with offspring having a 50% chance of inheriting
the same disease-causing genetic variant. A discussion
about the role of genetic testing is considered a standard
part of the clinical engagement of patients with HCM, in-
cluding appropriate pre- and posttest genetic counseling
performed either by a trained cardiac genetic counselor or
by someone knowledgeable in the genetics of cardiovas-
cular disease. It is essential to obtain a multigenerational
(preferably at least 3 generations) family history of HCM
and suspected SCD events. The importance of potential
psychological, social, legal, ethical, and professional impli-
cations of having a genetic disease33 should be conveyed.
Genetic assessment should ideally be performed in a spe-
cialized multidisciplinary HCM center with experience in
all aspects of the genetic counseling and testing process.1
Recommendation-Specific Supportive Text
1. Obtaining a family history facilitates the identifica-
tion of other clinically affected and at-risk family
members, patterns of disease transmission, con-
sanguinity within the family, and a history of SCD
in a relative. These findings may be relevant to
the diagnosis and management of individuals with
HCM in the family and subsequent clinical and
genetic screening of at-risk family members.23–25
2. Genetic testing in HCM has several clinical benefits,
including confirmation of the diagnosis, preclinical
diagnosis, cascade genetic testing in the family, and in
guiding reproductive decisions.8–11 Cascade genetic
testing in the family identifies those who carry the
disease-causing variant and require ongoing surveil-
lance, while those who do not carry the variant can
be released from lifelong clinical surveillance.
3. Genes associated with HCM phenocopies may be
included in first-tier genetic testing if there is clini-
cal suspicion based on phenotype evaluation of a
systemic disorder, including PRKAG2 (glycogen
storage disease), LAMP2 (Danon disease),13 GLA
(Fabry disease),34 transthyretin amyloid cardiomy-
opathy, and disease genes related to RASopathies.
In some circumstances, the genetic test result may
alter the management of the index case, such as
enzyme replacement therapy in patients with Fabry
disease or more aggressive clinical management
of patients with Danon disease.
4. Pretest genetic counseling is important to ensure the
patient undergoing genetic testing fully understands
and is informed of the benefits and potential harms
(including psychosocial, ethical, and insurability) of
finding a genetic cause of disease. Posttest genetic
counseling allows a clear explanation to be provided
for the genetic testing findings, regardless of whether
a pathogenic or likely pathogenic variant is identified,
and the implications of both a positive and a negative
result for the individual and for the family.1–3,15
5. HCM is predominantly a disease of the sarcomere,
and first-line genetic testing primarily includes panel
testing for genes with strong evidence for being
disease-causing.11 Genetic testing can be performed
using various platforms, including gene panels,
exome sequencing, or genome sequencing.9 Gene
panels include 8 sarcomere genes, including MYH7,
MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, and
ACTC1, and identify a disease-causing variant in
approximately 30% of sporadic and 60% of familial
cases.4,8–10 Expanding to larger panels usually does
Recommendations for Genetics and Family Screening (Continued)
COR LOE Recommendations
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not add diagnostic value.8,17 Initial genetic testing is
usually performed in the index case (proband).8 If tar-
geted gene panel testing does not reveal a causal
variant, exome sequencing may provide a second-tier
test on a clinical or research basis, recognizing the
chance of incidental findings. In up to 40% of patients
with HCM, no sarcomere variant is identified, and
there is no family history of disease.26 Identification
of a VUS is not a clinically actionable result but can
be investigated further at either a clinical or research
level to further clarify variant pathogenicity (eg,
through cosegregation analysis in family members,
DNA testing in parents to determine whether VUS is
de novo, functional studies) (Figures 1 and 2).
6. After genetic testing, a clinically actionable result (ie,
likely pathogenic or pathogenic) can provide diagnos-
tic clarification in the proband and offers the poten-
tial for cascade (predictive) testing of at-risk family
members.3,7,12,18,19 Cascade testing involves targeted
testing of first-degree relatives for the pathogenic or
likely pathogenic variant found in the proband. When
cascade testing is performed in an at-risk relative,
those who are found not to carry the disease-causing
gene variant can be released from further (lifelong)
clinical surveillance. Those who are found to carry the
disease-causing gene variant should undergo clinical
screening at regular intervals (Table 7). Family mem-
bers of a patient where genetic testing is not done
or is negative (ie, no likely pathogenic or pathogenic
variant is identified) also require clinical screening at
regular intervals because there is considerable phe-
notypic heterogeneity in age of onset and disease
progression within members of the same family.
7. Postmortem testing for HCM-associated variants
using blood or tissue collected at autopsy has been
reported, particularly in instances where the fam-
ily variant is unknown and no other affected family
members are still living.21,35,36 Access to a molec-
ular autopsy as well as considerations related to
costs and insurance coverage for this testing can
vary between jurisdictions. Nevertheless, identifi-
cation of a likely pathogenic or pathogenic variant
not only confirms the diagnosis of HCM but allows
cascade genetic testing of other at-risk relatives as
outlined previously (Figures 1 and 2).
8. Determining pathogenicity of variants relies on a
weight of collective evidence based on American
College of Medical Genetics and Genomics criteria16
and may change over time. This highlights the impor-
tance of periodic reevaluation of variants every few
years in case the variant has been reclassified (ie,
either upgraded to likely pathogenic or pathogenic),
in which case family cascade genetic testing can be
initiated, or downgraded to a VUS, likely benign, or
benign variant, whereby family screening would revert
to regular clinical surveillance.23–25 In 1 report, 11% of
HCM variants were either downgraded or upgraded
over 6 years into a category that would necessitate
a change in cascade screening of family members.29
This highlights the importance of having the neces-
sary expertise within a specialized multidisciplinary
clinic setting to not only perform genetic testing and
interpret the results but to reevaluate the pathoge-
nicity of variants during follow-up.23,24 The American
College of Medical Genetics and Genomics guide-
lines recommend clinical laboratories implement
policies to reevaluate variants based on new infor-
mation about the patient or family phenotype.32 The
American College of Medical Genetics and Genomics
also highlights the importance of notifying a patient
undergoing genetic testing that the genetic interpre-
tation may change over time, and that the patient may
be recontacted with updated results.31
9. In autosomal dominant HCM, there is a 1 in 2
(50%) chance of passing on the disease-causing
gene variant to each offspring of an affected indi-
vidual, although variable penetrance can result in
differences in onset and severity of clinical mani-
festations.37 Prenatal genetic counseling is helpful
in explaining the risk of transmission of disease,
as well as discussing potential reproductive
options.1–3,15 These options include in vitro fertiliza-
tion with preimplantation genetic diagnosis, prena-
tal genetic screening, and postnatal genetic testing.
The benefits and potential harms can be discussed
for each of these options, such that the individual
or couple can make a fully informed decision.
10. Although some evidence exists that adults who
carry >1 likely pathogenic or pathogenic variant
may have more severe disease, including SCD, the
role of the genetic test result in the determination
of risk in SCD remains uncertain and is therefore
not clinically used for this purpose. Similarly, a
genetic result in isolation does not influence deci-
sions related to implanting an ICD in adult patients
with HCM. Several studies have reported that
patients with HCM who carry pathogenic or likely
pathogenic sarcomere variants have a worse prog-
nosis compared with patients with HCM who are
sarcomere variant-negative.10,12,25,27,38 This includes
earlier onset of disease, higher incidence of SCD,
higher incidence of AF and ventricular arrhyth-
mias, HF, and overall mortality.10,12,25,27,38 In pediat-
ric patients, the presence of sarcomeric variants is
more closely associated with SCD and has been
incorporated into one of the SCD risk tools.38
11. Genetic testing for HCM is first performed in an indi-
vidual in the family with clear phenotypic evidence of
HCM, usually the proband (index case). If a definitive
likely pathogenic or pathogenic variant is identified,
then cascade genetic testing in at-risk relatives can
be offered (Figures 1 and 2). Genetic testing in a
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phenotype-negative relative without a known genetic
diagnosis in the proband has a very low yield of iden-
tifying a genetic cause of HCM, and a negative test
in this situation will not change recommendations
for ongoing clinical screening.4,7,8,28 Identification of a
VUS in a proband is not a clinically actionable result.
In select circumstances only, family member testing
may be offered at either a clinical or research level
to further clarify the pathogenicity of the variant (eg,
through cosegregation analysis in family members,
determine de novo status through parental testing,
functional studies). However, this is most appropri-
ate in the setting of guidance from a cardiovascular
genetics expert (Figures 1 and 2).
12. If genetic testing does not identify a pathogenic
variant in a patient with HCM (ie, only identifies
benign or likely benign variants), there is no indica-
tion to do genetic testing in family members as the
identification of such variants will not change clini-
cal management, including the need for continued
clinical screening.4,8–10
13. In genotype-negative relatives of individuals with
genotype-positive HCM, no further clinical
follow-up is required (Figures 1 and 2). Over
time, as more knowledge is gained, some vari-
ants previously thought to be likely pathogenic
or pathogenic may be downgraded to a VUS or
benign category.23,29,30 In such instances, family
relatives who were released from clinical surveil-
lance on the basis of the previous gene result
need to be notified and regular clinical screening
recommenced.31,32
Figure 1. Recommended Evaluation and Testing for HCM.
Colors correspond to Table 3. *The interval may be extended, particularly in adult patients who remain stable after multiple evaluations. AF indicates
atrial fibrillation; CMR, cardiovascular magnetic resonance; CPET, cardiopulmonary exercise test; ECG, electrocardiography/electrocardiogram; echo,
echocardiography/echocardiogram; HCM, hypertrophic cardiomyopathy; HF, heart failure; ICD, implantable cardioverter-defibrillator; LVOTO, left
ventricular outflow tract obstruction; P/LP, pathogenic or likely pathogenic variant; SCD, sudden cardiac death; and VUS, variant of unknown significance.
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6.9. Individuals Who Are Genotype-Positive,
Phenotype-Negative
Recommendations for Individuals Who Are Genotype-Positive,
Phenotype-Negative
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In individuals who are genotype-positive,
phenotype-negative for HCM, serial clinical assess-
ment, electrocardiography, and cardiac imaging are
recommended at periodic intervals depending on
age (every 1-2 years in children and adolescents
and every 3-5 years in adults) and change in
clinical status (Figures 1 and 2, Table 7).1–5
2a B-NR
2. In individuals who are genotype-positive,
phenotype-negative for HCM, participation in
competitive sports of any intensity is reasonable.6,7
3: No
benefit B-NR
3. In individuals who are genotype-positive,
phenotype-negative for HCM, ICD is not
recommended for primary prevention.2–6,8
Synopsis
Genotype-positive, phenotype-negative individuals are
those who carry a pathogenic or likely pathogenic HCM-
causing variant but are asymptomatic without evidence
of LVH on cardiac imaging. These individuals are also
described as having preclinical HCM. They need ongo-
ing cardiac surveillance for development of clinical HCM,
although the time from genetic diagnosis to clinical HCM
varies considerably within and between families.1,5,8 Stud-
ies have reported alterations in myocardial strain, LV re-
laxation abnormalities, myocardial crypts, mitral valve
leaflet abnormalities, abnormal trabeculae, myocardial
scarring, electrocardiographic abnormalities, and abnor-
mal serum NT-proBNP concentrations even in the ab-
sence of LVH.9–12 However, the clinical significance of
these subclinical structural and functional abnormalities
is unclear and, therefore, treatment decisions are usually
not made based on these findings alone.
Figure 2. Genetic Testing Process in HCM.
Colors correspond to Table 3. HCM indicates hypertrophic cardiomyopathy; LB/B, likely benign/benign; LP/P, likely pathogenic or pathogenic;
and VUS, variant of unknown significance.
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Recommendation Specific Supportive Text
1. The ongoing screening of genotype-positive,
phenotype-negative family members of all ages
is important. Previous small studies reported
onset of clinical HCM in adolescence or young
adulthood for most genotype-positive cases.1,5
However, large studies suggest that clinical HCM
can develop in younger family members, with 5%
to 10% being phenotype-positive at first screen-
ing and another 3% to 5% before 18 years of
age.2,4,8 A third of patients who developed clini-
cal HCM required medical, surgical, or device
therapy before 18 years of age.4 Phenotype
conversion can occur in young adults and, there-
fore, continued screening into adulthood is war-
ranted,1 although frequency of screening can be
lowered because disease penetrance is lower in
individuals who are >18 years of age.3 Although
there is an absence of systematic evidence,
most physicians continue clinical screening until
midlife (approximately 50 years of age) because
disease can manifest in adults, albeit at a lower
frequency.
2. Sudden death in genotype-positive, phenotype-
negative individuals is rare.6 No accurate risk
prediction models for SCD exist in genotype-
positive, phenotype-negative individuals currently.
In a recent prospective registry, no arrhythmic
events in genotype-positive, phenotype-negative
individuals (total of 126) were observed, includ-
ing those exercising vigorously or participating in
competitive athletics.7 Decisions about participa-
tion in competitive sports are usually made jointly
with the patient and family taking into consider-
ation family history of SCD, type of sports activity,
and patient and family risk tolerance. Because of
the low risk of sudden death, phenotype-negative
individuals are not restricted from competitive
sports and are not routinely monitored with ambu-
latory electrocardiography and exercise stress
testing unless the family history indicates a high
risk for SCD or as part of precompetitive athletic
screening. This is appropriate every 1 to 2 years
to assess the safety of ongoing competitive ath-
letics participation.
3. ICDs are not offered for primary prevention in
genotype-positive, phenotype-negative individu-
als given the low risk of SCD. Similarly, preemptive
medical therapy is not offered in genotype-positive,
phenotype-negative individuals. In a small pilot
randomized trial, preemptive treatment of sar-
comere variant-positive, phenotype-negative
individuals with diltiazem was associated with a
small improvement in LV diastolic function and
thickness:dimension ratio on 3-year follow-up.13
However, the trial was not powered to detect
effects on clinical outcomes.
7. SCD RISK ASSESSMENT AND
PREVENTION
7.1. SCD Risk Assessment
7.1.1. SCD Risk Assessment in Adults With HCM
Recommendations for SCD Risk Assessment in Adults With HCM
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In adult patients with HCM, a comprehensive,
systematic noninvasive SCD risk assessment at
initial evaluation and every 1 to 2 years thereafter
is recommended and should include evaluation of
these risk factors (Figures 1 and 3, Table 8)1–25:
a. Personal history of cardiac arrest or sustained
ventricular arrhythmias;
b. Personal history of syncope suspected by clinical
history to be arrhythmic;
c. Family history in close relative of premature
HCM-related sudden death, cardiac arrest, or
sustained ventricular arrhythmias;
d. Maximal LV wall thickness, EF, LV apical
aneurysm;
e. NSVT episodes on continuous ambulatory
electrocardiographic monitoring.
1 B-NR
2. For adult patients with HCM who are not otherwise
identified as high risk for SCD, or in whom a decision
to proceed with ICD placement remains uncertain
after clinical assessment that includes personal/
family history, echocardiography, and ambulatory
electrocardiographic monitoring, CMR imaging is
beneficial to assess for maximum LV wall thickness,
EF, LV apical aneurysm, and extent of myocardial
fibrosis with LGE (Table 8).1,11,12,15–20
2a B-NR
3. For patients who are ≥16 years of age with HCM, it
is reasonable to obtain echocardiography-derived left
atrial diameter and maximal LVOT gradient to aid in
calculating an estimated 5-year sudden death risk
that may be useful during shared decision-making
for ICD placement (Table 8).2,22
Synopsis
HCM has been regarded as one of the most com-
mon causes of SCD in young people in North
America.1,2,21,22,26–32 Among patients with HCM, young-
er patients are at higher risk for SCD than older
patients.6,26–30,33–36 There appears to be no sex- or race-
based differences in SCD risk.28,29 Over several decades,
a multitude of studies have focused on identification
of major clinical risk markers that stratify patients ac-
cording to level of risk to identify high-risk patients who
may be candidates for SCD prevention with ICDs (Ta-
ble 8).1–22,26–33,37–61 This risk stratification strategy and
the penetration of ICDs into clinical practice has sub-
stantially reduced disease-related mortality rates.31,32
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Predictive risk scores are also available that can derive
individualized estimated 5-year SCD risk to aid in risk
stratification and ICD decision-making in adults and
children.2,22,35,62,63 Given that the risk of SCD extends
over many decades of life, periodic reassessment of
SCD risk is an integral component of the longitudinal
evaluation of most patients with HCM.1,2,6,22,31,32
Recommendation-Specific Supportive Text
1. Numerous observational studies of patients with
HCM have identified variables associated with
increased risk for potentially life-threatening ventric-
ular tachyarrhythmias.1–22 For this reason, SCD risk
assessment at the initial visit and repeated every 1
to 2 years1,2,31 is a critical part of the evaluation of
patients with HCM and includes: (1) previous his-
tory of cardiac arrest or sustained (>30 seconds or
associated with hemodynamic compromise) ventric-
ular arrhythmias1,3; (2) family history of SCD, or sus-
tained ventricular arrhythmias judged definitively or
likely attributable to HCM in ≥1 first-degree or other
close family members ≤50 years of age1,2,5,6; (3)
continuous (24- to 48-hour) ambulatory electrocar-
diographic monitoring to detect NSVT or sustained
VT1,2,6,13,14,22; (4) history of syncope considered likely
to be caused by arrhythmia (eg, episodes occurring in
the previous 6 months because they carry the most
prognostic importance, whereas those occurring >5
years in the past have little significance)1,2,4,22; and
(5) cardiac imaging that helps determine maximal LV
wall thickness,7,9 E F,10,21,24,25 and presence of apical
aneurysm with transmural scar or LGE.11,12 Because
data suggest a lower SCD event rate in stable, older
patients with HCM (>60 years of age),32 the deci-
sion regarding ongoing risk assessment is individu-
alized in this subset of patients.
2. CMR imaging may more accurately measure
maximal LV wall thickness and detect LV apical
aneurysm in some patients with HCM.11,12,15–17
In addition, extensive myocardial replacement
fibrosis, as detected by CMR-derived LGE, is
associated with increased risk for potentially life-
threatening ventricular arrhythmias.18–20 For these
reasons, if a patient with HCM does not have
evidence of increased SCD risk after assess-
ment with family and personal history, echocar-
diography, and ambulatory monitoring, or risk
stratification otherwise remains uncertain, con-
trast-enhanced CMR imaging can provide further
characterization of maximum LV wall thickness
measurement in any segment, EF, presence of
LV apical aneurysm, and presence and extent of
LGE.1,10–12,15–21,24,25,31
Table 8. Clinical Sudden Death Risk Factors for Adults and Children With HCM
Family history of sudden death
from HCM
Sudden death judged definitively or likely attributable to HCM in ≥1 first-degree or close relatives who are ≤50 y of age. Close
relatives would generally be second-degree relatives; however, multiple SCDs in tertiary relatives should also be considered
relevant.30,31
Massive LVH Wall thickness ≥30 mm in any segment within the chamber by echocardiography or CMR imaging; consideration for this
morphologic marker is also given to borderline values of ≥28 mm in individual patients at the discretion of the treating
cardiologist. For pediatric patients with HCM, an absolute or z-score threshold for wall thickness has not been established;
however, a maximal wall thickness that corresponds to a z-score ≥20 (and >10 in conjunction with other risk factors)
appears reasonable.32,33
Unexplained syncope ≥1 unexplained episodes involving acute transient loss of consciousness, judged by history unlikely to be of neurocardiogenic
(vasovagal) etiology, not attributable to LVOTO, and especially when occurring within 6 mo of evaluation (events beyond 5 y in
the past do not appear to have relevance).34
HCM with LV systolic
dysfunction
Systolic dysfunction with EF <50% by echocardiography or CMR imaging.24,27
LV apical aneurysm Apical aneurysm defined as a discrete thin-walled dyskinetic or akinetic segment with transmural scar or LGE of the most distal
portion of the LV chamber, independent of size. (In children, apical aneurysm is uncommon, and the risk has not been
studied.)15,16
Extensive LGE on CMR
imaging
Extensive LGE, representing replacement fibrosis, either quantified or estimated by visual inspection, comprising ≥15% of LV
mass (extent of LGE conferring risk has not been defined in children).9–11,20–22,25
NSVT on ambulatory monitor ≥3 beats at ≥120 bpm has generally been used in studies. It would seem most appropriate to place greater weight
on NSVT as a risk marker when runs are frequent (eg, ≥3), longer (eg, ≥10 beats), or faster (eg, ≥200 bpm) occurring
usually over 24 to 48 h of monitoring. For pediatric patients, a VT rate that exceeds the baseline sinus rate by >20% is
considered significant.35–37
Genotype status Genotype-positive status (ie, harboring a putatively disease-causing pathogenic/likely pathogenic variant) is associated with
higher SCD risk in pediatric patients with HCM.12,14
bpm indicates beats/min; CMR, cardiovascular magnetic resonance; EF, ejection fraction; HCM, hypertrophic cardiomyopathy; LGE, late gadolinium enhancement;
LV, left ventricular; LVH, left ventricular hypertrophy; LVOTO, left ventricular outflow tract obstruction; NSVT, nonsustained ventricular tachycardia; SCD, sudden cardiac
death; and VT, ventricular tachycardia.
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3. To calculate estimated SCD 5-year risk estimates
for adults with HCM, echocardiographic left atrial
diameter and maximal instantaneous LVOT gradi-
ent with continuous-wave Doppler technique are
needed.2,22 The SCD risk estimate does not take
into account the impact of newer markers of SCD
risk, including systolic dysfunction (EF <50%), api-
cal aneurysm, and LGE. The impact of ≥1 of these
newer risk markers on the 5-year risk estimate for
an individual patient with HCM is undetermined.
7.1.2. SCD Risk Assessment in Children and
Adolescents With HCM
Recommendations for SCD Risk Assessment in Children and
Adolescents With HCM
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. For children and adolescents with HCM, a compre-
hensive, systematic noninvasive SCD risk assess-
ment at initial evaluation and every 1 to 2 years
thereafter is recommended and should include
evaluation of these risk factors (Figures 1 and 3,
Table 8)1–8:
a. Personal history of cardiac arrest or sustained
ventricular arrhythmias;
b. Personal history of syncope suspected by clinical
history to be arrhythmic;
c. Family history in close relative of premature
HCM-related sudden death, cardiac arrest, or
sustained ventricular arrhythmias;
d. Maximal LV wall thickness, EF, LV apical aneu-
rysm;
e. NSVT episodes on continuous ambulatory elec-
trocardiographic monitoring.
1 C-LD
2. For children and adolescents with HCM who have
a borderline risk for SCD, or in whom a decision to
proceed with ICD placement remains uncertain after
clinical assessment that includes personal and family
history, echocardiography, and ambulatory electro-
cardiographic monitoring, CMR imaging is beneficial
to assess for extent of myocardial fibrosis with LGE
(Table 8).9–11
2a B-NR
3. For patients <16 years of age with HCM, it is rea-
sonable to calculate an estimated 5-year sudden
death risk that includes echocardiographic param-
eters (interventricular septal thickness in diastole,
LV posterior wall thickness in end-diastole, left atrial
diameter, maximal LVOT gradient) and genotype,
which may be useful during shared decision-making
for ICD placement (Table 8).1,12
Synopsis
Historically, risk stratification for SCD in children has been
based on risk markers derived from adult HCM studies.
Several studies suggest that adult risk factors have lim-
ited ability to predict SCD in pediatric patients.1–8,13,14
More recent collaborative studies suggest some, but
not all, of the adult risk factors are important in pedi-
atric patients with HCM.1,4,5 Two risk prediction models
for children with HCM have been developed and are be-
ing used in clinical practice.1,12 The risk factors proposed
in these guidelines include a combination of adult risk
factors and currently available pediatric-specific informa-
tion. Ultimately, decisions regarding ICD placement must
be based on individual judgment for each patient, taking
into account all age-appropriate risk markers, strength of
the risk factor(s) identified, the overall clinical profile, the
level of risk acceptable to the patient and family, and the
potential complications related to device implants, includ-
ing psychological impact and inappropriate ICD shock.
Recommendation-Specific Supportive Text
1. SCD risk assessment at the initial visit and repeated
every 1 to 2 years is a critical part of the evalua-
tion of patients with HCM1–8,13,14 and includes: (1)
previous history of cardiac arrest or sustained (>30
seconds or associated with hemodynamic compro-
mise) ventricular arrhythmias; (2) family history of
sudden death, cardiac arrest, or sustained ventricu-
lar arrhythmias judged definitively or likely attrib-
utable to HCM in ≥1 first-degree or other close
family members ≤50 years of age; (3) continuous
(24- to 48-hour) ambulatory electrocardiographic
monitoring to detect NSVT or sustained VT; (4)
history of syncope considered likely to be caused
by arrhythmia; and (5) cardiac imaging that helps
determine maximal LV wall thickness, EF, and pres-
ence of apical aneurysm. In pediatric patients, LV
wall thickness is commonly reported both as an
absolute measurement and standardized z-score
adjusted for body surface area. The presence of
HCM-associated genetic variants is also included
in one of the risk calculators.
2. CMR imaging may more accurately measure maxi-
mal LV wall thickness and detect LV apical aneurysm
in some patients with HCM.15–19 In addition, exten-
sive myocardial replacement fibrosis, as detected
by CMR-derived LGE, is associated with increased
risk for potentially life-threatening ventricular
arrhythmias.20–22 For these reasons, if a patient with
HCM does not have evidence of increased SCD
risk after assessment with family and personal his-
tory, echocardiography, and ambulatory monitoring,
or risk stratification otherwise remains uncertain,
contrast-enhanced CMR imaging can provide fur-
ther characterization of maximum LV wall thick-
ness measurement in any segment, EF, presence
of LV apical aneurysm, and presence and extent of
LGE.15–28 Although CMR imaging may be helpful
in pediatric patients with HCM,9–11 this may require
sedation, the risk of which may outweigh the ben-
efits in an otherwise asymptomatic child. The use
of CMR imaging should be determined by the phy-
sician and family after evaluating the child’s indi-
vidual risk.
3. To calculate 5-year SCD risk estimates for chil-
dren with HCM, age, echocardiographic LV wall
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diameter z-scores, left atrial diameter z-score, max-
imal instantaneous LVOT gradient with continuous-
wave Doppler technique, in addition to history of
unexplained syncope, NSVT, with or without gen-
otype status are used.1,12 The SCD risk estimate
does not account for systolic dysfunction (EF
<50%), apical aneurysm, exercise-induced isch-
emia, or LGE.9–11,29 The contribution of ≥1 of these
newer risk markers on the 5-year risk estimate for
an individual patient with HCM is undetermined.
7.2. Patient Selection for ICD Placement
Recommendations for ICD Placement in High-Risk Patients With HCM
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 C-EO
1. In patients with HCM, application of individual
clinical judgment is recommended when assessing
the prognostic strength of conventional risk marker(s)
within the clinical profile of the individual patient, as
well as a thorough and balanced discussion of the
evidence, benefits, and estimated risks to engage
the fully informed patient’s active participation in ICD
decision-making.1–5
1 B-NR
2. For patients with HCM and previous documented
cardiac arrest or sustained VT, ICD placement is
recommended (Figure 3, Table 8).2–6
2a B-NR
3. For adult patients with HCM with ≥1 major risk
factors for SCD, it is reasonable to offer an ICD. These
major risk factors include (Figure 3, Table 8)2,3,7–21:
a. Sudden death judged definitively or likely
attributable to HCM in ≥1 first-degree or close
relatives who are ≤50 years of age;
b. Massive LVH ≥30 mm in any LV segment;
c. ≥ 1 recent episodes of syncope suspected by
clinical history to be arrhythmic (ie, unlikely to be
of neurocardiogenic [vasovagal] etiology, or related
to LVOTO);
d. LV apical aneurysm with transmural scar or LGE;
e. LV systolic dysfunction (EF <50%).
2a B-NR
4. For children with HCM who have ≥1 conventional risk
factors, including unexplained syncope, massive LVH,
NSVT, or family history of early HCM-related SCD,
ICD placement is reasonable after considering the
relatively high complication rates of long-term ICD
placement in younger patients (Figure 3,
Table 8).22–30
2a B-NR
5. For patients with HCM with ≥1 major SCD risk
factors, discussion of the estimated 5-year sudden
death risk and mortality rates can be useful during
the shared decision-making process for ICD
placement (Figure 3, Table 8).3,19,29,30
2b B-NR
6. In select adult patients with HCM and without major
SCD risk factors after clinical assessment, or in
whom the decision to proceed with ICD placement
remains otherwise uncertain, ICD may be considered
in patients with extensive LGE by contrast-enhanced
CMR imaging or NSVT present on ambulatory moni-
toring (Figure 3, Table 8).2,3,16,19,31–33
2b B-NR
7. In pediatric patients with HCM, it can be useful to
consider additional factors such as extensive LGE on
contrast-enhanced CMR imaging and systolic
dysfunction in risk stratification for ICD shared
decision-making (Figure 3, Table 8).34,35
3:
Harm B-NR 8. In patients with HCM without risk factors, ICD
placement should not be performed.2
3:
Harm B-NR
9. In patients with HCM, ICD placement for the sole
purpose of participation in competitive athletics
should not be performed.36
Synopsis
In patients with HCM, risk stratification and selection
of patients for prophylactic ICD therapy continues to
evolve.1–28,31–35,37 The proven efficacy of the ICD has
placed increasing weight on the importance of accurate
selection of patients for device therapy.4,5,28,31–33,38 In as-
sociation with clinical judgment and shared decision-
making, patients with HCM are considered potential
candidates for primary prevention ICDs by virtue of ≥1
major risk markers that have a high sensitivity in predict-
ing those patients with HCM at greatest risk SCD.1,2,4,38
More recently, risk estimate calculators have been devel-
oped for adult and pediatric patients with HCM.3,19,29,37
This 5-year risk estimate may help patients understand
the magnitude of their SCD risk and can be used dur-
ing shared decision-making discussions.3,19 Because in-
dividual patients may consider the impact of SCD risk
estimates differently, it is the consensus of the writing
committee that management recommendations should
not be assigned to prespecified risk estimates as the
sole arbiter of the decision to recommend an ICD. Con-
temporary SCD risk markers in HCM, including LV api-
cal aneurysm, LGE (with transmural scar), and systolic
dysfunction (EF <50%), are not included in the risk cal-
culator, and their impact on the calculated 5-year risk
estimate is uncertain.
Recommendation-Specific Supportive Text
1. Primary prevention ICD decision-making in HCM
can often be complex and challenging, because of
the low SCD event rates observed in this disease.
In addition, the relatively young age of patients
with HCM considered for SCD prevention means
risk periods can often extend over many years
and decades of an individual patient’s life. For
these reasons, decisions regarding primary pre-
vention ICD therapy should incorporate a discus-
sion with patients that includes risk for SCD and
the benefit that ICD therapy provides in protect-
ing against life-threatening ventricular tachyar-
rhythmias balanced with the understanding that
long-term device therapy can be associated with
complications.1,4,5
2. Patients with HCM who have experienced a previ-
ous documented cardiac arrest or hemodynamically
Recommendations for ICD Placement in High-Risk Patients With HCM
(Continued)
COR LOE Recommendations
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significant VT/ventricular fibrillation (VF) remain at
significantly increased risk for future life-threatening
ventricular tachyarrhythmias and should there-
fore be considered for secondary prevention ICD
therapy.2–6
3. Identification of adult patients with HCM at high
risk for SCD should be guided by the presence of
a number of acknowledged noninvasive SCD risk
factors (Table 8). Because each of these major risk
factors individually is associated with increased
risk, it would be reasonable to consider primary
prevention ICD for patients with ≥1 SCD risk fac-
tors (Figure 3, Table 8).2,4,5,7–18,20,21,31–33 This risk
stratification strategy provides high sensitivity for
identifying at-risk patients who may benefit from
life-saving ICD therapy and the opportunity to fully
incorporate a shared-decision making process that
takes into consideration the complete clinical pro-
file of the patient as well as physician judgment
and patient preference.1,2,38 Given the very low SCD
event rate observed in patients of advanced age
(>60 years) with HCM, the risk stratification strat-
egy with major markers is most applicable to young
adults and middle-aged patients with HCM.2,4,5,37,38
4. Risk stratification in children with HCM requires
evaluation of multiple age-appropriate risk
factors.22–30,39 It would be reasonable to consider
primary prevention ICD for pediatric patients with
≥1 SCD risk factors with the understanding that the
magnitude may be higher when multiple risk factors
coexist in a patient (Figure 3, Table 8).22–29,37,40,41 Risk
estimate scores that incorporate risk factors relative
to pediatric patients, along with left atrial diameter
z-score and genotype status, have been developed
in children with HCM.29,30 Although LV systolic dys-
function and apical aneurysms are uncommon in
children, it would seem prudent (based on adult
evidence) to consider these in the context of the
entire risk profile of the individual patient. Finally,
the complexity and potential psychological impact
of ICD decision-making in this age group must be
underscored, given the long periods of time with
exposure to ICD therapy in young patients and the
relatively higher complication rates of long-term
device therapy in this subgroup of patients.22–29
5. In patients with HCM with ≥1 major SCD risk fac-
tors, estimating 5-year SCD risk may aid patients
in understanding the magnitude of their individual
risk for SCD to further assist in ICD decision-mak-
ing.19,29,30 Because individual patients may consider
the impact of SCD risk estimates differently, it is the
consensus of the writing committee that prespeci-
fied risk thresholds should not be the sole arbiter of
the decision to insert an ICD. Contemporary SCD
risk markers in HCM, including LV apical aneurysm,
LGE, and systolic dysfunction (EF <50%), are not
included in the risk calculator, and their impact on
5-year risk estimates is uncertain. There are sepa-
rate risk calculations for adult patients19 and chil-
dren and adolescents.29,30
6. Extensive LGE often occupying multiple LV seg-
ments is associated with increased risk for future
potentially life-threatening ventricular arrhythmias
in adults, independent of location or pattern within
the LV wall.31–33 Some studies have promoted a
threshold for extensive LGE of ≥15% of the LV
mass as representing a significant increase in SCD
risk31,33; however, several methods are used to
quantify LGE that can yield different results, and no
consensus has been achieved about which method
is optimal. The strong cross-sectional relationship
between LGE and NSVT in patients with HCM
provides further support for LGE as representing
the structural nidus for ventricular tachyarrhyth-
mias in HCM. In addition, bursts of NSVT identified
on ambulatory monitoring performed over 24 to
48 hours are also associated with some increase
in SCD risk,2,4,5,16,17,19 with greatest weight as an
independent risk factor given to adult patients
with HCM with particularly frequent, long, and fast
runs of NSVT.17 In the absence of other major risk
markers, the impact of short, isolated bursts of
NSVT on SCD risk is less certain.14,17,38 The ben-
efit of extended monitoring period with longer-term
ambulatory monitoring devices for the purpose of
risk stratification in HCM remains uncertain.
7. The association between SCD risk and LGE in
children with HCM is not well defined. Although
nearly half of older children and adolescents have
LGE, the extent of LGE that constitutes high risk
in children has not been established.34,35 However,
given that LGE represents a structural nidus for VT
that can increase risk of SCD outcomes in adult
patients with HCM,31–33 it would seem appropriate
to consider extensive LGE as potentially increas-
ing SCD risk in children. LV systolic dysfunction
is uncommon in children but likely also increases
risk for adverse events, including SCD. Sedation
or general anesthesia may be required for CMR
imaging in young patients.
8. Given the long-term complications associated
with ICD placement, device therapy should not be
offered to patients with HCM without evidence of
increased risk based on the proposed risk factor
algorithm (Figure 3).4,5
9. Sudden death risk stratification and recommenda-
tions for ICD placement should be made in accor-
dance with the algorithm put forth in this guideline,
independent of decisions regarding sports partici-
pation. Inappropriate ICD utilization would expose
patients unnecessarily to device-related complica-
tions and should be avoided.36
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7.3. ICD Device Selection Considerations
Recommendations for ICD Device Selection Considerations
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with HCM who are receiving an ICD,
either a single-chamber transvenous ICD or a
subcutaneous ICD is recommended after a shared
decision-making discussion that takes into
consideration patient preferences, age, lifestyle,
and potential need for pacing for bradycardia or VT
termination.1–6
1 B-NR
2. In patients with HCM who are receiving a
transvenous ICD, single-coil ICD leads are
recommended in preference to dual-coil leads, if
defibrillation threshold is deemed adequate.7–9
2a B-NR
3. In patients with HCM who are receiving an ICD,
dual-chamber ICDs are reasonable for patients with
a need for atrial or atrioventricular sequential pacing
for bradycardia/conduction abnormalities, or as an
attempt to relieve symptoms of obstructive HCM
(most commonly in patients >65 years of age).10–13
2a C-LD
4. In selected adult patients with nonobstructive HCM
receiving an ICD who have NYHA class II to ambula-
tory class IV HF, left bundle branch block (LBBB), and
LVEF <50%, cardiac resynchronization therapy (CRT)
for symptom reduction is reasonable.14–18
2b C-LD
5. In patients with HCM in whom a decision has been
made for ICD implantation and who have paroxysmal
atrial tachycardias or AF, dual-chamber ICDs may be
reasonable, but this decision must be balanced against
higher complication rates of dual-chamber devices.19–24
Synopsis
The decision of which type of ICD to implant is nu-
anced. There are risks and benefits to consider. Con-
siderations include transvenous versus subcutaneous
ICD, single-chamber versus dual-chamber versus CRT
devices, and number of defibrillation coils with transve-
nous approach. Patients with HCM who receive ICDs
are usually younger than those with ischemic and even
nonischemic cardiomyopathies who receive a device
and, thus, life-long complications are likely to be higher
in those with HCM.
ICD implantation in children raises additional con-
cerns and challenges.1,25,26 Although selection for whom
should receive ICDs is discussed in Section 7.2, “Patient
Selection for ICD Placement,” the approach to implan-
tation will vary based on body size. Epicardial leads will
often be necessary in smaller children, usually <30 kg,
and for children requiring an LV/CRT lead. Complica-
tions of ICDs may be higher in children and adolescents
because of higher baseline heart rates, which can lead
to inappropriate shocks, somatic growth that increases
risk of lead fracture, and the need for multiple device
replacements or extractions over a lifetime.25 In younger
patients, transvenous leads have shown higher rates
of failure compared with in older patients. Smaller indi-
viduals with subcutaneous ICDs may also be at risk for
higher complication rates, including device erosion.1,26,27
Figure 3. Patient Selection for ICD Use.
Colors correspond to Table 3. *ICD
decisions in pediatric patients with HCM
are based on ≥1 of these major risk
factors: family history of HCM SCD,
NSVT on ambulatory monitor, massive
LVH, and unexplained syncope. †5-year
risk estimates can be considered to fully
inform patients during shared decision-
making discussions. ‡It would seem most
appropriate to place greater weight on
frequent, longer, and faster runs of NSVT.
