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ESC Guidelines
Guidelines on the management of valvular
heart disease
The Task Force on the Management of Valvular Heart Disease
of the European Society of Cardiology
Authors/Task Force Members, Alec Vahanian (Chairperson) Paris (France)
*
, Helmut Baumgartner,
Vienna (Austria), Jeroen Bax, Leiden (The Netherlands), Eric Butchart, Cardiff (UK), Robert Dion,
Leiden (The Netherlands), Gerasimos Filippatos, Athens (Greece), Frank Flachskampf, Erlangen
(Germany), Roger Hall, Norwich (UK), Bernard Iung, Paris (France), Jaroslaw Kasprzak, Lodz
(Poland), Patrick Nataf, Paris (France), Pilar Tornos, Barcelona (Spain), Lucia Torracca, Milan
(Italy), Arnold Wenink, Leiden (The Netherlands)
ESC Committee for Practice Guidelines (CPG), Silvia G. Priori (Chairperson) (Italy), Jean-Jacques Blanc (France),
Andrzej Budaj (Poland), John Camm (UK), Veronica Dean (France), Jaap Deckers (The Netherlands), Kenneth Dickstein
(Norway), John Lekakis (Greece), Keith McGregor (France), Marco Metra (Italy), Joa
˜
o Morais (Portugal), Ady Osterspey
(Germany), Juan Tamargo (Spain), Jose
´
Luis Zamorano (Spain)
Document Reviewers, Jose
´
Luis Zamorano (CPG Review Coordinator) (Spain), Annalisa Angelini (Italy), Manuel Antunes
(Portugal), Miguel Angel Garcia Fernandez (Spain), Christa Gohlke-Baerwolf (Germany), Gilbert Habib (France),
John McMurray (UK), Catherine Otto (USA), Luc Pierard (Belgium), Jose
`
L. Pomar (Spain), Bernard Prendergast (UK),
Raphael Rosenhek (Austria), Miguel Sousa Uva (Portugal), Juan Tamargo (Spain)
Table of Contents
Preamble ........................... 231
Introduction . . ....................... 232
Why do we need guidelines on valvular heart disease? 232
Contents of these guidelines . . . ........... 232
How to use these guidelines . . . ........... 233
Method of review ..................... 233
Definition of levels of recommendation ........ 233
General comments ..................... 233
Patient evaluation . . . ................. 233
Clinical evaluation . . ................. 233
Echocardiography . . ................. 233
Fluoroscopy ....................... 234
Radionuclide angiography . . . ........... 234
Stress testing ...................... 234
Other non-invasive imaging techniques ....... 235
Biomarkers . ...................... 235
Coronary angiography . ................ 235
Cardiac catheterization ................ 235
Assessment of comorbidity .............. 235
Endocarditis prophylaxis ............... 235
Risk stratification ..................... 235
Aortic regurgitation ..................... 236
Introduction . . ...................... 236
Evaluation . . . ...................... 236
Natural history ...................... 237
Results of surgery .................... 237
Indications for surgery . . ................ 237
Medical therapy ..................... 238
Serial testing . ...................... 238
& The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
*
Corresponding author. Chairperson: Alec Vahanian, Service de Cardiologie, Ho
ˆpital
Bichat AP-HP, 46 rue Henri Huchard, 75018 Paris, France. Tel: þ 33 1 40 25
67 60; fax: þ 33140256732.
E-mail address: alec.vahanian@bch.aphp.fr
European Heart Journal (2007) 28, 230
–
268
doi:10.1093/eurheartj/ehl428
The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized.
No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission
of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of
the ESC.
Disclaimer. The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were
written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override
the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that
patient, and where appropriate and necessary the patient’s guardian or carer. It is also the health professional’s responsibility to verify the rules and
regulations applicable to drugs and devices at the time of prescription.
Special patient populations . . ............. 238
Aortic stenosis ........................ 239
Introduction ........................ 239
Evaluation ......................... 239
Natural history . . . ................... 240
Results of intervention ................. 240
Indications for surgery .................. 241
Indications for balloon valvuloplasty . . . ...... 241
Medical therapy . . ................... 241
Serial testing ....................... 242
Special patient populations . . ............. 242
Mitral regurgitation . . ................... 243
Organic mitral regurgitation . ............. 243
Evaluation ....................... 243
Natural history . . ................... 243
Results of surgery ................... 244
Indications for intervention ............. 244
Medical therapy . ................... 245
Serial testing . . . ................... 245
Ischaemic mitral regurgitation ............. 246
Evaluation ....................... 246
Natural history . . ................... 246
Results of surgery ................... 246
Indications for surgery . . . ............. 246
Functional mitral regurgitation ............. 247
Mitral stenosis ........................ 247
Introduction ........................ 247
Evaluation ......................... 247
Natural history . . . ................... 248
Results of intervention ................. 248
Percutaneous balloon commissurotomy . ...... 248
Surgery ......................... 248
Indications for intervention . . ............. 248
Medical therapy . . ................... 250
Serial testing ....................... 250
Special patient populations . . ............. 250
Tricuspid disease . . . ................... 250
Tricuspid stenosis . . ................... 250
Evaluation ....................... 251
Surgery ......................... 251
Percutaneous intervention . ............. 251
Indications for intervention ............. 251
Medical therapy . ................... 251
Tricuspid regurgitation .................. 251
Evaluation ....................... 251
Natural history . . ................... 252
Results of surgery ................... 252
Indications for surgery . . . ............. 252
Medical therapy . ................... 252
Combined and multiple valve diseases .......... 252
Prosthetic valves . . . ................... 253
Choice of prosthetic valve . . ............. 253
Management after valve replacement . . . ...... 254
Baseline assessment and modalities of follow-up . 254
Antithrombotic management ............. 254
Management of valve thrombosis .......... 256
Management of thrombo-embolism . . . ...... 258
Management of haemolysis and paravalvular leak 258
Management of bioprosthetic failure . . ...... 258
Heart failure . . . ................... 258
Management during non-cardiac surgery . . ...... 258
Clinical predictors of increased perioperative
cardiovascular risk .................. 258
Preoperative clinical evaluation ............ 259
Specific valve lesions .................. 259
Aortic stenosis . . . .................. 259
Mitral stenosis . . . .................. 260
Aortic regurgitation and mitral regurgitation . . . 260
Prosthetic valves . . .................. 260
Endocarditis prophylaxis ................. 260
Perioperative monitoring ................ 260
Management during pregnancy . . ............ 260
Cardiac risk of pregnancy ................ 260
Evaluation of the pregnant patient with heart
valve disease . . . .................. 260
Specific risks related to pregnancy .......... 261
Native valve disease .................. 261
Patients with prosthetic valves ........... 261
Treatment ......................... 261
Aims . . ......................... 262
Methods ......................... 262
Management strategy ................. 262
Delivery ......................... 262
References . ......................... 263
Preamble
Guidelines and Expert Consensus Documents aim to present
management recommendations based on all of the relevant
evidence on a particular subject in order to help physicians
select the best possible management strategies for the indi-
vidual patient suffering from a specific condition, taking into
account the impact on outcome and also the risk
–
benefit
ratio of a particular diagnostic or therapeutic procedure.
Numerous studies have demonstrated that patient outcomes
improve when guideline recommendations, based on the rig-
orous assessment of evidence-based research, are applied in
clinical practice.
A great number of Guidelines and Expert Consensus
Documents have been issued in recent years by the
European Society of Cardiology (ESC) and also by other
organizations or related societies. The profusion of docu-
ments can put at stake the authority and credibility of
guidelines, particularly if discrepancies appear between
different documents on the same issue, as this can lead to
confusion in the minds of physicians. In order to avoid
these pitfalls, the ESC and other organizations have issued
recommendations for formulating and issuing Guidelines
and Expert Consensus Documents. The ESC recommen-
dations for guidelines production can be found on the ESC
website.
1
It is beyond the scope of this preamble to recall
all but the basic rules.
In brief, the ESC appoints experts in the field to carry out
a comprehensive review of the literature, with a view to
making a critical evaluation of the use of diagnostic and
therapeutic procedures and assessing the risk
–
benefit ratio
of the therapies recommended for management and/or pre-
vention of a given condition. Estimates of expected health
outcomes are included, where data exist. The strength of
evidence for or against particular procedures or treatments
is weighed according to predefined scales for grading
recommendations and levels of evidence, as outlined in
what follows.
The Task Force members of the writing panels, as well as
the document reviewers, are asked to provide disclosure
statements of all relationships they may have which might
ESC Guidelines 231
be perceived as real or potential conflicts of interest. These
disclosure forms are kept on file at the European Heart
House, headquarters of the ESC, and can be made available
by written request to the ESC President. Any changes in con-
flict of interest that arise during the writing period must be
notified to the ESC.
Guidelines and recommendations are presented in
formats that are easy to interpret. They should help phys-
icians make clinical decisions in their daily routine prac-
tice by describing the range of generally acceptable
approaches to diagnosis and treatment. However, the ulti-
mate judgement regarding the care of an individual
patient must be made by the physician in charge of the
patient’s care.
The ESC Committee for Practice Guidelines (CPG) super-
vises and coordinates the preparation of new Guidelines
and Expert Consensus Documents produced by Task Forces,
expert groups, or consensus panels. The Committee is also
responsible for the endorsement of these Guidelines and
Expert Consensus Documents or statements.