CMR indicates cardiovascular magnetic
resonance; EF, ejection fraction; FH, family
history; HCM, hypertrophic cardiomyopathy;
ICD, implantable cardioverter-defibrillator;
LGE, late gadolinium enhancement;
LVH, left ventricular hypertrophy; NSVT,
nonsustained ventricular tachycardia;
SCD, sudden cardiac death; VF, ventricular
fibrillation; and VT, ventricular tachycardia.
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Recommendation-Specific Supportive Text
1. The decision to implant an ICD includes additional
considerations, including transvenous versus sub-
cutaneous ICD.1–6 Benefits of transvenous devices
include the ability to pace for bradycardia, and
potential RV apical pacing for reduction of symp-
toms, antitachycardia pacing for VT, smaller size,
and extended battery longevity. The disadvantage
is the lead, which may fail over time, necessitating
additional leads and removal of older leads, which
is associated with significant risk and the poten-
tial for lead infections. Advantages of the subcu-
taneous ICD include the lack of a transvenous
lead, potentially fewer lead failures, and ease of
removal. Disadvantages include the larger size of
the device, the shorter battery longevity, potentially
increased inappropriate shocks, inability to pace,
and shorter history of use. Patients with HCM who
undergo subcutaneous ICD implantation should be
screened for potential oversensing after exercise
and even potentially on a treadmill after implanta-
tion. Shared decision-making conversations should
incorporate patient preferences, lifestyle, and
expected potential need for pacing for bradycar-
dia or VT termination. Providers should consider
the age of the patient, because complications with
transvenous systems are higher in young patients, 25
potential need for pacing, and concerns about
inappropriate shock and lead longevity.
2. Single-coil ICD leads are less complicated to
remove but carry the risk of elevated defibrilla-
tion thresholds.28 However, most individuals, both
with and without HCM, have an adequate safety
margin with single-coil leads.7–9,29 Single-coil leads
have almost exclusively been implanted with left-
sided implants, and data from populations without
HCM suggest that dual-coil leads are necessary
for right-sided implants. Thus, the recommendation
for single-coil leads should be applied only to left-
sided implants. Finally, strong consideration should
be given to defibrillation threshold testing in those
patients with single-coil leads, right-sided implants,
epicardial systems, and massive hypertrophy.
3. In patients with HCM with a need for atrial pac-
ing, a dual-chamber system would be needed.
Four RCTs have shown consistent findings on the
benefit of RV pacing in patients with HCM with
LVOT gradients ≥30 mm Hg. Acutely, RV apical
pacing reduces the LVOT gradient, but the long-
term clinical benefits have not been consistently
beneficial.10–14,30 However, in subgroup analysis,
some evidence has been seen that RV pacing may
benefit some individuals who are ≥65 years of age.
This potential advantage must be weighed against
the higher complication risk with dual-chamber
devices.
4. Although most of the evidence supporting the ben-
efit of CRT is derived from studies with minimal or
no patients with HCM, it would be reasonable to
offer this therapy to patients with HCM who meet
current recommendations of a CRT-defibrillator
in accordance with the AHA/ACC/HFSA HF
guideline,31 including patients with NYHA func-
tional class II to ambulatory class IV HF, LVEF
≤35%, and QRS duration with LBBB. In addition
to those patients, several small case series of CRT-
defibrillator in patients with HCM and LVEF >35%
have been published.14–18 Some patients will clini-
cally respond to CRT with an improvement in their
NYHA functional class or evidence of reverse LV
remodeling. The benefit appears to be greater in
those with LBBB and very prolonged QRS dura-
tion. Responders show a modest improvement in
LVEF. One study found a significantly longer time
to the combined endpoint of left ventricular assist
device (LVAD) placement, heart transplantation, or
death,16 while 2 other studies did not identify a sur-
vival benefit.14,18 RV pacing shares a similar physiol-
ogy to LBBB so that this recommendation may be
extended to those with LVEFs between 35% and
50% and expected to be paced >40% of the time,
similar to the recommendation in the 2018 AHA/
ACC/HRS bradycardia and cardiac conduction
delay guideline.32
5. An atrial lead may provide better discrimination
between ventricular and supraventricular arrhyth-
mias, although data are modest regarding reduced
inappropriate therapy in those with dual-chamber
devices, and data show that the complication rate
is higher with dual-chamber devices.19–24 However,
in pediatric patients with atrial tachyarrhythmias,
the rates of which can approach typical VT rates,
a dual-chamber device may aid in distinguishing
supraventricular tachycardia from VT. This poten-
tial advantage must be weighed against the higher
complication risk with the additional hardware.
8. MANAGEMENT OF HCM
8.1. Management of Symptomatic Patients With
Obstructive HCM
8.1.1. Pharmacological Management of
Symptomatic Patients With Obstructive HCM
Recommendations for Pharmacological Management of Symptomatic
Patients With Obstructive HCM
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with obstructive HCM and symptoms*
attributable to LVOTO, nonvasodilating beta
blockers, titrated to effectiveness or maximally
tolerated doses, are recommended.1–3
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1
B-NR† 2. In patients with obstructive HCM and symptoms*
attributable to LVOTO, for whom beta blockers are
ineffective or not tolerated, substitution with
nondihydropyridine calcium channel blockers
(eg, verapamil,† diltiazem‡) is recommended.4–6
C-LD‡
1 B-R
3. For patients with obstructive HCM who have
persistent symptoms* attributable to LVOTO despite
beta blockers or nondihydropyridine calcium
channel blockers, adding a myosin inhibitor (adult
patients only), or disopyramide (in combination
with an atrioventricular nodal blocking agent),
or SRT performed at experienced centers,§ is
recommended.7–14
1 C-LD
4. For patients with obstructive HCM and acute
hypotension who do not respond to fluid
administration, intravenous phenylephrine (or other
vasoconstrictors without inotropic activity), alone or
in combination with beta-blocking drugs, is
recommended.15
2b C-EO
5. For patients with obstructive HCM and persistent
dyspnea with clinical evidence of volume overload
and high left-sided filling pressures despite other
HCM GDMT, cautious use of low-dose oral diuretics
may be considered.
2b C-EO
6. For patients with obstructive HCM, discontinuation
of vasodilators (eg, angiotensin-converting enzyme
inhibitors, angiotensin receptor blockers,
dihydropyridine calcium channel blockers) or digoxin
may be reasonable because these agents can
worsen symptoms caused by dynamic outflow tract
obstruction.
3:
Harm C-LD
7. For patients with obstructive HCM and severe dys-
pnea at rest, hypotension, very high resting gradients
(eg, >100 mm Hg), as well as all children <6 weeks
of age, verapamil is potentially harmful.4,16
*Symptoms include effort-related dyspnea or chest pain and occasionally other
exertional symptoms (eg, syncope, near syncope) that are attributed to LVOTO
and interfere with everyday activity or quality of life.
†Symbol corresponds to the Level of Evidence for verapamil.
‡Symbol corresponds to the Level of Evidence for diltiazem.
§Comprehensive or primary HCM centers with demonstrated excellence in
clinical outcomes for these procedures (Tables 4 and 5).
Synopsis
The principal role of pharmacological therapy targeted
at the dynamic LV obstruction is that of symptom relief
because no convincing data are available to suggest
that pharmacological therapy alters the natural history
of HCM. Because the outflow tract obstruction is re-
markably variable throughout daily life, the success of a
given medication is determined by the patient’s symptom
response and not the measured gradient. In general,
nonvasodilating beta blockers are considered first-line
therapy. The calcium channel blockers—verapamil or
diltiazem—are reasonable alternatives to beta-blocker
therapy. For patients who do not respond to trials of ≥1
of these drugs, advanced therapies with disopyramide,
mavacamten (a cardiac myosin inhibitor), or septal re-
duction are often the next step. One of the other key
steps in managing symptomatic, obstructive HCM is to
eliminate medications that may promote outflow tract
obstruction, such as pure vasodilators (eg, dihydro-
pyridine class calcium channel blockers, angiotensin-
converting enzyme inhibitors, angiotensin receptor
blockers) and high-dose diuretics. Low-dose diuretics,
when added to other first-line medications, are some-
times useful for patients with persistent dyspnea or
congestive symptoms. The principles of pharmacologi-
cal management outlined here also apply to patients
with obstruction at the midventricular level.
Recommendation-Specific Supportive Text
1. Beta blockers were the first studied medication for
treatment of dynamic outflow tract obstruction and
are generally considered the first-line agent for
most patients with obstructive HCM. Medications
should be titrated to a dose where symptom ben-
efit is observed, but failure of beta-blockade should
not be declared until demonstrated physiologic evi-
dence of beta-blockade (ie, suppression of resting
heart rate) is reported.1–3
2. Diltiazem and verapamil both have been demon-
strated to provide relief of symptoms in patients
with obstructive HCM. These agents can have
vasodilating properties, in addition to the negative
inotropic and negative chronotropic effects, which
can be limiting. The use of calcium channel block-
ers in combination with beta blockers, as therapy
directed at HCM, is unsupported by evidence4–6;
however, these may have a role in management of
concomitant hypertension.
3. Patients with HCM who do not respond to first-line
therapy are candidates for escalation of therapy,
including cardiac myosin inhibitors (eg, mava-
camten) (in adult patients only), disopyramide,
and SRT when performed by experienced opera-
tors in comprehensive HCM centers (Tables 4
and 5). The choice among these options should
be approached through a comprehensive discus-
sion with the patient that includes the success
rates, benefits, and risks of each of the options.
Mavacamten is a cardiac myosin inhibitor and has
been shown to improve LVOT gradients, symp-
toms, and functional capacity in 30% to 60% of
patients with obstructive HCM.13,14 In the United
States, a risk evaluation and mitigation strat-
egy is required due to the observed decrease in
LVEF <50% in 7% to 10% of patients noted in
studies on which mavacamten was approved.17
Disopyramide has also been shown to provide
symptomatic benefit in patients with obstruc-
tive HCM who have failed first-line therapy.7–9
Recommendations for Pharmacological Management of Symptomatic
Patients With Obstructive HCM (Continued)
COR LOE Recommendations
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Because disopyramide can enhance conduction
through the atrioventricular node, which could
lead to rapid conduction with the onset of AF, this
medication should be used in combination with
another medication that has atrioventricular nodal
blocking properties (eg, beta blocker, verapamil,
or diltiazem). SRT, when performed by experi-
enced operators in comprehensive HCM centers
(Tables 4 and 5), is very effective for relieving
LVOTO and can be used instead of mavacamten
or disopyramide.10–12
4. Acute hypotension in patients with obstructive
HCM is a medical urgency. Maximizing preload
and afterload, while avoiding increases in con-
tractility or heart rate, is the critical focus in
treating acute hypotension. Intravenous vaso-
constrictors, such as phenylephrine, can also
reverse this dangerous situation. Beta-blockade
can also be useful in combination with the
vasoconstrictor as it dampens contractility and
improves preload by prolonging the diastolic fill-
ing period.15
5. When signs or symptoms of congestion are
observed, cautious use of low-dose diuretics may
provide some symptom relief. Aggressive diuresis
can be problematic, as decreasing the preload can
augment LVOTO.
6. Caution should be used when introducing ther-
apies in patients with HCM who will be treated
for coexisting conditions. Some medications can
cause or worsen symptoms related to LVOTO.
Examples include the use of diuretics and vaso-
dilators to treat hypertension or protect renal
function. Those medications can be used in
asymptomatic patients. However, if symptoms are
present, or emerge after the initiation of the medi-
cation, it may be necessary to uptitrate medica-
tions being used for obstructive HCM or consider
alternative therapies for the comorbid condition.
As a result, positive inotropic agents, pure vasodi-
lators, and high-dose diuretics can be considered
relatively contraindicated in patients with symp-
tomatic obstructive HCM.
7. Although verapamil and diltiazem can be very effec-
tive medications to relieve symptoms attributable to
LVOTO, in some patients, they have been reported
to have a more prominent vasodilatory action. This
afterload-reducing effect can be particularly dan-
gerous in patients with very high resting gradi-
ents (>80-100 mm Hg) and signs of congestive
HF. Several reports have been published of life-
threatening bradycardia and hypotension in new-
borns of <6 weeks of age who have received
intravenous verapamil for supraventricular tachy-
cardia.16 However, verapamil has been found to be
efficacious and well tolerated when administered
to older infants and children with HCM in con-
trolled conditions.18
8.1.2. Invasive Treatment of Symptomatic Patients
With Obstructive HCM
Recommendations for Invasive Treatment of Symptomatic Patients
With Obstructive HCM
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with obstructive HCM who remain
symptomatic despite GDMT, SRT in eligible patients,*
performed at experienced HCM centers,† is recom-
mended for relieving LVOTO (Tables 4 and 5).1–3
1 B-NR
2. In symptomatic patients with obstructive HCM
who have associated cardiac disease requiring
surgical treatment (eg, associated anomalous
papillary muscle, markedly elongated anterior mitral
leaflet, intrinsic mitral valve disease, multivessel CAD,
valvular aortic stenosis), surgical myectomy,
performed at experienced HCM centers,† is
recommended (Tables 4 and 5).4–7
1 C-LD
3. In adult patients with obstructive HCM who remain
severely symptomatic, despite GDMT and in whom
surgery is contraindicated or the risk is considered
unacceptable because of serious comorbidities or
advanced age, alcohol septal ablation in eligible
patients,* performed at experienced HCM centers,†
is recommended (Tables 4 and 5).8–10
2b B-NR
4. In patients with obstructive HCM, earlier (NYHA
class II) surgical myectomy performed at
comprehensive HCM centers (Tables 4 and 5) may
be reasonable in the presence of additional clinical
factors, including3,11–22:
a. Severe and progressive pulmonary hypertension
thought to be attributable to LVOTO or
associated MR;
b. Left atrial enlargement with ≥1 episodes of
symptomatic AF;
c. Poor functional capacity attributable to LVOTO as
documented on treadmill exercise testing;
d. Children and young adults with very high resting
LVOT gradients (>100 mm Hg).
2b C-LD
5. For symptomatic patients with obstructive HCM, SRT
in eligible patients,* performed at experienced HCM
centers† (Tables 4 and 5), may be considered as
an alternative to escalation of medical therapy after
shared decision-making including risks and benefits
of all treatment options.1,10,23–25
3:
Harm C-LD
6. For patients with HCM who are asymptomatic and
have normal exercise capacity, SRT is not
recommended.13,21
3:
Harm B-NR
7. For symptomatic patients with obstructive HCM in
whom SRT is an option, mitral valve replacement
should not be performed for the sole purpose of
relief of LVOTO.26,27
*General eligibility criteria for septal reduction therapy: (a) clinical: severe dys-
pnea or chest pain (usually NYHA functional class III or class IV), or occasion-
ally other exertional symptoms (eg, syncope, near syncope), when attributable
to LVOTO, that interferes with everyday activity or quality of life despite optimal
medical therapy; (b) hemodynamic: dynamic LVOT gradient at rest or with physi-
ologic provocation with approximate peak gradient of ≥50 mm Hg, associated
with septal hypertrophy and SAM of mitral valve; and (c) anatomic: targeted ante-
rior septal thickness sufficient to perform the procedure safely and effectively in
the judgment of the individual operator.
†Comprehensive or primary HCM centers with demonstrated excellence in
clinical outcomes for these procedures (Tables 4 and 5).
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Synopsis
SRT is generally reserved for drug-refractory symptoms
and should be performed in experienced HCM centers.28
Transaortic extended septal myectomy (ESM) is an ap-
propriate treatment for the broadest range of patients and
allows gradient relief at any level within the ventricle,29–31
with a mortality rate of <1% and clinical success >90%
to 95%.1,24,27,32–39 Successful ESM eliminates or reduces
SAM-mediated MR and its consequences.27,32,40,41 Long-
term survival after ESM is similar to an age-matched
general population. Recurrent outflow tract obstruction
is rare after ESM.42–44 ESM is especially advantageous
when associated cardiac disease or associated papillary
muscle abnormalities are present.4,37,45 In HCM centers
with experienced interventional teams, alcohol septal ab-
lation is also associated with a low procedural mortality
rate (<1%) but requires appropriate coronary anatomy.
Alcohol septal ablation avoids sternotomy, has a shorter
hospital stay, and is advantageous when frailty or comor-
bidities increase the risk of ESM. Alcohol septal ablation
is less effective with gradients ≥100 mm Hg and septal
thickness ≥30 mm9,46 and is associated with greater risk
of permanent pacemaker and greater need for repeat
intervention for residual obstruction.8–10 Although 5-year
survival is similar between alcohol septal ablation and
myectomy,8,9,47,48 at 10 years of follow-up, survival is lower
with alcohol septal ablation compared with ESM.
Recommendation-Specific Supportive Text
1. Generally, SRT performed by experienced opera-
tors in comprehensive centers (Tables 4 and 5)
is contemplated when patients continue to have
severe symptoms despite optimal medical therapy
or intolerant adverse effects from medical therapy.1
SRT with either surgical myectomy or alcohol sep-
tal ablation is rarely indicated for the asymptomatic
patient. Survival of patients with LVOTO is reduced
compared with those without obstruction, and relief
of obstruction may mitigate this incremental risk.2,3
Currently, however, insufficient evidence is avail-
able to recommend SRT to improve patient survival
as the only indication for the procedures. Highly
symptomatic patients should be able to participate
in a full discussion of all treatment options, includ-
ing the success rates, benefits, and risks. If either of
the procedures is unavailable for the patient at their
primary cardiology practice, referral to more com-
prehensive HCM centers is encouraged because
the literature demonstrates a volume-outcome
relationship. The classic approach of transaortic
septal myectomy is potentially limited in infants and
young children in whom the aortic annulus is small.
In such instances, the modified Konno procedure
has been reported to provide equally satisfac-
tory long-term results for basal obstruction and a
transapical approach (or combined transaortic and
transapical) for midventricular obstruction.49
2. In patients with symptomatic obstructive HCM who
have associated cardiac disease requiring surgi-
cal treatment (eg, associated anomalous papillary
muscle, markedly elongated anterior mitral leaflet,
intrinsic mitral valve disease, CAD, valvular aortic
stenosis), surgical myectomy performed by expe-
rienced operators provides the opportunity to cor-
rect all structural and anatomic issues with a single
procedure. Similarly, for patients with paroxysmal
AF, intraoperative pulmonary vein isolation or maze
procedure can also be added to septal myec-
tomy.50,51 Transaortic septal myectomy adds little
to the risk of other cardiac procedures, and relief
of LVOTO will minimize the risk of hemodynamic
instability early postoperatively.4–7
3. In adult patients with symptomatic obstructive HCM
in whom surgery is contraindicated or the risk is
considered unacceptably high because of serious
comorbidities or advanced age, alcohol septal abla-
tion when feasible and performed in experienced
HCM centers (Tables 4 and 5) becomes the pre-
ferred invasive strategy for relief of LVOTO.8–10
4. Although most patients who undergo SRT are
those with advanced symptoms (NYHA functional
class III to class IV), select patients who report
fewer symptoms but who have other evidence
of significant hemodynamic impairment may be
eligible for surgical myectomy at comprehen-
sive HCM centers (Tables 4 and 5) to relieve the
LVOTO and its sequelae. Data suggest that surgi-
cal myectomy can improve progressive pulmonary
hypertension,11,12,52 improve outcomes of those
with marked exercise impairment,13 reverse left
atrial enlargement,14,15,53 ameliorate occult gastro-
intestinal bleeding,41,42 and decrease rates of sub-
sequent atrial54 and ventricular arrhythmias.3,18,19
Similar to the recommendations for patients with
asymptomatic mitral valve disease, earlier surgery
in patients with HCM should be limited to those
comprehensive HCM centers with documented
evidence of the highest success rates and lowest
complication rates (ie, durable success is >90%
with an expected mortality rate <1%) (Table 5).20
Although successful alcohol septal ablation has
been shown to improve new onset AF burden and
NYHA functional class in those presenting with
NYHA functional class II symptoms and thereby
could be reasonably expected to offer similar ben-
efits at comprehensive HCM centers, this must be
balanced against the higher pacemaker and rein-
tervention rates in this lower risk cohort.8,9,55–58
5. Some patients with obstructive HCM and severe
symptoms might choose SRT as an alternative to
escalation of medical management after being fully
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informed through shared decision-making about
risks and benefits. Previously, SRT was reserved,
appropriately, for the most symptomatic patients
because a procedural mortality rate was 5% to
10%. This high mortality rate has been observed
in the recent era in HCM centers with less experi-
ence with the operation.23 In comprehensive HCM
centers, procedural complication rates are very
low, offering septal reduction to patients with sig-
nificant limiting HF symptoms without waiting for
progression to marked disability (ie, traditional
NYHA functional class III and class IV) and can be
seen as similar to offering early intervention in val-
vular heart disease in centers with demonstrated
excellent outcomes.1,10,24,25 However, symptoms
and impaired quality of life may be perceived very
differently by individual patients with HCM, under-
scoring the importance of shared decision-making
in establishing the optimal timing for intervention.
6. No definitive data have been published to suggest
benefit for SRT in adult patients with HCM who
are asymptomatic with normal exercise tolerance
or those whose symptoms are easily minimized on
optimal medical therapy.13,21
7. Mitral valve replacement is more common in gener-
alized HCM centers than in specialized HCM cen-
ters, and while valve replacement eliminates SAM
and associated MR as well as the outflow tract gra-
dient, the addition of mitral valve replacement with
or without myectomy increases the hospital mor-
tality rate (>10-fold) and length of hospitalization
compared with patients undergoing isolated sep-
tal myectomy.26 Further, when intervention on the
valve at the time of myectomy is needed because
of intrinsic mitral disease, every effort should be
made to repair the valve because early and long-
term mortality is worse in patients with prosthetic
replacement compared with patients who have
septal myectomy and mitral valve repair.27
8.2. Management of Patients With
Nonobstructive HCM With Preserved EF
Recommendations for Management of Patients With Nonobstructive
HCM With Preserved EF
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 C-LD
1. In patients with nonobstructive HCM with preserved
EF and symptoms of exertional angina or dyspnea,
beta blockers or nondihydropyridine calcium channel
blockers are recommended.1–5
2a C-EO
2. In patients with nonobstructive HCM with preserved
EF, it is reasonable to add oral diuretics when
exertional dyspnea persists despite the use of
beta blockers or nondihydropyridine calcium
channel blockers.
2b C-LD
3. In patients with nonobstructive HCM with preserved
EF, the usefulness of angiotensin-converting enzyme
inhibitors and angiotensin receptor blockers in the
treatment of symptoms (angina and dyspnea) is not
well established.6
2b C-LD
4. In highly selected patients with apical HCM with
severe dyspnea or angina (NYHA functional class
III or class IV) despite maximal medical therapy, and
with preserved EF and small LV cavity size (LV
end-diastolic volume <50 mL/m2 and LV stroke
volume <30 mL/m2), apical myectomy by experi-
enced surgeons at comprehensive centers may be
considered to reduce symptoms.7
2b C-EO
5. In asymptomatic patients with nonobstructive HCM,
the benefit of beta blockers or calcium channel
blockers is not well established.
2b B-R
6. For younger (eg, ≤45 years of age) patients with
nonobstructive HCM due to a pathogenic or likely
pathogenic cardiac sarcomere genetic variant, and a
mild phenotype,* valsartan may be beneficial to slow
adverse cardiac remodeling.8
*Mild phenotype indicates NYHA functional class I or II, maximal LV wall thick-
ness 13 to 25 mm, no secondary prevention ICDs, no history of appropriate ICD
shocks, and no AF.
Synopsis
Symptomatic, nonobstructive HCM is a diagnostic and
therapeutic challenge. This is related to differences in
disease onset, severity, and risk for adverse outcomes.9
The overall risk for HCM-related death appears similar
between patients with and without obstructive physiol-
ogy.10 Dyspnea and chest discomfort are common symp-
toms in patients with nonobstructive HCM. These can be
a result of increased LV filling pressures related to dia-
stolic dysfunction (including restrictive physiology) or de-
compensated HF, increased myocardial oxygen demand,
impaired microvascular function, or coincidental CAD.
The presence of restrictive physiology in association with
HCM has been described in children and appears to con-
fer higher risk of adverse outcomes.11 In patients with
angina or CAD risk factors, obstructive CAD should be
excluded.12 Comorbid conditions including hypertension,
diabetes, obesity, obstructive sleep apnea, and physical
inactivity are often major contributors to reduced fitness
and symptoms in patients with nonobstructive HCM.
Control of these comorbid conditions in combination with
pharmacological therapies for HCM can provide optimal
reduction of symptom burden. No trials have prospective-
ly evaluated the long-term outcomes with medications in
patients with nonobstructive HCM.
Recommendation-Specific Supportive Text
1. In patients with nonobstructive HCM without
obstructive CAD, pharmacological management
of chest discomfort is similar to that of dyspnea.
Recommendations for Management of Patients With Nonobstructive
HCM With Preserved EF (Continued)
COR LOE Recommendations
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Beta blockers and nondihydropyridine calcium
channel blockers are first-line agents. Both thera-
pies aim to slow the heart rate, improve diastolic
function, reduce LV filling pressures, and reduce
myocardial oxygen demand. These agents have
only been evaluated in a few small trials, with most
of the trials having a mix of patients with obstruc-
tive and nonobstructive HCM. In patients without
LVOTO, verapamil or diltiazem are effective at
reducing chest pain and improving exercise capac-
ity and may improve stress myocardial perfusion
defects.1–5 Alternatively, beta blockers are used in
symptomatic patients based on clinical experience
and extrapolation from obstructive HCM, rather
than trial data.13,14 The medication doses should
be titrated to effectiveness with monitoring for
bradycardia or atrioventricular conduction block,
especially if the calcium channel blockers and beta
blockers are used in combination. Beta blockers
should be the primary medical therapy in neonates
and children. Limited data suggest verapamil (in
patients >6 months of age) can be used safely as
an alternative to beta blockers.15
2. Loop or thiazide diuretics may be used to improve
dyspnea and volume overload in nonobstruc-
tive HCM when volume overload is present.
Aldosterone antagonists are also used in some
patients. Cautious use of any of these diuretics is
needed, usually as intermittent dosing as needed
or chronic low-dose therapy, to prevent symptom-
atic hypotension and hypovolemia.
3. Although several pilot trials suggested that
angiotensin receptor blockers and angiotensin-
converting enzyme inhibitors may have benefits
on myocardial structure and function, a 12-month
placebo-controlled trial of 124 patients with non-
obstructive and obstructive HCM (112 with LVOT
gradient <30 mm Hg) did not show any benefit of
losartan versus placebo on LV mass, fibrosis, or
functional class.6 However, treatment with losartan
was without clinically adverse consequences and
could be used for other indications, if needed.
4. Patients with extensive apical hypertrophy extend-
ing to the midventricle may have severely reduced
LV end-diastolic volume and severe diastolic dys-
function. This often leads to refractory angina, dys-
pnea, and ventricular arrhythmias with very limited
medical options. Transapical myectomy to augment
LV cavity size with an aim to increase stroke volume
and decrease LV end-diastolic pressure has been
found to be safe and reduced symptoms.7 Although
experience of only a single center has been pub-
lished,7 this surgical approach may be an option for
this rare subgroup of severely symptomatic patients
with nonobstructive HCM who have a small LV
cavity size refractory to routine therapy. Practically,
small cavity size has evolved to be defined as LV
end-diastolic volume <50 mL/m2 and LV stroke vol-
ume <30 mL/m2. This surgical approach requires
extensive surgical experience with HCM and should
be limited to centers of excellence with the highest
volumes, surgical experience, and expertise.
5. The aim of beta blockers and nondihydropyridine
calcium channel blockers is to reduce symptoms
by lowering LV diastolic pressures and improve
LV filling with a slower heart rate. In the absence
of symptoms, no data are available that indicate
a benefit, although the use of these agents may
paradoxically lead to chronotropic incompetence.
Iatrogenic chronotropic incompetence should be
considered in patients with symptoms and no iden-
tified obstructive physiology at rest or with provo-
cation. Assessment may include an ambulatory
ECG to look for a heart rate plateau or a stress test
to look for an inappropriate heart rate response. No
prospective data are available that demonstrating
benefit of these agents on long-term outcomes in
patients with nonobstructive HCM.
6. A randomized, double-blind placebo controlled
trial of valsartan, titrated to maximum US Food
and Drug Administration–approved doses, in 178
patients who had nonobstructive HCM and were 8
to 45 years of age with pathogenic or likely patho-
genic sarcomeric variants, NYHA functional class
I to II symptoms, normal EF, no secondary preven-
tion ICDs, no history of appropriate ICD shocks,
and no prior SRT demonstrated an attenuation in a
composite endpoint of LV wall thickness, LV mass,
LV volume, left atrial size, diastolic parameters, and
biomarkers.8 Trials of other angiotensin recep-
tor blockers tended to be smaller, included older
patients with more advanced phenotypic expres-
sion, and/or those without sarcomeric variants.
8.3. Management of Patients With HCM and
Advanced HF
Recommendations for Management of Patients With HCM and
Advanced HF
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 C-LD
1. In patients with HCM who develop systolic
dysfunction with an LVEF <50%, GDMT for HF with
reduced EF is recommended.1–3
1 C-LD
2. In patients with HCM and systolic dysfunction,
diagnostic testing to assess for concomitant causes
of systolic dysfunction (eg, CAD) is recommended.4,5
1 B-NR
3. In patients with nonobstructive HCM and advanced
HF (NYHA functional class III to class IV despite
GDMT), CPET should be performed to quantify the
degree of functional limitation and aid in selection
of patients for heart transplantation or mechanical
circulatory support.6,7
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1 B-NR
4. In patients with nonobstructive HCM and advanced
HF (NYHA functional class III to class IV despite
GDMT) or with life-threatening ventricular
arrhythmias refractory to maximal GDMT,
assessment for heart transplantation in accordance
with current listing criteria is recommended.8–13
1 B-R
5. In patients with HCM who develop persistent systolic
dysfunction (LVEF <50%), cardiac myosin inhibitors
should be discontinued.14
2a C-EO
6. For patients with HCM who develop systolic
dysfunction (LVEF <50%), it is reasonable to
discontinue previously indicated negative inotropic
agents (specifically, verapamil, diltiazem, or
disopyramide).
2a B-NR
7. In patients with nonobstructive HCM and advanced
HF (NYHA functional class III to class IV despite
GDMT) who are candidates for heart transplantation,
continuous-flow LVAD therapy is reasonable as a
bridge to heart transplantation.15–19
2a C-LD 8. In patients with HCM and persistent LVEF <50%,
ICD placement can be beneficial.3,20
2a C-LD
9. In patients with HCM and LVEF <50%, NYHA
functional class II to class IV symptoms despite
GDMT, and LBBB, CRT can be beneficial to
improve symptoms.21–25
Synopsis
An approach to the management of HF symptoms is
shown in Figures 4 and 5. EF often overestimates myo-
cardial systolic function in patients with HCM. An EF
<50% is associated with worse outcomes and therefore
is considered to represent significantly reduced systolic
function.2,20,26–29 Although uncommon in patients with
HCM, an EF <35% confers a particularly high risk of
death, the need for advanced HF therapies, and malig-
nant ventricular arrhythmias.28 As such, in patients with
HCM, GDMT for HF with reduced EF is initiated for EF
<50% and otherwise is generally based on the AHA/
ACC/HFSA HF guideline.1 An ICD for the primary pre-
vention of SCD, or CRT in patients with EF <50% and
NYHA functional class III to class IV symptoms who
meet other criteria for CRT, is also reasonable. Regard-
less of LVEF, if patients experience recurrent ventricular
arrhythmias or severe (NYHA functional class III to class
IV) symptoms despite optimization of medical therapy
and SRT is not an option, heart transplant evaluation is
warranted,10,30 and CPET has a role in risk stratification.6 ,7
For patients with NYHA functional class III to class IV
symptoms, an LVAD is sometimes used.17,18
Recommendation-Specific Supportive Text
1. No RCTs have been performed in patients with
HCM and HF. When tested in RCTs in patients with
HCM and normal EF, neither losartan31 nor spirono-
lactone32 had any effect on markers of fibrosis, LV
dimensions, EF, or symptoms. Observational stud-
ies of patients with HCM and EF <50% indicate
worse survival than that of patients with HCM and
preserved EF,2,20,26–29 might be worse than that of
patients with dilated cardiomyopathy,33 and does not
vary based on the presence or absence of LV dila-
tion.34 Further, myocardial transcriptomic profiling
has identified substantial overlap in gene network
activation between dilated cardiomyopathy and
HCM.35,36 Thus, although HCM has typically been
excluded from RCTs in HF, no compelling reason
exists to indicate that HCM with reduced EF dif-
fers sufficiently to disqualify many highly effective,
evidence-based GDMTs for HF with reduced EF as
tolerated in the presence of restrictive physiology.1
2. Identification of reduced EF in the setting of HCM
is uncommon (approximately 5%) and should
prompt an appropriate search for other poten-
tial contributing causes of LV dysfunction.2,4,5,28,34
Those causes should include, but are not limited
to, HCM phenocopies, CAD, valvular heart disease,
and metabolic disorders as outlined in the AHA/
ACC/HFSA HF guideline.1
3. CPET provides a noninvasive method for assessing
the cardiovascular, pulmonary, and skeletal muscle
components of exercise performance. In patients
with HCM, exercise parameters such as peak oxy-
gen consumption, minute ventilation to CO2 pro-
duction, and ventilatory anaerobic threshold predict
death from HF and need for heart transplantation.6,7
4. Patients with HCM, particularly those with LVOTO
whose symptoms respond to appropriate thera-
pies, do not warrant evaluation for transplanta-
tion. However, advanced HF arises in a subset
(3%-8%) of patients with HCM.2,6,20,28,30 Referral
for transplantation should be in accordance with
current guidelines.11 Posttransplant survival in
patients with HCM is comparable, and possibly
superior, to that of patients with other forms of
heart disease.8,9,12,37,38 Importantly, 20% to 50% of
patients with HCM who have advanced HF have
preserved EF with restrictive physiology; hence,
transplant referral for HCM does not require a
reduced EF.12,30 Patients with HCM and advanced
HF are far less likely to receive mechanical cir-
culatory support.39 This is attributable to smaller
LV size and differing hemodynamic profiles, which
may increase the risk of adverse outcomes due to
prolonged wait time and limited options once listed
for transplant. The revised 2018 United Network
for Organ Sharing Heart Transplant Allocation
Policy addresses this disparity with separate list-
ing criteria and priority specific to patients with
HCM. These new listing criteria have significantly
increased transplantation rates and reduced wait-
list times in patients with HCM.13 Children with
Recommendations for Management of Patients With HCM and
Advanced HF (Continued)
COR LOE Recommendations
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HCM also warrant consideration for transplanta-
tion if they are not responsive to or appropriate
candidates for other therapies.40
5. Mavacamten is a first-in-class myosin inhibitor
that decreases myocardial contractility. Given this
mechanism of action, mavacamten reduces LVEF,
Figure 4. Management of Symptoms in Patients With HCM.
Colors correspond to Table 3. GL indicates guideline; and HCM, hypertrophic cardiomyopathy.
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
Figure 5. Heart Failure Algorithm.
Cardiac myosin inhibitor should be discontinued if LVEF <50% and can be restarted at a lower dose if the LVEF recovers. Colors correspond
to Table 3. CRT indicates cardiac resynchronization therapy; EF, ejection fraction; GDMT, guideline-directed management and therapy; HCM,
hypertrophic cardiomyopathy; ICD, implantable cardioverter-defibrillator; LBBB, left bundle branch block; LVAD, left ventricular assist device; LVEF,
left ventricular ejection fraction; and NYHA, New York Heart Association.
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and an LVEF <50% was a prespecified criterion
for temporary study drug discontinuation. In RCTs
of mavacamten, the LVEF decreased to <50%
in up to 10% of patients.14 Thus, in those who
develop LVEF <50%, interruption with resumption
at lower dose (if LVEF improves) or discontinua-
tion (if LVEF does not improve to >50%) of cardiac
myosin inhibitors is required regardless of associ-
ated signs and symptoms.41
6. Despite the absence of RCTs or observational data,
negative inotropic agents (specifically, verapamil,
diltiazem, and disopyramide) that are otherwise
indicated for management of HCM may need to
be discontinued in patients with systolic dysfunc-
tion and worsening HF symptoms. However, these
agents may be continued if needed for rate or
rhythm control of AF on a case-by-case basis.
7. Patients with HCM have traditionally been ineli-
gible for LVAD support because of small LV cavi-
ties and relatively preserved EF. However, several
case series have demonstrated that support with
continuous flow LVADs results in acceptable out-
comes in highly selected patients with HCM.15–19
Post-LVAD survival is superior in patients with
HCM and larger LV cavities (>46-50 mm).17,18
Only a small number of patients with HCM have
received an LVAD as destination therapy, perhaps
due to the younger age of this population relative
to those with dilated cardiomyopathy (mean, 52
versus 57 years).18 Limited data are available on
the role of temporary or biventricular mechanical
circulatory support in patients with HCM. Data on
the role of mechanical circulatory support in chil-
dren with HCM are similarly limited. One study of
20 children with advanced HF with preserved EF,
including 3 patients with HCM, showed poor sur-
vival, with only 50% either successfully weaned or
bridged to transplantation.42
8. Patients with HCM were not included in the pri-
mary prevention ICD trials for patients with HF. A
retrospective study of 706 patients with nonob-
structive HCM demonstrated a 68% lower mortal-
ity rate over 5 years in patients with ICDs; however,
only 11% had an ICD, 8% had EF ≤50%, and
specific causes of death were not provided, pre-
cluding a causal association.3 Among patients with
HCM whose EF was 35% to 50% and who had an
ICD, 9% to 17% received appropriate ICD thera-
pies, and sudden death event rates were approxi-
mately 2.5% per year.2,20,28 Therefore, prophylactic
ICD implantation is the generally accepted clinical
practice for patients with HCM and systolic dys-
function (EF ≤50%).1 SHaRe (Sarcomeric Human
Cardiomyopathy Registry) further demonstrated a
graded spectrum of risk with a very high burden of
malignant arrhythmias in those with EF <35%.28
In the pediatric population, small body size may
impact the feasibility and risk of ICD implantation
and should be taken into account when discussing
ICD implantation.