Once the document has been finalized and approved by all
the experts involved in the Task Force, it is submitted to
outside specialists for review. In some cases, the document
can be presented to a panel of key opinion leaders in
Europe, specialists in the relevant condition in question,
for discussion and critical review. If necessary, the document
is revised once more and finally approved by the CPG and
selected members of the Board of the ESC and subsequently
published.
After publication, dissemination of the message is of
paramount importance. Publication of executive summaries
and the production of pocket-sized and PDA-downloadable
versions of the recommendations are helpful. However,
surveys have shown that the intended end-users are often
not aware of the existence of guidelines or simply do not
put them into practice. Implementation programmes are
thus necessary and form an important component of the dis-
semination of knowledge. Meetings are organized by the ESC
and directed towards its member National Societies and key
opinion leaders in Europe. Implementation meetings can
also be undertaken at a national level, once the guidelines
have been endorsed by the ESC member societies, and trans-
lated into the local language, when necessary.
All in all, the task of writing Guidelines or Expert
Consensus Document covers not only the integration of
the most recent research, but also the creation of edu-
cational tools, and implementation programmes for the rec-
ommendations. The loop between clinical research, writing
of guidelines, and implementing them into clinical practice
can then only be completed if surveys and registries are
organized to verify that actual clinical practice is in
keeping with what is recommended in the guidelines. Such
surveys and registries also make it possible to check the
impact of strict implementation of the guidelines on
patient outcome.
Introduction
Why do we need guidelines on valvular heart
disease?
Although valvular heart disease (VHD) is less common in
industrialized countries than coronary disease, heart
failure, or hypertension, guidelines are of interest in this
field for several reasons:
.
VHD is common and often requires intervention.
.
Substantial advances have been made in the understand-
ing of its pathophysiology.
.
In recent years, the pati ent population has changed. The con-
tinuousdecline of acute rheumatic fever owing to better pro-
phylaxis of streptococcus infections explains the decrease in
the inci dence of rhe umatic valve disease, whereas increased
life expectancy partially accounts for the increase in the inci-
dence of degenerative valvular diseases in industrialized
countries. The incidence of endocarditis remains stable and
other causes of valve disease are rare.
2,3
Becauseofthepre-
dominance of degenerative valve disease, the two most fre-
quent valve diseases are now calcific aortic stenosis (AS) and
mitral regurgitation (MR), whereas aortic regurgitation (AR)
and mitra l stenosis (MS) have become less common.
3
Older
age is associated with a higher frequency of comorbidity,
which contributes to increased operative risk and renders
decision-making for intervention more complex. Another
important aspect of contemporary heart valve disease is
the growing proportion of previously operated patients who
present with further problems.
3
Conversely, rheumatic
valve disease still remains a major public health problem in
developing countries, where it predominantly affects young
adults.
4
However, rheumatic heart disease is still present in
industrialized countries owing to immigration and sequelae
of rheumatic fever in older patients.
.
Diagnosis is now dominated by echocardiography, which
has become the standard to evaluate valve structure and
function.
.
Treatment has not only developed through the continuing
progress in prosthetic valve technology, but has also been
reoriented by the development of conservative surgical
approaches and the introduction of percutaneous inter-
ventional techniques.
When compared with other heart diseases, there are few
trials in the field of VHD, and randomized clinical trials are
particularly scarce.
The same is true with guidelines: there is only one set of
guidelines in the field of VHD in the USA
5
and four national
guidelines in Europe.
6
–
9
Moreover, published guidelines are
not always consistent due to the lack of randomized clinical
trials as well as the constant evolution of practice. Finally,
data from the recent Euro Heart Survey on VHD show that
there is a real gap between the existing guidelines and
their effective application.
3
It is for this reason that the ESC has produced these guide-
lines, which are the first European guidelines on this topic.
Contents of these guidelines
The guidelines focus on VHD in adults and adolescents, are
oriented towards management, and will not deal with endo-
carditis and congenital valve diseases in adults and
adolescents, since recent guidelines have been produced
by the ESC on these topics.
10,11
Finally, these guidelines
are not intended to include detailed information covered
in ESC Guidelines on other topics, ESC Expert Consensus
Documents, recommendations from the working group on
VHD, and the specific sections of the ESC Textbook on
Cardiology.
12
–
15
232 ESC Guidelines
How to use these guidelines
The committee emphasizes the fact that many factors ulti-
mately determine the most appropriate treatment in indi-
vidual patients within a given community. These factors
include availability of diagnostic equipment, the expertise
of interventional cardiologists and surgeons, especially in
the field of conservative techniques, and, notably, the
wishes of well-informed patients. Furthermore, owing to
the lack of evidence-based data in the field of VHD, most
recommendations are largely the result of expert consensus
opinion. Therefore, deviations from these guidelines may be
appropriate in certain clinical circumstances.
Method of review
A literature review was performed using Medline (PubMed)
for peer-reviewed published literature focusing on the
studies published within the last 10 years. The use of
abstracts was avoided in these guidelines.
Definition of levels of recommendation
The Task Force has classified and ranked the usefulness or
efficacy of the recommended procedures and/or treatments
and the level of evidence as indicated in Table 1. The levels
of recommendation were graded on the basis of the ESC rec-
ommendations.
1
Unlike in the ACC/AHA levels of recommen-
dation, class III (‘conditions for which there is evidence and/
or general agreement that the procedure is not useful/
effective and in some cases may be harmful’) is usually
not used in the ESC guidelines.
General comments
The aims of the evaluation of patients with VHD are to diag-
nose, quantify, and assess the mechanism of VHD as well as
its consequences. The consistency between the results of
investigations and clinical findings should be checked at
each step. Indications for interventions rely mainly on the
comparative assessment of spontaneous prognosis and the
results of intervention according to the characteristics of
VHD and comorbidities.
Patient evaluation
Diagnosis and evaluation of the severity of VHD should be
based on the combined analysis of clinical findings and the
results of investigations.
Clinical evaluation
The aim of analysing case history is to assess present and
past symptoms, as well as looking for associated comorbid-
ity. The patient is questioned on her/his lifestyle to detect
progressive changes in the daily activity in order to limit
the subjectivity of symptom analysis, in particular, in the
elderly.
13
Questioning the patient is also important to
check the quality of follow-up, the effectiveness of prophy-
laxis of endocarditis and, where applicable, of rheumatic
fever. In patients receiving chronic anticoagulant therapy,
it is necessary to assess the stability of anticoagulation
and look for thrombo-embolism or bleeding.
Clinical examination plays a major role in the detection of
VHD in asymptomatic patients. It is the first step in the diag-
nosis of VHD and the assessment of its severity. In patients
with a heart valve prosthesis, it is necessary to be aware
of any change in murmur or prosthetic sounds.
An electrocardiogram (ECG) and chest X-ray are usually
carried out alongside clinical examination. Besides cardiac
enlargement, analysis of pulmonary vascularization on the
chest X-ray is useful when interpreting dyspnoea or clinical
signs of heart failure.
16
Echocardiography
In addition to clinical findings, echocardiography is the key
technique to confirm the diagnosis of VHD, as well as to
assess its severity and prognosis. It is indicated in any
patient with a murmur when valve disease is suspected,
the only possible exception being young patients who only
have a trivial (grade 1/6) mid-systolic murmur.
The evaluation of the severity of stenotic VHD should
combine the assessment of valve area and flow-dependent
indices such as mean gradient and/or maximal flow vel-
ocity.
17
Flow-dependent indices such as mean gradient or
maximal flow velocity add further information and have a
prognostic value.
18
The assessment of valvular regurgitation should combine
different indices including quantitative Doppler echocardio-
graphy, such as the effective regurgitant orifice area (ERO),
which is less dependent on flow conditions than colour
Doppler jet size.
19
However, all quantitative evaluations,
such as the continuity equation or flow convergence, have
limitations. In particular, they combine a number of
measurements and are highly sensitive to errors of measure-
ment; therefore, their use requires experience.
Thus, when assessing the severity of VHD, it is necessary
to check consistency between the different echocardio-
graphic measurements as well as with the anatomy and
mechanisms of VHD. It is also necessary to check their
consistency with clinical assessment. In Table 2, this is
illustrated as it applies to the quantification of severe
regurgitation.
Echocardiography should include a comprehensive evalu-
ation of all valves, looking for associated valve diseases
and that of the ascending aorta.
Indices of left ventricular (LV) enlargement and function
are strong prognostic factors in AR and MR and, thus,
Table 1 Recommendation classes and levels of evidence
Class I Evidence and/or general agreement that
a given treatment or procedure
is beneficial, useful, and effective
Class II Conflicting evidence and/or a divergence
of opinion about the usefulness/efficacy
of a given treatment or procedure
Class IIa Weight of evidence/opinion is in
favour of usefulness/efficacy
Class IIb Usefulness/efficacy is less well established
by evidence/opinion
Level of
evidence A
Data derived from multiple randomized
clinical trials or meta-analyses
Level of
evidence B
Data derived from a single randomized
clinical trial or large non-randomized studies
Level of
evidence C
Consensus of opinion of the experts and/or
small studies, retrospective studies,
registries
ESC Guidelines 233
play an important role in decision-making. It is also
important to index LV dimensions to body surface area
(BSA) to take into account patient’s body size. However,
the validity of indexed values is uncertain for extreme
body size.