9. CRT is established to improve symptoms, reduce
HF hospitalizations, and increase survival in patients
with HF with EF ≤35% and LBBB with QRS dura-
tion ≥150 ms.1 Whether the same benefits apply to
patients with HCM is unclear. Patients with HCM
were specifically excluded from some RCTs of CRT
in HF,43,44 and, in others, the proportion of patients
with HCM was not clearly defined.45,46 Furthermore,
case series offer conflicting results on the effect
of CRT on symptoms, EF, and survival.21–25 Future
studies are needed to identify CRT responders and
establish disease-specific eligibility criteria. Thus,
the usefulness of CRT in patients with HCM and
reduced EF is not well established, but CRT may
improve symptoms and LV chamber dimensions in
select patients.
8.4. Management of Patients With HCM and AF
Recommendations for Management of Patients With HCM and AF
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with HCM and clinical AF, anticoagulation
is recommended with direct-acting oral anticoagu-
lants (DOACs) as first-line option and vitamin K
antagonists as second-line option, independent of
CHA2DS2-VASc score.1–5
1 C-LD
2. In patients with HCM and subclinical AF detected by
internal or external cardiac device or monitor of >24
hours’ duration for a given episode, anticoagulation
is recommended with DOACs as first-line option and
vitamin K antagonists as second-line option, inde-
pendent of CHA2DS2-VASc score.1,6–8
1 C-LD
3. In patients with AF in whom rate control strategy is
planned, beta blockers, verapamil, or diltiazem are
recommended, with the choice of agents according
to patient preferences and comorbid conditions.9,10
2a C-LD
4. In patients with HCM and subclinical AF detected by
internal or external device or monitor, of >5 minutes’
duration but <24 hours’ duration for a given episode,
anticoagulation with DOACs as first-line option and
vitamin K antagonists as second-line option can be
beneficial, taking into consideration duration of AF
episodes, total AF burden, underlying risk factors,
and bleeding risk.1,6–8,11
2a B-NR
5. In patients with HCM and poorly tolerated AF, a
rhythm-control strategy with cardioversion or antiar-
rhythmic drugs can be beneficial with the choice of
an agent according to AF symptom severity, patient
preferences, and comorbid conditions.9,12–24
2a B-NR
6. In patients with HCM and symptomatic AF, as part of
an AF rhythm-control strategy, catheter ablation for
AF can be effective when drug therapy is ineffective,
contraindicated, or not the patient’s preference.12,25,26
2a B-NR
7. In patients with HCM and AF who require surgical
myectomy, concomitant surgical AF ablation proce-
dure can be beneficial for AF rhythm control.13,27–29
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Synopsis
AF, commonly observed in patients with HCM, is asso-
ciated with significant morbidity, impaired quality of life,
and substantial stroke risk. Therapy includes prevention
of thromboembolic events and controlling symptoms.
Traditional stroke risk scoring systems used in the gen-
eral population are not predictive in patients with HCM.
Vitamin K antagonists are effective for stroke prevention,
and recent studies support the use of DOACs as well.1–5
Asymptomatic AF detected by cardiac devices or moni-
tors also increases risk of stroke, so the decision to an-
ticoagulate should take into consideration the duration
of episodes as well as underlying risk factors. When a
rhythm-control strategy is needed, several antiarrhythmic
drugs have been shown to be safe and effective, allowing
for individualization according to underlying substrate and
patient preference. Catheter ablation is also an option, al-
though the procedure is less effective than in the general
population, and there is a more frequent need of repeat
procedures and concomitant use of antiarrhythmic drugs.
Surgical AF ablation is a potential rhythm management
option in patients undergoing surgical myectomy. Other
supraventricular arrhythmias and atrial flutter are likely
not increased in incidence in patients with HCM, and
treatment is usually similar to populations without HCM.
Recommendation-Specific Supportive Text
1. Clinical AF is AF that causes symptoms for which
patients seek medical attention. Although no RCTs
have been published, the risk of systemic embo-
lization is high in patients with HCM with AF. A
meta-analysis that included 33 studies and 7381
patients revealed an overall prevalence of throm-
boembolism in patients with HCM with AF of
27.09% and incidence of 3.75 per 10 patients.1
The stroke risk is independent of CHA2DS2-
VASc score,30 with a significant number of strokes
observed in patients with a score of 0. Several
studies have shown that anticoagulation, particu-
larly warfarin with target international normalized
ratio 2 to 3, reduces the stroke risk in this popu-
lation,2,30 whereas other publications have shown
DOACs to be at least as effective as warfarin, with
additional advantages reported, such as improved
patient satisfaction and long-term outcomes.3–5
Although left atrial appendage occlusion devices
have been evaluated in populations, the number of
patients with HCM in these trials was limited. Thus,
the role of left atrial appendage occlusion devices
in HCM remains untested. The recommendations
for anticoagulation of patients with atrial flutter are
the same as those for patients with AF.14
2. Similar to patients without HCM, asymptomatic
or subclinical AF (SCAF) is detected by cardiac
devices in patients with HCM as well. SCAF was
reported in 16 of 30 patients with HCM (53%) after
a median follow-up of 595 days.7 Device-detected
AF was identified in 29 of 114 patients with HCM
(25%), resulting in an annualized incidence of 4%
per year.6 In patients without HCM, SCAF has been
associated with an increased risk of thromboem-
bolism, albeit lower than the risk described for clini-
cal AF.8 Considerable debate exists regarding the
AF duration threshold for initiating anticoagulation
in SCAF because the duration used to define and
quantify AF varied significantly between different
studies. Nevertheless, the data increasingly show
that longer duration episodes are associated with
greatest risk. One study suggested only episodes
>24 hours were associated with increased risk.15
Also influencing risk are the total AF burden11 and
the presence of traditional risk factors, whereas
very short episodes lasting a few seconds do not
appear to increase risk.16,17 When making the
diagnosis of device-detected AF, review of stored
intracardiac ECGs is essential to exclude artifact or
false-positives.
3. Given the poor tolerance of AF in patients with
HCM, a rhythm-control strategy is often preferred,
because data support improved outcomes with a
rhythm-control strategy compared with historical
controls.9,10 For those patients for whom a rate-
control strategy is chosen (eg, because of patient
choice, antiarrhythmic drug failure, or intolerance),
a nondihydropyridine calcium channel blocker, a
beta blocker, or a combination of the 2 is prefer-
able. A theoretical concern exists that digoxin
could exacerbate LVOTO attributable to a positive
inotropic effect. However, in the absence of a gra-
dient, digoxin is a potential option, although data on
efficacy in this population are lacking. Medication
choice should be individually determined accord-
ing to age, underlying substrate, comorbidities, and
severity of symptoms. Dose adjustments are based
on the balance between adequate rate control ver-
sus adverse effects, including excessive bradycar-
dia. In patients with hypotension, dyspnea at rest,
and very high resting gradients (eg, >100 mm Hg),
verapamil should be avoided. Atrioventricular node
ablation with pacemaker implantation can be a last
option in refractory cases.
4. SCAF is often observed in patients with HCM and
implanted cardiac devices6,7 and has been associ-
ated with an increased risk of thromboembolism.8
Yet, the minimum duration of SCAF that confers
increased risk has not been precisely defined,
because a gradient of risk appears to be evident
depending on underlying substrate. Although
ASSERT (Asymptomatic Atrial Fibrillation and
Stroke Evaluation in Pacemaker Patients and the
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Atrial Fibrillation Reduction Atrial Pacing Trial) data
suggested only episodes >24 hours increased
stroke risk,15 other evidence suggests that shorter
duration episodes may pose a risk in patients with
traditional risks factors.16 In ASSERT, the absolute
stroke risk increased with increasing CHADS2
score, reaching a rate of 3.78 per year in those with
score >2.18 Another group stratified risk according
to AF duration and CHADS2 score, with a CHADS2
score of 1 increasing the risk only if AF duration
was >24 hours, whereas for CHADS2 scores ≥2,
episodes >5 minutes increased risk.19 Similar risk
stratification is unavailable in HCM, yet risk fac-
tors for stroke in the population with HCM have
been identified and include advancing age, previ-
ous embolic events, NYHA functional class, left
atrial diameter, vascular disease, and maximal LV
wall thickness.30 When very short AF duration is
observed, continued surveillance should be main-
tained as the burden of AF is likely to progress.
5. Studies suggest that with current therapies, AF in
patients with HCM can be managed effectively,
leading to low morbidity and mortality compared
with historical controls.9,10 In general, drug selec-
tion for rhythm control in patients with HCM is
based on extrapolation from studies of the AF
population at large. Yet, reports suggest several
drugs are safe and effective in patients with HCM
(Table 9). Amiodarone has been used over many
years and is generally deemed a favored option.10,20
Disopyramide has been safely prescribed for
reduction of LVOTO, but its efficacy in AF is not
well established.2122 Data on NYHA functional
class IC antiarrhythmic agents are limited because
of concerns regarding their use in patients with
structural heart disease. When used, therapy with
NYHA functional class IC agents is safest in the
presence of an ICD.10 NYHA functional class III
agents have been used as well; a report in 25
patients with HCM showed dofetilide to be well
tolerated and facilitated AF management.13 Sotalol
has also been shown to be safe and is commonly
used in pediatric patients as well, either in oral or
intravenous forms.2324,31,32 The US Food and Drug
Administration–mandated safety precautions
should be adopted when prescribing antiarrhyth-
mic drugs.
6. Catheter ablation plays an important role in the
management of AF in HCM. Although no RCTs
exist in this area, several meta-analyses have been
published in patients with HCM undergoing cath-
eter ablation for drug refractory AF, including one
that compared catheter ablation between patients
with HCM versus a cohort without HCM.12,25 In
general, the procedure is safe and remains an
important tool. However, the results seem less
favorable compared with patients without HCM,
with a 2-fold higher risk of relapse, more fre-
quent need of repeat procedures, and higher
use of concomitant antiarrhythmic drugs. This
is attributed to the fact that patients with HCM
have a greater degree of electrophysiologic and
structural remodeling than the population without
HCM.25 Contributing factors for atrial remodel-
ing include LVOTO, diastolic impairment, MR, and
other factors. It can be postulated that aggressive
intervention in the earlier stages of disease would
be more effective, but this is unproven, and ongo-
ing remodeling is expected. Some authors have
suggested the need for a more extensive abla-
tion approach, with linear lesions and ablation of
triggers not associated with the pulmonary veins
often required to improve the long-term durability
of the procedure.26
7. AF in patients with HCM is often poorly tolerated;
therefore, aggressive rhythm-control strategies
Table 9. Antiarrhythmic Drug Therapy Options for Patients With HCM and AF
Antiarrhythmic Drug Efficacy for AF Adverse Effects Toxicities Use in HCM
Disopyramide Modest Anticholinergic
HF
Prolonged QTc
TdP
Particularly with early onset AF
Generally used in conjunction with
atrioventricular nodal blocking agents
Flecainide and propafenone … Prolonged QRS Proarrhythmia
Typical atrial flutter
Not generally recommended in the absence
of an ICD
Sotalol Modest Fatigue Bradycardia Prolonged QTc
TdP
Reasonable
Dofetilide Modest Headache Prolonged QTc
TdP
Reasonable
Dronedarone Low HF Prolonged QTc …
Amiodarone Modest-high Bradycardia Liver, lung, thyroid, skin, neurologic
Prolonged QTc
Reasonable
AF indicates atrial fibrillation; HCM, hypertrophic cardiomyopathy; HF, heart failure; ICD, implantable cardioverter-defibrillator; and TdP, torsades de pointes.
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are sometimes required. Because of the lower
success rate of catheter ablation in patients with
HCM compared with the general AF population,
surgical AF ablation is a potential rhythm manage-
ment option, especially in patients already under-
going open heart surgery for a surgical myectomy.
In combination with surgical relief of the LVOT
gradient and MR, which can limit or even reverse
negative atrial remodeling, concomitant surgical
AF ablation may be successful in decreasing AF
burden. Several studies have reported satisfac-
tory midterm efficacy, yet these reports univer-
sally include a small number of patients, and the
durability of the procedure appears to decrease
with time.27,29 In a study that represents the largest
series of patients with AF treated surgically, free-
dom from AF recurrence at 1 year was 44% for
ablation patients (n = 49) and 75% with the maze
procedure (n = 72) (P<0.001).10 In this study, with
concomitant surgical ablation, freedom from AF
at 3 years was 70%, with left atrial size being a
predictor of recurrence.10
8.5. Management of Patients With HCM and
Ventricular Arrhythmias
Recommendations for the Management of Patients With HCM and
Ventricular Arrhythmias
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. In patients with HCM and recurrent, poorly toler-
ated life-threatening ventricular tachyarrhythmias
refractory to maximal antiarrhythmic drug therapy
and ablation, heart transplantation assessment is
indicated in accordance with current listing criteria.1,2
1
B-NR*
2. In adults with HCM and symptomatic ventricu-
lar arrhythmias or recurrent ICD shocks despite
beta-blocker use, antiarrhythmic drug therapy (eg,
amiodarone,* dofetilide,† mexiletine,† or sotalol†) is
recommended, with the choice of agent guided by
age, underlying comorbidities, severity of disease,
patient preferences, and balance between efficacy
and safety.3–6
C-LD†
1 C-LD
3. In children with HCM and recurrent ventricular
arrhythmias despite beta-blocker use,
antiarrhythmic drug therapy (eg, amiodarone,3,4
mexiletine,6 sotalol3,4) is recommended, with the
choice of agent guided by age, underlying
comorbidities, severity of disease, patient prefer-
ences, and balance of efficacy and safety.
1 C-LD
4. In patients with HCM and pacing-capable ICDs,
programming antitachycardia pacing is
recommended to minimize risk of shocks.7,8
2a C-LD
5. In patients with HCM and recurrent symptomatic
sustained monomorphic VT, or recurrent ICD shocks
despite optimal device programming, and in whom
antiarrhythmic drug therapy is either ineffective, not
tolerated, or not preferred, catheter ablation can be
useful for reducing arrhythmia burden.9–11
*Indicates the LOE for amiodarone. †Indicates the LOE for dofetilide, mexi-
letine, or sotalol.
Synopsis
In patients with HCM and ICDs, preventing recurrent VT
is an important goal of therapy, because ICD shocks have
been associated with impaired quality of life and worse
outcomes.12 Most studies on secondary prevention of
VT are extrapolated from studies in patients without
HCM because data on VT management in patients with
HCM are limited. The choice of pharmacological therapy
should be individualized according to individual substrate,
but amiodarone is generally considered superior, albeit
at the expense of increased adverse effects and with no
effect on overall survival. Programming ICDs with antit-
achycardia pacing may minimize risk of shocks because
monomorphic VT and ventricular flutter are common. In
cases refractory to antiarrhythmic drugs and to optimal
ICD programming, catheter ablation is an option.
Recommendation-Specific Supportive Text
1. Referral for transplantation should be in accor-
dance with current guidelines.13 Transplant referral
does not absolutely require reduced EF, because
patients with preserved EF may also develop
advanced HF with restrictive physiology or intrac-
table ventricular arrhythmias.1,2
2. Most patients with HCM and VT are likely already
receiving beta blockers, generally the first treatment
option. Because no study has investigated phar-
macological therapies for preventing ICD shocks
specifically in the population with HCM, recommen-
dations are extrapolated from studies that enrolled
different disease substrates. In the OPTIC (Optimal
Pharmacological Therapy in Cardioverter Defibrillator
Patients) trial, 412 patients with documented ven-
tricular arrhythmias were randomized to amiodarone
plus beta blocker, sotalol, or beta blocker alone. At
1 year, shocks occurred in 38.5% assigned to beta
blocker alone, 24.3% assigned to sotalol, and 10.3%
assigned to amiodarone plus beta blocker.3 Thus,
amiodarone was most effective but at the expense
of increased adverse effects.3 In an observational
study that included 30 patients, dofetilide was found
to decrease the number of ICD therapies even after
other agents were ineffective.5 Proof of efficacy
for mexiletine is limited but is often adjunctive to
amiodarone.6 A meta-analysis that involved 8 stud-
ies and 2268 patients confirmed that the benefit
of antiarrhythmic drug therapy was driven mainly by
amiodarone, with no effect on overall survival.4 The
safety and efficacy of propafenone and flecainide is
uncertain, in addition to safety concerns when used
in patients with ischemic heart disease.14
3. In pediatric patients with HCM, recurrent episodes of
VT are generally treated with beta blockers as first-
line therapy. If VT is recurrent (with greater empha-
sis placed on episodes that are faster or longer and
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those that may trigger ICD shocks), additional anti-
arrhythmic agents may be used either to address
symptoms, suppress recurrent life-threatening
events, or to prevent unnecessary ICD shocks.
Drugs with risk for proarrhythmia are often initiated
in the hospital. ICD shocks, even when appropri-
ate, have been linked to psychological trauma in
pediatric patients, and thus it is reasonable to con-
sider management options that minimize shocks.
For children with recurrent ICD shocks despite
maximal antiarrhythmic therapy, data regarding
alternative therapies such as catheter ablation are
limited. Sympathetic denervation has been reported,
although data are limited to case reports.15–17
4. ICD therapy has been shown to prevent SCD and
improve survival in patients with HCM.18 Historically,
it has been the general belief that the mechanism
of SCD in this population was VF. Yet, it appears
that ventricular arrhythmias amenable to termina-
tion by antitachycardia pacing, including monomor-
phic VT and ventricular flutter, are more common
than previously thought. Among 71 patients with
HCM and ICDs who received appropriate thera-
pies, 74 were VF, 18 ventricular flutter, and 57 were
for monomorphic VT. Further, when antitachycardia
pacing was available, it was successful in 74% of
episodes.7 This is especially important in those at
risk for monomorphic VT, such as those with apical
aneurysms, although patients with fast ventricular
arrhythmias may benefit as well.
5. In patients with HCM and recurrent ventricular
arrhythmias, despite pharmacological therapy, addi-
tional therapies are required. Of 22 patients who
underwent ablation, there was a 73% success rate
with no major complications; of note, epicardial abla-
tion was required in 58%.9 Freedom from VT 12
months postablation was found in 11 of 14 patients
with VT and apical aneurysms, which is a common
source of sustained monomorphic VT in this popu-
lation,10 and 78% VT-free survival was reported
after combined epicardial and endocardial ablation
in 9 patients with sustained monomorphic VT.11
Therefore, it appears that in selected patients with
HCM, combined epicardial and endocardial ablation
is a reasonably safe and effective option for treating
monomorphic VT refractory to antiarrhythmic drugs
and to optimal ICD programming. A recent meta-
analysis that included 6 studies confirmed the find-
ings.19 In 1 case series, surgical aneurysmectomy
proved effective in 3 patients with apical aneurysms
and incessant ventricular arrhythmias as an alterna-
tive to ablation.20 In pediatric patients, age and heart
size must be taken into account when considering
ablation. An additional option in cases of refrac-
tory VT/VF is left cardiac sympathetic denervation,
which has efficacy in individual case reports.15
9. LIFESTYLE CONSIDERATIONS FOR
PATIENTS WITH HCM
9.1. Recreational Physical Activity and
Competitive Sports
Recommendations for Recreational Physical Activity and
Competitive Sports
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-R
1. For patients with HCM, mild- to moderate-intensity*
recreational† exercise is beneficial to improve
cardiorespiratory fitness, physical functioning, and
quality of life, and for overall health in keeping with
physical activity guidelines for the general
population.1–3
1 C-EO
2. For athletes with HCM, a comprehensive evaluation
and shared decision-making about sports
participation with an expert professional is
recommended.4
2a B-NR
3. In individuals who are genotype-positive,
phenotype-negative for HCM, participation in
competitive sports of any intensity is reasonable.5,6
2a B-NR
4. For patients with HCM, participation in vigorous*
recreational activities is reasonable after an
annual comprehensive evaluation and shared
decision-making with an expert professional who
balances potential benefits and risks, with this
process being repeated annually.4,5,7,8
2b B-NR
5. For patients with HCM who are capable of a high
level of physical performance, participation in
competitive sports† may be considered after review
by an expert provider with experience managing
athletes with HCM who conducts an annual
comprehensive evaluation and shared decision-
making that balances potential benefits and
risks.5,9–14
3: No
benefit B-NR
6. For most patients with HCM, universal restriction
from vigorous physical activity or competitive sports
is not indicated.5,11–13
3:
Harm C-EO
7. In patients with HCM, ICD placement for the sole
purpose of participation in competitive sports
should not be performed.10
*Exercise intensity can be gauged by metabolic equivalents (METs): light <3
METs, moderate 3-6 METs, and vigorous >6 METs,15 by percentage of maximum
heart rate achieved (light 40%-50%, moderate 50%-70%, vigorous >70%), or
by level of perceived exertion on the Borg scale (light 7-12, moderate 13-14,
vigorous ≥15).16
†Recreational exercise is done for the purpose of leisure with no requirement
for systematic training and without the purpose to excel or compete against oth-
ers. Competitive sports involve systematic training for the primary purpose of
competition against others, at multiple levels, including high school, collegiate,
master’s level, semiprofessional, or professional sporting activities.
Synopsis
Regular physical activity promotes longevity and re-
duces overall cardiovascular disease risk. Most patients
with HCM can benefit from at least mild- to moderate-
intensity exercise. Some patients with HCM who have no
or minimal symptomatic limitation are capable of vigorous
activities or competitive sports and place a high personal
value on physical fitness, performance, or both. Recom-
mendations for recreational exercise and competitive
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sports for patients with HCM are evolving with emer-
gence of data and emphasis on promoting patient auton-
omy and shared decision-making.4,17,18 Although previous
observational studies identify HCM as a common cause
of SCD among competitive athletes,19 in prospective
registries, HCM is the cause of SCD in <10% of young
individuals, including athletes.20–31 Although uncertainty
around the risk of SCD associated with exercise exists, a
disproportionate risk of SCD has not been demonstrated
in athletes in contemporary registries.5,11–13,30 Although
these data provide some reassurance, the nuances and
unique individual considerations regarding vigorous ex-
ercise or competitive sports warrant annual evaluation by
an expert professional, including a shared balanced dis-
cussion of potential benefits and risks and an individual
emergency preparedness plan.4,17,18,32,33
Recommendation-Specific Supportive Text
1. Inactivity is prevalent among patients with
HCM.34,35 “The Physical Activity Guidelines for
Americans” recommend that adults engage in at
least 150 to 300 minutes of moderate-intensity
or 75 to 150 minutes of vigorous-intensity aero-
bic exercise weekly, and that children engage
in at least 60 minutes of moderate-to-vigorous
exercise daily.36 In a randomized trial of exercise
training, adult patients with HCM who followed
prescriptions of moderate-intensity exercise for
4 months, compared with those doing their usual
activity, showed significant improvements in peak
oxygen consumption and subjective improve-
ments in physical functioning.1 No major adverse
events and no increase in nonlethal arrhythmias
with exercise training were observed. Exercise
intensity can be gauged by METs: light <3 METs,
moderate 3 to 6 METs, and vigorous >6 METs,15
by percentage of maximum heart rate achieved
(light 40%-50%, moderate 50%-70%, vigorous
>70%), or by level of perceived exertion on the
Borg scale (light 7-12, moderate 13-14, vigorous
≥15).16 An initial period of supervised exercise
may be warranted in some patients. Children with
HCM can typically participate in physical educa-
tion at school, with an option not to grade, time, or
score for performance.
2. Expert professionals will be familiar with the evi-
dence and ongoing studies relevant to discussions
about vigorous exercise and sports participation
and will be in the best position to provide guidance
in the context of shared decision-making.4 Advice
to avoid dehydration or exposures to extreme
environmental conditions (eg, heat, humidity) is
important, particularly for patients with obstructive
physiology. This discussion also provides an oppor-
tunity to devise plans for emergency preparedness.
3. Sudden death in genotype-positive, phenotype-
negative individuals is rare.6 Currently, no accurate
risk prediction models for SCD in genotype-
positive, phenotype-negative individuals are avail-
able. In a recent prospective registry, no arrhythmic
events were observed in genotype-positive,
phenotype-negative individuals (total of 126),
including those exercising vigorously or partici-
pating in competitive athletics.5 Decisions about
participation in competitive sports are usually
made jointly with the patient and family taking
into consideration family history of SCD, type of
sports activity, and patient and family risk toler-
ance. Because of the low risk of sudden death,
phenotype-negative individuals are not restricted
from competitive sports and are not routinely
monitored with ambulatory electrocardiography
and exercise stress testing unless the family his-
tory indicates a high risk for SCD or as part of
precompetitive athletic screening. This is appro-
priate every 1 to 2 years to assess safety of ongo-
ing competitive athletics participation.
4. Many patients with HCM with no or minimal symp-
tomatic limitation are capable of vigorous-intensity
exercise and place a high personal value on physi-
cal fitness. Retrospective data have not shown a
higher rate of ventricular arrhythmias in individuals
with HCM who exercise vigorously.7 Additionally, a
prospective nationwide population-based cohort
study in South Korea showed that among individu-
als with a diagnosis of HCM (mean age, 59 years),
those in the highest tertile of exercise (including
those exercising vigorously ≥8 METs) had the low-
est cardiovascular mortality (2.7% versus 3.8% in
midtertile and 4.7% in lowest tertile; P < 0.001).8 In
a recently published prospective observational reg-
istry of adult and pediatric patients (8-60 years of
age) with HCM who were NYHA functional class I
to II, those who engaged in vigorous exercise were
not more likely to experience an arrhythmic event
compared with those exercising moderately or who
were less active.5 Notably, most patients in this
study were managed at experienced HCM cen-
ters and receiving close follow-up and surveillance.
Therefore, although these data can inform discus-
sion between patients and physicians regarding
participation in vigorous exercise, these discus-
sions should occur in the context of an annual com-
prehensive clinical evaluation and risk assessment
using an individualized shared decision-making
framework by an expert professional with experi-
ence in managing patients with HCM.
5. Some patients with HCM who have no or minimal
symptomatic limitation are capable of vigorous-
intensity training and place a high personal value
on physical performance for the purpose of
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competition. Prospective studies over the past
decade have demonstrated a similar burden of
ventricular arrhythmias in adult patients with HCM
who have continued to engage in competitive ath-
letics compared with those who have withdrawn
from competition.11–13 In those athletes with ICDs,
shock rates in athletes with HCM are similar to
those reported in nonathletic populations, with
most shocks occurring outside training or compe-
tition, and with no reported shock-related injuries
or death.9,10 A large prospective registry examined
the impact of recreational exercise and competi-
tive athletics on arrhythmic events and included
259 individuals engaging in competitive athletics,
including 42 high school and collegiate athletes
with HCM with >3 years’ follow-up. Competitive
athletes with HCM did not experience an increased
arrhythmic risk compared with individuals exercis-
ing moderately or not at all.5 Although these data
provide some reassurance and can inform discus-
sions between patients and physicians regarding
participation in competitive athletics, not all types
of athletes are well-represented in these studies.
Evaluations and shared decision-making with ath-
letes who have HCM regarding sports participation
should therefore be individualized, be undertaken
by professionals with expertise in managing com-
petitive athletes with HCM, and be repeated on at
least an annual basis.4,32 Final eligibility decisions
for organized sports participation may involve third
parties (eg, team physicians, consultants, institu-
tional leadership) acting on the behalf of schools
or teams.
6. Prospective studies to date have suggested that
patients with HCM who engage in competitive ath-
letics are not at increased risk of SCD compared
with less active individuals,5 or athletes who with-
draw from competitive sports.11–13
7. Sudden death risk stratification and recommenda-
tions for ICD placement should be made in accor-
dance with the algorithm put forth in this guideline,
independent of decisions regarding sports partici-
pation. Inappropriate ICD utilization would expose
patients unnecessarily to device-related complica-
tions and should be avoided.37,38
9.2. Occupation in Patients With HCM
Recommendations for Occupation in Patients With HCM
COR LOE Recommendations
2a C-EO
1. For patients with HCM, it is reasonable to follow
Federal Motor Carrier Safety Administration
cardiovascular disease guidelines that permit driving
commercial motor vehicles, if they do not have an
ICD or any major risk factors for SCD and are using
a GDMT plan.1
2a C-EO
2. For pilot aircrew with a diagnosis of HCM, it is
reasonable to follow Federal Aviation Administration
guidelines that permit consideration of multicrew
flying duties, provided they are asymptomatic, are
deemed low risk for SCD, and can complete a maxi-
mal treadmill stress test at 85% peak heart rate.2
2b C-EO
3. It is reasonable for patients with HCM to consider
occupations that require manual labor, heavy lifting,
or a high level of physical performance after a
comprehensive clinical evaluation, risk stratification
for SCD, and implementation of GDMT in the con-
text of shared decision-making.
Synopsis
Several occupational considerations are important for
patients with HCM, particularly when potential for loss of
consciousness could occur that can place the patient or
others in a harmful situation. For some occupations (com-
mercial driving and piloting an aircraft), federal guidelines
and restrictions cannot be superseded by this guideline.
Recommendation-Specific Supportive Text
1. The Federal Motor Carrier Safety Administration
updated its guidelines in 2015.1 A permit for driving a
commercial vehicle can be obtained by patients with
HCM who do not have an ICD and do not possess
any of the major risk factors for SCD (see Section
7, “SCD Risk Assessment and Prevention”).
2. The Federal Aviation Administration guidelines do
not explicitly list HCM as a disqualifying diagnosis for
piloting an aircraft. However, a report from an occu-
pational aviation work group states that for patients
with HCM who are asymptomatic, they may be con-
sidered for multicrew flying duties.2 No restrictions
exist for patients with HCM to be nonpilot aircrew.
3. Occupations that require considerable heavy manual
labor (eg, construction work) or a high level of phys-
ical performance (eg, law enforcement, firefighters)
may impose some risk to patients with HCM but
also potentially to a coworker or the public, in the
event of loss of consciousness. Therefore, these
decisions should be approached on an individual
basis and in the context of shared decision-making.
9.3. Pregnancy in Patients With HCM
Recommendations for Pregnancy in Patients With HCM
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 B-NR
1. For pregnant women with HCM and AF or other
indications for anticoagulation, low-molecular-weight
heparin or vitamin K antagonists (at maximum
therapeutic dose of <5 mg daily) are recommended
for stroke prevention.1,2
Recommendations for Occupation in Patients With HCM (Continued)
COR LOE Recommendations
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1 C-LD
2. In pregnant women with HCM, selected beta
blockers should be administered for symptoms
related to outflow tract obstruction or arrhythmias,
with monitoring of fetal growth.3,4
1 C-LD 3. In most pregnant women with HCM, vaginal delivery
is recommended as the first-choice delivery option.3,5
1 B-NR
4. In affected families with HCM, preconceptional and
prenatal reproductive and genetic counseling should
be offered.3–6
1 C-EO
5. For pregnant women with HCM, care should be
coordinated between their cardiologist and an
obstetrician. For patients with HCM who are deemed
high risk, consultation is advised with an expert in
maternal-fetal medicine.
2a C-LD
6. For women with clinically stable HCM who wish to
become pregnant, it is reasonable to advise that
pregnancy is generally safe as part of a shared
discussion regarding potential maternal and fetal
risks, and initiation of GDMT.7–10
2a C-LD
7. In pregnant women with HCM, cardioversion for new
or recurrent AF, particularly if symptomatic, is
reasonable.6,11
2a C-LD
8. In pregnant women with HCM, general or epidural
anesthesia is reasonable, with precautions to avoid
hypotension.8
2a C-EO
9. In pregnant women with HCM, it is reasonable to
perform serial echocardiography, particularly during
the second or third trimester when hemodynamic
load is highest, or if clinical symptoms develop.
2b C-EO
10. In pregnant women with HCM, fetal
echocardiography may be considered for diagnosis
of fetal HCM in the context of prenatal counseling.
3:
Harm C-EO 11. In pregnant women, use of mavacamten is
contraindicated due to potential teratogenic effects.
Synopsis
Pregnancy in most women with HCM is well tolerated.
Maternal mortality is very low, with only 3 sudden deaths
reported in the literature, all in high-risk (and 1 undiag-
nosed) patients, over the past 17 years.7–10 Symptoms
(dyspnea, chest pain, palpitations) and complications (HF
and arrhythmias) occur in approximately 25% of preg-
nant women with HCM for whom most had symptoms
preceding their pregnancy. No difference in outcomes
was reported for women with LVOTO compared with
those without obstruction.
Recommendation-Specific Supportive Text
1. AF is associated with stroke in HCM and can
be mitigated by anticoagulation.12–14 Both low-
molecular-weight heparin and low-dose warfa-
rin carry acceptable risk during pregnancy2 and
should be administered in accordance with the
2020 ACC/AHA valvular heart disease guideline.1
Insufficient safety data regarding DOACs in preg-
nancy are available, and a recent meta-analysis
suggests that they are associated with a higher
rate of fetal complications compared with low-
molecular-weight heparin or warfarin.15
2. Most beta blockers (ie, metoprolol, bisoprolol,
labetalol, pindolol, propranolol) are generally con-
sidered safe to use during pregnancy; however,
atenolol has some evidence of potential fetal risk.
Closer monitoring of fetal growth and surveillance
for fetal bradycardia may be considered for preg-
nant women on beta blockers.3,4
3. In pregnant women with cardiovascular disease,
including cardiomyopathies, adverse outcomes
during delivery are low (3%-4%) and similar
between vaginal delivery and cesarean section.5
Valsalva maneuver during labor has also been
shown to be well tolerated. Bleeding rates, includ-
ing serious bleeding requiring transfusions, are
higher in women who undergo cesarean section.
Therefore, cesarean section should be reserved
only for obstetric reasons or for emergency cardiac
or other maternal health reasons. A delivery plan
should ideally be established by the end of the sec-
ond trimester.
4. Prenatal genetic counseling is helpful in explain-
ing the risk of transmission of disease, as well as
discussing potential reproductive options. These
reproductive options include preimplantation
genetic testing, fetal screening, prenatal test-
ing, and postnatal genetic testing. The benefits
and potential harms can be discussed for each of
these options, such that the individual or couple
can make a fully informed decision about prenatal
genetic testing and fetal screening.3–6
5. A multidisciplinary care team that includes cardiol-
ogists and maternal-fetal medicine specialists can
provide comprehensive management of pregnant
women with HCM.
6. Decisions regarding pregnancy in women with
HCM include a shared discussion that conveys that
maternal mortality with pregnancy is very low, and
cardiac events occur primarily in those with preex-
isting symptoms and previous cardiac events.7–10 In
those women who are very symptomatic, options
for mitigating risk before conception are discussed.
Depending on the individual circumstance, these
options might include SRT for women with medi-
cally refractory symptomatic LVOTO, advanced HF
therapies for women with HF, or ICD implantation
for women with high-risk features for ventricular
arrhythmias.
7. Some antiarrhythmic agents are contraindicated
during pregnancy because of potential terato-
genic effects, while others are not recommended
for patients with HCM. Cardioversion during preg-
nancy can be performed with minimal risk to the
fetus and is therefore preferred for restoring sinus
Recommendations for Pregnancy in Patients With HCM (Continued)
COR LOE Recommendations
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
rhythm in pregnant women with HCM, particu-
larly if they are symptomatic.6 Anticoagulation to
decrease the risk of thromboembolism associated
with cardioversion would need to be individualized
based on the trimester of pregnancy and the risk of
anticoagulation to the fetus.
8. Epidural and general anesthesia are common
modes of anesthesia to make the delivery more
comfortable for the patient. There are generally no
contraindications to either of these forms of anes-
thesia in pregnant patients with HCM as long as
care is taken to avoid hypotension.8
9. Most complications that arise during pregnancy
occur in the third trimester. Therefore, it would be
reasonable to perform echocardiography in the
latter stages of pregnancy or if new symptoms
arise.
10. Fetal echocardiography is available for prena-
tal diagnosis of HCM and is used in some select
families, particularly if a history of pediatric disease
onset or severe disease manifestations in parents
or other family members are present.
11. Myosin inhibitors may cause fetal toxicity when
administered to a pregnant woman, based on
unpublished findings in animal studies.16
9.4. Patients With Comorbidities
Recommendations for Patients With Comorbidities
Referenced studies that support the recommendations are
summarized in the Online Data Supplement.
COR LOE Recommendations
1 C-EO
1. In patients with HCM, adherence to the ACC/AHA
primary prevention guideline is recommended to
reduce risk of cardiovascular events.1
1 B-NR
2. In patients with HCM who are overweight or obese,
counseling and comprehensive lifestyle interventions
are recommended for achieving and maintaining
weight loss1 and possibly lowering the risk of
developing LVOTO, HF, and AF.2–4
1 C-LD
3. In patients with HCM and hypertension, lifestyle
modifications and medical therapy for hypertension
are recommended,1 with preference for beta blockers
and nondihydropyridine calcium channel blockers in
patients with obstructive HCM.
1 C-LD
4. In patients with HCM, assessment for symptoms
of sleep-disordered breathing is recommended,
and, if present, referral to a sleep medicine
specialist for evaluation and treatment is
recommended.5–8
Synopsis
Comorbid conditions, including hypertension, obesity, and
sleep-disordered breathing, are common in patients with
HCM and may contribute to increased symptom burden,
LVOTO, HF, and AF. Appropriate counseling and man-
agement of these conditions in patients with HCM is a
critical component of their care.
Recommendation-Specific Supportive Text
1. Patients with HCM are frequently affected by other
health conditions, including hypertension, diabetes,
hyperlipidemia, and obesity, and may also maintain
unhealthy lifestyle practices, including inactivity
and tobacco abuse, which together can compro-
mise their overall cardiovascular health. In addition
to treatment of their HCM, implementation of well-
proven primary prevention strategies is warranted
in symptomatic and asymptomatic patients.1
2. Excess weight is very common in adult patients
with HCM, with >70% having a body mass index of
>25 kg/m2 and >30% having a body mass index
of >30 kg/m2.2–4 Obesity is also common in pedi-
atric patients with HCM, with almost 30% having a
body mass index in the 99th percentile for age and
sex.9 Patients who are obese have an increased
burden of LVH and mass,2,3,9 are more symptom-
atic, are more likely to have LVOTO, and have
reduced exercise capacity.2–4 In a large prospective,
multicenter registry of patients with HCM, obesity
was independently associated with a composite
outcome of death, HF, AF, ventricular arrhythmias,
and stroke, with hazard ratios ranging from 1.4 to
1.9.4 Although patients who were obese were less
likely to carry a sarcomere gene variant, obesity
increased risk in genotype-positive and genotype-
negative patients. Obesity is also associated with
increased susceptibility for developing HCM in
genotype-negative patients.10 Weight loss interven-
tions in patients who are obese with HCM there-
fore have the potential to reduce symptoms and
adverse outcomes, in addition to being an impor-
tant component of primary prevention for overall
cardiovascular health.
3. Hypertension is commonly coexistent in adult
patients with HCM, with a prevalence of approxi-
mately 35% to 50%, and affects sarcomere
variant-negative patients disproportionately.11,12
Intuitively, LV pressure overload imposed by ele-
vated systemic blood pressure could trigger the
onset of, or exacerbate, LVH. Hypertension has
been associated with increased penetrance in
gene variant carriers,13 and diastolic hypertension is
associated with a 4-fold risk of developing HCM in
genotype-negative individuals.10 Target blood pres-
sure should be in keeping with ACC/AHA primary
prevention guideline.1 In patients with symptomatic
obstructive HCM, beta blockers or nondihydropyri-
dine calcium channel blockers are often used as
first-line therapy. Low-dose diuretics may also be
used as antihypertensive agents. Although some
patients with obstructive physiology may tolerate
vasodilator therapy, these agents can exacerbate
LVOTO and symptoms. In younger patients with
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
nonobstructive HCM due to a pathogenic or likely
pathogenic cardiac sarcomere genetic variant, who
have concomitant hypertension, valsartan may be
a good option because of its potential to slow dis-
ease progression.14
4. Sleep-disordered breathing is highly prevalent in
patients with HCM, affecting 55% to 70%. Patients
with obstructive sleep apnea are older, more often
hypertensive, and have greater symptom burden
and reduced exercise capacity.5,7 Obstructive sleep
apnea has also been associated with a greater
prevalence of AF and NSVT.6,8 Diagnosis and treat-
ment of obstructive sleep apnea could reduce
symptoms and arrhythmic complications in patients
with HCM but has not been systematically tested.
10. EVIDENCE GAPS AND FUTURE
DIRECTIONS
10.1. Refining the Diagnosis of HCM
The diagnosis of HCM is currently based on binary cut-
offs for LV wall thickness. However, due to imprecision in
measurement and variability based on sex, body size, and
comorbidities, relying on this single dichotomous metric
will result in overdiagnosis in some groups and underdi-
agnosis in others.1 Additionally, the phenotype of HCM
extends beyond LVH. Evolving toward a more molecular
or pathway-based approach to diagnosis, when possible,
will enable greater diagnostic accuracy, improve patient
stratification, and facilitate implementation of increas-
ingly targeted therapies.
10.2. Developing Therapies to Attenuate or
Prevent Disease Progression
Developing safe, effective medical therapy that can
forestall disease progression is a major therapeutic
goal, either with existing medications (eg, valsartan)1 or
emerging medications (eg, cardiac myosin inhibitors).2
If the specific genetic etiology is identified, gene-based
therapies offer the potential for durably impacting dis-
ease with a single intervention, and testing is starting in
humans. However, for disease-modifying and preventive
therapies to be established, much more robust and gran-
ular understanding of disease pathogenesis is needed,
including identifying predictors of disease development,
predictors of adverse outcomes, and intermediate phe-
notypes that accurately track disease progression and, in
turn, response to therapy.
10.3. Improving Care for Nonobstructive HCM
Managing patients with symptomatic nonobstructive
HCM remains a major clinical challenge. In contrast to
obstructive HCM, where obstructive physiology can be
effectively targeted and treated with medical and surgi-
cal approaches,1–5 determining the driving pathophysiol-
ogy of nonobstructive HCM remains somewhat elusive.
Diastolic abnormalities, including restrictive physiology
and myocardial energetics, are thought to be important
but are currently not well addressed. The role of cardiac
myosin inhibitors in nonobstructive HCM is being inves-
tigated in clinical trials.4 With clinical benefit shown with
sodium-glucose cotransporter-2 inhibitors and mineralo-
corticoid receptor antagonists in patients with HF with
preserved EF, investigating whether patients with nonob-
structive HCM may also benefit will be important. Clinical
trials that test lifestyle interventions to reduce symptom
burden are also needed. Given the benefits of cardiopul-
monary rehabilitation in other cardiac diseases, adding
HCM to the list of reimbursable diagnoses would extend
these benefits to this population.
10.4. Improving and Expanding Risk
Stratification
Despite several large, prospective studies1–3 examin-
ing risk predictors of SCD, risk stratification algorithms
still have low positive-predictive values such that many
ICDs are placed unnecessarily. Conversely, sudden car-
diac arrest or SCD occurs in patients with no established
risk factors, albeit rarely. New risk factors and tools to
enhance the power of risk stratification algorithms are
needed, particularly in children.
Similarly, the ability to predict which patients with
HCM will suffer other adverse outcomes, such as HF and
AF, is limited. Artificial intelligence could prove useful in
screening, risk stratification, and/or disease progression
monitoring. The presence, pattern, or progression of LGE
or abnormal 3D strain on CMR,4–6 alone or in concert with
other biomarkers such as troponin levels, may become
useful predictors but must be consistent with existing
tools and show value against other risk metrics before
clinical adoption. These questions will benefit from con-
tinued assembly and growth of large, prospective regis-
tries that track clinical outcomes in well-genotyped and
-phenotyped patients with HCM. Studies including larger
numbers of pediatric and underrepresented racial and
ethnic group patients with HCM are particularly needed.
10.5. Arrhythmia Management
AF affects a large proportion of adult patients with
HCM, is often poorly tolerated, and may be more refrac-
tory to pharmacological and catheter-based interven-
tions than in patients without HCM.1–5 Further work is
needed to identify more robust predictors of developing
AF, refine risk scores, and better stratify for thrombo-
embolic complications.6 Technical advances in ablative
therapy for AF may increase the success rate in pa-
tients with HCM.7
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
10.6. Expanding Understanding of the Genetic
Architecture of HCM
Genetic evaluation and counseling are not widely avail-
able outside of experienced HCM centers. Greater ac-
cess to genetic counseling and testing, including expert
interpretation of results in the clinical context, is needed
for all patients with HCM to advance individual care, to
improve family management, and to advance the knowl-
edge base. Improved algorithms for the interpretation of
variants that are currently classified as variants of un-
certain significance are also evolving, including ongoing
efforts in expert variant curation by the Clinical Genome
Resource (ClinGen), a resource of the National Institutes
of Health (https://clinicalgenome.org/).1
Approximately 50% of cases of HCM are genetically
elusive. New gene discovery is needed to identify addi-
tional causal genes, recognizing that many of these cases
result from a combination of polygenic variants and envi-
ronmental factors.2,3 Additionally, better understanding of
the complex genetics underlying HCM and developing
polygenic risk scores will further advance patient stratifi-
cation and family management, including refining longi-
tudinal screening to be more limited in situations where
the risk of heritable disease can be predicted to be low.
Investigation into the correlations between genotype
and phenotype and clinical outcomes continues to be
an important endeavor as the field moves toward more
precise and tailored therapies—including gene-specific
therapeutics.
PEER REVIEW COMMITTEE MEMBERS
Mark S. Link, MD, FACC, FAHA, FHRS, Chair; Anandita
Agarwala, MD; Chad Asplund, MD, MPH, FAMSSM*;
Michael Ayers, MD, FACC; C. Anwar Chahal, MD, PhD,
FACC, FHRS; Jonathan Chrispin, MD, FACC; Aarti
Dalal, DO, FACC, FHRS; Alejandro E. De Feria Alsina,
MD; Jonathan Drezner, MD, FAMSSM; Rajesh Kabra,
MD, FACC, FHRS; Sabeeda Kadavath, MD; Elizabeth S.
Kaufman, MD, FACC, FAHA, FHRS†; Sabra Lewsey, MD,
MPH, FACC; James P. MacNamara, MD; Anjali Owens,
MD; Hena Patel, MD; Nosheen Reza, MD, FACC‡; Aldo
L. Schenone, MD; Daniel Swistel, MD; Jose Vargas, MD
AHA/ACC JOINT COMMITTEE ON
CLINICAL PRACTICE GUIDELINES
Joshua A. Beckman, MD, MS, FACC, FAHA, Chair;
Catherine M. Otto, MD, FACC, FAHA, Chair-Elect;
Anastasia L. Armbruster, PharmD, FACC; Leslie L. Da-
vis, PhD, ANP-BC, FACC, FAHA; Lisa de las Fuentes,
MD, MS, FAHA*; Anita Deswal, MD, MPH, FACC, FAHA*;
Victor A. Ferrari, MD, FACC, FAHA, MSCMR; Adrian F.
Hernandez, MD, FAHA*; Hani Jneid, MD, FACC, FAHA,
FSCAI; Heather M. Johnson, MD, MS, FACC, FAHA; W.
Schuyler Jones, MD, FACC; Sadiya S. Kahn, MD, MSc,
FACC, FAHA; Prateeti Khazanie, MD, MPH, FAHA; Mi-
chelle M. Kittleson, MD, PhD, FACC, FAHA; Venu Menon,
MD, FACC, FAHA; Debabrata Mukherjee, MD, FACC,
FAHA; Latha Palaniappan, MD, MS, FACC, FAHA*; Tan-
veer Rab, MD, FACC; Daichi Shimbo, MD; Jacqueline E.
Tamis-Holland, MD, FACC, FAHA; Y. Joseph Woo, MD,
FACC, FAHA; Boback Ziaeian, MD, PhD, FACC, FAHA
PRESIDENTS AND STAFF
American College of Cardiology
Cathleen Biga, MSN, FACC, President
Cathleen C. Gates, Chief Executive Officer
Richard J. Kovacs, MD, MACC, Chief Medical Officer
Mindy J. Saraco, MHA, Director, Clinical Policy and
Guidelines
Grace D. Ronan, Senior Production and Operations
Manager, Clinical Policy Publications
Leah Patterson, Project Manager, Clinical Content
Development
American Heart Association/American
College of Cardiology
Thomas S.D. Getchius, National Senior Director, Guide-
lines
Abdul R. Abdullah, MD, Director, Guideline Science and
Methodology
Shae Martinez, MLS, Reference Consultant, Medical
Librarian
American Heart Association
Joseph C. Wu, PhD, FAHA, President
Nancy Brown, Chief Executive Officer
Mariell Jessup, MD, FAHA, Chief Science and Medical
Officer
Nicole Aiello Sapio, EdD, Executive Vice President, Office
of Science Strategies and Operations
Radhika Rajgopal Singh, PhD, Senior Vice President,
Office of Science and Medicine
Prashant Nedungadi, BPharm, PhD, Vice President, Sci-
ence and Medicine, Clinical Guidelines
Anne Leonard, MPH, BSN, RN, FAHA, National Senior
Director, Science and Medicine
Jody Hundley, Senior Production and Operations
Manager, Scientific Publications, Office of Science
Operations
*AMSSM representative.
†HRS representative.
‡ACC/AHA Joint Committee on Performance Measures representative.
*Former Joint Committee on Clinical Practice Guidelines member; current member
during the writing effort.
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
ARTICLE INFORMATION
This document was approved by the American College of Cardiology Clinical
Policy Approval Committee and the American Heart Association Science Advi-
sory and Coordinating Committee in January 2024, and the American College of
Cardiology Science and Quality Committee and the American Heart Association
Executive Committee in February 2024.
Supplemental materials are available with this article at https://www.ahajournals.
org/doi/suppl/10.1161/CIR.0000000000001250
This article has been copublished in the Journal of the American College of
Cardiology.
Copies: This document is available on the websites of the American Heart
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The expert peer review of AHA-commissioned documents (eg, scientific
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Permissions: Multiple copies, modification, alteration, enhancement, and dis-
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REFERENCES
PREAMBLE
1. Committee on Standards for Developing Trustworthy Clinical Practice
Guidelines, Institute of Medicine (US). Clinical Practice Guidelines We Can
Trust. National Academies Press; 2011.
2. Committee on Standards for Systematic Reviews of Comparative Ef-
fectiveness Research, Institute of Medicine (US). Finding What Works
in Health Care: Standards for Systematic Reviews. National Academies
Press; 2011.
3. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA statement on
cost/value methodology in clinical practice guidelines and performance
measures: a report of the American College of Cardiology/ American Heart
Association Task Force on Performance Measures and Task Force on Prac-
tice Guidelines. Circulation. 2014;129:2329–2345.
4. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and
Policies From the ACCF/AHA Task Force on Practice Guidelines. American
College of Cardiology and American Heart Association. 2010. Accessed
September 23, 2023. https://www.acc.org/Guidelines/About-Guidelines-
and-Clinical-Documents/Methodology and https://professional.heart.
org/-/media/phd-files/guidelines-and-statements/methodology_manual_
and_policies_ucm_319826.pdf.
5. Halperin JL, Levine GN, Al-Khatib SM, et al. Further evolution of the
ACC/AHA clinical practice guideline recommendation classification sys-
tem: a report of the American College of Cardiology/American Heart
Association Task Force on Clinical Practice Guidelines. Circulation.
2016;133:1426–1428.
6. Arnett DK, Goodman RA, Halperin JL, et al. AHA/ACC/HHS strategies to
enhance application of clinical practice guidelines in patients with cardio-
vascular disease and comorbid conditions: from the American Heart Asso-
ciation, American College of Cardiology, and US Department of Health and
Human Services. Circulation. 2014;130:1662–1667.
7. Levine GN, O’Gara PT, Beckman JA, et al. Recent innovations, modifications,
and evolution of ACC/AHA clinical practice guidelines: an update for our
constituencies: a report of the American College of Cardiology/American
Heart Association Task Force on Clinical Practice Guidelines. Circulation.
2019;139:e879–e886.
1.1. Methodology and Evidence Review
1. Animal Studies-Standard-PubMed. In: CADTH Search Filters Database. Ot-
tawa: CADTH; 2022. Accessed September 14, 2022. https://searchfilters.
cadth.ca/link/54.
2. Guidelines-Broad-PubMed. In: CADTH Search Filters Database. Ottawa:
CADTH; 2022. Accessed September 14, 2022. https://searchfilters.cadth.
ca/link/75.
3. Guidelines-Standard-PubMed. In: CADTH Search Filters Database. Ottawa:
CADTH; 2022. Accessed September 14, 2022. https://searchfilters.cadth.
ca/link/77.
4. RCT/ CCT-PubMed. In: CADTH Search Filters Database. Ottawa: CADTH;
2022. Accessed September 14, 2022. https://searchfilters.cadth.ca/
link/108.
5. SR/ MA/ HTA/ ITC-PubMed. In: CADTH Search Filters Database. Ottawa:
CADTH; 2022: Accessed September 14, 2022. https://searchfilters.cadth.
ca/link/99.
6. Donahue KE, Gartlehner G, Schulman ER, et al. Drug Therapy for Early
Rheumatoid Arthritis: A Systematic Review Update [Internet]. (Compara-
tive Effectiveness Review, No. 211.) Appendix A, Search Strings. Agency
for Healthcare Research and Quality (US); 2018. Accessed September 14,
2022. https://www.ncbi.nlm.nih.gov/books/NBK524945/.
1.4. Scope of the Guideline
1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the
diagnosis and treatment of hypertrophic cardiomyopathy: a report of the
American College of Cardiology Foundation/American Heart Association
Task Force on Practice Guidelines. Circulation. 2011;124:e783–e831.
2. Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC guidelines on di-
agnosis and management of hypertrophic cardiomyopathy: the Task Force
for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the
European Society of Cardiology (ESC). Eur Heart J. 2014;35:2733–2779.
3. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the diag-
nosis and treatment of patients with hypertrophic cardiomyopathy: a report of
the American College of Cardiology/American Heart Association Joint Com-
mittee on Clinical Practice Guidelines. Circulation. 2020;142:e558–e631.
4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for
the management of patients with atrial fibrillation: a report of the American
College of Cardiology/American Heart Association Task Force on Practice
Guidelines and the Heart Rhythm Society. Circulation. 2014;130:e199–
e267.
5. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused up-
date of the 2014 AHA/ACC/HRS guideline for the management of pa-
tients with atrial fibrillation: a report of the American College of Cardiology/
American Heart Association Task Force on Clinical Practice Guidelines and
the Heart Rhythm Society. Circulation. 2019;140:e125–e151.
6. Joglar JA, Chung MK, et al. 2023 ACC/AHA/ACCP/HRS guideline for
the diagnosis and management of atrial fibrillation: a report of the Ameri-
can College of Cardiology/American Heart Association Joint Committee on
Clinical Practice Guidelines. Circulation. 2024;149:e1–e156.
7. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the
management of heart failure: a report of the American College of Cardiol-
ogy Foundation/American Heart Association Task Force on Practice Guide-
lines. Circulation. 2013;128:e240–e327.
8. Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA focused
update on new pharmacological therapy for heart failure: an update of the
2013 ACCF/AHA guideline for the management of heart failure: a report
of the American College of Cardiology/American Heart Association Task
Force on Clinical Practice Guidelines and the Heart Failure Society of Amer-
ica. Circulation. 2016;134:e282–e293.
9. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guide-
line for the management of heart failure: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Prac-
tice Guidelines. Circulation. 2022;145:e895–e1032.
10. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on
the primary prevention of cardiovascular disease: a report of the American
College of Cardiology/American Heart Association Task Force on Clinical
Practice Guidelines. Circulation. 2019;140:e596–e646.
11. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline
for the management of overweight and obesity in adults: a report of the
American College of Cardiology/American Heart Association Task Force on
Practice Guidelines and The Obesity Society. Circulation. 2014;129(suppl
2):s102–s138.
12. Epstein AE, Dimarco JP, Ellenbogen KA, et al. 2012 ACCF/AHA/HRS
focused update incorporated into the ACCF/AHA/HRS 2008 guidelines
for device-based therapy of cardiac rhythm abnormalities: A report of the
American College of Cardiology Foundation/American Heart Association
Task Force on Practice Guidelines and the Heart Rhythm Society. Circula-
tion. 2013;127:e283–e352.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e53
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
13. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/
HRS guideline for management of patients with ventricular arrhythmias
and the prevention of sudden cardiac death: a report of the Ameri-
can College of Cardiology/American Heart Association Task Force on
Clinical Practice Guidelines and the Heart Rhythm Society. Circulation.
2018;138:e272–e391.
14. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/
HRS guideline on the evaluation and management of patients with
bradycardia and cardiac conduction delay: a report of the American
College of Cardiology/American Heart Association Task Force on
Clinical Practice Guidelines and the Heart Rhythm Society. Circulation.
2019;140:e382–e482.
15. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guide-
lines for the prevention of cardiovascular disease in women-2011
update: a guideline from the American Heart Association. Circulation.
2011;123:1243–1262.
16. Smith SC Jr, Benjamin EJ, Bonow RO, et al. AHA/ACCF secondary preven-
tion and risk reduction therapy for patients with coronary and other ath-
erosclerotic vascular disease: 2011 update: a guideline from the American
Heart Association and American College of Cardiology Foundation. Circula-
tion. 2011;124:2458–2473.
17. Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for
assessment of cardiovascular risk in asymptomatic adults: a report of the
American College of Cardiology Foundation/American Heart Association
Task Force on Practice Guidelines. Circulation. 2010;122:e584–e636.
18. Jones DW, Hall JE. Seventh report of the Joint National Committee on Pre-
vention, Detection, Evaluation, and Treatment of High Blood Pressure and
evidence from new hypertension trials. Hypertension. 2004;43:1–3.
19. Nishimura RA, O’Gara PT, Bavaria JE, et al. 2019 AATS/ACC/ASE/SCAI/
STS expert consensus systems of care document: a proposal to optimize
care for patients with valvular heart disease: a joint report of the American
Association for Thoracic Surgery, American College of Cardiology, Ameri-
can Society of Echocardiography, Society for Cardiovascular Angiography
and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol.
2019;73:2609–2635.
2.1. Prevalence
1. Burns J, Jean-Pierre P. Disparities in the diagnosis of hypertrophic obstruc-
tive cardiomyopathy: a narrative review of current literature. Cardiol Res
Pract. 2018;2018:3750879.
2. Semsarian C, Ingles J, Maron MS, et al. New perspectives on the prevalence
of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65:1249–1254.
3. Maron MS, Hellawell JL, Lucove JC, et al. Occurrence of clinically diag-
nosed hypertrophic cardiomyopathy in the United States. Am J Cardiol.
2016;117:1651–1654.
4. Eberly LA, Day SM, Ashley EA, et al. Association of race with disease ex-
pression and clinical outcomes among patients with hypertrophic cardiomy-
opathy. JAMA Cardiol. 2020;5:83–91.
2.2. Nomenclature and Differential Diagnosis
1. Maron BJ, Desai MY, Nishimura RA, et al. Diagnosis and evaluation of hy-
pertrophic cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol.
2022;79:372–389.
2. Maron BJ, Ommen SR, Semsarian C, et al. Hypertrophic cardiomyopathy:
present and future, with translation into contemporary cardiovascular medi-
cine. J Am Coll Cardiol. 2014;64:83–99.
3. Maron BJ. Clinical course and management of hypertrophic cardiomyopa-
thy. N Engl J Med. 2018;379:655–668.
4. Maron BJ, Rowin EJ, Casey SA, et al. How hypertrophic cardiomyopathy be-
came a contemporary treatable genetic disease with low mortality: shaped
by 50 years of clinical research and practice. JAMA Cardiol. 2016;1:98–
105.
5. Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in adult-
hood associated with low cardiovascular mortality with contemporary man-
agement strategies. J Am Coll Cardiol. 2015;65:1915–1928.
6. Keegan MT, Sinak LJ, Nichols DA, et al. Dynamic left ventricular outflow tract
obstruction in acute coronary syndromes. Mayo Clin Proc. 2000;75:216–
217.
7. Sherrid MV, Riedy K, Rosenzweig B, et al. Distinctive hypertrophic cardiomy-
opathy anatomy and obstructive physiology in patients admitted with Takot-
subo Syndrome. Am J Cardiol. 2020;125:1700–1709.
2.3. Definition, Clinical Diagnosis, and Phenotype
1. Geske JB, Ommen SR, Gersh BJ. Hypertrophic cardiomyopathy: clinical up-
date. J Am Coll Cardiol HF. 2018;6:364–375.
2. Marian AJ, Braunwald E. Hypertrophic cardiomyopathy: genetics,
pathogenesis, clinical manifestations, diagnosis, and therapy. Circ Res.
2017;121:749–770.
3. Maron BJ, Ommen SR, Semsarian C, et al. Hypertrophic cardiomyopathy:
present and future, with translation into contemporary cardiovascular medi-
cine. J Am Coll Cardiol. 2014;64:83–99.
4. Maron BJ. Clinical course and management of hypertrophic cardiomyopa-
thy. N Engl J Med. 2018;379:655–668.
2.4. Etiology
1. Burke MA, Cook SA, Seidman JG, et al. Clinical and mechanistic insights
into the genetics of cardiomyopathy. J Am Coll Cardiol. 2016;68:2871–
2886.
2. Ingles J, Burns C, Bagnall RD, et al. Nonfamilial hypertrophic cardiomyop-
athy: prevalence, natural history, and clinical implications. Circ Cardiovasc
Genet. 2017;10:e001620.
3. Tadros R, Francis C, Xu X, et al. Shared genetic pathways contribute to risk
of hypertrophic and dilated cardiomyopathies with opposite directions of
effect. Nat Genet. 2021;53:128–134.
4. Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of disease
in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Car-
diomyopathy Registry (SHaRE). Circulation. 2018;138:1387–1398.
2.5. Natural History and Clinical Course
1. Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of disease
in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Car-
diomyopathy Registry (SHaRE). Circulation. 2018;138:1387–1398.
2. Maron BJ, Rowin EJ, Casey SA, et al. How hypertrophic cardiomyopathy be-
came a contemporary treatable genetic disease with low mortality: shaped
by 50 years of clinical research and practice. JAMA Cardiol. 2016;1:98–
105.
3. Maron BJ. Clinical course and management of hypertrophic cardiomyopa-
thy. N Engl J Med. 2018;379:655–668.
4. Lopes LR, Losi MA, Sheikh N, et al. Association between common cardio-
vascular risk factors and clinical phenotype in patients with hypertrophic
cardiomyopathy from the European Society of Cardiology (ESC) EurObser-
vational Research Programme (EORP) Cardiomyopathy/Myocarditis Regis-
try. Eur Heart J Qual Care Clin Outcomes. 2022;9:42–53.
3.1. Left Ventricular Outflow Tract Obstruction
1. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is
predominantly a disease of left ventricular outflow tract obstruction. Circula-
tion. 2006;114:2232–2239.
2. Geske JB, Sorajja P, Ommen SR, et al. Variability of left ventricular outflow
tract gradient during cardiac catheterization in patients with hypertrophic
cardiomyopathy. J Am Coll Cardiol Intv. 2011;4:704–709.
3. Adams JC, Bois JP, Masaki M, et al. Postprandial hemodynamics in hyper-
trophic cardiomyopathy. Echocardiography. 2015;32:1614–1620.
4. Jain R, Osranek M, Jan MF, et al. Marked respiratory-related fluctuations
in left ventricular outflow tract gradients in hypertrophic obstructive car-
diomyopathy: an observational study. Eur Heart J Cardiovasc Imaging.
2018;19:1126–1133.
5. Ayoub C, Geske JB, Larsen CM, et al. Comparison of Valsalva maneuver,
amyl nitrite, and exercise echocardiography to demonstrate latent left ven-
tricular outflow obstruction in hypertrophic cardiomyopathy. Am J Cardiol.
2017;120:2265–2271.
6. Nistri S, Olivotto I, Maron MS, et al. Timing and significance of exercise-
induced left ventricular outflow tract pressure gradients in hypertrophic car-
diomyopathy. Am J Cardiol. 2010;106:1301–1306.
7. Reant P, Dufour M, Peyrou J, et al. Upright treadmill vs. semi-supine bi-
cycle exercise echocardiography to provoke obstruction in symptomatic
hypertrophic cardiomyopathy: a pilot study. Eur Heart J Cardiovasc Imaging.
2018;19:31–38.
8. Joshi S, Patel UK, Yao S-S, et al. Standing and exercise Doppler echocar-
diography in obstructive hypertrophic cardiomyopathy: the range of gradi-
ents with upright activity. J Am Soc Echocardiogr. 2011;24:75–82.
9. Feiner E, Arabadjian M, Winson G, et al. Post-prandial upright exercise
echocardiography in hypertrophic cardiomyopathy. J Am Coll Cardiol.
2013;61:2487–2488.
10. Pellikka PA, Oh JK, Bailey KR, et al. Dynamic intraventricular obstruction
during dobutamine stress echocardiography. A new observation. Circulation.
1992;86:1429–1432.
11. Elesber A, Nishimura RA, Rihal CS, et al. Utility of isoproterenol to provoke
outflow tract gradients in patients with hypertrophic cardiomyopathy. Am J
Cardiol. 2008;101:516–520.
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Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
3.2. Diastolic Dysfunction
1. Paulus WJ, Lorell BH, Craig WE, et al. Comparison of the effects of nitro-
prusside and nifedipine on diastolic properties in patients with hypertrophic
cardiomyopathy: altered left ventricular loading or improved muscle inactiva-
tion? J Am Coll Cardiol. 1983;2:879–886.
2. Soullier C, Obert P, Doucende G, et al. Exercise response in hypertro-
phic cardiomyopathy: blunted left ventricular deformational and twisting
reserve with altered systolic-diastolic coupling. Circ Cardiovasc Imaging.
2012;5:324–332.
3. Villemain O, Correia M, Mousseaux E, et al. Myocardial stiffness evaluation
using noninvasive shear wave imaging in healthy and hypertrophic cardio-
myopathic adults. J Am Coll Cardiol Img. 2019;12:1135–1145.
4. Ho CY, Carlsen C, Thune JJ, et al. Echocardiographic strain imaging to as-
sess early and late consequences of sarcomere mutations in hypertrophic
cardiomyopathy. Circ Cardiovasc Genet. 2009;2:314–321.
5. Dass S, Cochlin LE, Suttie JJ, et al. Exacerbation of cardiac energetic im-
pairment during exercise in hypertrophic cardiomyopathy: a potential mech-
anism for diastolic dysfunction. Eur Heart J. 2015;36:1547–1554.
6. Desai MY, Bhonsale A, Patel P, et al. Exercise echocardiography in asymp-
tomatic HCM: exercise capacity, and not LV outflow tract gradient predicts
long-term outcomes. J Am Coll Cardiol Img. 2014;7:26–36.
3.3. Mitral Regurgitation
1. Maron MS, Olivotto I, Harrigan C, et al. Mitral valve abnormalities identified
by cardiovascular magnetic resonance represent a primary phenotypic ex-
pression of hypertrophic cardiomyopathy. Circulation. 2011;124:40–47.
2. Groarke JD, Galazka PZ, Cirino AL, et al. Intrinsic mitral valve alterations
in hypertrophic cardiomyopathy sarcomere mutation carriers. Eur Heart J
Cardiovasc Imaging. 2018;19:1109–1116.
3. Sherrid MV, Balaram S, Kim B, et al. The mitral valve in obstructive hypertro-
phic cardiomyopathy: a test in context. J Am Coll Cardiol. 2016;67:1846–
1858.
4. Hang D, Schaff HV, Nishimura RA, et al. Accuracy of jet direction on
Doppler echocardiography in identifying the etiology of mitral regurgita-
tion in obstructive hypertrophic cardiomyopathy. J Am Soc Echocardiogr.
2019;32:333–340.
5. Hodges K, Rivas CG, Aguilera J, et al. Surgical management of left ven-
tricular outflow tract obstruction in a specialized hypertrophic obstructive
cardiomyopathy center. J Thorac Cardiovasc Surg. 2019;157:2289–2299.
6. Hong JH, Schaff HV, Nishimura RA, et al. Mitral regurgitation in patients
with hypertrophic obstructive cardiomyopathy: implications for concomitant
valve procedures. J Am Coll Cardiol. 2016;68:1497–1504.
3.4. Myocardial Ischemia
1. Cannon RO III, Rosing DR, Maron BJ, et al. Myocardial ischemia in pa-
tients with hypertrophic cardiomyopathy: contribution of inadequate va-
sodilator reserve and elevated left ventricular filling pressures. Circulation.
1985;71:234–243.
2. Maron BJ, Wolfson JK, Epstein SE, et al. Intramural (“small vessel”) coro-
nary artery disease in hypertrophic cardiomyopathy. J Am Coll Cardiol.
1986;8:545–557.
3. Karamitsos TD, Dass S, Suttie J, et al. Blunted myocardial oxygenation re-
sponse during vasodilator stress in patients with hypertrophic cardiomyopa-
thy. J Am Coll Cardiol. 2013;61:1169–1176.
4. Raphael CE, Cooper R, Parker KH, et al. Mechanisms of myocardial isch-
emia in hypertrophic cardiomyopathy: insights from wave intensity analysis
and magnetic resonance. J Am Coll Cardiol. 2016;68:1651–1660.
5. Sorajja P, Ommen SR, Nishimura RA, et al. Adverse prognosis of patients
with hypertrophic cardiomyopathy who have epicardial coronary artery dis-
ease. Circulation. 2003;108:2342–2348.
6. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic cardiomyopathy with left
ventricular apical aneurysm: implications for risk stratification and manage-
ment. J Am Coll Cardiol. 2017;69:761–773.
7. Binder J, Attenhofer Jost CH, Klarich KW, et al. Apical hypertrophic car-
diomyopathy: prevalence and correlates of apical outpouching. J Am Soc
Echocardiogr. 2011;24:775–781.
8. Hostiuc S, Rusu MC, Hostiuc M, et al. Cardiovascular consequences
of myocardial bridging: a meta-analysis and meta-regression. Sci Rep.
2017;7:14644.
9. Sharzehee M, Chang Y, Song JP, et al. Hemodynamic effects of myocardial
bridging in patients with hypertrophic cardiomyopathy. Am J Physiol Heart
Circ Physiol. 2019;317:H1282–H1291.
10. Tian T, Wang YL, Wang JZ, et al. Myocardial bridging as a common pheno-
type of hypertrophic cardiomyopathy has no effect on prognosis. Am J Med
Sci. 2014;347:429–433.
11. Yetman AT, McCrindle BW, MacDonald C, et al. Myocardial bridging in chil-
dren with hypertrophic cardiomyopathy–a risk factor for sudden death. N
Engl J Med. 1998;339:1201–1209.
12. Zhai SS, Fan CM, An SY, et al. Clinical outcomes of myocardial bridging
versus no myocardial bridging in patients with apical hypertrophic cardiomy-
opathy. Cardiology. 2018;139:161–168.
3.5. Autonomic Dysfunction
1. Patel V, Critoph CH, Finlay MC, et al. Heart rate recovery in patients with
hypertrophic cardiomyopathy. Am J Cardiol. 2014;113:1011–1017.
2. Frenneaux MP, Counihan PJ, Caforio AL, et al. Abnormal blood pressure
response during exercise in hypertrophic cardiomyopathy. Circulation.
1990;82:1995–2002.
3. Sadoul N, Prasad K, Elliott PM, et al. Prospective prognostic assessment
of blood pressure response during exercise in patients with hypertrophic
cardiomyopathy. Circulation. 1997;96:2987–2991.
4. Olivotto I, Maron BJ, Montereggi A, et al. Prognostic value of systemic blood
pressure response during exercise in a community-based patient population
with hypertrophic cardiomyopathy. J Am Coll Cardiol. 1999;33:2044–2051.
4. Shared Decision-Making
1. Agency for Healthcare Research and Quality. Strategy 6I: Shared Decisionmak-
ing. The CAHPS Ambulatory Care Improvement Guide: Practical Strategies for
Improving Patient Experience. 2017. Accessed April 29, 2020. https://www.
ahrq.gov/cahps/quality-improvement/improvement-guide/6-strategies-for-
improving/communication/strategy6i-shared-decisionmaking.html.
2. Greenfield S, Kaplan SH, Ware JE Jr, et al. Patients’ participation in medical
care: effects on blood sugar control and quality of life in diabetes. J Gen
Intern Med. 1988;3:448–457.
3. Greenfield S, Kaplan S, Ware JE Jr. Expanding patient involvement in care.
Effects on patient outcomes. Ann Intern Med. 1985;102:520–528.
4. Kaplan SH, Greenfield S, Ware JE Jr. Assessing the effects of
physician-patient interactions on the outcomes of chronic disease. Med
Care. 1989;27:S110–127.
5. Guadagnoli E, Ward P. Patient participation in decision-making. Soc Sci Med.
1998;47:329–339.
6. Legare F, Adekpedjou R, Stacey D, et al. Interventions for increasing the use
of shared decision making by healthcare professionals. Cochrane Database
Syst Rev. 2018;7:CD006732.
5. Multidisciplinary HCM Centers
1. Kim LK, Swaminathan RV, Looser P, et al. Hospital volume outcomes after
septal myectomy and alcohol septal ablation for treatment of obstructive hy-
pertrophic cardiomyopathy: US nationwide inpatient database, 2003-2011.
JAMA Cardiol. 2016;1:324–332.
2. Panaich SS, Badheka AO, Chothani A, et al. Results of ventricular septal
myectomy and hypertrophic cardiomyopathy (from Nationwide Inpatient
Sample [1998-2010]). Am J Cardiol. 2014;114:1390–1395.
3. Sorajja P, Ommen SR, Holmes DR Jr, et al. Survival after alcohol sep-
tal ablation for obstructive hypertrophic cardiomyopathy. Circulation.
2012;126:2374–2380.
4. Maron BJ, Nishimura RA, Maron MS. Shared decision-making in HCM. Nat
Rev Cardiol. 2017;14:125–126.
5. Chambers JB, Prendergast B, Iung B, et al. Standards defining a “heart
valve centre”: ESC Working Group on Valvular Heart Disease and Eu-
ropean Association for Cardiothoracic Surgery Viewpoint. Eur Heart J.
2017;38:2177–2183.
6. Semsarian C, Ingles J, Maron MS, et al. New perspectives on the prevalence
of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65:1249–1254.
7. Maron BJ, Ommen SR, Semsarian C, et al. Hypertrophic cardiomyopathy:
present and future, with translation into contemporary cardiovascular medi-
cine. J Am Coll Cardiol. 2014;64:83–99.
8. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal
myectomy on survival in patients with obstructive hypertrophic cardiomy-
opathy. J Am Coll Cardiol. 2005;46:470–476.
9. Desai MY, Bhonsale A, Smedira NG, et al. Predictors of long-term outcomes
in symptomatic hypertrophic obstructive cardiomyopathy patients undergo-
ing surgical relief of left ventricular outflow tract obstruction. Circulation.
2013;128:209–216.
10. Lim K-K, Maron BJ, Knight BP. Successful catheter ablation of hemody-
namically unstable monomorphic ventricular tachycardia in a patient with hy-
pertrophic cardiomyopathy and apical aneurysm. J Cardiovasc Electrophysiol.
2009;20:445–447.
11. Dukkipati SR, d’Avila A, Soejima K, et al. Long-term outcomes of combined
epicardial and endocardial ablation of monomorphic ventricular tachycardia
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e55
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
related to hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol.
2011;4:185–194.
12. Rowin EJ, Maron BJ, Abt P, et al. Impact of advanced therapies for improving
survival to heart transplant in patients with hypertrophic cardiomyopathy. Am
J Cardiol. 2018;121:986–996.
13. Pasqualucci D, Fornaro A, Castelli G, et al. Clinical spectrum, therapeutic
options, and outcome of advanced heart failure in hypertrophic cardiomy-
opathy. Circ Heart Fail. 2015;8:1014–1021.
14. Garmany R, Bos JM, Ommen SR, et al. Clinical course of patients with hy-
pertrophic cardiomyopathy away from tertiary referral care. ESC Heart Fail.
2023;10:1919–1927.
15. Nishimura RA, O’Gara PT, Bavaria JE, et al. 2019 AATS/ACC/ASE /SCAI/STS
expert consensus systems of care document: a proposal to optimize care for
patients with valvular heart disease: a joint report of the American Association
for Thoracic Surgery, American College of Cardiology, American Society of
Echocardiography, Society for Cardiovascular Angiography and Interventions,
and Society of Thoracic Surgeons. J Am Coll Cardiol. 2019;73:2609–2635.
16. Polanco AR, D’Angelo A, Shea N, et al. Impact of septal myectomy volume
on mitral-valve replacement rate in hypertrophic cardiomyopathy patients.
Cardiology. 2020;145:161–167.
17. Holst KA, Hanson KT, Ommen SR, et al. Septal myectomy in hypertrophic
cardiomyopathy: national outcomes of concomitant mitral surgery. Mayo Clin
Proc. 2019;94:66–73.
6.1. Clinical Diagnosis
1. Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopa-
thy after 20 years: clinical perspectives. J Am Coll Cardiol. 2012;60:705–
715.
2. Ingles J, Yeates L, Semsarian C. The emerging role of the cardiac genetic
counselor. Heart Rhythm. 2011;8:1958–1962.
3. Ahmad F, McNally EM, Ackerman MJ, et al. Establishment of specialized
clinical cardiovascular genetics programs: recognizing the need and meet-
ing standards: a scientific statement from the American Heart Association.