Transoesophageal echocardiography (TEE) should be con-
sidered when transthoracic examination is of suboptimal
quality or when thrombosis, prosthetic dysfunction, or endo-
carditis is suspected. It should be performed intraopera-
tively to monitor the results of valve repair or complex
procedures.
Three-dimensional echocardiography is a promising tech-
nique, particularly for the evaluation of valve anatomy.
However, its incremental usefulness in decision-making has
not been validated so far.
Fluoroscopy
Fluoroscopy can be used to assess annular or valvular calci-
fication, as it enables calcification to be distinguished from
fibrosis with a higher specificity than echocardiography.
Fluoroscopy is also useful to assess the kinetics of the
mobile part of a mechanical prosthesis.
Radionuclide angiography
Radionuclide angiography provides a reproducible evalu-
ation of LV ejection fraction (EF) in patients in sinus
rhythm. This aids decision-making in asymptomatic patients
with valvular regurgitation, in particular, when echocardio-
graphic examination is of suboptimal quality.
20
Stress testing
Exercise electrocardiogram
The primary purpose of exercise testing is to unmask the
objective occurrence of symptoms in patients who claim
to be asymptomatic. In truly asymptomatic patients, it has
an additional value for risk stratification in AS.
21,22
Exercise testing will also determine the level of authorized
physical activity, including participation in sports.
23
Exercise echocardiography
Promising recent reports suggest that the estimation of the
prognosis of VHD and indications for intervention may be
refined by measuring changes in gradients or degree of
regurgitation on exercise.
24,25
Echocardiography performed
immediately after exercise has shown to be useful to
assess the prognosis of degenerative MR.
26
However, these
preliminary findings need to be confirmed before this can
be recommended in practice.
Other stress tests
Low-dose dobutamine stress echocardiography is useful in
AS with impaired LV function.
27
The use of stress tests to
detect coronary artery disease associated with severe VHD
is discouraged because of their low diagnostic value.
Table 2 Criteria for the definition of severe valve regurgitation—an integrative approach
AR MR TR
Specific signs of severe
regurgitation
Central jet, width 65%
of LVOT
a
Vena contracta .0.6 cm
a
Vena contracta width 0.7 cm with
large central MR jet (area .40% of LA)
or with a wall impinging jet of any
size, swirling in LA
a
Vena contracta width
.0.7 cm in echo
Large flow convergence
b
Systolic reversal in the
Large flow convergence
b
hepatic veins
Systolic reversal in pulmonary veins
Prominent flail MV or ruptured
papillary muscle
Supportive signs Pressure
half-time ,200 ms
Dense, triangular CW, Doppler MR jet
E-wave dominant mitral inflow
Dense, triangular CW TR
signal with early peak
Holodiastolic aortic flow
reversal in descending
aorta
(E .1.2 m/s)
c
Enlarged LV and LA size
e
(particularly when
normal LV function is present)
Inferior cava dilatation and
respiratory diameter
variation 50%
Moderate or greater LV
enlargement
d
Prominent transtricuspid
E-wave, especially if
.1m/s
RA, RV dilatation
Quantitative parameters
R Vol, mL/beat 60 60
RF, % 50 50
ERO, cm
2
0.30 0.40
AR ¼ aortic regurgitation, CW ¼ continuous wave, ERO ¼ effective regurgitant orifice area, LA ¼ left atrium, LV ¼ left ventricle, LVOT ¼ LV outflow tract,
MR ¼ mitral regurgitation, MS ¼ mitral stenosis, MV ¼ mitral valve, R Vol ¼ regurgitant volume, RA ¼ right atrium, RF ¼ regurgitant fraction, RV ¼ right ven-
tricle, TR ¼ tricuspid regurgitation.
a
At a Nyquist limit of 50
–
60 cm/s.
b
Large flow convergence defined as flow convergence radius 0.9 cm for central jets, with a baseline shift at a Nyquist of 40 cm/s; cut-offs for eccentric
jets are higher and should be angled correctly.
c
Usually above 50 years of age or in conditions of impaired relaxation, in the absence of MS or other causes of elevated LA pressure.
d
In the absence of other aetiologies of LV dilatation.
e
In the absence of other aetiologies of LV and LA dilatation and acute MR.
Adapted from Zoghbi et al.
19
234 ESC Guidelines
Other non-invasive imaging techniques
Computed tomography
Preliminary data show that computed tomography (CT) scan-
ning enables valve calcification to be accurately quantified
with good reproducibility. Valve calcification is linked to
the severity of VHD and provides additional prognostic infor-
mation.
28
In expert centres, multislice CT can be useful to
exclude coronary artery disease in patients who are at low
risk of atherosclerosis.
Magnetic resonance imaging
At present, magnetic resonance imaging (MRI) is not indi-
cated in VHD in routine clinical practice; however, most
measurements usually acquired by Doppler echocardiogra-
phy can also be acquired with MRI and thus MRI can be
used as an alternative technique when echocardiography is
not feasible. In particular, quantification of cardiac func-
tion, dimensions, and regurgitant volume is very accurate
with MRI.
29
Biomarkers
Natriuretic peptide serum level, in particular, of the B-type,
has been shown to be related to functional class and progno-
sis, particularly in AS and MR.
30,31
However, data regarding
their incremental value in risk-stratification so far remain
limited.
Coronary angiography
Coronary angiography is widely indicated to detect associ-
ated coronary artery disease when surgery is planned
(Table 3). Knowledge of coronary anatomy improves
risk-stratification and determines whether coronary revas-
cularization is indicated in association with valvular surgery.
Coronary angiography can be omitted in young patients
with no risk factors and in rare circumstances when its risk
outweighs benefit, e.g. in acute aortic dissection, a large
aortic vegetation in front of coronary ostia, or occlusive
prosthetic thrombosis leading to an unstable haemodynamic
condition.
Cardiac catheterization
The measurement of pressures and cardiac output, or the
performance of ventricular angiography, is restricted to
situations where non-invasive evaluation is inconclusive
or discordant with clinical findings. Given its potential
risks, cardiac catheterization to assess haemodynamics
should not be systematically associated with coronary
angiography, although this remains common in current
practice.
3,32
Assessment of comorbidity
The choice of specific examinations to assess comorbidity is
directed by the clinical evaluation. The most frequently
encountered are peripheral atherosclerosis, renal failure,
and chronic obstructive pulmonary disease.
3
Endocarditis prophylaxis
Endocarditis prophylaxis should be considered in any patient
with VHD and adapted to the individual patient risk.
10
Risk stratification
The Euro Heart Survey has shown that, in current practice,
there is general agreement between the decision to
operate and the existing guidelines in asymptomatic
patients. However, in patients with severe symptoms, inter-
vention is underused for reasons that are often unjusti-
fied.
3,33
This stresses the importance of the widespread
use of careful risk stratification.
In the absence of evidence from randomized clinical
trials, the decision to intervene in a patient with VHD
relies on an individual risk
–
benefit analysis, suggesting
that improvement of prognosis compared with natural
history outweighs the risk of intervention and its potential
late consequences, in particular, prosthesis-related
complications.
The evaluation of the prognosis of VHD depends on the
type of VHD and is derived from studies on natural history,
which are frequently old and not always applicable to
current presentations of VHD. Only a few contemporary
studies enable spontaneous prognosis to be assessed accord-
ing to patient characteristics.
34
Factors predicting operative mortality have been ident-
ified from large series of patients undergoing cardiac
surgery or, more specifically, heart valve surgery.
35
–
39
They
are related to heart disease, the patient’s age, comorbidity,
and the type of surgery. The easiest way to integrate the
weight of the different predictable factors is to combine
them in multivariate scores, enabling operative mortality
to be estimated. The Euroscore (Table 4) is widely used in
this setting. Although it has been elaborated for cardiac
surgery in general, it has been validated in valvular
surgery.
35,39
One recent analysis of a database from the UK
led to a simple scoring system, which has been specifically
elaborated and validated in patients operated on for
VHD.
37
However, no scoring systems enable the spontaneous
outcome to be assessed.
Despite limitations and the need for further validation,
the use of these scores reduces the subjectivity of the evalu-
ation of the operative risk and, thus, of the risk
–
benefit
ratio. Of course, this is only one of the elements in decision-
making, which should also take into account the patient’s
life expectancy, quality of life, wishes, as well as local
resources, in particular, the availability of valve repair and
surgical outcome in the specified centre. Finally, very impor-
tantly, the decision to intervene should take into account
the decision of the patient and the relatives after they
Table 3 Indications for coronary angiography in patients with
valvular heart disease
Class
Before valve surgery in patients with severe VHD
and any of the following:
IC
History of coronary artery disease
Suspected myocardial ischaemia
a
LV systolic dysfunction
In men aged over 40 and post-menopausal
women
1 Cardiovascular risk factor
When coronary artery disease is suspected to be
the cause of severe MR (ischaemic MR)
IC
LV ¼ left ventricle, MR ¼ mitral regurgitation, VHD ¼ valvular heart
disease.
a
Chest pain, abnormal non-invasive testing.
ESC Guidelines 235
have been thoroughly informed of the risks and benefits of
the different therapeutic possibilities.
Aortic regurgitation
Introduction
AR may be the consequence of diverse aetiologies, the dis-
tribution of which has changed over time. The most frequent
causes of AR are now those related to aortic root disease
and bicuspid aortic valve. The inherent consequence is the
frequent involvement of the ascending aorta,
2,3
which may
need surgical treatment.
Evaluation
Initial examination should include a detailed clinical
evaluation. AR is diagnosed by the presence of a diastolic
murmur. Exaggerated arterial pulsations and low diastolic
pressure represent the first and main clinical signs
for quantifying AR.
15
Peripheral signs are attenuated
in acute AR, which contrasts with a poor functional
tolerance.
The general principles for the use of invasive and non-
invasive investigations follow the recommendations made
in the General comments section.
Specific issues in AR are as follows:
Echocardiography is the key examination, its aim being to:
.
Diagnose and quantify the severity of AR, using colour
Doppler (extension or, better, width of regurgitant jet) and
continuous-wave Doppler (rate of decline of aortic regurgi-
tant flow and holodiastolic flow reversal in the descending
aorta). All these indices are influenced by loading conditions
and the compliance of the ascending aorta and the LV.
Quantitative Doppler echocardiography, using the continuity
equation or analysis of proximal isovelocity surface area, is
less sensitive to loading conditions. The criteria for defining
severe AR are described in Tab le 2 .
19
The evaluation of sever-
ity, using quantitative measurements, is less well established
than in MR, and consequently, the results of quantitative
measurements should be integrated with other data to
come to a final conclusion as regards severity.
.
Assess the mechanisms of regurgitation, describe the valve
anatomy, and determine the feasibility of valve repair.
.
Image the aorta at four different levels: annulus, sinuses
of Valsalva, sino-tubular junction, and ascending aorta.
40
Indexing for BSA could be recommended, especially in
patients of small body size and women.
41
.
Evaluate LV function. LV dimensions should also be indexed
as described earlier.
42
Table 4 Defintions of risk factors in the EuroSCORE
Risk factor EuroSCORE defintion Points
Age ,60 years 0
60
–
64 1
65
–
69 2
70
–
74 3
75
–
79 4
80
–
84 5
85
–
89 6
90
–
94 7
95 8
Sex Female 1
Chronic pulmonary disease Long-term use of bronchodilators or steroids for lung disease 1
Extracardiac arteriopathy Claudication, carotid occlusion or stenosis .50%, previous or planned intervention
on the abdominal aorta, limb arteries or carotids
2
Neurological dysfunction Severely affecting ambulation or day-to-day functioning 2
Previous cardiac surgery Requiring opening of the pericardium 3
Serum creatinine .200 mM/L preoperatively 2
Active endocarditis Patient still under antibiotic treatment for endocarditis at the time of surgery 3
Critical preoperative state Ventricular tachycardia, fibrillation or aborted sudden death, preoperative cardiac
massage, preoperative ventilation, preoperative inotropic support, intra-aortic
balloon counterpulsation, or preoperative acute renal failure (anuria or oliguria
,10 mL/h)
3
Unstable angina Rest angina requiring intravenous nitrates until arrival in the anaesthetic room 2
LV dysfunction Moderate (LVEF 30
–
50%) 1
Poor (LVEF ,30%) 3
Recent MI ,90 days 2
Pulmonary hypertension Systolic pulmonary artery pressure .60 mmHg 2
Emergency Carried out on referral before the beginning of the next working day 2
Other than isolated CABG Major cardiac procedure other than or in addition to CABG 2
Surgery on thoracic aorta For disorder of ascending, arch, or descending aorta 3
Post-infarct septal rupture 4
CABG ¼ coronary artery bypass grafting, LV ¼ left ventricular, EF ¼ ejection fraction, MI ¼ myocardial infarction.
The estimation of the operative mortality for a given patient can be obtained using a calculator accessible at http://ww w.euroscore.org/calc.html.
From Roques et al.
35
236 ESC Guidelines
TEE may be performed to better define the anatomy of
the valve and ascending aorta, especially when valve-
sparing intervention is considered.
At the present time, clinical decisions should not be based
on changes in EF on exercise, nor on data from stress echo-
cardiography because these indices, although potentially
interesting, have not been adequately validated.
When available, MRI can be used to assess the severity of
regurgitation and LV function, particularly when echocardio-
graphic images are of poor quality.
MRI or CT scanning, according to availability and exper-
tise, is recommended for the evaluation of the aorta in
patients with an enlarged aorta as detected by echocardio-
graphy, especially in cases of bicuspid valves or Marfan’s
syndrome.
Natural history
Patients with acute AR have a poor prognosis without inter-
vention owing to the significant increase in diastolic LV
pressure, leading to poor haemodynamic tolerance. There
is little information in the literature on the progression
from mild to severe AR. Patients with severe AR and symp-
toms have a poor prognosis.
43
In asymptomatic patients with severe AR and normal LV
function, the number of events during follow-up is low:
development of asymptomatic LV dysfunction, ,1.3% per
year; sudden death, ,0.2% per year; and symptoms, LV
impairment, or death, 4.3% per year. Age, end-systolic
diameter or volume, and EF at rest are predictors
of outcome. On multivariate analysis, age and end-
systolic diameter, when it is .50 mm, predict a poor
outcome.
43
–
46
Recent data suggest that it could be more
appropriate to use thresholds related to BSA and the pro-
posed value is an end-systolic diameter .25 mm/m
2
BSA.
42
The natural history of aortic root aneurysm has been
mainly studied in patients with Marfan’s syndrome. The
strongest predictors of complication are the diameter of
the aortic root at the level of the sinuses of Valsalva and
the presence of a family history of cardiovascular events
(aortic dissection, sudden cardiac death).
40,47
–
49
When the
aorta has reached 6 cm in size, yearly rates of rupture, dis-
section, and death are, respectively, 3.6, 3.7, and 10.8%.
There is a rising incidence of dissection or rupture with
the increase in aneurysm size.
47
–
49
Recent data using
indexed values show a 4, 8, and . 20% risk of complications,
respectively, when the measurements are 2.75, 2.75
–
4.24,
and .4.25 cm/m
2
.
41
Patients with bicuspid valves
50
may
also present a rapid progression rate. Less information is
available for other aetiologies such as annulo-aortic ectasia.
Results of surgery
Surgical treatment of AR is aortic valve replacement when
there is no associated aortic aneurysm. When an aneurysm
of the aortic root is associated, surgery also comprises repla-
cement of the ascending aorta with re-implantation of the
coronary arteries, combined with either replacement of
the valve or valve-sparing techniques. In current practice,
valve replacement remains the standard and the other pro-
cedures are performed in only a small percentage of
patients. Supra-coronary replacement of ascending aorta
can be performed when Valsalva sinuses are preserved.
Operative mortality is low (1
–
3%)
3,43,51,52
(Table 5)in
asymptomatic patients submitted to isolated aortic valve
surgery. In symptomatic patients, in patients with combined
aortic valve and root surgery, and in patients with
concomitant coronary artery bypass grafting (CABG),
operative mortality ranges from 3 to 7%. The strongest pre-
operative predictors of heart failure or death after surgery
are age, preoperative functional class, resting EF ,50% or
shortening fraction , 25%, and LV end-systolic diameter
.55 mm.
43
–
45,53
–
56
Immediate and late results of the replacement of the
ascending aorta, using a composite graft, are excellent in
Marfan’s syndrome when performed by experienced teams
on an elective basis.
40,57
Data on conservative surgery are
more limited and come from expert centres. In such set-
tings, recent series have reported an operative mortality
of 1.6%, 10 year survival of 88%, freedom from aortic valve
replacement of 99%, and freedom from at least moderate
AR of 83%.
58,59
Indications for sur gery
In symptomatic acute AR, urgent intervention is indicated.
In chronic AR, the goals of the operation are to improve
outcome, to diminish symptoms, to prevent the develop-
ment of postoperative heart failure and cardiac death,
and to avoid aortic complications in patients who present
with aortic aneurysm.
46,60
On the basis of robust observational evidence, recom-
mended surgical indications are as follows (Tab l e 6, Figure 1):
Symptom onset is an indication for surgery. Surgery should
not be denied in symptomatic patients with LV dysfunction
or marked LV dilatation after careful exclusion of other
possible causes. Although in these patients postoperative
outcome is worse than in patients operated at an earlier
stage, acceptable operative mortality, improvement of
Table 5 Operative mortality after surgery for valvular heart
disease
STS
(2001)
UKCSR
(1999
–
2000)
EHS
(2001)
Aortic valve
replacement, no
CABG (%)
3.7 3.1 2.7
Aortic valve
replacement
þCABG (%)
6.3 7 4.3
Mitral valve
repair, no CABG (%)
2.2 2.8 0
Mitral valve
replacement, no
CABG (%)
5.8 6.2 1.7
Mitral valve repair or
replacement
þCABG (%)
10.1 8.6 8.2
CABG ¼ coronary artery bypass grafting.
STS ¼ Society of Thoracic Surgeons (USA). Mortality for STS includes
first and redo interventions.
51
UKCSR ¼ United Kingdom Cardiac Surgical
Register. Mortality for UKCSR corresponds to first interventions only.
52
EHS ¼ Euro Heart Survey.
3
CABG ¼ coronary artery bypass grafting.
ESC Guidelines 237
clinical symptoms, and acceptable long-term survival can be
obtained.