Circ Genom Precis Med. 2019;12:e000054.
4. van Velzen HG, Schinkel AFL, Baart SJ, et al. Outcomes of contemporary
family screening in hypertrophic cardiomyopathy. Circ Genom Precis Med.
2018;11:e001896.
5. Ranthe MF, Carstensen L, Oyen N, et al. Risk of cardiomyopathy in younger
persons with a family history of death from cardiomyopathy: a nationwide
family study in a cohort of 3.9 million persons. Circulation. 2015;132:1013–
1019.
6. Lafreniere-Roula M, Bolkier Y, Zahavich L, et al. Family screening for hyper-
trophic cardiomyopathy: is it time to change practice guidelines? Eur Heart
J. 2019;40:3672–3681.
6.2. Echocardiography
1. Adabag AS, Kuskowski MA, Maron BJ. Determinants for clinical diagnosis
of hypertrophic cardiomyopathy. Am J Cardiol. 2006;98:1507–1511.
2. Afonso LC, Bernal J, Bax JJ, et al. Echocardiography in hypertrophic car-
diomyopathy: the role of conventional and emerging technologies. J Am Coll
Cardiol Img. 2008;1:787–800.
3. Klues HG, Schiffers A, Maron BJ. Phenotypic spectrum and patterns of left
ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic obser-
vations and significance as assessed by two-dimensional echocardiography
in 600 patients. J Am Coll Cardiol. 1995;26:1699–1708.
4. Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy.
The importance of the site and the extent of hypertrophy. A review. Prog
Cardiovasc Dis. 1985;28:1–83.
5. Shapiro LM, McKenna WJ. Distribution of left ventricular hypertrophy in hy-
pertrophic cardiomyopathy: a two-dimensional echocardiographic study. J
Am Coll Cardiol. 1983;2:437–444.
6. Nagueh SF, Bierig SM, Budoff MJ, et al. American Society of Echocar-
diography clinical recommendations for multimodality cardiovascular imag-
ing of patients with hypertrophic cardiomyopathy. J Am Soc Echocardiogr.
2011;24:473–498.
7. Melacini P, Basso C, Angelini A, et al. Clinicopathological profiles of
progressive heart failure in hypertrophic cardiomyopathy. Eur Heart J.
2010;31:2111–2123.
8. Thaman R, Gimeno JR, Murphy RT, et al. Prevalence and clinical sig-
nificance of systolic impairment in hypertrophic cardiomyopathy. Heart.
2005;91:920–925.
9. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and signifi-
cance of left ventricular remodeling in the end-stage phase of hypertrophic
cardiomyopathy. Circulation. 2006;114:216–225.
10. Olivotto I, Cecchi F, Poggesi C, et al. Patterns of disease progression in
hypertrophic cardiomyopathy: an individualized approach to clinical staging.
Circ Heart Fail. 2012;5:535–546.
11. Todiere G, Aquaro GD, Piaggi P, et al. Progression of myocardial fibrosis
assessed with cardiac magnetic resonance in hypertrophic cardiomyopathy.
J Am Coll Cardiol. 2012;60:922–929.
12. Norrish G, Ding T, Field E, et al. A validation study of the European Society
of Cardiology guidelines for risk stratification of sudden cardiac death in
childhood hypertrophic cardiomyopathy. Europace. 2019;21:1559–1565.
13. Balaji S, DiLorenzo MP, Fish FA, et al. Risk factors for lethal arrhythmic
events in children and adolescents with hypertrophic cardiomyopathy and
an implantable defibrillator: an international multicenter study. Heart Rhythm.
2019;16:1462–1467.
14. Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/HFSA/
HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echo-
cardiography: a report of the American College of Cardiology Foundation
Appropriate Use Criteria Task Force, American Society of Echocardiogra-
phy, American Heart Association, American Society of Nuclear Cardiology,
Heart Failure Society of America, Heart Rhythm Society, Society for Cardio-
vascular Angiography and Interventions, Society of Critical Care Medicine,
Society of Cardiovascular Computed Tomography, and Society for Cardio-
vascular Magnetic Resonance. J Am Coll Cardiol. 2011;57:1126–1166.
15. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract
obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J
Med. 2003;348:295–303.
16. Woo A, Williams WG, Choi R, et al. Clinical and echocardiographic determi-
nants of long-term survival after surgical myectomy in obstructive hypertro-
phic cardiomyopathy. Circulation. 2005;111:2033–2041.
17. Geske JB, Sorajja P, Nishimura RA, et al. Evaluation of left ventricular fill-
ing pressures by Doppler echocardiography in patients with hypertrophic
cardiomyopathy: correlation with direct left atrial pressure measurement at
cardiac catheterization. Circulation. 2007;116:2702–2708.
18. Kumar S, Van Ness G, Bender A, et al. Standardized goal-directed Valsalva
maneuver for assessment of inducible left ventricular outflow tract obstruc-
tion in hypertrophic cardiomyopathy. J Am Soc Echocardiogr. 2018;31:791–
798.
19. Marwick TH, Nakatani S, Haluska B, et al. Provocation of latent left ven-
tricular outflow tract gradients with amyl nitrite and exercise in hypertrophic
cardiomyopathy. Am J Cardiol. 1995;75:805–809.
20. Joshi S, Patel UK, Yao S-S, et al. Standing and exercise Doppler echocar-
diography in obstructive hypertrophic cardiomyopathy: the range of gradi-
ents with upright activity. J Am Soc Echocardiogr. 2011;24:75–82.
21. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is
predominantly a disease of left ventricular outflow tract obstruction. Circula-
tion. 2006;114:2232–2239.
22. Ayoub C, Geske JB, Larsen CM, et al. Comparison of Valsalva maneuver,
amyl nitrite, and exercise echocardiography to demonstrate latent left ven-
tricular outflow obstruction in hypertrophic cardiomyopathy. Am J Cardiol.
2017;120:2265–2271.
23. Jensen MK, Havndrup O, Pecini R, et al. Comparison of Valsalva manoeu-
vre and exercise in echocardiographic evaluation of left ventricular out-
flow tract obstruction in hypertrophic cardiomyopathy. Eur J Echocardiogr.
2010;11:763–769.
24. Reant P, Dufour M, Peyrou J, et al. Upright treadmill vs. semi-supine bi-
cycle exercise echocardiography to provoke obstruction in symptomatic
hypertrophic cardiomyopathy: a pilot study. Eur Heart J Cardiovasc Imaging.
2018;19:31–38.
25. Shah JS, Esteban MTT, Thaman R, et al. Prevalence of exercise-induced
left ventricular outflow tract obstruction in symptomatic patients with non-
obstructive hypertrophic cardiomyopathy. Heart. 2008;94:1288–1294.
26. Grigg LE, Wigle ED, Williams WG, et al. Transesophageal Doppler echo-
cardiography in obstructive hypertrophic cardiomyopathy: clarification of
pathophysiology and importance in intraoperative decision making. J Am
Coll Cardiol. 1992;20:42–52.
27. Marwick TH, Stewart WJ, Lever HM, et al. Benefits of intraoperative echo-
cardiography in the surgical management of hypertrophic cardiomyopathy. J
Am Coll Cardiol. 1992;20:1066–1072.
28. Nampiaparampil RG, Swistel DG, Schlame M, et al. Intraoperative two-
and three-dimensional transesophageal echocardiography in combined
myectomy-mitral operations for hypertrophic cardiomyopathy. J Am Soc
Echocardiogr. 2018;31:275–288.
29. Ommen SR, Park SH, Click RL, et al. Impact of intraoperative transesopha-
geal echocardiography in the surgical management of hypertrophic cardio-
myopathy. Am J Cardiol. 2002;90:1022–1024.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e56
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
30. Faber L, Seggewiss H, Ziemssen P, et al. Intraprocedural myocardial con-
trast echocardiography as a routine procedure in percutaneous trans-
luminal septal myocardial ablation: detection of threatening myocardial
necrosis distant from the septal target area. Catheter Cardiovasc Interv.
1999;47:462–466.
31. Faber L, Ziemssen P, Seggewiss H. Targeting percutaneous translumi-
nal septal ablation for hypertrophic obstructive cardiomyopathy by in-
traprocedural echocardiographic monitoring. J Am Soc Echocardiogr.
2000;13:1074–1079.
32. Nagueh SF, Zoghbi WA. Role of imaging in the evaluation of patients at
risk for sudden cardiac death: genotype-phenotype intersection. J Am Coll
Cardiol Img. 2015;8:828–845.
33. Faber L, Seggewiss H, Welge D, et al. Echo-guided percutaneous septal
ablation for symptomatic hypertrophic obstructive cardiomyopathy: 7 years
of experience. Eur J Echocardiogr. 2004;5:347–355.
34. Kuhn H, Gietzen FH, Schäfers M, et al. Changes in the left ventricular out-
flow tract after transcoronary ablation of septal hypertrophy (TASH) for
hypertrophic obstructive cardiomyopathy as assessed by transoesophageal
echocardiography and by measuring myocardial glucose utilization and per-
fusion. Eur Heart J. 1999;20:1808–1817.
35. Sorajja P, Valeti U, Nishimura RA, et al. Outcome of alcohol septal ablation
for obstructive hypertrophic cardiomyopathy. Circulation. 2008;118:131–
139.
36. Faber L, Seggewiss H, Gleichmann U. Percutaneous transluminal septal
myocardial ablation in hypertrophic obstructive cardiomyopathy: results with
respect to intraprocedural myocardial contrast echocardiography. Circula-
tion. 1998;98:2415–2421.
37. Qin JX, Shiota T, Lever HM, et al. Outcome of patients with hypertro-
phic obstructive cardiomyopathy after percutaneous transluminal sep-
tal myocardial ablation and septal myectomy surgery. J Am Coll Cardiol.
2001;38:1994–2000.
38. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal
myectomy on survival in patients with obstructive hypertrophic cardiomy-
opathy. J Am Coll Cardiol. 2005;46:470–476.
39. Jensen MK, Havndrup O, Christiansen M, et al. Penetrance of hy-
pertrophic cardiomyopathy in children and adolescents. Circulation.
2013;127:48–54.
40. Lafreniere-Roula M, Bolkier Y, Zahavich L, et al. Family screening for hyper-
trophic cardiomyopathy: is it time to change practice guidelines? Eur Heart
J. 2019;40:3672–3681.
41. Maurizi N, Michels M, Rowin EJ, et al. Clinical course and significance of
hypertrophic cardiomyopathy without left ventricular hypertrophy. Circulation.
2019;139:830–833.
42. Norrish G, Jager J, Field E, et al. Yield of clinical screening for hypertro-
phic cardiomyopathy in child first-degree relatives: evidence for a change in
paradigm. Circulation. 2019;140:184–192.
43. Vermeer AMC, Clur S-AB, Blom NA, et al. Penetrance of hypertro-
phic cardiomyopathy in children who are mutation positive. J Pediatr.
2017;188:91–95.
44. Thanigaraj S, Pérez JE. Apical hypertrophic cardiomyopathy: echocardio-
graphic diagnosis with the use of intravenous contrast image enhancement.
J Am Soc Echocardiogr. 2000;13:146–149.
45. Porter TR, Mulvagh SL, Abdelmoneim SS, et al. Clinical applications of
ultrasonic enhancing agents in echocardiography: 2018 American So-
ciety of Echocardiography guidelines update. J Am Soc Echocardiogr.
2018;31:241–274.
46. Feiner E, Arabadjian M, WinsonG, G, et al. Post-prandial upright exer-
cise echocardiography in hypertrophic cardiomyopathy. J Am Coll Cardiol.
2013;61:2487–2488.
47. Faber L, Welge D, Fassbender D, et al. Percutaneous septal ablation
for symptomatic hypertrophic obstructive cardiomyopathy: managing
the risk of procedure-related AV conduction disturbances. Int J Cardiol.
2007;119:163–167.
48. Liebregts M, Vriesendorp PA, Mahmoodi BK, et al. A systematic review and
meta-analysis of long-term outcomes after septal reduction therapy in pa-
tients with hypertrophic cardiomyopathy. J Am Coll Cardiol HF. 2015;3:896–
905.
49. Charron P, Arad M, Arbustini E, et al. Genetic counselling and testing in
cardiomyopathies: a position statement of the European Society of Cardiol-
ogy Working Group on Myocardial and Pericardial Diseases. Eur Heart J.
2010;31:2715–2726.
50. Vigneault DM, Yang E, Jensen PJ, et al. Left ventricular strain is abnormal
in preclinical and overt hypertrophic cardiomyopathy: cardiac MR feature
tracking. Radiology. 2019;290:640–648.
51. Nagueh SF, McFalls J, Meyer D, et al. Tissue Doppler imaging predicts the
development of hypertrophic cardiomyopathy in subjects with subclinical
disease. Circulation. 2003;108:395–398.
52. Ho CY, Sweitzer NK, McDonough B, et al. Assessment of diastolic function
with Doppler tissue imaging to predict genotype in preclinical hypertrophic
cardiomyopathy. Circulation. 2002;105:2992–2997.
53. Hershberger RE, Cowan J, Morales A, et al. Progress with genetic cardio-
myopathies: screening, counseling, and testing in dilated, hypertrophic, and
arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Heart Fail.
2009;2:253–261.
6.3. CMR Imaging
1. Maron MS, Maron BJ, Harrigan C, et al. Hypertrophic cardiomyopathy phe-
notype revisited after 50 years with cardiovascular magnetic resonance. J
Am Coll Cardiol. 2009;54:220–228.
2. Rickers C, Wilke NM, Jerosch-Herold M, et al. Utility of cardiac magnetic
resonance imaging in the diagnosis of hypertrophic cardiomyopathy. Circu-
lation. 2005;112:855–861.
3. Moon JCC, Fisher NG, McKenna WJ, et al. Detection of apical hypertrophic
cardiomyopathy by cardiovascular magnetic resonance in patients with non-
diagnostic echocardiography. Heart. 2004;90:645–649.
4. Hindieh W, Weissler-Snir A, Hammer H, et al. Discrepant measurements of
maximal left ventricular wall thickness between cardiac magnetic resonance
imaging and echocardiography in patients with hypertrophic cardiomyopa-
thy. Circ Cardiovasc Imaging. 2017;10:e006309.
5. Corona-Villalobos CP, Sorensen LL, Pozios I, et al. Left ventricular wall thick-
ness in patients with hypertrophic cardiomyopathy: a comparison between
cardiac magnetic resonance imaging and echocardiography. Int J Cardio-
vasc Imaging. 2016;32:945–954.
6. Bois JP, Geske JB, Foley TA, et al. Comparison of maximal wall thickness in
hypertrophic cardiomyopathy differs between magnetic resonance imaging
and transthoracic echocardiography. Am J Cardiol. 2017;119:643–650.
7. Maron MS, Rowin EJ, Maron BJ. How to image hypertrophic cardiomyopa-
thy. Circ Cardiovasc Imaging. 2017;10:e005372.
8. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic cardiomyopathy with left
ventricular apical aneurysm: implications for risk stratification and manage-
ment. J Am Coll Cardiol. 2017;69:761–773.
9. Kebed KY, Al Adham RI, Bishu K, et al. Evaluation of apical pouches in
hypertrophic cardiomyopathy using cardiac MRI. Int J Cardiovasc Imaging.
2014;30:591–597.
10. Maron MS, Lesser JR, Maron BJ. Management implications of massive left
ventricular hypertrophy in hypertrophic cardiomyopathy significantly under-
estimated by echocardiography but identified by cardiovascular magnetic
resonance. Am J Cardiol. 2010;105:1842–1843.
11. Weng Z, Yao J, Chan RH, et al. Prognostic value of LGE-CMR in HCM: a
meta-analysis. J Am Coll Cardiol Img. 2016;9:1392–1402.
12. Chan RH, Maron BJ, Olivotto I, et al. Prognostic value of quantitative
contrast-enhanced cardiovascular magnetic resonance for the evaluation of
sudden death risk in patients with hypertrophic cardiomyopathy. Circulation.
2014;130:484–495.
13. Mentias A, Raeisi-Giglou P, Smedira NG, et al. Late gadolinium enhance-
ment in patients with hypertrophic cardiomyopathy and preserved systolic
function. J Am Coll Cardiol. 2018;72:857–870.
14. Ismail TF, Jabbour A, Gulati A, et al. Role of late gadolinium enhancement
cardiovascular magnetic resonance in the risk stratification of hypertrophic
cardiomyopathy. Heart. 2014;100:1851–1858.
15. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and signifi-
cance of left ventricular remodeling in the end-stage phase of hypertrophic
cardiomyopathy. Circulation. 2006;114:216–225.
16. Patel P, Dhillon A, Popovic ZB, et al. Left ventricular outflow tract obstruction
in hypertrophic cardiomyopathy patients without severe septal hypertrophy:
implications of mitral valve and papillary muscle abnormalities assessed
using cardiac magnetic resonance and echocardiography. Circ Cardiovasc
Imaging. 2015;8:e003132.
17. Rowin EJ, Maron BJ, Chokshi A, et al. Clinical spectrum and management
implications of left ventricular outflow obstruction with mild ventricular septal
thickness in hypertrophic cardiomyopathy. Am J Cardiol. 2018;122:1409–
1420.
18. Sherrid MV, Balaram S, Kim B, et al. The mitral valve in obstructive hypertro-
phic cardiomyopathy: a test in context. J Am Coll Cardiol. 2016;67:1846–
1858.
19. Kwon DH, Setser RM, Thamilarasan M, et al. Abnormal papillary muscle morphol-
ogy is independently associated with increased left ventricular outflow tract
obstruction in hypertrophic cardiomyopathy. Heart. 2008;94:1295–1301.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e57
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
20. Rowin EJ, Maron BJ, Lesser JR, et al. Papillary muscle insertion directly into
the anterior mitral leaflet in hypertrophic cardiomyopathy, its identification
and cause of outflow obstruction by cardiac magnetic resonance imaging,
and its surgical management. Am J Cardiol. 2013;111:1677–1679.
21. Rubinshtein R, Glockner JF, Ommen SR, et al. Characteristics and clinical
significance of late gadolinium enhancement by contrast-enhanced mag-
netic resonance imaging in patients with hypertrophic cardiomyopathy. Circ
Heart Fail. 2010;3:51–58.
22. Todiere G, Aquaro GD, Piaggi P, et al. Progression of myocardial fibrosis
assessed with cardiac magnetic resonance in hypertrophic cardiomyopathy.
J Am Coll Cardiol. 2012;60:922–929.
23. Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/HFSA/
HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echo-
cardiography: a report of the American College of Cardiology Foundation
Appropriate Use Criteria Task Force, American Society of Echocardiogra-
phy, American Heart Association, American Society of Nuclear Cardiology,
Heart Failure Society of America, Heart Rhythm Society, Society for Cardio-
vascular Angiography and Interventions, Society of Critical Care Medicine,
Society of Cardiovascular Computed Tomography, and Society for Cardio-
vascular Magnetic Resonance. J Am Coll Cardiol. 2011;57:1126–1166.
6.4. Cardiac CT
1. Nagueh SF, Bierig SM, Budoff MJ, et al. American Society of Echocar-
diography clinical recommendations for multimodality cardiovascular imag-
ing of patients with hypertrophic cardiomyopathy. J Am Soc Echocardiogr.
2011;24:473–498.
2. Langer C, Lutz M, Eden M, et al. Hypertrophic cardiomyopathy in cardiac CT:
a validation study on the detection of intramyocardial fibrosis in consecutive
patients. Int J Cardiovasc Imaging. 2014;30:659–667.
3. Zhao L, Ma X, Feuchtner GM, et al. Quantification of myocardial delayed
enhancement and wall thickness in hypertrophic cardiomyopathy: multide-
tector computed tomography versus magnetic resonance imaging. Eur J
Radiol. 2014;83:1778–1785.
6.5. Heart Rhythm Assessment
1. Maron BJ. The electrocardiogram as a diagnostic tool for hypertrophic car-
diomyopathy: revisited. Ann Noninvasive Electrocardiol. 2001;6:277–279.
2. Panza JA, Maron BJ. Relation of electrocardiographic abnormalities to
evolving left ventricular hypertrophy in hypertrophic cardiomyopathy during
childhood. Am J Cardiol. 1989;63:1258–1265.
3. Zorzi A, Calore C, Vio R, et al. Accuracy of the ECG for differential diagnosis
between hypertrophic cardiomyopathy and athlete’s heart: comparison be-
tween the European Society of Cardiology (2010) and International (2017)
criteria. Br J Sports Med. 2018;52:667–673.
4. Maron BJ, Savage DD, Wolfson JK, et al. Prognostic significance of 24 hour
ambulatory electrocardiographic monitoring in patients with hypertrophic
cardiomyopathy: a prospective study. Am J Cardiol. 1981;48:252–257.
5. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained ventricular tachy-
cardia in hypertrophic cardiomyopathy: an independent marker of sudden
death risk in young patients. J Am Coll Cardiol. 2003;42:873–879.
6. Adabag AS, Casey SA, Kuskowski MA, et al. Spectrum and prognostic sig-
nificance of arrhythmias on ambulatory Holter electrocardiogram in hyper-
trophic cardiomyopathy. J Am Coll Cardiol. 2005;45:697–704.
7. Wilke I, Witzel K, Münch J, et al. High incidence of de novo and subclinical
atrial fibrillation in patients with hypertrophic cardiomyopathy and cardiac
rhythm management device. J Cardiovasc Electrophysiol. 2016;27:779–784.
8. van Velzen HG, Theuns DAMJ, Yap S-C, et al. Incidence of device-detected
atrial fibrillation and long-term outcomes in patients with hypertrophic car-
diomyopathy. Am J Cardiol. 2017;119:100–105.
9. Rowin EJ, Hausvater A, Link MS, et al. Clinical profile and conse-
quences of atrial fibrillation in hypertrophic cardiomyopathy. Circulation.
2017;136:2420–2436.
10. Rowin EJ, Orfanos A, Estes NAM, et al. Occurrence and natural history of
clinically silent episodes of atrial fibrillation in hypertrophic cardiomyopathy.
Am J Cardiol. 2017;119:1862–1865.
11. Siontis KC, Geske JB, Ong K, et al. Atrial fibrillation in hypertrophic cardio-
myopathy: prevalence, clinical correlations, and mortality in a large high-risk
population. J Am Heart Assoc. 2014;3:e001002.
12. Carrick RT, Maron MS, Adler A, et al. Development and validation of a clini-
cal predictive model for identifying hypertrophic cardiomyopathy patients at
risk for atrial fibrillation: the HCM-AF Score. Circ Arrhythm Electrophysiol.
2021;14:e009796.
13. Finocchiaro G, Sheikh N, Biagini E, et al. The electrocardiogram in the diag-
nosis and management of patients with hypertrophic cardiomyopathy. Heart
Rhythm. 2020;17:142–151.
14. Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and disqualification rec-
ommendations for competitive athletes with cardiovascular abnormalities:
Task Force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular
cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific
statement from the American Heart Association and American College of
Cardiology. Circulation. 2015;132:e273–e280.
15. Wang W, Lian Z, Rowin EJ, et al. Prognostic implications of nonsustained
ventricular tachycardia in high-risk patients with hypertrophic cardiomyopa-
thy. Circ Arrhythm Electrophysiol. 2017;10:e004604.
16. Weissler-Snir A, Chan RH, Adler A, et al. Usefulness of 14-day Holter for
detection of nonsustained ventricular tachycardia in patients with hypertro-
phic cardiomyopathy. Am J Cardiol. 2016;118:1258–1263.
6.6. Angiography and Invasive Hemodynamic Assessment
1. Geske JB, Sorajja P, Nishimura RA, et al. Evaluation of left ventricular fill-
ing pressures by Doppler echocardiography in patients with hypertrophic
cardiomyopathy: correlation with direct left atrial pressure measurement at
cardiac catheterization. Circulation. 2007;116:2702–2708.
2. Geske JB, Sorajja P, Ommen SR, et al. Variability of left ventricular outflow
tract gradient during cardiac catheterization in patients with hypertrophic
cardiomyopathy. J Am Coll Cardiol Intv. 2011;4:704–709.
3. Prasad M, Geske JB, Sorajja P, et al. Hemodynamic changes in systolic and
diastolic function during isoproterenol challenge predicts symptomatic re-
sponse to myectomy in hypertrophic cardiomyopathy with labile obstruction.
Catheter Cardiovasc Interv. 2016;88:962–970.
4. Elesber A, Nishimura RA, Rihal CS, et al. Utility of isoproterenol to provoke
outflow tract gradients in patients with hypertrophic cardiomyopathy. Am J
Cardiol. 2008;101:516–520.
5. Sorajja P, Ommen SR, Nishimura RA, et al. Adverse prognosis of patients
with hypertrophic cardiomyopathy who have epicardial coronary artery dis-
ease. Circulation. 2003;108:2342–2348.
6. Thalji NM, Suri RM, Daly RC, et al. Assessment of coronary artery disease
risk in 5463 patients undergoing cardiac surgery: when is preoperative cor-
onary angiography necessary? J Thorac Cardiovasc Surg. 2013;146:1055–
1063.
6.7. Exercise Stress Testing
1. Joshi S, Patel UK, Yao S-S, et al. Standing and exercise Doppler echocar-
diography in obstructive hypertrophic cardiomyopathy: the range of gradi-
ents with upright activity. J Am Soc Echocardiogr. 2011;24:75–82.
2. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is
predominantly a disease of left ventricular outflow tract obstruction. Circula-
tion. 2006;114:2232–2239.
3. Ayoub C, Geske JB, Larsen CM, et al. Comparison of Valsalva maneuver,
amyl nitrite, and exercise echocardiography to demonstrate latent left ven-
tricular outflow obstruction in hypertrophic cardiomyopathy. Am J Cardiol.
2017;120:2265–2271.
4. Jensen MK, Havndrup O, Pecini R, et al. Comparison of Valsalva manoeu-
vre and exercise in echocardiographic evaluation of left ventricular out-
flow tract obstruction in hypertrophic cardiomyopathy. Eur J Echocardiogr.
2010;11:763–769.
5. Reant P, Dufour M, Peyrou J, et al. Upright treadmill vs. semi-supine bi-
cycle exercise echocardiography to provoke obstruction in symptomatic
hypertrophic cardiomyopathy: a pilot study. Eur Heart J Cardiovasc Imaging.
2018;19:31–38.
6. Shah JS, Esteban MTT, Thaman R, et al. Prevalence of exercise-
induced left ventricular outflow tract obstruction in symptomatic
patients with non-obstructive hypertrophic cardiomyopathy. Heart.
2008;94:1288–1294.
7. Coats CJ, Rantell K, Bartnik A, et al. Cardiopulmonary exercise testing and
prognosis in hypertrophic cardiomyopathy. Circ Heart Fail. 2015;8:1022–
1031.
8. Magrì D, Re F, Limongelli G, et al. Heart failure progression in hypertrophic
cardiomyopathy-possible insights from cardiopulmonary exercise testing.
Circ J. 2016;80:2204–2211.
9. Bayonas-Ruiz A, Muñoz-Franco FM, Ferrer V, et al. Cardiopulmonary exer-
cise test in patients with hypertrophic cardiomyopathy: a systematic review
and meta-analysis. J Clin Med. 2021;10:2312.
10. Conway J, Min S, Villa C, et al. The prevalence and association of ex-
ercise test abnormalities with sudden cardiac death and transplant-
free survival in childhood hypertrophic cardiomyopathy. Circulation.
2023;147:718–727.
11. Ciampi Q, Olivotto I, Peteiro J, et al. Prognostic Value of Reduced Heart
Rate Reserve during Exercise in hypertrophic cardiomyopathy. J Clin Med.
2021;10:1347.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e58
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
12. Rodrigues T, Raposo SC, Brito D, et al. Prognostic relevance of exercise
testing in hypertrophic cardiomyopathy. A systematic review. Int J Cardiol.
2021;339:83–92.
13. Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract
obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J
Med. 2003;348:295–303.
14. Marwick TH, Nakatani S, Haluska B, et al. Provocation of latent left ven-
tricular outflow tract gradients with amyl nitrite and exercise in hypertrophic
cardiomyopathy. Am J Cardiol. 1995;75:805–809.
15. Cui H, Schaff HV, Olson TP, et al. Cardiopulmonary exercise test in patients
with obstructive hypertrophic cardiomyopathy. J Thorac Cardiovasc Surg.
2022:S0022-5223(22)00619-5.
16. Smith JR, Layrisse V, Medina-Inojosa JR, et al. Predictors of exercise capac-
ity following septal myectomy in patients with hypertrophic cardiomyopathy.
Eur J Prev Cardiol. 2020;27:1066–1073.
17. Woo A, Williams WG, Choi R, et al. Clinical and echocardiographic determi-
nants of long-term survival after surgical myectomy in obstructive hypertro-
phic cardiomyopathy. Circulation. 2005;111:2033–2041.
18. Feiner E, Arabadjian M, Winson G, et al. Post-prandial upright exercise
echocardiography in hypertrophic cardiomyopathy. J Am Coll Cardiol.
2013;61:2487–2488.
6.8. Genetics and Family Screening
1. Ahmad F, McNally EM, Ackerman MJ, et al. Establishment of specialized
clinical cardiovascular genetics programs: recognizing the need and meet-
ing standards: a scientific statement from the American Heart Association.
Circ Genom Precis Med. 2019;12:e000054.
2. Charron P, Arad M, Arbustini E, et al. Genetic counselling and testing in
cardiomyopathies: a position statement of the European Society of Cardiol-
ogy Working Group on Myocardial and Pericardial Diseases. Eur Heart J.
2010;31:2715–2726.
3. Maron BJ, Maron MS, Semsarian C. Genetics of hypertrophic cardiomyopa-
thy after 20 years: clinical perspectives. J Am Coll Cardiol. 2012;60:705–
715.
4. Ingles J, Sarina T, Yeates L, et al. Clinical predictors of genetic testing out-
comes in hypertrophic cardiomyopathy. Genet Med. 2013;15:972–977.
5. van Velzen HG, Schinkel AFL, Baart SJ, et al. Outcomes of contemporary
family screening in hypertrophic cardiomyopathy. Circ Genom Precis Med.
2018;11:e001896.
6. Ranthe MF, Carstensen L, Oyen N, et al. Risk of cardiomyopathy in younger
persons with a family history of death from cardiomyopathy: a nationwide
family study in a cohort of 3.9 million persons. Circulation. 2015;132:1013–
1019.
7. Lafreniere-Roula M, Bolkier Y, Zahavich L, et al. Family screening for hyper-
trophic cardiomyopathy: is it time to change practice guidelines? Eur Heart
J. 2019;40:3672–3681.
8. Alfares AA, Kelly MA, McDermott G, et al. Results of clinical genetic testing
of 2 912 probands with hypertrophic cardiomyopathy: expanded panels of-
fer limited additional sensitivity. Genet Med. 2015;17:880–888.
9. Bagnall RD, Ingles J, Dinger ME, et al. Whole genome sequencing improves
outcomes of genetic testing in patients with hypertrophic cardiomyopathy. J
Am Coll Cardiol. 2018;72:419–429.
10. Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of disease
in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Car-
diomyopathy Registry (SHaRE). Circulation. 2018;138:1387–1398.
11. Ingles J, Goldstein J, Thaxton C, et al. Evaluating the clinical validity of hyper-
trophic cardiomyopathy genes. Circ Genom Precis Med. 2019;12:e002460.
12. Ingles J, Burns C, Funke B. Pathogenicity of hypertrophic cardiomyopathy
variants: a path forward together. Circ Cardiovasc Genet. 2017;10:e001916.
13. Maron BJ, Roberts WC, Arad M, et al. Clinical outcome and phenotypic ex-
pression in LAMP2 cardiomyopathy. JAMA. 2009;301:1253–1259.
14. Desai MY, Ommen SR, McKenna WJ, et al. Imaging phenotype ver-
sus genotype in hypertrophic cardiomyopathy. Circ Cardiovasc Imaging.
2011;4:156–168.
15. Ingles J, Yeates L, Semsarian C. The emerging role of the cardiac genetic
counselor. Heart Rhythm. 2011;8:1958–1962.
16. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the inter-
pretation of sequence variants: a joint consensus recommendation of the
American College of Medical Genetics and Genomics and the Association
for Molecular Pathology. Genet Med. 2015;17:405–424.
17. Ouellette AC, Mathew J, Manickaraj AK, et al. Clinical genetic testing in
pediatric cardiomyopathy: is bigger better? Clin Genet. 2018;93:33–40.
18. Jensen MK, Havndrup O, Christiansen M, et al. Penetrance of hypertro-
phic cardiomyopathy in children and adolescents: a 12-year follow-up
study of clinical screening and predictive genetic testing. Circulation.
2013;127:48–54.
19. Morita H, Rehm HL, Menesses A, et al. Shared genetic causes of cardiac
hypertrophy in children and adults. N Engl J Med. 2008;358:1899–1908.
20. Christiaans I, Birnie E, Bonsel GJ, et al. Manifest disease, risk factors for
sudden cardiac death, and cardiac events in a large nationwide cohort of pre-
dictively tested hypertrophic cardiomyopathy mutation carriers: determining
the best cardiological screening strategy. Eur Heart J. 2011;32:1161–1170.
21. Semsarian C, Ingles J, Wilde AAM. Sudden cardiac death in the young: the
molecular autopsy and a practical approach to surviving relatives. Eur Heart
J. 2015;36:1290–1296.
22. Bagnall RD, Weintraub RG, Ingles J, et al. A prospective study of sud-
den cardiac death among children and young adults. N Engl J Med.
2016;374:2441–2452.
23. Das KJ, Ingles J, Bagnall RD, et al. Determining pathogenicity of genetic
variants in hypertrophic cardiomyopathy: importance of periodic reassess-
ment. Genet Med. 2014;16:286–293.
24. Manrai AK, Funke BH, Rehm HL, et al. Genetic misdiagnoses and the po-
tential for health disparities. N Engl J Med. 2016;375:655–665.
25. Mathew J, Zahavich L, Lafreniere-Roula M, et al. Utility of genetics for
risk stratification in pediatric hypertrophic cardiomyopathy. Clin Genet.
2018;93:310–319.
26. Ingles J, Burns C, Bagnall RD, et al. Nonfamilial hypertrophic cardiomyop-
athy: prevalence, natural history, and clinical implications. Circ Cardiovasc
Genet. 2017;10:e001620.
27. Ingles J, Doolan A, Chiu C, et al. Compound and double mutations in pa-
tients with hypertrophic cardiomyopathy: implications for genetic testing
and counselling. J Med Genet. 2005;42:e59.
28. Norrish G, Jager J, Field E, et al. Yield of clinical screening for hypertro-
phic cardiomyopathy in child first-degree relatives: evidence for a change in
paradigm. Circulation. 2019;140:184–192.
29. Aronson SJ, Clark E H, Varugheese M, et al. Communicating new knowledge
on previously reported genetic variants. Genet Med. 2012;14:713–719.
30. Semsarian C, Ingles J, Maron MS, et al. New perspectives on the prevalence
of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65:1249–1254.
31. David KL, Best RG, Brenman LM, et al. Patient re-contact after revision
of genomic test results: points to consider—a statement of the Ameri-
can College of Medical Genetics and Genomics (ACMG). Genet Med.
2019;21:769–771.
32. Deignan JL, Chung WK, Kearney HM, et al. Points to consider in the re-
evaluation and reanalysis of genomic test results: a statement of the
American College of Medical Genetics and Genomics (ACMG). Genet Med.
2019;21:1267–1270.
33. Caleshu C, Kasparian NA, Edwards KS, et al. Interdisciplinary psychosocial
care for families with inherited cardiovascular diseases. Trends Cardiovasc
Med. 2016;26:647–653.
34. Elliott P, Baker R, Pasquale F, et al. Prevalence of Anderson-Fabry disease in
patients with hypertrophic cardiomyopathy: the European Anderson-Fabry
Disease survey. Heart. 2011;97:1957–1960.
35. Rueda M, Wagner JL, Phillips TC, et al. Molecular autopsy for sudden death
in the young: is data aggregation the key? Front Cardiovasc Med. 2017;4:72.
36. Torkamani A, Muse ED, Spencer EG, et al. Molecular autopsy for sudden
unexpected death. JAMA. 2016;316:1492–1494.
37. Garcia J, Tahiliani J, Johnson NM, et al. Clinical genetic testing for the car-
diomyopathies and arrhythmias: a systematic framework for establishing
clinical validity and addressing genotypic and phenotypic heterogeneity.
Front Cardiovasc Med. 2016;3:20.
38. Miron A, Lafreniere-Roula M, Steve Fan CP, et al. A validated model for sud-
den cardiac death risk prediction in pediatric hypertrophic cardiomyopathy.
Circulation. 2020;142:217–229.
6.9. Individuals Who Are Genotype-Positive,
Phenotype-Negative
1. Jensen MK, Havndrup O, Christiansen M, et al. Penetrance of hypertrophic
cardiomyopathy in children and adolescents. Circulation. 2013;127:48–54.
2. Lafreniere-Roula M, Bolkier Y, Zahavich L, et al. Family screening for hyper-
trophic cardiomyopathy: is it time to change practice guidelines? Eur Heart
J. 2019;40:3672–3681.
3. Maurizi N, Michels M, Rowin EJ, et al. Clinical course and significance of
hypertrophic cardiomyopathy without left ventricular hypertrophy. Circulation.
2019;139:830–833.
4. Norrish G, Jager J, Field E, et al. Yield of clinical screening for hypertro-
phic cardiomyopathy in child first-degree relatives: evidence for a change in
paradigm. Circulation. 2019;140:184–192.
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AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e59
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
5. Vermeer AMC, Clur S-AB, Blom NA, et al. Penetrance of hypertrophic car-
diomyopathy in children who are mutation positive. J Pediatr. 2017;188:91–
95.
6. Christiaans I, Birnie E, Bonsel GJ, et al. Manifest disease, risk factors for
sudden cardiac death, and cardiac events in a large nationwide cohort of
predictively tested hypertrophic cardiomyopathy mutation carriers: determin-
ing the best cardiological screening strategy. Eur Heart J. 2011;32:1161–
1170.
7. Lampert R, Ackerman MJ, Marino BS, et al. Vigorous exercise in patients
with hypertrophic cardiomyopathy. JAMA Cardiol. 2023;8:595–605.
8. Gray B, Ingles J, Semsarian C. Natural history of genotype positive-
phenotype negative patients with hypertrophic cardiomyopathy. Int J Cardiol.
2011;152:258–259.
9. Captur G, Lopes LR, Mohun TJ, et al. Prediction of sarcomere muta-
tions in subclinical hypertrophic cardiomyopathy. Circ Cardiovasc Imaging.