53,56
Surgery should also be considered in asymptomatic patients
with severe AR and impaired LV function at rest [resting
EF 50% and/or LV end-diastolic diameter .70 mm and/or
end-systolic diameter .50 mm (or .25 mm/m
2
BSA)] since
the likelihood of early development of symptoms is high,
perioperative mortality low, and postoperative results
excellent. A rapid increase in ventricular parameters on
serial testing is another reason to consider surgery. Good-
quality echocardiograms and data confirmation with
repeated measurements are strongly recommended before
surgery in asymptomatic patients.
The rationale for an aggressive approach in patients with
mild AR and aortic dilatation is better defined in patients
with Marfan’s syndrome than in patients with bicuspid
valves, and even more so in annulo-aortic ectasia. In border-
line cases, the decision to replace the ascending aorta also
relies on perioperative surgical findings as regards the
thickness of the aortic wall and the status of the rest of
the aorta.
Aortic root dilatation 55 mm should be a surgical indi-
cation, irrespective of the degree of AR. In cases of
Marfan’s syndrome or bicuspid aortic valves, even lower
degrees of root dilatation (45 and 50 mm, respectively)
have been proposed as indications for surgery, especially
when there is a rapid increase of aortic diameter between
serial measurements (5 mm per year) or family history of
aortic dissection.
48,49
For patients who have an indication for surgery on the
aortic valve, lower thresholds can be used for combining
surgery on the ascending aorta. Lower thresholds of aortic
diameters can also be considered for indicating surgery if
valve repair can be performed by experienced surgeons.
The choice of the surgical technique is adapted according
to the following factors: associated root aneurysm, charac-
teristics of leaflets, underlying pathology, life expectancy,
and desired anticoagulation status.
Medical therapy
Nitroprusside and inotropic agents (dopamine or dobuta-
mine) may be used before surgery in patients with poorly
tolerated acute AR to stabilize their clinical condition. In
patients with chronic severe AR and heart failure,
ACE-inhibitors are the treatment of choice when surgery is
contraindicated or in cases with persistent postoperative
LV dysfunction.
In asymptomatic patients with high blood pressure, the
indication for anti-hypertensive treatment with vasodilators
such as ACE-inhibitors or dihydropyridine calcium channel
blockers is warranted.
The role of vasodilators in the asymptomatic patients
without high blood pressure in order to delay surgery is
unproved.
61,62
In patients with Marfan’s syndrome, beta-blockers slow
the progression of the aortic dilatation
63
and should also
be given after operation. In patients with severe AR, the
use of beta-blockers should be very cautious because the
lengthening of diastole increases the regurgitant volume.
However, they can be used in patients with severe LV dys-
function. Recently, enalapril has also been used to delay
aortic dilatation
64
in patients with Marfan’s syndrome.
Whether the same beneficial effect occurs in patients with
bicuspid aortic valves is not known.
Patients with AR should be educated on endocarditis pre-
vention and antibiotic prophylaxis.
10
In patients with Marfan’s syndrome or in young patients
with aortic root aneurysm, the family needs to be screened
to detect asymptomatic cases.
Serial testing
Patients with mild-to-moderate AR can be seen on a yearly
basis and echocardiography performed every 2 years.
All patients with severe AR and normal LV function should
be seen for follow-up at 6 months after their initial examin-
ation. If LV diameter and/or EF show significant changes, or
they become close to the thresholds for intervention,
follow-up should continue at 6 month intervals. When par-
ameters are stable, follow-up can be yearly.
In patients with a dilated aortic root, and especially in
patients with Marfan’s syndrome or with bicuspid aortic
valves, examination of the aorta should be performed on a
yearly basis, but with closer intervals if aortic enlargement
is detected.
Special patient populations
In patients with moderate AR who undergo CABG or mitral
valve surgery, the decision to replace the aortic valve
should be individualized according to aetiology of AR, age,
disease progression, and possibility of valve repair.
Table 6 Indications for surgery in aortic regurgitation
Class
Severe AR
Symptomatic patients (dyspnoea, NYHA
class II, III, IV or angina)
IB
Asymptomatic patients with resting
LVEF 50%
IB
Patients undergoing CABG or surgery of
ascending aorta, or on another valve
IC
Asymptomatic patients with resting
LVEF .50% with severe LV dilatation:
End-diastolic dimension . 70 mm or IIaC
ESD . 50 mm (or . 25 mm/m
2
BSA)
a
IIaC
Whatever the severity of AR
Patients who have aortic root disease with
maximal aortic diameter
b
45 mm for patients with Marfan’s
syndrome
IC
50 mm for patients with bicuspid valves IIaC
55 mm for other patients IIaC
Severity is defined from clinical and echocardiographic assessment (see
text).
In asymptomatic patients, repeated and high-quality measures are
necessary before surgery.
AR ¼ aortic regurgitation, BSA ¼ body surface area, CABG ¼ coronary
artery bypass grafting, ESD ¼ end-systolic dimension, EF ¼ ejection frac-
tion, LV ¼ left ventricular.
a
Patient’s stature should be considered. Indexing is helpful. Changes in
sequential measurements should be taken into account.
b
Decision should take into account the shape and thickness of ascending
aorta as well as the shape of the other parts of aorta.
For patients who have an indication for surgery on the aortic valve,
lower thresholds can be used for combining surgery on the ascending aorta.
238 ESC Guidelines
Concurrent aortic valve replacement is more frequently
considered when mitral surgery is prosthetic valve replace-
ment than when it is mitral valve repair.
If AR requiring surgery is associated with severe MR, then
both should be operated on. Usually the aortic valve will
require replacement and the operation required on the
mitral valve will depend on the chances of successful
repair. Clearly, if the chances are low and the patient is
likely to require anticoagulants because of the aortic
surgery, then mitral valve replacement is likely to be prefer-
able. If the associated MR does not demand immediate
surgery, the decision is more difficult and needs to be indivi-
dualized, but if the regurgitation is organic and repair is
likely, then concurrent mitral valve surgery is attractive.
There will, however, be occasions when the patient’s clinical
condition mandates the quickest and most simple
procedure.
Aortic stenosis
Introduction
AS has become the most frequent type of VHD in Europe
and North America. It primarily presents as calcific AS in
adults of advanced age (2
–
7% of the population . 65
years).
2,3,65,66
The second most frequent aetiology, which
dominates in the younger age group, is congenital,
whereas rheumatic AS has become rare.
Evaluation
Patient history and physical examination remain essential.
Careful exploration for the presence of symptoms (exer-
tional shortness of breath, angina, dizziness, or syncope) is
critical for proper patient management and must take into
account that patients may deny symptoms because they sig-
nificantly reduce their activities.
The characteristic systolic murmur draws the attention
and guides the further diagnostic work in the right direction.
Occasionally, the murmur may, however, be faint and
primary presentation may be heart failure of unknown
cause. The disappearance of the second aortic sound is
specific to severe AS, although not a sensitive sign.
15
The general principles for the use of invasive and non-
invasive investigations follow the recommendations made
in the General comments section.
Specific issues that need to be addressed in AS are as
follows:
Echocardiography has become the key diagnostic tool. It
confirms the presence of AS, assesses the degree of valve
calcification, LV function and wall thickness, detects the
presence of other associated valve disease, and finally pro-
vides prognostic information.
Doppler echocardiography is the preferred technique to
assess severity.
17
Transvalvular pressure gradients are flow
dependent and measurement of valve area represents,
from a theoretical point of view, the ideal way to
quantify AS.
Nevertheless, it has to be emphasized that valve
area measurements also have their potential inaccuracies
and are less robust than gradient estimates in clinical
practice. Thus, valve area alone with absolute cut-off
points cannot be relied upon for clinical decision-
making and it should be considered in combination
with flow rate, pressure gradient and ventricular function,
as well as functional status. AS with a valve area , 1.0 cm
2
is considered severe; however, indexing to BSA, with
Figure 1 Management of aortic regurgitation.
ESC Guidelines 239
a cut-off value of 0.6 cm
2
/m
2
BSA is helpful, in particular in
patients with either unusually small or large BSA.
Severe AS is unlikely if cardiac output is normal, and there
is a mean pressure gradient ,50 mmHg. In the presence of
low flow, usually due to depressed LV function, low pressure
gradients may be encountered in patients with severe AS. As
soon as mean gradient is ,40 mmHg, even a small valve area
does not definitely confirm severe AS since
mild-to-moderately diseased valves may not open fully,
resulting in a ‘functionally small valve area’ (pseudosevere
AS).
67
Stress echocardiography using low-dose dobutamine may
be helpful in this setting to distinguish truly severe AS
from the rare cases of pseudosevere AS.
27
Truly severe AS
shows only small changes in valve area (increase
,0.2 cm
2
) with increasing flow rate but significant increase
in gradients (maximum value of mean gradient .50 mmHg),
whereas pseudosevere AS shows marked increase in valve
area but only minor changes in gradients.
27,68
In addition,
this test may detect the presence of contractile reserve
(increase .20% of stroke volume during low-dose dobuta-
mine test), which has prognostic implications.
27,68
Exercise stress echocardiography has been proposed for
risk stratification in asymptomatic severe AS
25
but more
data are necessary to determine its role.
Echocardiographic evaluation will identify coexistent
valvular lesions including mitral annular calcification in
degenerative disease and rheumatic mitral valve disease,
as well as asymmetric dynamic subvalvular obstruction
especially in elderly women.
TEE is rarely needed; however, it may provide images that
are good enough to allow valve planimetry and this is useful
when transthoracic visualization is poor and leaflets only
moderately calcified. TEE will also provide additional evalu-
ation of other mitral valve abnormalities.
Exercise testing is contraindicated in symptomatic
patients with AS but is useful for unmasking symptoms and
in the risk stratification of asymptomatic patients with
severe AS.
21,22
In such cases, it is safe, provided it is per-
formed under the supervision of an experienced physician,
with symptoms, changes in blood pressure, and ECG
closely monitored. In current practice, stress tests are
under-used in patients with asymptomatic AS.
3
CT and MRI could improve assessment of the ascending
aorta, if required. Preliminary data suggest that multislice
CT may be useful in quantifying valve calcification, which
aids in assessing prognosis,
28
as well as in measuring valve
area.
69
However, more data are required to determine the
full role of multislice CT.
Natriuretic peptides have been shown in preliminary
studies to predict symptom-free survival in AS.
30
However,
more data are required before recommending their serial
measurement to identify optimal timing of surgery.
Retrograde LV catheterization to assess the severity of AS
is seldom needed and should only be used with caution, as it
is not without risk.
32
Natural history
Calcific AS is a chronic progressive disease. During a long
latent period, patients remain asymptomatic.
70
–
72
However, it should be emphasized that duration of the
asymptomatic phase varies widely among individuals.
Sudden cardiac death is a frequent cause of death in symp-
tomatic patients but appears to be rare in the asymptomatic
(1% per year).
70
–
72
Reported average symptom-free survi-
val at 2 years ranges from 20 to more than 50%.
21,22,70
–
72
The lower numbers must be viewed with caution since
some patients in these studies underwent surgery without
symptoms. Finally, it has been speculated that myocardial
fibrosis and severe LV hypertrophy, which may not be revers-
ible after delayed surgery, could preclude an optimal post-
operative long-term outcome. However, there are, so far,
no data to confirm this hypothesis.
Predictors of the progression of AS and, therefore, of poor
outcome in asymptomatic patients have recently been
identified. They are:
.
Clinical: older age, presence of atherosclerotic risk
factors.
65,66
.
Echocardiography: valve calcification, peak aortic jet vel-
ocity, LVEF,
71,72
haemodynamic progression,
71
and
increase in gradient with exercise.
25
The combination of
a markedly calcified valve with a rapid increase in velocity
of 0.3 m/s within 1 year has been shown to identify a
high-risk group of patients ( 80% death or requirement
of surgery within 2 years
71
).
.
Exercise testing: symptom development on exercise
testing in physically active patients, particularly those
younger than 70 years, predicts a very high likelihood of
symptom development within 12 months. Recent data
demonstrates a lower positive predictive value for abnor-
mal blood pressure response, and even more so for
ST-segment depression, than symptoms for poor
outcome.
22
As soon as symptoms occur, the prognosis is dismal and
mortality has been reported to be quite significant even
within months of symptom onset,
73
which is often not
promptly reported by patients.
Results of intervention
Aortic valve replacement is the definitive therapy for severe
AS. In contemporary series, operative mortality of isolated
aortic valve replacement is 3
–
5% in patients below
70 years and 5
–
15% in older adults (Table 5).
3,51,52
The fol-
lowing factors increase the risk of operative mortality:
older age, associated comorbidities, female gender, higher
functional class, emergency operation, LV dysfunction, pul-
monary hypertension, coexisting coronary disease, and pre-
vious bypass or valve surgery. After successful valve
replacement, long-term survival rates are close to those
expected in the control population, symptoms are less
marked, and quality of life is greatly improved.
74
Risk
factors for late death include age, comorbidities, severe
functional condition, LV dysfunction, ventricular arrhyth-
mias, and untreated coexisting coronary artery disease.
In addition, poor postoperative outcome may result from
prosthesis-related complications and sub-optimal prosthetic
valve haemodynamic performance.
75
Balloon valvuloplasty plays an important role in the pae-
diatric population but a very limited role in adults because
its efficacy is low, complication rate is high (.10%), and
restenosis and clinical deterioration occur within 6
–
12
months in most patients, resulting in a mid-term and long-
term outcome similar to natural history.
76
Preliminary
240 ESC Guidelines
reports show that percutaneous aortic valve replacement is
feasible, but this procedure is at an early stage and further
studies are needed to evaluate its potential role.
77
Indications for surgery
Surgical indications are as follows (Table 7, Figure 2):
Early valve replacement should be strongly recommended
in all symptomatic patients with severe AS who are otherwise
candidates for surgery. As long as mean gradient is still
.40 mmHg, there is virtually no lower EF limit for surgery.
On the other hand, the management of patients with
low-flow, low-gradient AS (severely reduced EF and mean
gradient , 40 mmHg) is more controversial. The depressed
EF in many patients in this group is predominantly caused
by excessive afterload (afterload mismatch), and LV func-
tion usually improves after surgery.
78,79
Conversely, second-
ary improvement in LV function is uncertain if the primary
cause is scarring due to extensive myocardial infarction. In
patients with low gradient and with evidence of contractile
reserve, surgery is advised since it carries an acceptable risk
and improves long-term outcome in most patients.
Conversely, the outcome of patients without contractile
reserve is compromised by a high operative mortality
despite a trend towards better survival after surgery.
27
Surgery can, nonetheless, be performed in these patients
but decision-making should take into account clinical con-
dition (in particular, the presence of comorbidity), degree
of valve calcification, extent of coronary disease, and feasi-
bility of revascularization.
Management of asymptomatic patients with severe
AS remains a matter of controversy.
5,13,80
The decision
to operate on asymptomatic patients requires careful
weighing of benefits against risks. Early elective surgery,
at the asymptomatic stage, can only be recommended in
selected patients, at low operative risk. This could be the
case in:
.
The rare asymptomatic patients with depressed LV func-
tion not due to another cause
.
Those with echocardiographic predictors of poor outcome
suggested by the combination of a markedly calcified
valve with a rapid increase in peak aortic velocity of
0.3 m/s per year.
.
If the exercise test is abnormal, particularly if it shows
symptom development, which is a strong indication for
surgery in physically active patients.
.
However, on the other hand, breathlessness on exercise
may be difficult to interpret in patients with only low
physical activity, particularly the elderly, making decision-
making more difficult. There is no strict age limit for
performance of exercise testing and it is reasonable to
propose it in patients .70 years old who are still highly
active.
Indications for balloon valvuloplasty
This intervention can be considered as a bridge to surgery in
haemodynamically unstable patients who are at high
risk for surgery (Recommendation class IIb, Level of
evidence C) or in patients with symptomatic severe AS
who require urgent major non-cardiac surgery (Recommen-
dation class IIb, Level of evidence C). Occasionally, balloon
valvuloplasty could be considered as a palliative measure
in individual cases when surgery is contraindicated
because of severe comorbidities.
Medical therapy
The progression of degenerative AS is an active process
sharing a number of similarities with atherosclerosis.
81
Thus, modification of atherosclerotic risk factors must be
strongly recommended following the guidelines of secondary
prevention in atherosclerosis.
Although several retrospective reports have shown ben-
eficial effects of statins
82,83
and ACE-inhibitors,
84
data are
still conflicting and the only randomized trial assessing the
effect of statin therapy is negative.
85
It is, therefore, too
early for treatment recommendations.
Symptomatic patients require early surgery, as no medical
therapy for AS is able to delay the inevitability of surgery.
However, patients who are unsuitable candidates for
surgery may be treated with digitalis, diuretics,
ACE-inhibitors, or angiotensin receptor blockers if they are
experiencing heart failure. Beta-blockers should be
avoided in these circumstances. In selected patients with
pulmonary oedema, nitroprusside can be used under haemo-
dynamic monitoring.
Table 7 Indications for aortic valve replacement in aortic
stenosis
Class
Patients with severe AS and any symptoms IB
Patients with severe AS undergoing coronary artery
bypass surgery, surgery of the ascending aorta, or
on another valve
IC
Asymptomatic patients with severe AS and systolic
LV dysfunction (LVEF ,50%) unless due to other
cause
IC
Asymptomatic patients with severe AS and
abnormal exercise test showing symptoms on
exercise
IC
Asymptomatic patients with severe AS and
abnormal exercise test showing fall in blood
pressure below baseline
IIaC
Patients with moderate AS
a
undergoing coronary
artery bypass surgery, surgery of the ascending
aorta or another valve
IIaC
Asymptomatic patients with severe AS and
moderate-to-severe valve calcification, and a
rate of peak velocity progression 0.3 m/s
per year
IIaC
AS with low gradient (,40 mmHg) and LV
dysfunction with contractile reserve
IIaC
Asymptomatic patients with severe AS and
abnormal exercise test showing complex
ventricular arrhythmias
IIbC
Asymptomatic patients with severe AS and
excessive LV hypertrophy (15 mm) unless this is
due to hypertension
IIbC
AS with low gradient (,40 mmHg) and LV
dysfunction without contractile reserve
IIbC
AS ¼ aortic stenosis, EF ¼ ejection fraction, LV ¼ left ventricular.
a
Moderate AS is defined as valve area 1.0
–
1.5 cm
2
(0.6 cm
2
/m
2
to
0.9 cm
2
/m
2
BSA) or mean aortic gradient 30
–
50 mmHg in the presence
of normal flow conditions. However, clinical judgement is required.
ESC Guidelines 241
Co-existing hypertension should be treated; however,
treatment should be carefully titrated to avoid hypotension
and patients more frequently evaluated.