2014;7:863–871.
10. Ho CY, Day SM, Colan SD, et al. The burden of early phenotypes and the
influence of wall thickness in hypertrophic cardiomyopathy mutation carri-
ers: findings from the HCMNet study. JAMA Cardiol. 2017;2:419–428.
11. Vigneault DM, Yang E, Jensen PJ, et al. Left ventricular strain is abnormal
in preclinical and overt hypertrophic cardiomyopathy: cardiac MR feature
tracking. Radiology. 2019;290:640–648.
12. Williams LK, Misurka J, Ho CY, et al. Multilayer myocardial mechanics in
genotype-positive left ventricular hypertrophy-negative patients with hyper-
trophic cardiomyopathy. Am J Cardiol. 2018;122:1754–1760.
13. Ho CY, Lakdawala N K, Cirino AL, et al. Diltiazem treatment for pre-
clinical hypertrophic cardiomyopathy sarcomere mutation carriers: a pi-
lot randomized trial to modify disease expression. J Am Coll Cardiol HF.
2015;3:180–188.
7.1.1. SCD Risk Assessment in Adults With HCM
1. Maron MS, Rowin EJ, Wessler BS, et al. Enhanced American College of
Cardiology/American Heart Association strategy for prevention of sudden
cardiac death in high-risk patients with hypertrophic cardiomyopathy. JAMA
Cardiol. 2019;4:644–657.
2. O’Mahony C, Jichi F, Ommen SR, et al. International External Validation
Study of the 2014 European Society of Cardiology Guidelines on Sudden
Cardiac Death Prevention in Hypertrophic Cardiomyopathy (EVIDENCE-
HCM). Circulation. 2018;137:1015–1023.
3. Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest or sus-
tained ventricular tachycardia in patients with hypertrophic cardiomyopathy.
J Am Coll Cardiol. 1999;33:1596–1601.
4. Spirito P, Autore C, Rapezzi C, et al. Syncope and risk of sudden death in
hypertrophic cardiomyopathy. Circulation. 2009;119:1703–1710.
5. Bos JM, Maron BJ, Ackerman MJ, et al. Role of family history of sud-
den death in risk stratification and prevention of sudden death with im-
plantable defibrillators in hypertrophic cardiomyopathy. Am J Cardiol.
2010;106:1481–1486.
6. Dimitrow PP, Chojnowska L, Rudzinski T, et al. Sudden death in hypertrophic
cardiomyopathy: old risk factors re-assessed in a new model of maximalized
follow-up. Eur Heart J. 2010;31:3084–3093.
7. Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertro-
phy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med.
2000;342:1778–1785.
8. Autore C, Bernabò P, Barillà CS, et al. The prognostic importance of left ven-
tricular outflow obstruction in hypertrophic cardiomyopathy varies in relation
to the severity of symptoms. J Am Coll Cardiol. 2005;45:1076–1080.
9. Elliott PM, Gimeno Blanes JR, Mahon NG, et al. Relation between severity
of left-ventricular hypertrophy and prognosis in patients with hypertrophic
cardiomyopathy. Lancet. 2001;357:420–424.
10. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and signifi-
cance of left ventricular remodeling in the end-stage phase of hypertrophic
cardiomyopathy. Circulation. 2006;114:216–225.
11. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic cardiomyopathy with left
ventricular apical aneurysm: implications for risk stratification and manage-
ment. J Am Coll Cardiol. 2017;69:761–773.
12. Ichida M, Nishimura Y, Kario K. Clinical significance of left ventricular apical
aneurysms in hypertrophic cardiomyopathy patients: the role of diagnostic
electrocardiography. J Cardiol. 2014;64:265–272.
13. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained ventricular tachy-
cardia in hypertrophic cardiomyopathy: an independent marker of sudden
death risk in young patients. J Am Coll Cardiol. 2003;42:873–879.
14. Wang W, Lian Z, Rowin EJ, et al. Prognostic implications of nonsustained
ventricular tachycardia in high-risk patients with hypertrophic cardiomyopa-
thy. Circ Arrhythm Electrophysiol. 2017;10:e004604.
15. Corona-Villalobos CP, Sorensen LL, Pozios I, et al. Left ventricular wall thick-
ness in patients with hypertrophic cardiomyopathy: a comparison between
cardiac magnetic resonance imaging and echocardiography. Int J Cardio-
vasc Imaging. 2016;32:945–954.
16. Bois JP, Geske JB, Foley TA, et al. Comparison of maximal wall thickness in
hypertrophic cardiomyopathy differs between magnetic resonance imaging
and transthoracic echocardiography. Am J Cardiol. 2017;119:643–650.
17. Maron MS, Lesser JR, Maron BJ. Management implications of massive left
ventricular hypertrophy in hypertrophic cardiomyopathy significantly under-
estimated by echocardiography but identified by cardiovascular magnetic
resonance. Am J Cardiol. 2010;105:1842–1843.
18. Weng Z, Yao J, Chan RH, et al. Prognostic value of LGE-CMR in HCM: a
meta-analysis. J Am Coll Cardiol Img. 2016;9:1392–1402.
19. Chan RH, Maron BJ, Olivotto I, et al. Prognostic value of quantitative
contrast-enhanced cardiovascular magnetic resonance for the evaluation of
sudden death risk in patients with hypertrophic cardiomyopathy. Circulation.
2014;130:484–495.
20. Mentias A, Raeisi-Giglou P, Smedira NG, et al. Late gadolinium enhance-
ment in patients with hypertrophic cardiomyopathy and preserved systolic
function. J Am Coll Cardiol. 2018;72:857–870.
21. Ismail TF, Jabbour A, Gulati A, et al. Role of late gadolinium enhancement
cardiovascular magnetic resonance in the risk stratification of hypertrophic
cardiomyopathy. Heart. 2014;100:1851–1858.
22. O’Mahony C, Jichi F, Pavlou M, et al. A novel clinical risk prediction model for
sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur
Heart J. 2014;35:2010–2020.
23. Binder J, Attenhofer Jost CH, Klarich KW, et al. Apical hypertrophic car-
diomyopathy: prevalence and correlates of apical outpouching. J Am Soc
Echocardiogr. 2011;24:775–781.
24. Rowin EJ, Maron BJ, Carrick RT, et al. Outcomes in patients with hyper-
trophic cardiomyopathy and left ventricular systolic dysfunction. J Am Coll
Cardiol. 2020;75:3033–3043.
25. Marstrand P, Han L, Day SM, et al. Hypertrophic Cardiomyopathy with Left
Ventricular Systolic Dysfunction: Insights from the SHaRe Registry. Circula-
tion. 2020;1371–1383.
26. Maron BJ, Spirito P, Shen W-K, et al. Implantable cardioverter-defibrillators
and prevention of sudden cardiac death in hypertrophic cardiomyopathy.
JAMA. 2007;298:405–412.
27. Vriesendorp PA, Schinkel AFL, Van Cleemput J, et al. Implantable
cardioverter-defibrillators in hypertrophic cardiomyopathy: patient out-
comes, rate of appropriate and inappropriate interventions, and complica-
tions. Am Heart J. 2013;166:496–502.
28. Wells S, Rowin EJ, Bhatt V, et al. Association between race and clinical
profile of patients referred for hypertrophic cardiomyopathy. Circulation.
2018;137:1973–1975.
29. Olivotto I, Maron MS, Adabag AS, et al. Gender-related differences in the
clinical presentation and outcome of hypertrophic cardiomyopathy. J Am
Coll Cardiol. 2005;46:480–487.
30. Elliott PM, Poloniecki J, Dickie S, et al. Sudden death in hypertrophic
cardiomyopathy: identification of high risk patients. J Am Coll Cardiol.
2000;36:2212–2218.
31. Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in adult-
hood associated with low cardiovascular mortality with contemporary man-
agement strategies. J Am Coll Cardiol. 2015;65:1915–1928.
32. Maron BJ, Rowin EJ, Casey SA, et al. Risk stratification and outcome of
patients with hypertrophic cardiomyopathy ≥60 years of age. Circulation.
2013;127:585–593.
33. Ostman-Smith I, Wettrell G, Keeton B, et al. Age- and gender-specific
mortality rates in childhood hypertrophic cardiomyopathy. Eur Heart J.
2008;29:1160–1167.
34. Maron BJ. Risk stratification and role of implantable defibrillators for pre-
vention of sudden death in patients with hypertrophic cardiomyopathy. Circ
J. 2010;74:2271–2282.
35. Miron A, Lafreniere-Roula M, Steve Fan CP, et al. A validated model for sud-
den cardiac death risk prediction in pediatric hypertrophic cardiomyopathy.
Circulation. 2020;142:217–229.
36. Norrish G, Ding T, Field E, et al. Development of a novel risk prediction
model for sudden cardiac death in childhood hypertrophic cardiomyopathy
(HCM Risk-Kids). JAMA Cardiol. 2019;4:918–927.
37. Romeo F, Cianfrocca C, Pelliccia F, et al. Long-term prognosis in children
with hypertrophic cardiomyopathy: an analysis of 37 patients aged less than
or equal to 14 years at diagnosis. Clin Cardiol. 1990;13:101–107.
38. Yetman AT, Hamilton RM, Benson LN, et al. Long-term outcome and prog-
nostic determinants in children with hypertrophic cardiomyopathy. J Am Coll
Cardiol. 1998;32:1943–1950.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e60
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
39. McMahon CJ, Nagueh SF, Pignatelli RH, et al. Characterization of
left ventricular diastolic function by tissue Doppler imaging and clini-
cal status in children with hypertrophic cardiomyopathy. Circulation.
2004;109:1756–1762.
40. Nugent AW, Daubeney PEF, Chondros P, et al. Clinical features and out-
comes of childhood hypertrophic cardiomyopathy: results from a national
population-based study. Circulation. 2005;112:1332–1338.
41. Ostman-Smith I, Wettrell G, Keeton B, et al. Echocardiographic and elec-
trocardiographic identification of those children with hypertrophic cardio-
myopathy who should be considered at high-risk of dying suddenly. Cardiol
Young. 2005;15:632–642.
42. Colan SD, Lipshultz SE, Lowe AM, et al. Epidemiology and cause-specific
outcome of hypertrophic cardiomyopathy in children: findings from the Pe-
diatric Cardiomyopathy Registry. Circulation. 2007;115:773–781.
43. Kaski JP, Tomé Esteban MT, Lowe M, et al. Outcomes after implantable
cardioverter-defibrillator treatment in children with hypertrophic cardiomy-
opathy. Heart. 2007;93:372–374.
44. Decker JA, Rossano JW, Smith EO, et al. Risk factors and mode of death
in isolated hypertrophic cardiomyopathy in children. J Am Coll Cardiol.
2009;54:250–254.
45. Maskatia SA, Decker JA, Spinner JA, et al. Restrictive physiology is asso-
ciated with poor outcomes in children with hypertrophic cardiomyopathy.
Pediatr Cardiol. 2012;33:141–149.
46. Moak JP, Leifer ES, Tripodi D, et al. Long-term follow-up of children and
adolescents diagnosed with hypertrophic cardiomyopathy: risk factors for
adverse arrhythmic events. Pediatr Cardiol. 2011;32:1096–1105.
47. Hickey EJ, McCrindle BW, Larsen S-H, et al. Hypertrophic cardiomyopathy
in childhood: disease natural history, impact of obstruction, and its influence
on survival. Ann Thorac Surg. 2012;93:840–848.
48. Chaowu Y, Shihua Z, Jian L, et al. Cardiovascular magnetic resonance
characteristics in children with hypertrophic cardiomyopathy. Circ Heart Fail.
2013;6:1013–1020.
49. Lipshultz SE, Orav EJ, Wilkinson JD, et al. Risk stratification at diagnosis
for children with hypertrophic cardiomyopathy: an analysis of data from the
Pediatric Cardiomyopathy Registry. Lancet. 2013;382:1889–1897.
50. Kamp AN, Von Bergen NH, Henrikson CA, et al. Implanted defibrillators in
young hypertrophic cardiomyopathy patients: a multicenter study. Pediatr
Cardiol. 2013;34:1620–1627.
51. Maron BJ, Spirito P, Ackerman MJ, et al. Prevention of sudden car-
diac death with implantable cardioverter-defibrillators in children and
adolescents with hypertrophic cardiomyopathy. J Am Coll Cardiol.
2013;61:1527–1535.
52. Smith BM, Dorfman AL, Yu S, et al. Clinical significance of late gadolinium
enhancement in patients <20 years of age with hypertrophic cardiomyopa-
thy. Am J Cardiol. 2014;113:1234–1239.
53. El-Saiedi SA, Seliem ZS, Esmail RI. Hypertrophic cardiomyopathy: prognos-
tic factors and survival analysis in 128 Egyptian patients. Cardiol Young.
2014;24:702–708.
54. Bharucha T, Lee KJ, Daubeney PEF, et al. Sudden death in childhood car-
diomyopathy: results from a long-term national population-based study. J
Am Coll Cardiol. 2015;65:2302–2310.
55. Windram JD, Benson LN, Dragelescu A, et al. Distribution of hypertrophy
and late gadolinium enhancement in children and adolescents with hyper-
trophic cardiomyopathy. Congenit Heart Dis. 2015;10:E258–E267.
56. Ziólkowska L, Turska-Kmiec A, Petryka J, et al. Predictors of long-term
outcome in children with hypertrophic cardiomyopathy. Pediatr Cardiol.
2016;37:448–458.
57. Mathew J, Zahavich L, Lafreniere-Roula M, et al. Utility of genetics for
risk stratification in pediatric hypertrophic cardiomyopathy. Clin Genet.
2018;93:310–319.
58. Maurizi N, Passantino S, Spaziani G, et al. Long-term outcomes of pediatric-
onset hypertrophic cardiomyopathy and age-specific risk factors for lethal
arrhythmic events. JAMA Cardiol. 2018;3:520–525.
59. Balaji S, DiLorenzo MP, Fish FA, et al. Risk factors for lethal arrhythmic
events in children and adolescents with hypertrophic cardiomyopathy and
an implantable defibrillator: an international multicenter study. Heart Rhythm.
2019;16:1462–1467.
60. Norrish G, Ding T, Field E, et al. A validation study of the European
Society of Cardiology guidelines for risk stratification of sudden car-
diac death in childhood hypertrophic cardiomyopathy. Europace.
2019;21:1559–1565.
61. Norrish G, Cantarutti N, Pissaridou E, et al. Risk factors for sudden cardiac
death in childhood hypertrophic cardiomyopathy: a systematic review and
meta-analysis. Eur J Prev Cardiol. 2017;24:1220–1230.
62. Norrish G, Qu C, Field E, et al. External validation of the HCM Risk-Kids
model for predicting sudden cardiac death in childhood hypertrophic cardio-
myopathy. Eur J Prev Cardiol. 2022;29:678–686.
63. Conway J, Min S, Villa C, et al. The prevalence and association of exercise
test abnormalities with sudden cardiac death and transplant-free survival in
childhood hypertrophic cardiomyopathy. Circulation. 2023;147:718–727.
7.1.2. SCD Risk Assessment in Children and Adolescents
With HCM
1. Miron A, Lafreniere-Roula M, Steve Fan CP, et al. A validated model for sud-
den cardiac death risk prediction in pediatric hypertrophic cardiomyopathy.
Circulation. 2020;142:217–229.
2. Norrish G, Ding T, Field E, et al. Development of a novel risk prediction
model for sudden cardiac death in childhood hypertrophic cardiomyopathy
(HCM Risk-Kids). JAMA Cardiol. 2019;4:918–927.
3. Maurizi N, Passantino S, Spaziani G, et al. Long-term outcomes of pediatric-
onset hypertrophic cardiomyopathy and age-specific risk factors for lethal
arrhythmic events. JAMA Cardiol. 2018;3:520–525.
4. Balaji S, DiLorenzo MP, Fish FA, et al. Risk factors for lethal arrhythmic
events in children and adolescents with hypertrophic cardiomyopathy and
an implantable defibrillator: an international multicenter study. Heart Rhythm.
2019;16:1462–1467.
5. Norrish G, Ding T, Field E, et al. A validation study of the European Society
of Cardiology guidelines for risk stratification of sudden cardiac death in
childhood hypertrophic cardiomyopathy. Europace. 2019;21:1559–1565.
6. Norrish G, Cantarutti N, Pissaridou E, et al. Risk factors for sudden cardiac
death in childhood hypertrophic cardiomyopathy: a systematic review and
meta-analysis. Eur J Prev Cardiol. 2017;24:1220–1230.
7. Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in
children, adolescents, and young adults associated with low cardiovas-
cular mortality with contemporary management strategies. Circulation.
2016;133:62–73.
8. Rowin EJ, Sridharan A, Madias C, et al. Prediction and prevention of sudden
death in young patients (<20 years) with hypertrophic cardiomyopathy. Am
J Cardiol. 2020;128:75–83.
9. Chaowu Y, Shihua Z, Jian L, et al. Cardiovascular magnetic resonance
characteristics in children with hypertrophic cardiomyopathy. Circ Heart Fail.
2013;6:1013–1020.
10. Smith BM, Dorfman AL, Yu S, et al. Clinical significance of late gadolinium
enhancement in patients <20 years of age with hypertrophic cardiomyopa-
thy. Am J Cardiol. 2014;113:1234–1239.
11. Windram JD, Benson LN, Dragelescu A, et al. Distribution of hypertrophy
and late gadolinium enhancement in children and adolescents with hyper-
trophic cardiomyopathy. Congenit Heart Dis. 2015;10:E258–E267.
12. Norrish G, Qu C, Field E, et al. External validation of the HCM Risk-Kids
model for predicting sudden cardiac death in childhood hypertrophic cardio-
myopathy. Eur J Prev Cardiol. 2022;29:678–686.
13. Bharucha T, Lee KJ, Daubeney PEF, et al. Sudden death in childhood car-
diomyopathy: results from a long-term national population-based study. J
Am Coll Cardiol. 2015;65:2302–2310.
14. Mathew J, Zahavich L, Lafreniere-Roula M, et al. Utility of genetics for
risk stratification in pediatric hypertrophic cardiomyopathy. Clin Genet.
2018;93:310–319.
15. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic cardiomyopathy with left
ventricular apical aneurysm: implications for risk stratification and manage-
ment. J Am Coll Cardiol. 2017;69:761–773.
16. Ichida M, Nishimura Y, Kario K. Clinical significance of left ventricular apical
aneurysms in hypertrophic cardiomyopathy patients: the role of diagnostic
electrocardiography. J Cardiol. 2014;64:265–272.
17. Corona-Villalobos CP, Sorensen LL, Pozios I, et al. Left ventricular wall thick-
ness in patients with hypertrophic cardiomyopathy: a comparison between
cardiac magnetic resonance imaging and echocardiography. Int J Cardio-
vasc Imaging. 2016;32:945–954.
18. Bois JP, Geske JB, Foley TA, et al. Comparison of maximal wall thickness in
hypertrophic cardiomyopathy differs between magnetic resonance imaging
and transthoracic echocardiography. Am J Cardiol. 2017;119:643–650.
19. Maron MS, Lesser JR, Maron BJ. Management implications of massive left
ventricular hypertrophy in hypertrophic cardiomyopathy significantly under-
estimated by echocardiography but identified by cardiovascular magnetic
resonance. Am J Cardiol. 2010;105:1842–1843.
20. Weng Z, Yao J, Chan RH, et al. Prognostic value of LGE-CMR in HCM: a
meta-analysis. J Am Coll Cardiol Img. 2016;9:1392–1402.
21. Chan RH, Maron BJ, Olivotto I, et al. Prognostic value of quantitative
contrast-enhanced cardiovascular magnetic resonance for the evaluation of
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e61
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
sudden death risk in patients with hypertrophic cardiomyopathy. Circulation.
2014;130:484–495.
22. Mentias A, Raeisi-Giglou P, Smedira NG, et al. Late gadolinium enhance-
ment in patients with hypertrophic cardiomyopathy and preserved systolic
function. J Am Coll Cardiol. 2018;72:857–870.
23. Maron MS, Rowin EJ, Wessler BS, et al. Enhanced American College of
Cardiology/American Heart Association strategy for prevention of sudden
cardiac death in high-risk patients with hypertrophic cardiomyopathy. JAMA
Cardiol. 2019;4:644–657.
24. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and signifi-
cance of left ventricular remodeling in the end-stage phase of hypertrophic
cardiomyopathy. Circulation. 2006;114:216–225.
25. Ismail TF, Jabbour A, Gulati A, et al. Role of late gadolinium enhancement
cardiovascular magnetic resonance in the risk stratification of hypertrophic
cardiomyopathy. Heart. 2014;100:1851–1858.
26. Rowin EJ, Maron BJ, Carrick RT, et al. Outcomes in patients with hyper-
trophic cardiomyopathy and left ventricular systolic dysfunction. J Am Coll
Cardiol. 2020;75:3033–3043.
27. Marstrand P, Han L, Day SM, et al. Hypertrophic cardiomyopathy with left
ventricular systolic dysfunction: insights from the SHaRe Registry. Circula-
tion. 2020;141:1371–1383.
28. Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in adult-
hood associated with low cardiovascular mortality with contemporary man-
agement strategies. J Am Coll Cardiol. 2015;65:1915–1928.
29. Conway J, Min S, Villa C, et al. The prevalence and association of exercise
test abnormalities with sudden cardiac death and transplant-free survival in
childhood hypertrophic cardiomyopathy. Circulation. 2023;147:718–727.
30. Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest or sus-
tained ventricular tachycardia in patients with hypertrophic cardiomyopathy.
J Am Coll Cardiol. 1999;33:1596–1601.
31. Bos JM, Maron BJ, Ackerman MJ, et al. Role of family history of sud-
den death in risk stratification and prevention of sudden death with im-
plantable defibrillators in hypertrophic cardiomyopathy. Am J Cardiol.
2010;106:1481–1486.
32. Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertro-
phy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med.
2000;342:1778–1785.
33. Elliott PM, Gimeno Blanes JR, Mahon NG, et al. Relation between severity
of left-ventricular hypertrophy and prognosis in patients with hypertrophic
cardiomyopathy. Lancet. 2001;357:420–424.
34. Spirito P, Autore C, Rapezzi C, et al. Syncope and risk of sudden death in
hypertrophic cardiomyopathy. Circulation. 2009;119:1703–1710.
35. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained ventricular tachy-
cardia in hypertrophic cardiomyopathy: an independent marker of sudden
death risk in young patients. J Am Coll Cardiol. 2003;42:873–879.
36. Wang W, Lian Z, Rowin EJ, et al. Prognostic implications of nonsustained
ventricular tachycardia in high-risk patients with hypertrophic cardiomyopa-
thy. Circ Arrhythm Electrophysiol. 2017;10:e004604.
37. Ostman-Smith I, Wettrell G, Keeton B, et al. Echocardiographic and elec-
trocardiographic identification of those children with hypertrophic cardio-
myopathy who should be considered at high-risk of dying suddenly. Cardiol
Young. 2005;15:632–642.
7.2. Patient Selection for ICD Placement
1. Maron BJ, Nishimura RA, Maron MS. Shared decision-making in HCM. Nat
Rev Cardiol. 2017;14:125–126.
2. Maron MS, Rowin EJ, Wessler BS, et al. Enhanced American College of
Cardiology/American Heart Association strategy for prevention of sudden
cardiac death in high-risk patients with hypertrophic cardiomyopathy. JAMA
Cardiol. 2019;4:644–657.
3. O’Mahony C, Tome-Esteban M, Lambiase PD, et al. A validation study of the
2003 American College of Cardiology/European Society of Cardiology and
2011 American College of Cardiology Foundation/American Heart Asso-
ciation risk stratification and treatment algorithms for sudden cardiac death
in patients with hypertrophic cardiomyopathy. Heart. 2013;99:534–541.
4. Maron BJ, Spirito P, Shen W-K, et al. Implantable cardioverter-defibrillators
and prevention of sudden cardiac death in hypertrophic cardiomyopathy.
JAMA. 2007;298:405–412.
5. Vriesendorp PA, Schinkel AFL, Van Cleemput J, et al. Implantable
cardioverter-defibrillators in hypertrophic cardiomyopathy: patient out-
comes, rate of appropriate and inappropriate interventions, and complica-
tions. Am Heart J. 2013;166:496–502.
6. Elliott PM, Sharma S, Varnava A, et al. Survival after cardiac arrest or sus-
tained ventricular tachycardia in patients with hypertrophic cardiomyopathy.
J Am Coll Cardiol. 1999;33:1596–1601.
7. Spirito P, Autore C, Rapezzi C, et al. Syncope and risk of sudden death in
hypertrophic cardiomyopathy. Circulation. 2009;119:1703–1710.
8. Bos JM, Maron BJ, Ackerman MJ, et al. Role of family history of sud-
den death in risk stratification and prevention of sudden death with im-
plantable defibrillators in hypertrophic cardiomyopathy. Am J Cardiol.
2010;106:1481–1486.
9. Dimitrow PP, Chojnowska L, Rudzinski T, et al. Sudden death in hypertrophic
cardiomyopathy: old risk factors re-assessed in a new model of maximalized
follow-up. Eur Heart J. 2010;31:3084–3093.
10. Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertro-
phy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med.
2000;342:1778–1785.
11. Autore C, Bernabo P, Barillà CS, et al. The prognostic importance of left ven-
tricular outflow obstruction in hypertrophic cardiomyopathy varies in relation
to the severity of symptoms. J Am Coll Cardiol. 2005;45:1076–1080.
12. Elliott PM, Gimeno Blanes JR, Mahon NG, et al. Relation between severity
of left-ventricular hypertrophy and prognosis in patients with hypertrophic
cardiomyopathy. Lancet. 2001;357:420–424.
13. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and signifi-
cance of left ventricular remodeling in the end-stage phase of hypertrophic
cardiomyopathy. Circulation. 2006;114:216–225.
14. Rowin EJ, Maron BJ, Haas TS, et al. Hypertrophic cardiomyopathy with left
ventricular apical aneurysm: implications for risk stratification and manage-
ment. J Am Coll Cardiol. 2017;69:761–773.
15. Ichida M, Nishimura Y, Kario K. Clinical significance of left ventricular apical
aneurysms in hypertrophic cardiomyopathy patients: the role of diagnostic
electrocardiography. J Cardiol. 2014;64:265–272.
16. Monserrat L, Elliott PM, Gimeno JR, et al. Non-sustained ventricular tachy-
cardia in hypertrophic cardiomyopathy: an independent marker of sudden
death risk in young patients. J Am Coll Cardiol. 2003;42:873–879.
17. Wang W, Lian Z, Rowin EJ, et al. Prognostic implications of nonsustained
ventricular tachycardia in high-risk patients with hypertrophic cardiomyopa-
thy. Circ Arrhythm Electrophysiol. 2017;10:e004604.
18. Ismail TF, Jabbour A, Gulati A, et al. Role of late gadolinium enhancement
cardiovascular magnetic resonance in the risk stratification of hypertrophic
cardiomyopathy. Heart. 2014;100:1851–1858.
19. O’Mahony C, Jichi F, Pavlou M, et al. A novel clinical risk prediction model for
sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur
Heart J. 2014;35:2010–2020.
20. Rowin EJ, Maron BJ, Carrick RT, et al. Outcomes in patients with hyper-
trophic cardiomyopathy and left ventricular systolic dysfunction. J Am Coll
Cardiol. 2020;75:3033–3043.
21. Marstrand P, Han L, Day SM, et al. Hypertrophic cardiomyopathy with left
ventricular systolic dysfunction: insights from the SHaRe Registry. Circula-
tion. 2020;1371–1383.
22. Maron BJ, Spirito P, Ackerman MJ, et al. Prevention of sudden cardiac death
with implantable cardioverter-defibrillators in children and adolescents with
hypertrophic cardiomyopathy. J Am Coll Cardiol. 2013;61:1527–1535.
23. Norrish G, Cantarutti N, Pissaridou E, et al. Risk factors for sudden cardiac
death in childhood hypertrophic cardiomyopathy: a systematic review and
meta-analysis. Eur J Prev Cardiol. 2017;24:1220–1230.
24. Moak JP, Leifer ES, Tripodi D, et al. Long-term follow-up of children and
adolescents diagnosed with hypertrophic cardiomyopathy: risk factors for
adverse arrhythmic events. Pediatr Cardiol. 2011;32:1096–1105.
25. Yetman AT, Hamilton RM, Benson LN, et al. Long-term outcome and prog-
nostic determinants in children with hypertrophic cardiomyopathy. J Am Coll
Cardiol. 1998;32:1943–1950.
26. Bharucha T, Lee KJ, Daubeney PEF, et al. Sudden death in childhood car-
diomyopathy: results from a long-term national population-based study. J
Am Coll Cardiol. 2015;65:2302–2310.
27. Kamp AN, Von Bergen NH, Henrikson CA, et al. Implanted defibrillators in
young hypertrophic cardiomyopathy patients: a multicenter study. Pediatr
Cardiol. 2013;34:1620–1627.
28. Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in
children, adolescents, and young adults associated with low cardiovas-
cular mortality with contemporary management strategies. Circulation.
2016;133:62–73.
29. Miron A, Lafreniere-Roula M, Steve Fan CP, et al. A validated model for sud-
den cardiac death risk prediction in pediatric hypertrophic cardiomyopathy.
Circulation. 2020;142:217–229.
30. Norrish G, Qu C, Field E, et al. External validation of the HCM Risk-Kids
model for predicting sudden cardiac death in childhood hypertrophic cardio-
myopathy. Eur J Prev Cardiol. 2022;29:678–686.
31. Chan RH, Maron BJ, Olivotto I, et al. Prognostic value of quantitative
contrast-enhanced cardiovascular magnetic resonance for the evaluation of
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e62
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
sudden death risk in patients with hypertrophic cardiomyopathy. Circulation.
2014;130:484–495.
32. Weng Z, Yao J, Chan RH, et al. Prognostic value of LGE-CMR in HCM: a
meta-analysis. J Am Coll Cardiol Img. 2016;9:1392–1402.
33. Mentias A, Raeisi-Giglou P, Smedira NG, et al. Late gadolinium enhance-
ment in patients with hypertrophic cardiomyopathy and preserved systolic
function. J Am Coll Cardiol. 2018;72:857–870.
34. Smith BM, Dorfman AL, Yu S, et al. Clinical significance of late gadolinium
enhancement in patients <20 years of age with hypertrophic cardiomyopa-
thy. Am J Cardiol. 2014;113:1234–1239.
35. Axelsson Raja A, Farhad H, Valente AM, et al. Prevalence and progression of
late gadolinium enhancement in children and adolescents with hypertrophic
cardiomyopathy. Circulation. 2018;138:782–792.
36. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of sports for athletes
with implantable cardioverter-defibrillators: long-term results of a prospec-
tive multinational registry. Circulation. 2017;135:2310–2312.
37. Maron BJ, Rowin EJ, Casey SA, et al. Risk stratification and outcome of
patients with hypertrophic cardiomyopathy ≥60 years of age. Circulation.
2013;127:585–593.
38. Maron BJ, Rowin EJ, Casey SA, et al. Hypertrophic cardiomyopathy in adult-
hood associated with low cardiovascular mortality with contemporary man-
agement strategies. J Am Coll Cardiol. 2015;65:1915–1928.
39. Rowin EJ, Sridharan A, Madias C, et al. Prediction and prevention of sudden
death in young patients (<20 years) with hypertrophic cardiomyopathy. Am
J Cardiol. 2020;128:75–83.
40. Balaji S, DiLorenzo MP, Fish FA, et al. Risk factors for lethal arrhythmic
events in children and adolescents with hypertrophic cardiomyopathy and
an implantable defibrillator: an international multicenter study. Heart Rhythm.
2019;16:1462–1467.
41. Decker JA, Rossano JW, Smith EO, et al. Risk factors and mode of death
in isolated hypertrophic cardiomyopathy in children. J Am Coll Cardiol.
2009;54:250–254.
7.3. ICD Device Selection Considerations
1. Silvetti MS, Pazzano V, Verticelli L, et al. Subcutaneous implantable
cardioverter-defibrillator: is it ready for use in children and young adults? A
single-centre study. Europace. 2018;20:1966–1973.
2. Hauser RG, Maisel WH, Friedman PA, et al. Longevity of Sprint Fidelis im-
plantable cardioverter-defibrillator leads and risk factors for failure: implica-
tions for patient management. Circulation. 2011;123:358–363.
3. O’Mahony C, Lambiase PD, Quarta G, et al. The long-term survival and the
risks and benefits of implantable cardioverter defibrillators in patients with
hypertrophic cardiomyopathy. Heart. 2012;98:116–125.
4. Lambiase PD, Gold MR, Hood M, et al. Evaluation of subcutaneous ICD
early performance in hypertrophic cardiomyopathy from the pooled EF-
FORTLESS and IDE cohorts. Heart Rhythm. 2016;13:1066–1074.
5. Frommeyer G, Dechering DG, Zumhagen S, et al. Long-term follow-up of
subcutaneous ICD systems in patients with hypertrophic cardiomyopathy: a
single-center experience. Clin Res Cardiol. 2016;105:89–93.
6. Weinstock J, Bader YH, Maron MS, et al. Subcutaneous implantable car-
dioverter defibrillator in patients with hypertrophic cardiomyopathy: an initial
experience. J Am Heart Assoc. 2016;5:e002488.
7. Francia P, Adduci C, Semprini L, et al. Prognostic implications of defibrilla-
tion threshold testing in patients with hypertrophic cardiomyopathy. J Car-
diovasc Electrophysiol. 2017;28:103–108.
8. Okamura H, Friedman PA, Inoue Y, et al. Single-coil defibrillator leads yield
satisfactory defibrillation safety margin in hypertrophic cardiomyopathy. Circ
J. 2016;80:2199–2203.
9. Quin EM, Cuoco FA, Forcina MS, et al. Defibrillation thresholds in hypertro-
phic cardiomyopathy. J Cardiovasc Electrophysiol. 2011;22:569–572.
10. Nishimura RA, Trusty JM, Hayes DL, et al. Dual-chamber pacing for hyper-
trophic cardiomyopathy: a randomized, double-blind, crossover trial. J Am
Coll Cardiol. 1997;29:435–441.
11. Kappenberger L, Linde C, Daubert C, et al. Pacing in hypertrophic obstruc-
tive cardiomyopathy. A randomized crossover study. PIC Study Group. Eur
Heart J. 1997;18:1249–1256.
12. Maron BJ, Nishimura RA, McKenna WJ, et al. Assessment of permanent
dual-chamber pacing as a treatment for drug-refractory symptomatic
patients with obstructive hypertrophic cardiomyopathy. A randomized,
double-blind, crossover study (M-PATHY). Circulation. 1999;99:2927–2933.
13. Mickelsen S, Bathina M, Hsu P, et al. Doppler evaluation of the descending
aorta in patients with hypertrophic cardiomyopathy: potential for assess-
ing the functional significance of outflow tract gradients and for optimizing
pacemaker function. J Interv Card Electrophysiol. 2004;11:47–53.
14. Killu AM, Park J-Y, Sara J D, et al. Cardiac resynchronization therapy in pa-
tients with end-stage hypertrophic cardiomyopathy. Europace 2018;20:82–
88.
15. Gu M, Jin H, Hua W, et al. Clinical outcome of cardiac resynchronization
therapy in dilated-phase hypertrophic cardiomyopathy. J Geriatr Cardiol.
2017;14:238–244.
16. Rogers DPS, Marazia S, Chow AW, et al. Effect of biventricular pacing on
symptoms and cardiac remodelling in patients with end-stage hypertrophic
cardiomyopathy. Eur J Heart Fail. 2008;10:507–513.
17. Rowin EJ, Mohanty S, Madias C, et al. Benefit of cardiac resynchronization
therapy in end-stage nonobstructive hypertrophic cardiomyopathy. J Am Coll
Cardiol EP. 2019;5:131–133.
18. Cappelli F, Morini S, Pieragnoli P, et al. Cardiac resynchronization therapy
for end-stage hypertrophic cardiomyopathy: the need for disease-specific
criteria. J Am Coll Cardiol. 2018;71:464–466.
19. Friedman PA, McClelland RL, Bamlet WR, et al. Dual-chamber versus
single-chamber detection enhancements for implantable defibrillator
rhythm diagnosis: the Detect Supraventricular Tachycardia Study. Circula-
tion. 2006;113:2871–2879.
20. Theuns DAMJ, Klootwijk APJ, Goedhart DM, et al. Prevention of inappropri-
ate therapy in implantable cardioverter-defibrillators: results of a prospec-
tive, randomized study of tachyarrhythmia detection algorithms. J Am Coll
Cardiol. 2004;44:2362–2367.
21. Kolb C, Sturmer M, Sick P, et al. Reduced risk for inappropriate implantable
cardioverter-defibrillator shocks with dual-chamber therapy compared with
single-chamber therapy: results of the randomized OPTION study. J Am Coll
Cardiol HF. 2014;2:611–619.
22. Peterson PN, Greenlee RT, Go AS, et al. Comparison of inappropriate shocks
and other health outcomes between single- and dual-chamber implantable
cardioverter-defibrillators for primary prevention of sudden cardiac death:
results from the Cardiovascular Research Network longitudinal study of im-
plantable cardioverter-defibrillators. J Am Heart Assoc. 2017;6:e006937.
23. Defaye P, Boveda S, Klug D, et al. Dual- vs. single-chamber defibrillators for
primary prevention of sudden cardiac death: long-term follow-up of the De-
fibrillateur Automatique Implantable-Prevention Primaire registry. Europace.
2017;19:1478–1484.
24. Hu Z-Y, Zhang J, Xu Z-T, et al. Efficiencies and complications of dual cham-
ber versus single chamber implantable cardioverter defibrillators in sec-
ondary sudden cardiac death prevention: a meta-analysis. Heart Lung Circ.
2016;25:148–154.
25. Maron BJ, Spirito P, Ackerman MJ, et al. Prevention of sudden cardiac death
with implantable cardioverter-defibrillators in children and adolescents with
hypertrophic cardiomyopathy. J Am Coll Cardiol. 2013;61:1527–1535.
26. Bettin M, Larbig R, Rath B, et al. Long-term experience with the subcutane-
ous implantable cardioverter-defibrillator in teenagers and young adults. J
Am Coll Cardiol EP. 2017;3:1499–1506.
27. Pettit SJ, McLean A, Colquhoun I, et al. Clinical experience of subcutane-
ous and transvenous implantable cardioverter defibrillators in children and
teenagers. Pacing Clin Electrophysiol. 2013;36:1532–1538.
28. Kumar KR, Mandleywala SN, Madias C, et al. Single coil implantable cardio-
verter defibrillator leads in patients with hypertrophic cardiomyopathy. Am J
Cardiol. 2020;125:1896–1900.