Maintenance of sinus rhythm is particularly important.
Endocarditis prophylaxis is indicated in all patients with
AS.
10
Serial testing
The wide variability of the rate of progression of AS height-
ens the need for patients to be carefully educated about the
importance of follow-up and reporting symptoms as soon as
they develop. In the asymptomatic patient, stress tests
should determine the recommended level of physical
activity. Follow-up visits should include echocardiographic
assessment since the rate of haemodynamic progression is
important for management decisions. Type and interval of
follow-up should be determined on the basis of the initial
examination.
In cases of moderate-to-severe calcification of the valve
and peak aortic jet velocity . 4 m/s at initial evaluation,
patients should be re-evaluated every 6 months for the
occurrence of symptoms and change in exercise tolerance
or in echo-parameters. If peak aortic jet velocity has
increased since the last visit (.0.3 m/s per year) or if
other evidence of haemodynamic progression is present,
surgery should be considered. If no change has occurred
and the patient remains asymptomatic, six-monthly clinical
and six- to 12-monthly clinical and echocardiographic
re-evaluations are recommended.
In patients who do not meet these criteria, a clinical
yearly follow-up is necessary, follow-up being closer in
those with borderline values. The frequency of echocardio-
graphic examinations should be adapted to clinical findings.
Special patient populations
In patients with severe AS and severe coronary disease, the
performance of concomitant CABG provides a lower mor-
tality rate than that observed in patients who do not
undergo combined bypass surgery. However, combined
surgery carries a higher risk than isolated valve replacement
in patients without coronary disease. Thus, CABG should be
combined whenever possible with valve surgery. On the
other hand, aortic valve replacement is not necessary
during CABG in patients with only mild AS.
Finally, although there are no prospective randomized
trials, data from retrospective analysis indicate that
patients with moderate AS (mean gradient in the presence
of normal flow 30
–
50 mmHg, valve area 1.0
–
1.5 cm
2
) will
in general benefit from valve replacement at the time of
coronary surgery.
86
However, individual judgement must be
recommended considering BSA, individual haemodynamic
data, life expectancy, expected progression rate of AS,
expected outcome from associated disease (particularly
comorbidity), and individual risk of valve replacement or
eventual re-operation.
Patients with severe symptomatic AS and diffuse coronary
artery disease, which cannot be revascularized, should not
be denied aortic valve replacement, even though this is a
high-risk group.
Recent studies have suggested the potential use of percu-
taneous coronary revascularization in place of bypass
Figure 2 Management of severe aortic stenosis.
242 ESC Guidelines
surgery in patients with AS.
87
However, available data are
not sufficient to currently recommend this approach,
except for selected high-risk patients with acute coronary
syndromes or in patients with non-severe AS.
AS is increasingly observed in octogenarians and even in
nonagenarians who experience higher morbidity and oper-
ative mortality during aortic valve replacement. However,
surgery can prolong and improve the quality of life.
88
Even though valve replacement is the procedure of
choice in this population, a large percentage of suitable
candidates currently are, unfortunately, not referred for
surgery.
3,33
Age, per se, should not be considered a contra-
indication for surgery. Decisions should be made on an
individual basis, taking into account patients’ wishes and
cardiac and non-cardiac factors (see also General com-
ments section). In this population, the need for an emer-
gency operation, or, at the other end of the clinical
spectrum, very early intervention at an asymptomatic
stage, should be avoided.
When MR is associated with AS, colour jet size and
other Doppler findings may be increased by the high ven-
tricular pressures. As long as there are no morphological
abnormalities (flail or prolapse, post-rheumatic changes
or signs of infective endocarditis), mitral annulus dilata-
tion, or marked abnormalities of LV geometry, surgical
intervention on the mitral valve is in general not necess-
ary, and functional MR often resolves after the aortic
valve is replaced.
Bicuspid valves are common in AS, and there is a clear
relationship between the presence of bicuspid valves
and abnormalities of the aortic root even in the absence
of severe AS. Concomitant treatment of a dilated aorta
is, therefore, recommended at the same thresholds as
in AR.
89
Mitral regurgitation
MR is now the second most frequent valve disease after AS.
The treatment has been re-orientated as a result of the good
results of valve repair. This section deals with organic,
ischaemic, and functional MR.
Organic mitral regurgitation
Organic MR covers all aetiologies in which leaflet abnormal-
ity is the primary cause of the disease, in opposition to
ischaemic and functional MR, in which MR is the conse-
quence of LV disease.
Reduced prevalence of rheumatic fever and increased life
span in industrialized countries have progressively changed
the distribution of aetiologies. Degenerative MR is the
most common aetiology in Europe, whereas ischaemic and
functional MR are increasingly frequent.
3
Endocarditis is
dealt with in separate specific ESC guidelines.
10
Evaluation
Clinical examination usually provides the first clues that
MR is present and may be significant as suggested by
the intensity and duration of the systolic murmur and
the presence of the third sound.
15
The general principles
for the use of invasive and non-invasive investigations
follow the recommendations made in the General
comments section.
The specific issues in MR are as follows:
Echocardiography is the principal examination and must
include an assessment of severity, mechanisms and repair-
ability, and, finally, consequences.
Several methods can be used to determine the severity of
MR. Colour-flow mapping of the regurgitant jet is the easiest
method but its accuracy is limited. The width of the vena
contracta—the narrowest part of the jet—correlates with
quantitative measurements of MR. The two quantitative
methods of evaluating regurgitant volume and calculating
ERO are useful in experienced hands.
90,91
The criteria for
defining severe organic MR are described in Table 2.
It should be emphasized again here that the assessment
of severity should not rely entirely on one single par-
ameter, but requires an approach integrating blood flow
data from Doppler with morphologic information and
careful cross-checking of the validity of such data against
the consequences on LV and pulmonary pressures
19
(Table 2).
In case of acute severe MR, physical examination and aus-
cultation may be misleading, in particular, with a murmur of
low intensity, and colour Doppler flow may underestimate
the severity of the lesion. The presence of hyperdynamic
function in acute heart failure suggests the presence of
severe MR.
Transthoracic echocardiography provides precise anatom-
ical definition of the different lesions, which must be related
to the segmental and functional anatomy according to the
Carpentier classification in order to subsequently assess
the feasibility of repair.
92
TEE is frequently carried out before surgery for this
purpose,
93
although transthoracic echocardiography, in
experienced hands and when using recent imaging tech-
niques, can be sufficient when images are of high
quality.
94
The results of mitral valve repair should be
assessed intraoperatively by TEE to enable immediate
further surgical correction if necessary.
The consequences of MR are assessed by measuring left
atrial diameter, LV diameter and EF, and systolic pulmonary
arterial pressure.
Evaluation of contractile reserve may be accomplished by
exercise echocardiography, but the usefulness of this
method for decision-making requires validation.
26
Preliminary series have also suggested the value of elev-
ated BNP levels as predictors of long-term outcome but
this also remains to be validated.
31
Natural history
Acute MR is poorly tolerated and carries a poor prognosis in
the absence of intervention.
Our knowledge of the natural history of chronic MR
has greatly improved due to recent observational
studies.
34,91,95,96
In asymptomatic MR, the estimated 5 year rates (+
standard error) of death from any cause, death from
cardiac causes, and cardiac events (death from cardiac
causes, heart failure, or new AF) with medical management
were 22 + 3, 14 + 3, and 33 + 3%, respectively.
91
In addition to symptoms, age, atrial fibrillation, degree of
MR (particularly ERO), left atrial dilatation, LV dilatation,
and low LVEF are all predictors of poor outcome.
In patients with chordal rupture, clinical condition may
stabilize after an initial symptomatic period. However, it
ESC Guidelines 243
carries a poor spontaneous prognosis owing to subsequent
development of pulmonary hypertension.
Results of surgery
Despite the absence of randomized comparison between the
results of valve replacement and repair and the possible
inherent biases resulting from this, it is widely accepted
that valve repair, when feasible, is the optimal surgical
treatment in patients with severe MR. When compared
with valve replacement, repair has a lower perioperative
mortality (Table 5), improved survival, better preservation
of postoperative LV function, and lower long-term
morbidity.
97
–
101
Besides symptoms, the most important predictors of post-
operative outcome after surgery for MR are age, AF, preo-
perative LV function, and the reparability of the valve.
The best results of surgery are observed in the patients
with a preoperative LVEF .60%. A preoperative end-systolic
diameter ,45 mm (no indexed value has been validated in
MR) is also closely correlated with a good postoperative
prognosis.
93,95
–
98
However, a value about which postopera-
tive LV dysfunction will not occur has not been demon-
strated, rendering prediction of the postoperative
dysfunction difficult in the individual patient. In addition
to the initial measurements, the temporal changes of LV
function should also be taken into account when making
decisions about surgery. Progressive development of pul-
monary hypertension is also a marker for poor prognosis.
The probability of a durable valve repair is of crucial
importance.
102,103
Degenerative MR due to segmental valve
prolapse can usually be repaired with a low risk of reopera-
tion. The reparability of extensive prolapse, rheumatic
lesions, and, even more so, MR with leaflet calcification or
extensive annulus calcification is not as consistent even in
experienced hands.
The results of valve repair are also highly dependent on
the experience of the surgeon; this holds to be even more
true as the lesions get more complex.