29. Vamos M, Healey JS, Wang J, et al. Implantable cardioverter-defibrillator
therapy in hypertrophic cardiomyopathy: a SIMPLE substudy. Heart Rhythm.
2018;15:386–392.
30. Daubert J- C, Saxon L, Adamson PB, et al. 2012 EHRA/HRS expert
consensus statement on cardiac resynchronization therapy in heart fail-
ure: implant and follow-up recommendations and management. Europace.
2012;14:1236–1286.
31. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guide-
line for the management of heart failure: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Prac-
tice Guidelines. Circulation. 2022;145:e895–e1032.
32. Kusumoto FM, Schoenfeld MH, Barrett C, et al. 2018 ACC/AHA/HRS
guideline on the evaluation and management of patients with bradycardia
and cardiac conduction delay: a report of the American College of Cardiol-
ogy/American Heart Association Task Force on Clinical Practice Guidelines
and the Heart Rhythm Society. Circulation. 2019;140:e382–e482.
8.1.1. Pharmacological Management of Symptomatic
Patients With Obstructive HCM
1. Cohen LS, Braunwald E. Amelioration of angina pectoris in idiopathic hy-
pertrophic subaortic stenosis with beta-adrenergic blockade. Circulation.
1967;35:847–851.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e63
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
2. Adelman AG, Shah PM, Gramiak R, et al. Long-term propranolol therapy in
muscular subaortic stenosis. Br Heart J. 1970;32:804–811.
3. Stenson RE, Flamm MD Jr, Harrison DC, et al. Hypertrophic subaortic ste-
nosis. Clinical and hemodynamic effects of long-term propranolol therapy.
Am J Cardiol. 1973;31:763–773.
4. Bonow RO, Rosing DR, Bacharach SL, et al. Effects of verapamil on left
ventricular systolic function and diastolic filling in patients with hypertrophic
cardiomyopathy. Circulation. 1981;64:787–796.
5. Rosing DR, Kent KM, Maron BJ, et al. Verapamil therapy: a new approach
to the pharmacologic treatment of hypertrophic cardiomyopathy. II. Effects
on exercise capacity and symptomatic status. Circulation. 1979;60:1208–
1213.
6. Toshima H, Koga Y, Nagata H, et al. Comparable effects of oral diltiazem
and verapamil in the treatment of hypertrophic cardiomyopathy. Double-
blind crossover study. Jpn Heart J. 1986;27:701–715.
7. Sherrid MV, Barac I, McKenna WJ, et al. Multicenter study of the efficacy
and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J
Am Coll Cardiol. 2005;45:1251–1258.
8. Sherrid MV, Shetty A, Winson G, et al. Treatment of obstructive hypertrophic
cardiomyopathy symptoms and gradient resistant to first-line therapy with
β-blockade or verapamil. Circ Heart Fail. 2013;6:694–702.
9. Adler A, Fourey D, Weissler-Snir A, et al. Safety of outpatient initiation of
disopyramide for obstructive hypertrophic cardiomyopathy patients. J Am
Heart Assoc. 2017;6:e005152.
10. Maron BJ, Dearani JA, Ommen SR, et al. Low operative mortality achieved
with surgical septal myectomy: role of dedicated hypertrophic cardiomyopa-
thy centers in the management of dynamic subaortic obstruction. J Am Coll
Cardiol. 2015;66:1307–1308.
11. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is
predominantly a disease of left ventricular outflow tract obstruction. Circula-
tion. 2006;114:2232–2239.
12. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal
myectomy on survival in patients with obstructive hypertrophic cardiomy-
opathy. J Am Coll Cardiol. 2005;46:470–476.
13. Desai MY, Owens A, Geske JB, et al. Myosin inhibition in patients with ob-
structive hypertrophic cardiomyopathy referred for septal reduction therapy.
J Am Coll Cardiol. 2022;80:95–108.
14. Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of
symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM):
a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet.
2020;396:759–769.
15. Braunwald E, Ebert PA. Hemogynamic alterations in idiopathic hypertro-
phic subaortic stenosis induced by sympathomimetic drugs. Am J Cardiol.
1962;10:489–495.
16. Kirk CR, Gibbs JL, Thomas R, et al. Cardiovascular collapse after verapamil
in supraventricular tachycardia. Arch Dis Child. 1987;62:1265–1266.
17. CAMZYOS [package insert]. Bristol-Myers Squibb Company; 2022. Ac-
cessed September 14, 2022. https://packageinserts.bms.com/pi/pi_
camzyos.pdf.
18. Moran AM, Colan SD. Verapamil therapy in infants with hypertrophic cardio-
myopathy. Cardiol Young. 1998;8:310–319.
8.1.2. Invasive Treatment of Symptomatic Patients With
Obstructive HCM
1. Maron BJ, Dearani JA, Ommen SR, et al. Low operative mortality achieved
with surgical septal myectomy: role of dedicated hypertrophic cardiomyopa-
thy centers in the management of dynamic subaortic obstruction. J Am Coll
Cardiol. 2015;66:1307–1308.
2. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is
predominantly a disease of left ventricular outflow tract obstruction. Circula-
tion. 2006;114:2232–2239.
3. Ommen SR, Maron BJ, Olivotto I, et al. Long-term effects of surgical septal
myectomy on survival in patients with obstructive hypertrophic cardiomy-
opathy. J Am Coll Cardiol. 2005;46:470–476.
4. Rowin EJ, Maron BJ, Lesser JR, et al. Papillary muscle insertion directly into
the anterior mitral leaflet in hypertrophic cardiomyopathy, its identification
and cause of outflow obstruction by cardiac magnetic resonance imaging,
and its surgical management. Am J Cardiol. 2013;111:1677–1679.
5. Teo EP, Teoh JG, Hung J. Mitral valve and papillary muscle abnormalities in
hypertrophic obstructive cardiomyopathy. Curr Opin Cardiol. 2015;30:475–
482.
6. Di Tommaso L, Stassano P, Mannacio V, et al. Asymmetric septal hypertro-
phy in patients with severe aortic stenosis: the usefulness of associated
septal myectomy. J Thorac Cardiovasc Surg. 2013;145:171–175.
7. Kayalar N, Schaff HV, Daly RC, et al. Concomitant septal myectomy at the
time of aortic valve replacement for severe aortic stenosis. Ann Thorac Surg.
2010;89:459–464.
8. Batzner A, Pfeiffer B, Neugebauer A, et al. Survival after alcohol septal ab-
lation in patients with hypertrophic obstructive cardiomyopathy. J Am Coll
Cardiol. 2018;72:3087–3094.
9. Nguyen A, Schaff HV, Hang D, et al. Surgical myectomy versus alcohol sep-
tal ablation for obstructive hypertrophic cardiomyopathy: a propensity score-
matched cohort. J Thorac Cardiovasc Surg. 2019;157:306–315.e303.
10. Kimmelstiel C, Zisa DC, Kuttab JS, et al. Guideline-based referral for
septal reduction therapy in obstructive hypertrophic cardiomyopathy
is associated with excellent clinical outcomes. Circ Cardiovasc Interv.
2019;12:e007673.
11. Mitra A, Ghosh RK, Bandyopadhyay D, et al. Significance of pulmo-
nary hypertension in hypertrophic cardiomyopathy. Curr Probl Cardiol.
2020;45:100398.
12. Ong KC, Geske JB, Hebl VB, et al. Pulmonary hypertension is associated
with worse survival in hypertrophic cardiomyopathy. Eur Heart J Cardiovasc
Imaging. 2016;17:604–610.
13. Desai MY, Bhonsale A, Patel P, et al. Exercise echocardiography in asymp-
tomatic HCM: exercise capacity, and not LV outflow tract gradient predicts
long-term outcomes. J Am Coll Cardiol Img. 2014;7:26–36.
14. Nguyen A, Schaff HV, Nishimura RA, et al. Determinants of reverse re-
modeling of the left atrium after transaortic myectomy. Ann Thorac Surg.
2018;106:447–453.
15. Finocchiaro G, Haddad F, Kobayashi Y, et al. Impact of septal reduction on
left atrial size and diastole in hypertrophic cardiomyopathy. Echocardiogra-
phy. 2016;33:686–694.
16. Blackshear JL, Kusumoto H, Safford RE, et al. Usefulness of von Willebrand
factor activity indexes to predict therapeutic response in hypertrophic car-
diomyopathy. Am J Cardiol. 2016;117:436–442.
17. Blackshear JL, Stark ME, Agnew RC, et al. Remission of recurrent gastroin-
testinal bleeding after septal reduction therapy in patients with hypertrophic
obstructive cardiomyopathy-associated acquired von Willebrand syndrome.
J Thromb Haemost. 2015;13:191–196.
18. Desai MY, Smedira NG, Dhillon A, et al. Prediction of sudden death risk in
obstructive hypertrophic cardiomyopathy: potential for refinement of current
criteria. J Thorac Cardiovasc Surg. 2018;156:750–759.e3.
19. McLeod CJ, Ommen SR, Ackerman MJ, et al. Surgical septal myectomy
decreases the risk for appropriate implantable cardioverter defibrilla-
tor discharge in obstructive hypertrophic cardiomyopathy. Eur Heart J.
2007;28:2583–2588.
20. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the
management of patients with valvular heart disease: a report of the Ameri-
can College of Cardiology/American Heart Association Joint Committee on
Clinical Practice Guidelines. Circulation. 2021;143:e72–e227.
21. Sorajja P, Nishimura RA, Gersh BJ, et al. Outcome of mildly symptomatic or
asymptomatic obstructive hypertrophic cardiomyopathy: a long-term follow-
up study. J Am Coll Cardiol. 2009;54:234–241.
22. Ball W, Ivanov J, Rakowski H, et al. Long-term survival in patients with rest-
ing obstructive hypertrophic cardiomyopathy comparison of conservative
versus invasive treatment. J Am Coll Cardiol. 2011;58:2313–2321.
23. Kim LK, Swaminathan RV, Looser P, et al. Hospital volume outcomes after
septal myectomy and alcohol septal ablation for treatment of obstructive hy-
pertrophic cardiomyopathy: US nationwide inpatient database, 2003-2011.
JAMA Cardiol. 2016;1:324–332.
24. Hodges K, Rivas CG, Aguilera J, et al. Surgical management of
left ventricular outflow tract obstruction in a specialized hypertro-
phic obstructive cardiomyopathy center. J Thorac Cardiovasc Surg.
2019;157:2289–2299.
25. Cui H, Schaff HV, Nishimura RA, et al. Conduction abnormalities and long-
term mortality following septal myectomy in patients with obstructive hyper-
trophic cardiomyopathy. J Am Coll Cardiol. 2019;74:645–655.
26. Holst KA, Hanson KT, Ommen SR, et al. Septal myectomy in hypertrophic
cardiomyopathy: national outcomes of concomitant mitral surgery. Mayo Clin
Proc. 2019;94:66–73.
27. Hong JH, Schaff HV, Nishimura RA, et al. Mitral regurgitation in patients
with hypertrophic obstructive cardiomyopathy: implications for concomitant
valve procedures. J Am Coll Cardiol. 2016;68:1497–1504.
28. Holst KA, Schaff HV, Smedira NG, et al. Impact of hospital volume on out-
comes of septal myectomy for hypertrophic cardiomyopathy. Ann Thorac
Surg. 2022;114:2131–2138.
29. Nguyen A, Schaff HV. Surgical myectomy: subaortic, midventricular, and api-
cal. Cardiol Clin. 2019;37:95–104.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e64
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
30. Hang D, Schaff HV, Ommen SR, et al. Combined transaortic and transapical
approach to septal myectomy in patients with complex hypertrophic cardio-
myopathy. J Thorac Cardiovasc Surg. 2018;155:2096–2102.
31. Kunkala MR, Schaff HV, Nishimura RA, et al. Transapical approach to my-
ectomy for midventricular obstruction in hypertrophic cardiomyopathy. Ann
Thorac Surg. 2013;96:564–570.
32. Nguyen A, Schaff HV, Nishimura RA, et al. Does septal thickness influence
outcome of myectomy for hypertrophic obstructive cardiomyopathy? Eur J
Cardiothorac Surg. 2018;53:582–589.
33. Balaram SK, Ross RE, Sherrid MV, et al. Role of mitral valve plication in
the surgical management of hypertrophic cardiomyopathy. Ann Thorac Surg.
2012;94:1990–1997.
34. Rastegar H, Boll G, Rowin EJ, et al. Results of surgical septal myectomy for
obstructive hypertrophic cardiomyopathy: the Tufts experience. Ann Cardio-
thorac Surg. 2017;6:353–363.
35. Vriesendorp PA, Schinkel AF, Soliman OI, et al. Long-term benefit of myec-
tomy and anterior mitral leaflet extension in obstructive hypertrophic cardio-
myopathy. Am J Cardiol. 2015;115:670–675.
36. Ferrazzi P, Spirito P, Iacovoni A, et al. Transaortic chordal cutting mitral valve
repair for obstructive hypertrophic cardiomyopathy with mild septal hyper-
trophy. J Am Coll Cardiol. 2015;66:1687–1696.
37. Minakata K, Dearani JA, Nishimura RA, et al. Extended septal myectomy
for hypertrophic obstructive cardiomyopathy with anomalous mitral papillary
muscles or chordae. J Thorac Cardiovasc Surg. 2004;127:481–489.
38. Kaple RK, Murphy RT, DiPaola LM, et al. Mitral valve abnormalities in hyper-
trophic cardiomyopathy: echocardiographic features and surgical outcomes.
Ann Thorac Surg. 2008;85:1527–1535.
39. Schoendube FA, Klues HG, Reith S, et al. Long-term clinical and echocar-
diographic follow-up after surgical correction of hypertrophic obstructive
cardiomyopathy with extended myectomy and reconstruction of the subval-
vular mitral apparatus. Circulation. 1995;92:II122-II127.
40. Hang D, Schaff HV, Nishimura RA, et al. Accuracy of jet direction on
Doppler echocardiography in identifying the etiology of mitral regurgita-
tion in obstructive hypertrophic cardiomyopathy. J Am Soc Echocardiogr.
2019;32:333–340.
41. Deb SJ, Schaff HV, Dearani JA, et al. Septal myectomy results in regres-
sion of left ventricular hypertrophy in patients with hypertrophic obstructive
cardiomyopathy. Ann Thorac Surg. 2004;78:2118–2122.
42. Cho YH, Quintana E, Schaff HV, et al. Residual and recurrent gradients
after septal myectomy for hypertrophic cardiomyopathy-mechanisms
of obstruction and outcomes of reoperation. J Thorac Cardiovasc Surg.
2014;148:909–915.
43. Smedira NG, Lytle BW, Lever HM, et al. Current effectiveness and risks of
isolated septal myectomy for hypertrophic obstructive cardiomyopathy. Ann
Thorac Surg. 2008;85:127–133.
44. Ralph-Edwards A, Woo A, McCrindle BW, et al. Hypertrophic obstructive car-
diomyopathy: comparison of outcomes after myectomy or alcohol ablation
adjusted by propensity score. J Thorac Cardiovasc Surg. 2005;129:351–
358.
45. Kwon DH, Setser RM, Thamilarasan M, et al. Abnormal papillary muscle mor-
phology is independently associated with increased left ventricular outflow
tract obstruction in hypertrophic cardiomyopathy. Heart. 2008;94:1295–
1301.
46. Sorajja P, Binder J, Nishimura RA, et al. Predictors of an optimal clinical
outcome with alcohol septal ablation for obstructive hypertrophic cardiomy-
opathy. Catheter Cardiovasc Interv. 2013;81:E58–E67.
47. Agarwal S, Tuzcu EM, Desai MY, et al. Updated meta-analysis of septal al-
cohol ablation versus myectomy for hypertrophic cardiomyopathy. J Am Coll
Cardiol. 2010;55:823–834.
48. Singh K, Qutub M, Carson K, et al. A meta analysis of current status of
alcohol septal ablation and surgical myectomy for obstructive hypertrophic
cardiomyopathy. Catheter Cardiovasc Interv. 2016;88:107–115.
49. Laredo M, Khraiche D, Raisky O, et al. Long-term results of the modified
Konno procedure in high-risk children with obstructive hypertrophic cardio-
myopathy. J Thorac Cardiovasc Surg. 2018;156: 2285–2294.e2.
50. Chen MS, McCarthy PM, Lever HM, et al. Effectiveness of atrial fibrilla-
tion surgery in patients with hypertrophic cardiomyopathy. Am J Cardiol.
2004;93:373–375.
51. Rowin EJ, Hausvater A, Link MS, et al. Clinical profile and conse-
quences of atrial fibrillation in hypertrophic cardiomyopathy. Circulation.
2017;136:2420–2436.
52. Geske JB, Konecny T, Ommen SR, et al. Surgical myectomy improves pul-
monary hypertension in obstructive hypertrophic cardiomyopathy. Eur Heart
J. 2014;35:2032–2039.
53. Woo A, Williams WG, Choi R, et al. Clinical and echocardiographic determi-
nants of long-term survival after surgical myectomy in obstructive hypertro-
phic cardiomyopathy. Circulation. 2005;111:2033–2041.
54. Rowin EJ, Cooper C, Carrick RT, et al. Ventricular septal myectomy decreas-
es long-term risk for atrial fibrillation in patients with hypertrophic cardiomy-
opathy. Am J Cardiol. 2022;179:70–73.
55. Osman M, Kheiri B, Osman K, et al. Alcohol septal ablation vs myectomy for
symptomatic hypertrophic obstructive cardiomyopathy: systematic review
and meta-analysis. Clin Cardiol. 2019;42:190–197.
56. Vriesendorp PA, Liebregts M, Steggerda RC, et al. Long-term outcomes
after medical and invasive treatment in patients with hypertrophic cardiomy-
opathy. J Am Coll Cardiol HF 2014;2:630–636.
57. Liebregts M, Vriesendorp PA, Mahmoodi BK, et al. A systematic review and
meta-analysis of long-term outcomes after septal reduction therapy in pa-
tients with hypertrophic cardiomyopathy. J Am Coll Cardiol HF. 2015;3:896–
905.
58. Li P, Xue Y, Sun J, et al. Outcome of alcohol septal ablation in mildly symp-
tomatic patients with hypertrophic obstructive cardiomyopathy: a compari-
son with medical therapy. Clin Cardiol. 2021;44:1409–1415.
8.2. Management of Patients With Nonobstructive HCM
With Preserved EF
1. Bourmayan C, Razavi A, Fournier C, et al. Effect of propranolol on left ven-
tricular relaxation in hypertrophic cardiomyopathy: an echographic study. Am
Heart J. 1985;109:1311–1316.
2. Wilmshurst PT, Thompson DS, Juul SM, et al. Effects of verapamil on hae-
modynamic function and myocardial metabolism in patients with hypertro-
phic cardiomyopathy. Br Heart J. 1986;56:544–553.
3. Udelson JE, Bonow RO, O’Gara PT, et al. Verapamil prevents silent myocar-
dial perfusion abnormalities during exercise in asymptomatic patients with
hypertrophic cardiomyopathy. Circulation. 1989;79:1052–1060.
4. Toshima H, Koga Y, Nagata H, et al. Comparable effects of oral diltiazem
and verapamil in the treatment of hypertrophic cardiomyopathy. Double-
blind crossover study. Jpn Heart J. 1986;27:701–715.
5. Sugihara H, Taniguchi Y, Ito K, et al. Effects of diltiazem on myocardial perfu-
sion abnormalities during exercise in patients with hypertrophic cardiomy-
opathy. Ann Nucl Med. 1998;12:349–354.
6. Axelsson A, Iversen K, Vejlstrup N, et al. Efficacy and safety of the angio-
tensin II receptor blocker losartan for hypertrophic cardiomyopathy: the IN-
HERIT randomised, double-blind, placebo-controlled trial. Lancet Diabetes
Endocrinol. 2015;3:123–131.
7. Nguyen A, Schaff HV, Nishimura RA, et al. Apical myectomy for patients with
hypertrophic cardiomyopathy and advanced heart failure. J Thorac Cardio-
vasc Surg. 2019;S0022-5223(0019)30772-X.
8. Ho CY, Day SM, Axelsson A, et al. Valsartan in early-stage hyper-
trophic cardiomyopathy: a randomized phase 2 trial. Nat Med.
2021;27:1818–1824.
9. Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of disease
in hypertrophic cardiomyopathy: insights from the Sarcomeric Human Car-
diomyopathy Registry (SHaRE). Circulation. 2018;138:1387–1398.
10. Pelliccia F, Pasceri V, Limongelli G, et al. Long-term outcome of nonobstruc-
tive versus obstructive hypertrophic cardiomyopathy: a systematic review
and meta-analysis. Int J Cardiol. 2017;243:379–384.
11. Webber SA, Lipshultz SE, Sleeper LA, et al. Outcomes of restrictive cardio-
myopathy in childhood and the influence of phenotype: a report from the
Pediatric Cardiomyopathy Registry. Circulation. 2012;126:1237–1244.
12. Sorajja P, Ommen SR, Nishimura RA, et al. Adverse prognosis of patients
with hypertrophic cardiomyopathy who have epicardial coronary artery dis-
ease. Circulation. 2003;108:2342–2348.
13. Gilligan DM, Chan WL, Joshi J, et al. A double-blind, placebo-controlled
crossover trial of nadolol and verapamil in mild and moderately symptomatic
hypertrophic cardiomyopathy. J Am Coll Cardiol. 1993;21:1672–1679.
14. Spoladore R, Maron MS, D’Amato R, et al. Pharmacological treatment op-
tions for hypertrophic cardiomyopathy: high time for evidence. Eur Heart J.
2012;33:1724–1733.
15. Spicer RL, Rocchini AP, Crowley DC, et al. Hemodynamic effects of vera-
pamil in children and adolescents with hypertrophic cardiomyopathy. Circula-
tion. 1983;67:413–420.
8.3. Management of Patients With HCM and Advanced HF
1. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guide-
line for the management of heart failure: a report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Prac-
tice Guidelines. Circulation. 2022;145:e895–e1032.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e65
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
2. Harris KM, Spirito P, Maron MS, et al. Prevalence, clinical profile, and signifi-
cance of left ventricular remodeling in the end-stage phase of hypertrophic
cardiomyopathy. Circulation. 2006;114:216–225.
3. Hebl VB, Miranda WR, Ong KC, et al. The natural history of nonobstructive
hypertrophic cardiomyopathy. Mayo Clin Proc. 2016;91:279–287.
4. Melacini P, Basso C, Angelini A, et al. Clinicopathological profiles of
progressive heart failure in hypertrophic cardiomyopathy. Eur Heart J.
2010;31:2111–2123.
5. Rowin EJ, Maron MS, Chan RH, et al. Interaction of adverse disease related
pathways in hypertrophic cardiomyopathy. Am J Cardiol. 2017;120:2256–
2264.
6. Coats CJ, Rantell K, Bartnik A, et al. Cardiopulmonary exercise testing and
prognosis in hypertrophic cardiomyopathy. Circ Heart Fail. 2015;8:1022–
1031.
7. Magri D, Re F, Limongelli G, et al. Heart failure progression in hypertrophic
cardiomyopathy-possible insights from cardiopulmonary exercise testing.
Circ J. 2016;80:2204–2211.
8. Kato TS, Takayama H, Yoshizawa S, et al. Cardiac transplantation in patients
with hypertrophic cardiomyopathy. Am J Cardiol. 2012;110:568–574.
9. Lee MS, Zimmer R, Kobashigawa J. Long-term outcomes of orthotopic
heart transplantation for hypertrophic cardiomyopathy. Transplant Proc.
2014;46:1502–1505.
10. Rowin EJ, Maron BJ, Kiernan MS, et al. Advanced heart failure with pre-
served systolic function in nonobstructive hypertrophic cardiomyopathy:
under-recognized subset of candidates for heart transplant. Circ Heart Fail.
2014;7:967–975.
11. Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society
for Heart Lung Transplantation listing criteria for heart transplantation: a
10-year update. J Heart Lung Transplant. 2016;35:1–23.
12. Rowin EJ, Maron BJ, Abt P, et al. Impact of advanced therapies for improving
survival to heart transplant in patients with hypertrophic cardiomyopathy. Am
J Cardiol. 2018;121:986–996.
13. Fowler CC, Helmers MR, Smood B, et al. The modified US heart allocation
system improves transplant rates and decreases status upgrade utilization
for patients with hypertrophic cardiomyopathy. J Heart Lung Transplant.
2021;40:1181–1190.
14. Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of
symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM):
a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet.
2020;396:759–769.
15. Topilsky Y, Pereira NL, Shah DK, et al. Left ventricular assist device therapy
in patients with restrictive and hypertrophic cardiomyopathy. Circ Heart Fail.
2011;4:266–275.
16. Muthiah K, Phan J, Robson D, et al. Centrifugal continuous-flow left ven-
tricular assist device in patients with hypertrophic cardiomyopathy: a case
series. ASAIO J. 2013;59:183–187.
17. Grupper A, Park SJ, Pereira NL, et al. Role of ventricular assist
therapy for patients with heart failure and restrictive physiology:
improving outcomes for a lethal disease. J Heart Lung Transplant.
2015;34:1042–1049.
18. Patel SR, Saeed O, Naftel D, et al. Outcomes of restrictive and hypertro-
phic cardiomyopathies after LVAD: an INTERMACS analysis. J Card Fail.
2017;23:859–867.
19. Yagi N, Seguchi O, Mochizuki H, et al. Implantation of ventricular assist de-
vices in hypertrophic cardiomyopathy with left ventricular systolic dysfunc-
tion. ESC Heart Fail. 2021;8:5513–5522.
20. Rowin EJ, Maron BJ, Carrick RT, et al. Outcomes in patients with hyper-
trophic cardiomyopathy and left ventricular systolic dysfunction. J Am Coll
Cardiol. 2020;75:3033–3043.
21. Rogers DP, Marazia S, Chow AW, et al. Effect of biventricular pacing on
symptoms and cardiac remodelling in patients with end-stage hypertrophic
cardiomyopathy. Eur J Heart Fail. 2008;10:507–513.
22. Gu M, Jin H, Hua W, et al. Clinical outcome of cardiac resynchronization
therapy in dilated-phase hypertrophic cardiomyopathy. J Geriatr Cardiol.
2017;14:238–244.
23. Cappelli F, Morini S, Pieragnoli P, et al. Cardiac resynchronization therapy
for end-stage hypertrophic cardiomyopathy: the need for disease-specific
criteria. J Am Coll Cardiol. 2018;71:464–466.
24. Killu AM, Park JY, Sara JD, et al. Cardiac resynchronization therapy
in patients with end-stage hypertrophic cardiomyopathy. Europace.
2018;20:82–88.
25. Rowin EJ, Mohanty S, Madias C, et al. Benefit of cardiac resynchronization
therapy in end-stage nonobstructive hypertrophic cardiomyopathy. J Am Coll
Cardiol EP. 2019;5:131–133.
26. Biagini E, Coccolo F, Ferlito M, et al. Dilated-hypokinetic evolution of
hypertrophic cardiomyopathy: prevalence, incidence, risk factors, and
prognostic implications in pediatric and adult patients. J Am Coll Cardiol.
2005;46:1543–1550.
27. Ismail TF, Jabbour A, Gulati A, et al. Role of late gadolinium enhancement
cardiovascular magnetic resonance in the risk stratification of hypertrophic
cardiomyopathy. Heart. 2014;100:1851–1858.
28. Marstrand P, Han L, Day SM, et al. Hypertrophic cardiomyopathy with left
ventricular systolic dysfunction: insights from the SHaRe Registry. Circula-
tion. 2020;141:1371–1383.
29. Wasserstrum Y, Larranaga-Moreira JM, Martinez-Veira C, et al. Hypokinetic
hypertrophic cardiomyopathy: clinical phenotype, genetics, and prognosis.
ESC Heart Fail. 2022;9:2301–2312.
30. Pasqualucci D, Fornaro A, Castelli G, et al. Clinical spectrum, therapeutic
options, and outcome of advanced heart failure in hypertrophic cardiomy-
opathy. Circ Heart Fail. 2015;8:1014–1021.
31. Axelsson A, Iversen K, Vejlstrup N, et al. Efficacy and safety of the angio-
tensin II receptor blocker losartan for hypertrophic cardiomyopathy: the IN-
HERIT randomised, double-blind, placebo-controlled trial. Lancet Diabetes
Endocrinol. 2015;3:123–131.
32. Maron MS, Chan RH, Kapur NK, et al. Effect of spironolactone on myocar-
dial fibrosis and other clinical variables in patients with hypertrophic cardio-
myopathy. Am J Med. 2018;131:837–841.
33. Hamada T, Kubo T, Kitaoka H, et al. Clinical features of the dilated phase of
hypertrophic cardiomyopathy in comparison with those of dilated cardiomy-
opathy. Clin Cardiol. 2010;33:E24–E28.
34. Cheng S, Choe YH, Ota H, et al. CMR assessment and clinical outcomes of
hypertrophic cardiomyopathy with or without ventricular remodeling in the
end-stage phase. Int J Cardiovasc Imaging. 2018;34:597–605.
35. Burke MA, Chang S, Wakimoto H, et al. Molecular profiling of dilated cardio-
myopathy that progresses to heart failure. JCI Insight. 2016;1:e86898.
36. Chaffin M, Papangeli I, Simonson B, et al. Single-nucleus profiling of human
dilated and hypertrophic cardiomyopathy. Nature. 2022;608:174–180.
37. Maron MS, Kalsmith BM, Udelson JE, et al. Survival after cardiac trans-
plantation in patients with hypertrophic cardiomyopathy. Circ Heart Fail.
2010;3:574–579.
38. Zuñiga Cisneros J, Stehlik J, Selzman CH, et al. Outcomes in patients with
hypertrophic cardiomyopathy awaiting heart transplantation. Circ Heart Fail.
2018;11:e004378.
39. Sridharan L, Wayda B, Truby LK, et al. Mechanical circulatory support device
utilization and heart transplant waitlist outcomes in patients with restrictive
and hypertrophic cardiomyopathy. Circ Heart Fail. 2018;11:e004665.
40. Singh TP, Almond CS, Piercey G, et al. Current outcomes in US chil-
dren with cardiomyopathy listed for heart transplantation. Circ Heart Fail.
2012;5:594–601.
41. CAMZYOS [package insert]. Bristol-Myers Squibb Company; 2022. Ac-
cessed September 14, 2022. https://packageinserts.bms.com/pi/pi_
camzyos.pdf.
42. Su JA, Menteer J. Outcomes of Berlin Heart EXCOR((R)) pediatric ven-
tricular assist device support in patients with restrictive and hypertrophic
cardiomyopathy. Pediatr Transplant. 2017;21:e13048.
43. Bristow MR, Feldman AM, Saxon LA. Heart failure management using im-
plantable devices for ventricular resynchronization: Comparison of Medical
Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION)
trial. J Card Fail. 2000;6:276–285.
44. Tang AS, Wells GA, Arnold M, et al. Resynchronization/defibrillation for
ambulatory heart failure trial: rationale and trial design. Curr Opin Cardiol.
2009;24:1–8.
45. Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resyn-
chronization on morbidity and mortality in heart failure. N Engl J Med.
2005;352:1539–1549.
46. Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization
therapy for the prevention of heart-failure events. N Engl J Med.
2009;361:1329–1338.
8.4. Management of Patients With HCM and AF
1. Guttmann OP, Rahman MS, O’Mahony C, et al. Atrial fibrillation and throm-
boembolism in patients with hypertrophic cardiomyopathy: systematic re-
view. Heart. 2014;100:465–472.
2. Maron BJ, Olivotto I, Bellone P, et al. Clinical profile of stroke in 900 patients
with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002;39:301–307.
3. Jung H, Yang P-S, Jang E, et al. Effectiveness and safety of non-vitamin K an-
tagonist oral anticoagulants in patients with atrial fibrillation with hypertrophic
cardiomyopathy: a nationwide cohort study. Chest. 2019;155:354–363.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e66
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
4. Noseworthy PA, Yao X, Shah ND, et al. Stroke and bleeding risks in NOAC-
and warfarin-treated patients with hypertrophic cardiomyopathy and atrial
fibrillation. J Am Coll Cardiol. 2016;67:3020–3021.
5. Dominguez F, Climent V, Zorio E, et al. Direct oral anticoagulants in pa-
tients with hypertrophic cardiomyopathy and atrial fibrillation. Int J Cardiol.
2017;248:232–238.
6. van Velzen HG, Theuns DAMJ, Yap S-C, et al. Incidence of device-detected
atrial fibrillation and long-term outcomes in patients with hypertrophic car-
diomyopathy. Am J Cardiol. 2017;119:100–105.
7. Wilke I, Witzel K, Münch J, et al. High incidence of de novo and subclinical
atrial fibrillation in patients with hypertrophic cardiomyopathy and cardiac
rhythm management device. J Cardiovasc Electrophysiol. 2016;27:779–784.
8. Mahajan R, Perera T, Elliott AD, et al. Subclinical device-detected atrial fibril-
lation and stroke risk: a systematic review and meta-analysis. Eur Heart J.
2018;39:1407–1415.
9. Rowin EJ, Hausvater A, Link MS, et al. Clinical profile and conse-
quences of atrial fibrillation in hypertrophic cardiomyopathy. Circulation.
2017;136:2420–2436.
10. Olivotto I, Cecchi F, Casey SA, et al. Impact of atrial fibrillation on
the clinical course of hypertrophic cardiomyopathy. Circulation.
2001;104:2517–2524.
11. Boriani G, Glotzer TV, Santini M, et al. Device-detected atrial fibrillation and
risk for stroke: an analysis of >10 000 patients from the SOS AF project
(Stroke preventiOn Strategies based on Atrial Fibrillation information from
implanted devices). Eur Heart J. 2014;35:508–516.
12. Zhao D-S, Shen Y, Zhang Q, et al. Outcomes of catheter ablation of atrial
fibrillation in patients with hypertrophic cardiomyopathy: a systematic review
and meta-analysis. Europace. 2016;18:508–520.
13. Bassiouny M, Lindsay BD, Lever H, et al. Outcomes of nonpharmacologic
treatment of atrial fibrillation in patients with hypertrophic cardiomyopathy.
Heart Rhythm. 2015;12:1438–1447.
14. Page RL, Joglar JA, Caldwell MA, et al. 2015 ACC/AHA/HRS guideline
for the management of adult patients with supraventricular tachycardia: a
report of the American College of Cardiology/American Heart Association
Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.
Circulation. 2016;133:e506–e574.
15. Van Gelder IC, Healey JS, Crijns HJGM, et al. Duration of device-detected
subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart
J. 2017;38:1339–1344.
16. Gorenek B, Bax J, Boriani G, et al. Device-detected subclinical atrial
tachyarrhythmias: definition, implications and management-an Europe-
an Heart Rhythm Association (EHRA) consensus document. Europace.
2017;19:1556–1578.
17. Swiryn S, Orlov MV, Benditt DG, et al. Clinical implications of brief device-
detected atrial tachyarrhythmias in a cardiac rhythm management device
population: results from the Registry of Atrial Tachycardia and Atrial Fibrilla-
tion Episodes. Circulation. 2016;134:1130–1140.
18. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the
risk of stroke. N Engl J Med. 2012;366:120–129.
19. Botto GL, Padeletti L, Santini M, et al. Presence and duration of atri-
al fibrillation detected by continuous monitoring: crucial implications
for the risk of thromboembolic events. J Cardiovasc Electrophysiol.
2009;20:241–248.
20. Robinson K, Frenneaux MP, Stockins B, et al. Atrial fibrillation in hypertro-
phic cardiomyopathy: a longitudinal study. J Am Coll Cardiol. 1990;15:1279–
1285.
21. Sherrid MV, Barac I, McKenna WJ, et al. Multicenter study of the efficacy
and safety of disopyramide in obstructive hypertrophic cardiomyopathy. J
Am Coll Cardiol. 2005;45:1251–1258.
22. Adler A, Fourey D, Weissler-Snir A, et al. Safety of outpatient initiation of
disopyramide for obstructive hypertrophic cardiomyopathy patients. J Am
Heart Assoc. 2017;6:e005152.
23. Moore JC, Trager L, Anzia LE, et al. Dofetilide for suppression of atrial fibril-
lation in hypertrophic cardiomyopathy: a case series and literature review.
Pacing Clin Electrophysiol. 2018;41:396–401.
24. Miller CAS, Maron MS, Estes NAM III, et al. Safety, side effects and relative
efficacy of medications for rhythm control of atrial fibrillation in hypertrophic
cardiomyopathy. Am J Cardiol. 2019;123:1859–1862.
25. Providencia R, Elliott P, Patel K, et al. Catheter ablation for atrial fibrillation in
hypertrophic cardiomyopathy: a systematic review and meta-analysis. Heart.
2016;102:1533–1543.
26. Santangeli P, Di Biase L, Themistoclakis S, et al. Catheter ablation of
atrial fibrillation in hypertrophic cardiomyopathy: long-term outcomes
and mechanisms of arrhythmia recurrence. Circ Arrhythm Electrophysiol.
2013;6:1089–1094.
27. Chen MS, McCarthy PM, Lever HM, et al. Effectiveness of atrial fibrilla-
tion surgery in patients with hypertrophic cardiomyopathy. Am J Cardiol.
2004;93:373–375.
28. Bogachev-Prokophiev AV, Afanasyev AV, Zheleznev SI, et al. Concomi-
tant ablation for atrial fibrillation during septal myectomy in patients with
hypertrophic obstructive cardiomyopathy. J Thorac Cardiovasc Surg.
2018;155:1536–1542.e2.
29. Lapenna E, Pozzoli A, De Bonis M, et al. Mid-term outcomes of concomitant
surgical ablation of atrial fibrillation in patients undergoing cardiac surgery
for hypertrophic cardiomyopathy. Eur J Cardiothorac Surg. 2017;51:1112–
1118.
30. Guttmann OP, Pavlou M, O’Mahony C, et al. Prediction of thrombo-embolic
risk in patients with hypertrophic cardiomyopathy (HCM Risk-CVA). Eur J
Heart Fail. 2015;17:837–845.
31. Valdés SO, Miyake CY, Niu MC, et al. Early experience with intravenous
sotalol in children with and without congenital heart disease. Heart Rhythm.
2018;15:1862–1869.
32. Tanel RE, Walsh EP, Lulu JA, et al. Sotalol for refractory arrhythmias in pediat-
ric and young adult patients: initial efficacy and long-term outcome. Heart J.
1995;130:791–797.
8.5. Management of Patients With HCM and Ventricular
Arrhythmias
1. Rowin EJ, Maron BJ, Abt P, et al. Impact of advanced therapies for improving
survival to heart transplant in patients with hypertrophic cardiomyopathy. Am
J Cardiol. 2018;121:986–996.
2. Rowin EJ, Maron BJ, Kiernan MS, et al. Advanced heart failure with pre-
served systolic function in nonobstructive hypertrophic cardiomyopathy:
under-recognized subset of candidates for heart transplant. Circ Heart Fail.
2014;7:967–975.
3. Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers,
amiodarone plus beta-blockers, or sotalol for prevention of shocks from
implantable cardioverter defibrillators: the OPTIC study: a randomized trial.
JAMA. 2006;295:165–171.
4. Santangeli P, Muser D, Maeda S, et al. Comparative effectiveness of antiar-
rhythmic drugs and catheter ablation for the prevention of recurrent ven-
tricular tachycardia in patients with implantable cardioverter-defibrillators: a
systematic review and meta-analysis of randomized controlled trials. Heart
Rhythm. 2016;13:1552–1559.
5. Baquero GA, Banchs JE, Depalma S, et al. Dofetilide reduces the frequency
of ventricular arrhythmias and implantable cardioverter defibrillator thera-
pies. J Cardiovasc Electrophysiol. 2012;23:296–301.
6. Gao D, Van Herendael H, Alshengeiti L, et al. Mexiletine as an adjunctive
therapy to amiodarone reduces the frequency of ventricular tachyarrhythmia
events in patients with an implantable defibrillator. J Cardiovasc Pharmacol.
2013;62:199–204.
7. Link MS, Bockstall K, Weinstock J, et al. Ventricular tachyarrhyth-
mias in patients with hypertrophic cardiomyopathy and defibrillators:
triggers, treatment, and implications. J Cardiovasc Electrophysiol.
2017;28:531–537.
8. Wilkoff BL, Fauchier L, Stiles MK, et al. 2015 HRS/EHRA/APHRS/SO-
LAECE expert consensus statement on optimal implantable cardioverter-
defibrillator programming and testing. J Arrhythm. 2016;32:1–28.
9. Santangeli P, Di Biase L, Lakkireddy D, et al. Radiofrequency catheter abla-
tion of ventricular arrhythmias in patients with hypertrophic cardiomyopathy:
safety and feasibility. Heart Rhythm. 2010;7:1036–1042.
10. Igarashi M, Nogami A, Kurosaki K, et al. Radiofrequency catheter ablation
of ventricular tachycardia in patients with hypertrophic cardiomyopathy and
apical aneurysm. J Am Coll Cardiol EP. 2018;4:339–350.
11. Dukkipati SR, d’Avila A, Soejima K, et al. Long-term outcomes of combined
epicardial and endocardial ablation of monomorphic ventricular tachycar-
dia related to hypertrophic cardiomyopathy. Circ Arrhythm Electrophysiol.
2011;4:185–194.
12. Borne RT, Varosy PD, Masoudi FA. Implantable cardioverter-defibrillator
shocks: epidemiology, outcomes, and therapeutic approaches. JAMA Intern
Med. 2013;173:859–865.
13. Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society
for Heart Lung Transplantation listing criteria for heart transplantation: a
10-year update. J Heart Lung Transplant. 2016;35:1–23.
14. Echt DS, Liebson PR, Mitchell LB, et al. Mortality and morbidity in patients
receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Sup-
pression Trial. N Engl J Med. 1991;324:781–788.
15. Raskin JS, Liu JJ, Abrao A, et al. Minimally invasive posterior extrapleural
thoracic sympathectomy in children with medically refractory arrhythmias.
Heart Rhythm. 2016;13:1381–1385.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e67
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
16. Price J, Mah DY, Fynn-Thompson FL, et al. Successful bilateral thora-
coscopic sympathectomy for recurrent ventricular arrhythmia in a pedi-
atric patient with hypertrophic cardiomyopathy. HeartRhythm Case Rep.
2020;6:23–26.
17. Pfammatter JP, Paul T, Lehmann C, et al. Efficacy and proarrhythmia
of oral sotalol in pediatric patients. J Am Coll Cardiol. 1995;26:1002–
1007.
18. Maron BJ, Shen WK, Link MS, et al. Efficacy of implantable cardioverter-
defibrillators for the prevention of sudden death in patients with hypertro-
phic cardiomyopathy. N Engl J Med. 2000;342:365–373.
19. Garg J, Kewcharoen J, Shah K, et al. Clinical outcomes of radiofrequency
catheter ablation of ventricular tachycardia in patients with hypertrophic car-
diomyopathy. J Cardiovasc Electrophysiol. 2023;34:219–224.
20. Nguyen A, Schaff HV. Electrical storms in patients with apical aneurysms
and hypertrophic cardiomyopathy with midventricular obstruction: a case
series. J Thorac Cardiovasc Surg. 2017;154:e101–e103.
9.1. Recreational Physical Activity and Competitive Sports
1. Saberi S, Wheeler M, Bragg-Gresham J, et al. Effect of moderate-
intensity exercise training on peak oxygen consumption in patients
with hypertrophic cardiomyopathy: a randomized clinical trial. JAMA.
2017;317:1349–1357.
2. Klempfner R, Kamerman T, Schwammenthal E, et al. Efficacy of exercise
training in symptomatic patients with hypertrophic cardiomyopathy: results
of a structured exercise training program in a cardiac rehabilitation center.
Eur J Prev Cardiol. 2015;22:13–19.
3. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on
the primary prevention of cardiovascular disease: a report of the American
College of Cardiology/American Heart Association Task Force on Clinical
Practice Guidelines. Circulation. 2019;140:e596–e646.
4. Baggish AL, Ackerman MJ, Lampert R. Competitive sport participation
among athletes with heart disease: a call for a paradigm shift in decision
making. Circulation. 2017;136:1569–1571.
5. Lampert R, Ackerman MJ, Marino BS, et al. Vigorous exercise in patients
with hypertrophic cardiomyopathy. JAMA Cardiol. 2023;8:595–605.
6. Christiaans I, Birnie E, Bonsel GJ, et al. Manifest disease, risk factors
for sudden cardiac death, and cardiac events in a large nationwide co-
hort of predictively tested hypertrophic cardiomyopathy mutation carri-
ers: determining the best cardiological screening strategy. Eur Heart J.
2011;32:1161–1170.
7. Dejgaard LA, Haland TF, Lie OH, et al. Vigorous exercise in patients with
hypertrophic cardiomyopathy. Int J Cardiol. 2018;250:157–163.
8. Kwon S, Lee HJ, Han KD, et al. Association of physical activity with all-
cause and cardiovascular mortality in 7666 adults with hypertrophic car-
diomyopathy (HCM): more physical activity is better. Br J Sports Med.
2021;55:1034–1040.
9. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of sports for athletes
with implantable cardioverter-defibrillators: results of a prospective, multina-
tional registry. Circulation. 2013;127:2021–2030.
10. Lampert R, Olshansky B, Heidbuchel H, et al. Safety of sports for athletes
with implantable cardioverter-defibrillators: long-term results of a prospec-
tive multinational registry. Circulation. 2017;135:2310–2312.
11. Pelliccia A, Lemme E, Maestrini V, et al. Does sport participation
worsen the clinical course of hypertrophic cardiomyopathy? Clini-
cal outcome of hypertrophic cardiomyopathy in athletes. Circulation.
2018;137:531–533.
12. Turkowski KL, Bos JM, Ackerman NC, et al. Return-to-play for athletes with
genetic heart diseases. Circulation. 2018;137:1086–1088.
13. Tobert KE, Bos JM, Garmany R, et al. Return-to-play for athletes with long
QT syndrome or genetic heart diseases predisposing to sudden death. J Am
Coll Cardiol. 2021;78:594–604.
14. Martinez KA, Bos JM, Baggish AL, et al. Return-to-play for elite athletes
with genetic heart diseases predisposing to sudden cardiac eeath. J Am Coll
Cardiol. 2023;82:661–670.
15. Ainsworth B E, Haskell WL, Herrmann SD, et al. 2011 compendium of physi-
cal activities: a second update of codes and MET values. Med Sci Sports
Exerc. 2011;43:1575–1581.
16. Borg G. Ratings of perceived exertion and heart rates during short-term
cycle exercise and their use in a new cycling strength test. Int J Sports Med.
1982;3:153–158.
17. Saberi S, Day SM. Exercise and hypertrophic cardiomyopathy: time for a
change of heart. Circulation. 2018;137:419–421.
18. Maron BJ, Nishimura RA, Maron MS. Shared decision-making in HCM. Nat
Rev Cardiol. 2017;14:125–126.
19. Maron BJ, Doerer JJ, Haas TS, et al. Sudden deaths in young competitive
athletes: analysis of 1866 deaths in the United States, 1980-2006. Circula-
tion. 2009;119:1085–1092.
20. Thiene G, Rizzo S, Schiavon M, et al. Structurally normal hearts are uncom-
monly associated with sudden deaths in athletes and young people. J Am
Coll Cardiol. 2019;73:3031–3032.
21. Bagnall RD, Weintraub RG, Ingles J, et al. A prospective study of sud-
den cardiac death among children and young adults. N Engl J Med.
2016;374:2441–2452.
22. Corrado D, Basso C, Rizzoli G, et al. Does sports activity enhance the
risk of sudden death in adolescents and young adults? J Am Coll Cardiol.
2003;42:1959–1963.
23. Harmon KG, Drezner JA, Maleszewski JJ, et al. Pathogeneses of sudden
cardiac death in National Collegiate Athletic Association athletes. Circ Ar-
rhythm Electrophysiol. 2014;7:198–204.
24. Ullal AJ, Abdelfattah RS, Ashley EA, et al. Hypertrophic cardiomyopathy as
a cause of sudden cardiac death in the young: a meta-analysis. Am J Med.
2016;129:486–496. e482.
25. Eckart RE, Shry EA, Burke AP, et al. Sudden death in young adults: an
autopsy-based series of a population undergoing active surveillance. J Am
Coll Cardiol. 2011;58:1254–1261.
26. Harmon KG, Asif IM, Klossner D, et al. Incidence of sudden cardiac
death in National Collegiate Athletic Association athletes. Circulation.
2011;123:1594–1600.
27. Weissler-Snir A, Allan K, Cunningham K, et al. Hypertrophic cardiomyopathy-
related sudden cardiac death in young people in Ontario. Circulation.
2019;140:1706–1716.
28. Aro AL, Nair SG, Reinier K, et al. Population burden of sudden
death associated with hypertrophic cardiomyopathy. Circulation.
2017;136:1665–1667.
29. Landry CH, Allan KS, Connelly KA, et al. Sudden cardiac arrest during par-
ticipation in competitive sports. N Engl J Med. 2017;377:1943–1953.
30. Finocchiaro G, Radaelli D, D’Errico S, et al. Sudden cardiac death
among adolescents in the United Kingdom. J Am Coll Cardiol.
2023;81:1007–1017.
31. Petek BJ, Churchill TW, Moulson N, et al. Sudden cardiac death in Na-
tional Collegiate Athletic Association athletes: a 20-year study. Circulation.
2024;149:80–89.
32. Etheridge SP, Saarel EV, Martinez MW. Exercise participation and shared
decision-making in patients with inherited channelopathies and cardiomy-
opathies. Heart Rhythm. 2018;15:915–920.
33. Pelto HF, Drezner JA. Design and implementation of an emergency ac-
tion plan for sudden cardiac arrest in sport. J Cardiovasc Transl Res.
2020;13:331–338.
34. Reineck E, Rolston B, Bragg-Gresham JL, et al. Physical activity and other
health behaviors in adults with hypertrophic cardiomyopathy. Am J Cardiol.
2013;111:1034–1039.
35. Sweeting J, Ingles J, Timperio A, et al. Physical activity in hypertrophic car-
diomyopathy: prevalence of inactivity and perceived barriers. Open Heart.
2016;3:e000484.
36. Piercy KL, Troiano RP, Ballard R M, et al. The Physical Activity Guidelines for
Americans. JAMA. 2018;320:2020–2028.
37. Ommen SR, Mital S, Burke MA, et al. 2020 AHA/ACC guideline for the
diagnosis and treatment of patients with hypertrophic cardiomyopathy:
a report of the American College of Cardiology/American Heart As-
sociation Joint Committee on Clinical Practice Guidelines. Circulation.
2020;142:e558–e631.
38. Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC guidelines on
diagnosis and management of hypertrophic cardiomyopathy: the Task
Force for the Diagnosis and Management of Hypertrophic Cardio-
myopathy of the European Society of Cardiology (ESC). Eur Heart J.
2014;35:2733–2779.
9.2. Occupation in Patients With HCM
1. US Department of Transportation, Federal Aviation Administration. Medical
Certification. Accessed September 14, 2022. https://www.fmcsa.dot.gov/
regulations/medical/cardiovascular-advisory-panelguidelines-medical-
examination-commercial-motor
2. D’Arcy JL, Manen O, Davenport ED, et al. Heart muscle disease manage-
ment in aircrew. Heart. 2019;105:s50–s56.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e68
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
9.3. Pregnancy in Patients With HCM
1. Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guide-
line for the management of patients with valvular heart disease: a
report of the American College of Cardiology/American Heart Asso-
ciation Joint Committee on Clinical Practice Guidelines. Circulation.
2021;143:e72–e227.
2. Xu Z, Fan J, Luo X, et al. Anticoagulation regimens during pregnancy in pa-
tients with mechanical heart valves: a systematic review and meta-analysis.
Can J Cardiol. 2016;32:1248.e1–1248.e9.
3. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. 2018 ESC
guidelines for the management of cardiovascular diseases during preg-
nancy. Eur Heart J. 2018;39:3165–3241.
4. Pieper PG, Walker F. Pregnancy in women with hypertrophic cardiomyopa-
thy. Neth Heart J. 2013;21:14–18.
5. Easter SR, Rouse CE, Duarte V, et al. Planned vaginal delivery and car-
diovascular morbidity in pregnant women with heart disease. Am J Obstet
Gynecol. 2020;222:77.e1–77.e11.
6. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC guidelines for
the management of cardiomyopathies. Eur Heart J. 2023;44:3503–
3626.
7. Goland S, van Hagen IM, Elbaz-Greener G, et al. Pregnancy in women with
hypertrophic cardiomyopathy: data from the European Society of Cardiology
initiated Registry of Pregnancy and Cardiac disease (ROPAC). Eur Heart J.
2017;38:2683–2690.
8. Thaman R, Varnava A, Hamid MS, et al. Pregnancy related complications in
women with hypertrophic cardiomyopathy. Heart. 2003;89:752–756.
9. Billebeau G, Etienne M, Cheikh-Khelifa R, et al. Pregnancy in women with a
cardiomyopathy: outcomes and predictors from a retrospective cohort. Arch
Cardiovasc Dis. 2018;111:199–209.
10. Autore C, Conte MR, Piccininno M, et al. Risk associated with pregnan-
cy in hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002;40:1864–
1869.
11. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagno-
sis and management of atrial fibrillation developed in collaboration with the
European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J.
2021;42:373–498.
12. Guttmann OP, Rahman MS, O’Mahony C, et al. Atrial fibrillation and throm-
boembolism in patients with hypertrophic cardiomyopathy: systematic re-
view. Heart. 2014;100:465–472.
13. Guttmann OP, Pavlou M, O’Mahony C, et al. Prediction of thrombo-embolic
risk in patients with hypertrophic cardiomyopathy (HCM Risk-CVA). Eur J
Heart Fail. 2015;17:837–845.
14. Maron BJ, Olivotto I, Bellone P, et al. Clinical profile of stroke in
900 patients with hypertrophic cardiomyopathy. J Am Coll Cardiol.
2002;39:301–307.
15. Areia AL, Mota-Pinto A. Experience with direct oral anticoagulants in
pregnancy-a systematic review. J Perinat Med. 2022;50:457–461.
16. CAMZYOS [package insert]. Bristol-Myers Squibb Company; 2022. Ac-
cessed September 14, 2022. https://packageinserts.bms.com/pi/pi_
camzyos.pdf.
9.4. Patients With Comorbidities
1. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA
guideline on the primary prevention of cardiovascular disease: a
report of the American College of Cardiology/American Heart As-
sociation Task Force on Clinical Practice Guidelines. Circulation.
2019;140:e596–e646.
2. Canepa M, Sorensen LL, Pozios I, et al. Comparison of clinical presentation,
left ventricular morphology, hemodynamics, and exercise tolerance in obese
versus nonobese patients with hypertrophic cardiomyopathy. Am J Cardiol.
2013;112:1182–1189.
3. Olivotto I, Maron BJ, Tomberli B, et al. Obesity and its association to pheno-
type and clinical course in hypertrophic cardiomyopathy. J Am Coll Cardiol.
2013;62:449–457.
4. Fumagalli C, Maurizi N, Day SM, et al. Association of obesity with ad-
verse long-term outcomes in hypertrophic cardiomyopathy. JAMA Cardiol.
2020;5:65–72.
5. Eleid MF, Konecny T, Orban M, et al. High prevalence of abnormal nocturnal
oximetry in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol.
2009;54:1805–1809.
6. Konecny T, Brady PA, Orban M, et al. Interactions between sleep disordered
breathing and atrial fibrillation in patients with hypertrophic cardiomyopathy.
Am J Cardiol. 2010;105:1597–1602.
7. Konecny T, Geske JB, Ludka O, et al. Decreased exercise capacity and
sleep-disordered breathing in patients with hypertrophic cardiomyopathy.
Chest. 2015;147:1574–1581.
8. Wang S, Cui H, Song C, et al. Obstructive sleep apnea is associated with
nonsustained ventricular tachycardia in patients with hypertrophic obstruc-
tive cardiomyopathy. Heart Rhythm. 2019;16:694–701.
9. Balaji S, DiLorenzo MP, Fish FA, et al. Impact of obesity on left ventricu-
lar thickness in children with hypertrophic cardiomyopathy. Pediatr Cardiol.
2019;40:1253–1257.
10. Harper AR, Goel A, Grace C, et al. Common genetic variants and modifi-
able risk factors underpin hypertrophic cardiomyopathy susceptibility and
expressivity. Nat Genet. 2021;53:135–142.
11. Ho CY, Day SM, Ashley EA, et al. Genotype and lifetime burden of
disease in hypertrophic cardiomyopathy: insights from the Sar-
comeric Human Cardiomyopathy Registry (SHaRE). Circulation.
2018;138:1387–1398.
12. Gruner C, Ivanov J, Care M, et al. Toronto hypertrophic cardiomyopathy
genotype score for prediction of a positive genotype in hypertrophic cardio-
myopathy. Circ Cardiovasc Genet. 2013;6:19–26.
13. Claes GR, van Tienen FH, Lindsey P, et al. Hypertrophic remodelling in car-
diac regulatory myosin light chain (MYL2) founder mutation carriers. Eur
Heart J. 2016;37:1815–1822.
14. Ho CY, Day SM, Axelsson A, et al. Valsartan in early-stage hypertrophic car-
diomyopathy: a randomized phase 2 trial. Nat Med. 2021;27:1818–1824.
10.1. Refining the Diagnosis of HCM
1. Captur G, Manisty CH, Raman B, et al. Maximal wall thickness measurement
in hypertrophic cardiomyopathy: biomarker variability and its impact on clini-
cal care. J Am Coll Cardiol Img. 2021;14:2123–2134.
10.2. Developing Therapies to Attenuate or Prevent
Disease Progression
1. Ho CY, Day SM, Axelsson A, et al. Valsartan in early-stage hypertrophic car-
diomyopathy: a randomized phase 2 trial. Nat Med. 2021;27:1818–1824.
2. Green EM, Wakimoto H, Anderson RL, et al. A small-molecule inhibitor of
sarcomere contractility suppresses hypertrophic cardiomyopathy in mice.
Science. 2016;351:617–621.
10.3. Improving Care for Nonobstructive HCM
1. Heitner SB, Jacoby D, Lester SJ, et al. Mavacamten treatment for ob-
structive hypertrophic cardiomyopathy: a clinical trial. Ann Intern Med.
2019;170:741–748.
2. Ho CY, Olivotto I, Jacoby D, et al. Study design and rationale of EXPLOR-
ER-HCM: evaluation of mavacamten in adults with symptomatic obstruc-
tive hypertrophic cardiomyopathy. Circ Heart Fail. 2020;13:e006853.
3. Desai MY, Owens A, Geske JB, et al. Dose-blinded myosin inhibi-
tion in patients with obstructive hypertrophic cardiomyopathy referred
for septal reduction therapy: outcomes through 32 weeks. Circulation.
2023;147:850–863.
4. Ho CY, Mealiffe ME, Bach RG, et al. Evaluation of mavacamten in symptom-
atic patients with nonobstructive hypertrophic cardiomyopathy. J Am Coll
Cardiol. 2020;75:2649–2660.
5. Maron MS, Masri A, Choudhury L, et al. Phase 2 study of aficamten in
patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol.
2023;81:34–45.
10.4. Improving and Expanding Risk Stratification
1. Maron MS, Rowin EJ, Wessler BS, et al. Enhanced American College of
Cardiology/American Heart Association strategy for prevention of sudden
cardiac death in high-risk patients with hypertrophic cardiomyopathy. JAMA
Cardiol. 2019;4:644–657.
2. O’Mahony C, Tome-Esteban M, Lambiase PD, et al. A validation study of
the 2003 American College of Cardiology/European Society of Cardi-
ology and 2011 American College of Cardiology Foundation/American
Heart Association risk stratification and treatment algorithms for sud-
den cardiac death in patients with hypertrophic cardiomyopathy. Heart.
2013;99:534–541.
3. Maron BJ, Spirito P, Shen W-K, et al. Implantable cardioverter-defibrillators
and prevention of sudden cardiac death in hypertrophic cardiomyopathy.
JAMA. 2007;298:405–412.
4. Habib M, Adler A, Fardfini K, et al. Progression of myocardial fibrosis in hy-
pertrophic cardiomyopathy: a cardiac magnetic resonance study. J Am Coll
Cardiol Img. 2021;14:947–958.
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e69
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
5. Heydari BSA, Jerosch-Herold M, et al. 3-Dimensional strain analysis of
hypertrophic cardiomyopathy: insights from the NHLBI international HCM
registry. J Am Coll Cardiol Img. 2023;16:478–491.
6. Fahmy ASRE, Jaafar N, et al. Radiomics of late gadolinium enhance-
ment reveals prognostic value of myocardial scar heterogeneity in
hypertrophic cardiomyopathy. J Am Coll Cardiol Img. 2023;S1936-
1878X(1923)00222-X.
10.5. Arrhythmia Management
1. Moore JC, Trager L, Anzia LE, et al. Dofetilide for suppression of atrial fibril-
lation in hypertrophic cardiomyopathy: a case series and literature review.
Pacing Clin Electrophysiol. 2018;41:396–401.
2. Robinson K, Frenneaux MP, Stockins B, et al. Atrial fibrillation in hy-
pertrophic cardiomyopathy: a longitudinal study. J Am Coll Cardiol.
1990;15:1279–1285.
3. Miller CAS MM, Estes NAM, et al. Safety, side effects and relative efficacy
of medications for rhythm control of atrial fibrillation in hypertrophic cardio-
myopathy. Am J Cardiol. 2019;123:1859–1862.
4. Providencia R, Elliott P, Patel K, et al. Catheter ablation for atrial fibrillation in
hypertrophic cardiomyopathy: a systematic review and meta-analysis. Heart.
2016;102:1533–1543.
5. Zhao D-S, Shen Y, Zhang Q, et al. Outcomes of catheter ablation of atrial
fibrillation in patients with hypertrophic cardiomyopathy: a systematic review
and meta-analysis. Europace. 2016;18:508–520.
6. Kramer CM, DiMarco JP, Kolm P, et al. Predictors of major atrial fibrillation
endpoints in the National Heart, Lung, and Blood Institute HCMR. J Am Coll
Cardiol EP. 2021;7:1376–1386.
7. Reddy VY, Neuzil P, Koruth JS, et al. Pulsed field ablation for pulmonary vein
isolation in atrial fibrillation. J Am Coll Cardiol. 2019;74:315–326.
10.6. Expanding Understanding of the Genetic
Architecture of HCM
1. Kelly MA, Caleshu C, Morales A, et al. Adaptation and validation of the
ACMG/AMP variant classification framework for MYH7-associated inher-
ited cardiomyopathies: recommendations by ClinGen’s Inherited Cardiomy-
opathy Expert Panel. Genet Med. 2018;20:351–359.
2. Harper AR, Goel A, Grace C, et al. Common genetic variants and modifi-
able risk factors underpin hypertrophic cardiomyopathy susceptibility and
expressivity. Nat Genet. 2021;53:135–142.
3. Tadros R, Francis C, Xu X, et al. Shared genetic pathways contribute to risk
of hypertrophic and dilated cardiomyopathies with opposite directions of
effect. Nat Genet. 2021;53:128–134.
Appendix 1. Author Relationships With Industry and Other Entities—2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline
for the Management of Hypertrophic Cardiomyopathy
Committee
Member Employment Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal
Research
Institutional,
Organizational,
or Other
Financial Benefit Expert Witness
Steve R.
Ommen, Chair
Mayo Clinic—Director,
Hypertrophic
Cardiomyopathy Clinic
None None None None None None
Carolyn Y. Ho,
Vice Chair
Brigham & Women’s
Hospital—Director,
Cardiovascular
Genetics Center
RELEVANT
• Bristol Myers
Squibb
• Cytokinetics
NOT RELEVANT
• Rocket
Pharmaceuticals
• Viz.ai
None None RELEVANT
• Cytokinetics,
PI*
• Pfizer, PI*
NOT RELEVANT
• Biomarin*
• Novartis‡
RELEVANT
• Bristol Myers
Squibb*
None
Irfan M. Asif University of Alabama
at Birmingham—
Associate Dean,
Primary Care and Rural
Health; Professor and
Chair, Department of
Family and Community
None None None None NOT RELEVANT
• CMS*
• HRSA*
None
Seshadri Balaji Oregon Health & Sci-
ence University—Pro-
fessor of Pediatrics,
Division of Cardiology,
School of Medicine;
Director, Pediatric
Electrophysiology
RELEVANT
• Janssen
Pharmaceuticals
• Milestone
Pharmaceuticals
None None RELEVANT
• Medtronic† None NOT RELEVANT
• Defendant,
Sudden death
evaluation,
2022
Michael A.
Burke
Emory University
School of
Medicine—Associate
Professor of Medicine
None None None None NOT RELEVANT
• Pfizer‡ None
Sharlene M.
Day
University of Pennsyl-
vania—Director, Trans-
lational Research, Divi-
sion of Cardiovascular
Medicine and Cardio-
vascular Institute
None None None RELEVANT
• Bristol Myers
Squibb*
• Lexicon Phar-
maceuticals*
NOT RELEVANT
• Cytokinetics
(DSMB)
None None
(Continued )
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e70
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
Committee
Member Employment Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal
Research
Institutional,
Organizational,
or Other
Financial Benefit Expert Witness
Joseph A.
Dearani
Mayo Clinic—Director
of Pediatric and Adult
Congenital Heart
Surgery; Professor of
Surgery
None None None None None None
Kelly C. Epps Inova—Interventional
Cardiologist
None None None None None None
Lauren
Evanovich
Patient Representative None None None None None None
Victor A. Ferrari University of Penn-
sylvania—Chair, Penn
Cardiovascular Imaging
Council, Depts. of Med-
icine, Radiology and
Penn Cardiovascular
Institute; Professor Car-
diovascular Medicine;
Professor, Radiology
None None None NOT RELEVANT
• NHLBI/NIH
(DSMB)†
• JCMR†
None None
José A. Joglar UT Southwestern—
Program Director,
Clinical Cardiac
Electrophysiology
Fellowship Program
None None None None None None
Sadiya S. Khan Northwestern
University—Assistant
Professor of Medicine
None None None None None None
Jeffrey J. Kim Baylor College of
Medicine—Director,
Electrophysiology &
Pacing; Professor, Pe-
diatric Cardiology
None None None None None None
Michelle M.
Kittleson
Cedars-Sinai—Direc-
tor of Education in
Heart Failure and
Transplantation; Direc-
tor of Heart Failure
Research; Professor
of Medicine
None NOT RELEVANT
• Encore
Medical
Education
• Journal of
Heart and Lung
Transplantation
None None NOT RELEVANT
• Actelion‡
• Eidos‡
• Gilead (One
Legacy/Baylor)‡
• NIH‡
• Sanofi
(Genzyme)‡
• United
Therapeutics‡
None
Chayakrit
Krittanawong
Baylor College of
Medicine—Staff
Physician
None None None None None None
Matthew W.
Martinez
Atlantic Health
System/Morristown
Medical Center—
Director, Sports
Cardiology; Director,
Hypertrophic
Cardiomyopathy
Program
RELEVANT
• Bristol Myers
Squibb
NOT RELEVANT
• Major League
Soccer
None None None RELEVANT
• Cytokinetics‡ None
Seema Mital Hospital for Sick
Children—Head,
Cardiovascular
Research; Staff
Cardiologist, Heart
Function and
Transplant Program
RELEVANT
• Bristol Myers
Squibb
• Tenaya
Therapeutics
None None None None None
Appendix 1. Continued
(Continued )
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e71
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
Committee
Member Employment Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal
Research
Institutional,
Organizational,
or Other
Financial Benefit Expert Witness
Srihari S.
Naidu
New York Medical
College—Professor of
Medicine; Westches-
ter Medical Center—
Director, HCM Center
and Cardiac Cath
Labs
RELEVANT
• Bristol Myers
Squibb
• Cytokinetics
None None None None None
Sara Saberi University of Michigan
Health Systems—As-
sistant Profession,
Division of Cardiovas-
cular Medicine
RELEVANT
• Bristol Myers
Squibb*
• Cytokinetics
None None RELEVANT
• Bristol Myers
Squibb†
• Cytokinetics†
• Novartis†
NOT RELEVANT
• HCMS† None
Christopher
Semsarian
The University of
Sydney—Professor
of Medicine; Cente-
nary Institute—Head,
Molecular Cardiology
Program; Royal Prince
Alfred Hospital, Cen-
tral Clinical
School—Cardiologist
None None None None None None
Sabrina
Times§
AHA/ACC—Science
and Health Advisor,
Guidelines
None None None None None None
Cynthia
Burstein
Waldman
HCMBeat—Founder
and Editor; MGM,
Vice President, Library
Rights Management
None None None None None None
This table represents all relationships of committee members with industry and other entities that were reported by authors, including those not deemed to be relevant
to this document, at the time this document was under development. The table does not necessarily reflect relationships with industry at the time of publication. A person
is deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of
≥$5000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previ-
ous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted.
Please refer to https://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or
additional information about the ACC/AHA Disclosure Policy for Writing Committees.
*Significant relationship.
†No financial benefit.
‡This disclosure was entered under the Clinical Trial Enroller category in the ACC’s disclosure system. To appear in this category, the author acknowledges that there
is no direct or institutional relationship with the trial sponsor as defined in the (ACCF or AHA/ACC) Disclosure Policy for Writing Committees.
§Sabrina Times is an AHA/ACC joint staff member and acts as the Guideline Advisor for the “2024 AHA/ACC/AMSSM/HRS/PACES Guideline for the Manage-
ment of Hypertrophic Cardiomyopathy.” No relevant relationships to report. Nonvoting author on measures and not included/counted in the RWI balance for this writing
committee.
ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; AMSSM, American Medical
Society for Sports Medicine; CMS, Centers for Medicare & Medicaid Services; DSM B, data and safety monitoring board; HCM, hypertrophic cardiomyopathy; HCMS, Hy-
pertrophic Cardiomyopathy Medical Society; HRS, Heart Rhythm Society; H RSA, Health Resources & Services Administration; JCMR; Journal of Cardiovascular Magnetic
Resonance; NHLBI, National Heart, Lung, and Blood Institute; NIH, National Institutes of Health; PACES, Pediatric & Congenital Electrophysiology Society; PI, principal
investigator; RWI, relationships with industry and other entities; and UT, The University of Texas.
Appendix 1. Continued
Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive)—2024 AHA/ACC/AMSSM/HRS/
PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy
Reviewer Representation Employment Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal
Research
Institutional,
Organizational,
or Other
Financial Benefit
Expert
Witness
Mark S. Link,
Chair
AHA/ACC
HCM Guideline
Peer Review
Committee
UT
Southwestern
Medical Center
None None None None • Journal Watch
Cardiology
• Circulation,
Associate
Editor†
• UpToDate†
None
(Continued )
Downloaded from http://ahajournals.org by on May 10, 2024
CLINICAL STATEMENTS
AND GUIDELINES
TBD TBD, 2024 Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250e72
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
Reviewer Representation Employment Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal
Research
Institutional,
Organizational,
or Other
Financial Benefit
Expert
Witness
Anandita
Agarwala
AHA/ACC
HCM Guideline
Peer Review
Committee
Baylor Scott &
White
Health—The
Heart Hospital
Baylor Plano
None None None • NIH* None None
Chad Asplund AHA/ACC
HCM Guideline
Peer Review
Committee,
representing
AMSSM
Georgetown
University
None None None None None None
Michael Ayers AHA/ACC
HCM Guideline
Peer Review
Committee
University of
Virginia
• Atheneum
• Bristol Myers
Squibb†
• HFSA
• Bristol
Myers
Squibb†
None None • Cytokinetics‡ • Plaintiff,
Chest pain,
2023
C. Anwar
Chahal
AHA/ACC
HCM Guideline
Peer Review
Committee
Wellspan
Health;
Mayo Clinic
Barts Heart
Centre
None None None None None None
Jonathan
Chrispin
AHA/ACC
HCM Guideline
Peer Review
Committee
Johns Hopkins
University
• Abbott†
• Biosense
Webster
• Boston
Scientific*
None None None • Abbott‡
• Biosense
Webster‡
None
Aarti Dalal AHA/ACC
HCM Guideline
Peer Review
Committee
Vanderbilt
University
• Medtronic† None None None None None
Alejandro E.
De Feria Alsina
AHA/ACC
HCM Guideline
Peer Review
Committee
University of
Pennsylvania
None None None None None None
Jonathan
Drezner
AHA/ACC
HCM Guideline
Peer Review
Committee
University of
Washington
None None None • AMSSM*
• National
Center for
Catastrophic
Sports Injury
Research*
None None
Rajesh Kabra AHA/ACC
HCM Guideline
Peer Review
Committee
Kansas City
Heart Rhythm
Institute
University of
Tennessee
Health Science
Center
• Volta Medical None None None • Abbott,
Fellowship
Grant†
• Biosense
Webster,
Fellowship
Grant†
• Medtronic,
Fellowship
Grant†
• Iqvia Biotech‡
• Medtronic‡
None
Sabeeda
Kadavath
AHA/ACC
HCM Guideline
Peer Review
Committee
St. Bernards
Medical Center
None None None None None None
Elizabeth S.
Kaufman
AHA/ACC HCM
Guideline Peer
Review Commit-
tee Member, rep-
resenting HRS
The
MetroHealth
System
None None None None • CIH‡ None
(Continued )
Appendix 2. Continued
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CLINICAL STATEMENTS
AND GUIDELINES
Circulation. 2024;149:e00–e00. DOI: 10.1161/CIR.0000000000001250 TBD TBD, 2024 e73
Ommen et al 2024 Hypertrophic Cardiomyopathy Guideline
Appendix 2. Continued
Reviewer Representation Employment Consultant
Speakers
Bureau
Ownership/
Partnership/
Principal
Personal
Research
Institutional,
Organizational,
or Other
Financial Benefit
Expert
Witness
Sabra Lewsey AHA/ACC
HCM Guideline
Peer Review
Committee
Johns Hopkins
University
None None None None • Associate of
BlackCardiolo-
gists, Volunteer
position*
None
James P.
MacNamara
AHA/ACC
HCM Guideline
Peer Review
Committee
UT
Southwestern
Medical Center
• Lexicon None None • Boehringer
Ingelheim
• Bristol Myers
Squibb†
• Cytokinetics†
• Sardacor†
None None
Anjali Owens AHA/ACC
HCM Guideline
Peer Review
Committee
University of
Pennsylvania
• BioMarin
Pharmaceuti-
cals
• Bristol Myers
Squibb†
• Cytokinetics†
• Edgewise
Therapeutics
• Lexeo
Therapeutics
• Lexicon
• Myokardia†
• Pfizer
• Renovacor
• Stealth Bio-
therapeutics
• Tenaya
Therapeutics
None None • Array
Biopharma,
PI*
None None
Hena Patel AHA/ACC
HCM Guideline
Peer Review
Committee
University of
Chicago
None None None None None None
Nosheen Reza AHA/ACC
HCM Guideline
Peer Review
Committee, rep-
resenting ACC/
AHA JCPM
University of
Pennsylvania
• Bristol Myers
Squibb*
• Roche
Diagnostics
• Zoll
None None • NIH† • Alleviant
Medical, Inc.
• AstraZeneca*
• Bristol Myers
Squibb‡
• Cytokinetics*‡
• Pfizer‡
None
Aldo L.
Schenone
AHA/ACC
HCM Guideline
Peer Review
Committee
Montefiore
Medical Center
None • Bristol
Myers
Squibb
None None None None
Daniel Swistel AHA/ACC
HCM Guideline
Peer Review
Committee
New York
University
None None None None None None
Jose Vargas AHA/ACC
HCM Guideline
Peer Review
Committee
US
Department
of Veterans
Affairs
• Bioclinica† None None None None None
This table represents all reviewers’ relationships with industry and other entities that were reported at the time of peer review, including those not deemed to be rel-
evant to this document, at the time this document was under review. The table does not necessarily reflect relationships with industry at the time of publication. A person is
deemed to have a significant interest in a business if the interest represents ownership of ≥5% of the voting stock or share of the business entity, or ownership of ≥$5000
of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person’s gross income for the previous year.
Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Please
refer to https://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional
information about the ACC/AHA Disclosure Policy for Writing Committees.
*No financial benefit.
†Significant relationship.
‡This disclosure was entered under the Clinical Trial Enroller category in the ACC’s disclosure system. To appear in this category, the author acknowledges that there
is no direct or institutional relationship with the trial sponsor as defined in the (ACCF or AHA/ACC) Disclosure Policy for Writing Committees.
ACC indicates American College of Cardiology; ACCF, American College of Cardiology Foundation; AHA, American Heart Association; AMSSM; American Medical
Society for Sports Medicine; CIH, Canadian Institute of Health; HC M, hypertrophic cardiomyopathy; HFSA, Heart Failure Society of America; HRS, Heart Rhythm Society;
JCPM, ACC/AHA Joint Committee on Performance Measures, NIH, National Institutes of Health; PACES, Pediatric & Congenital Electrophysiology Society; PI, principal
investigator; and UT, University of Texas.
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