In current practice, surgical expertise in mitral valve
repair is growing and becoming widespread since it is used
in almost 50% of patients in registries in Europe
3
and the
USA and in up to 90% in experienced centres.
103
When repair is not feasible, mitral valve replacement with
chordal preservation is preferred.
Recently, additional anti-arrhythmic procedures derived
from the Cox maze intervention have been proposed in
patients with preoperative AF to return them to and main-
tain sinus rhythm. The data available are still limited and
the definitive role of these procedures remains to be
determined.
104
The first percutaneous mitral valve repairs in man have
been performed using either implants introduced via the
coronary sinus or stitches mimicking the Alfieri operation
(edge-to-edge method) introduced transseptally.
105,106
Further evaluation is needed before defining the potential
role of these approaches.
Indications for intervention
Indications for surgery in severe chronic organic MR are as
follows (Table 8, Figure 3):
Urgent surgery is indicated in symptomatic patients with
acute MR.
Surgery is indicated in patients who have symptoms due to
chronic MR, but no contraindications to surgery. Besides
valve anatomy, the decision of whether to replace or
repair depends very much on the surgical expertise avail-
able. When LVEF is ,30%, a durable surgical repair can
still improve symptoms, although the effect on survival is
largely unknown. In the latter situation, the decision
whether to operate will take into account the response to
medical therapy, comorbidity, and the likelihood of valve
repair.
The management of asymptomatic patients is an area of
controversy since there are no randomized trials to
support any particular course of action. On the one hand,
the good results of valve repair and the potential risk of
postoperative LV dysfunction are incentives for early
surgery. On the other hand, even in low-risk cases, there is
a small but definite risk of surgical mortality. The indications
for surgery depend on risk stratification, the possibility of
valve repair, and the preference of the informed patient.
Surgery can be recommended in selected asymptomatic
patients with severe MR:
.
Patients with signs of LV dysfunction (LVEF 60% and/or
end-systolic dimension . 45 mm). Surgery in this group
should be considered, even in patients with a high likeli-
hood of valve replacement. Lower end-systolic dimension
values can be considered for patients of small stature.
.
Patients with atrial fibrillation and preserved LV function.
.
Patients with preserved LV systolic function and pulmonary
hypertension.
Further proof of the validity of a strategy using the cri-
teria cited previously, in carefully followed-up patients,
has been provided by recent data showing that the use of
Table 8 Indications for surgery in severe chronic organic mitral
regurgitation
Class
Symptomatic patients with LVEF .30% and
ESD ,55 mm
IB
Asymptomatic patients with LV dysfunction
(ESD .45 mm
a
and/or LVEF 60%)
IC
Asymptomatic patients with preserved LV function
and atrial fibrillation or pulmonary hypertension
(systolic pulmonary artery pressure .50 mmHg
at rest)
IIaC
Patients with severe LV dysfunction (LVEF ,30%
and/or ESD .55 mm)
a
refractory to medical
therapy with high likelihood of durable repair,
and low comorbidity
IIaC
Asymptomatic patients with preserved LV function,
high likelihood of durable repair, and low risk for
surgery
IIbB
Patients with severe LV dysfunction (LVEF ,30%
and/or ESD .55 mm)
a
refractory to medical
therapy with low likelihood of repair and low
comorbidity
IIbC
Severity is based on clinical and echocardiographic assessment.
ESD ¼ end-systolic dimension, EF ¼ ejection fraction, LV ¼ left ventri-
cular, MR ¼ mitral regurgitation.
a
Lower values can be considered for patients of small stature.
244 ESC Guidelines
this strategy allows surgery at low risk and with good long-
term outcome.
107
Intervention is debatable in asymptomatic patients with
severe MR with neither signs of LV dysfunction, nor AF, nor
pulmonary hypertension. It can be considered if there is a
high likelihood of valve repair on the basis of valve lesion
and experience of the surgeon, and a low operative risk.
Conversely, attentive clinical follow-up is clearly rec-
ommended for patients at relatively high operative risk
(e.g. elderly) or with doubt about the feasibility of valve
repair. In this latter group of patients, operative risk and/
or prosthetic valve complications probably outweigh the
advantages of correcting MR. These patients should be
reviewed carefully and surgery indicated when symptoms
or objective signs of LV dysfunction occur.
Finally, solid data on the value of surgery are currently
lacking for patients with mitral valve prolapse and preserved
LV function with recurrent ventricular arrhythmias despite
medical therapy.
Medical therapy
In acute MR, reduction of filling pressures can be obtained
with nitrates and diuretics. Nitroprusside reduces afterload
and regurgitant fraction. Inotropic agents should be added
in case of hypotension.
Anticoagulant therapy, with a target international normal-
ized ratio (INR) range between 2 and 3, should be given in
patients with MR and permanent or paroxysmal AF or when-
ever there is a history of systemic embolism or evidence of
left atrial thrombus and during the first 3 months following
mitral valve repair.
108
In severe MR, maintenance of sinus rhythm after cardio-
version is unlikely unless the MR is treated surgically. If AF
occurs, heart rate should be controlled.
There is no evidence to support the use of vasodilators,
including ACE-inhibitors, in chronic MR without heart
failure and therefore they are not recommended in this
group of patients.
109
On the other hand, when heart failure has developed,
ACE-inhibitors have a benefit and may be used in patients
with advanced MR and severe symptoms who are not suit-
able for surgery or when there are still residual symptoms
following the operation, usually as a result of impaired LV
function. Beta-blockers and spironolactone should also be
considered as appropriate. Endocarditis prophylaxis is also
required.
10
Serial testing
Asymptomatic patients with moderate MR and preserved LV
function can be clinically followed-up on a yearly basis and
echocardiography should be performed every 2 years.
Asymptomatic patients with severe MR and preserved LV
function should be seen every 6 months and echocardiogra-
phy performed every year, the follow-up being closer if no
previous evaluation is available, and in patients with border-
line values, or significant changes since the last visit. These
patients should be instructed to promptly report any change
in functional status.
Following valve repair, as is the case after valve replace-
ment, it is sensible to establish a baseline for ECG, X-ray,
and echocardiography so that this is available for later com-
parison, particularly if clinical changes occur.
Figure 3 Management of severe chronic organic mitral regurgitation.
ESC Guidelines 245
Ischaemic mitral regurgitation
Ischaemic MR is a frequent entity, which is, however, fre-
quently overlooked in the setting of acute or chronic coron-
ary disease.
110,111
Chronic ischaemic MR is the consequence
of a restriction in leaflet motion, which is due to tethering
by the subvalvular apparatus in patients who have LV enlar-
gement and/or dysfunction, in particular of the postero-
lateral wall.
Evaluation
Acute MR due to papillary muscle rupture should be envi-
saged in a patient presenting with shock during acute myo-
cardial infarction. The murmur may even be inaudible,
which stresses the importance of performing echocardiogra-
phy urgently in this setting. In chronic ischaemic MR, the
murmur is of low intensity, which should not lead to the con-
clusion that MR is trivial.
It should be remembered that ischaemic MR is a dynamic
condition and its severity may vary from time to time in
relation to arrhythmias, ischaemia, hypertension, or exer-
cise. Acute pulmonary oedema may result from a large
exercise-induced increase in ischaemic MR.
112
Echocardiographic examination is useful for establishing
the diagnosis and differentiating true ischaemic MR, where
valves are normal, from organic MR in patients with coronary
disease.
After myocardial infarction, ischaemic MR should be routi-
nely looked for and Doppler assessment of MR should be
done. Colour flow mapping of the regurgitant jet overesti-
mates the severity of ischaemic MR. The use of quantitative
methods adds important information. In ischaemic MR,
lower thresholds of severity, using quantitative methods,
have been proposed (20 mm
2
for ERO and 30 mL for regurgi-
tant volume).
24,110
Ischaemic MR is a dynamic disease, which makes it logical
to think that stress testing is likely to play an important role
in the evaluation. Preliminary studies have shown that quan-
titation of MR during exercise is feasible, pro vides a good
appreciation of dynamic charact eristics , and has prognostic
importance.
24,112
–
114
The prognost ic value of exercise tests
to predict the results of surgery has, howe ver, to be evaluated.
TEE in the operating room should not be used to decide
upon treatment of MR because in some patients, the after-
load reduction during surgery decreases the degree of MR.
Limited studies using low-dose dobutamine or positron
emission tomography have explored preoperative myocar-
dial viability as a predictor of outcome.
115
The assessment of coronary status is of particular import-
ance since it completes the diagnosis and allows evaluation
of the revascularization options.
Natural history
Acute MR, secondary to papillary muscle rupture, has a
dismal short-term prognosis and requires urgent treatment.
Patients with chronic ischaemic MR have a poor progno-
sis.
110
Although coronary artery disease and LV dysfunction
have prognostic importance, the presence and severity of
MR are independently associated with increased mortality.
Results of surgery
The data are far more limited and heterogeneous in ischae-
mic MR than in organic MR. Overall, surgery of ischaemic MR
remains a challenge. Operative mortality is higher than in
organic MR, and long-term prognosis is less satisfactory
with a higher recurrence rate of MR after valve repair.
116
These less favourable results are partly due to the more
severe comorbidities in ischaemic MR patients.
116
–
119
If
intervention is indicated, the preferred surgical procedure
remains controversial. There is a trend favouring valve
repair even if it carries a higher risk of mortality and of
recurrence of MR than in the other aetiologies. Most patients
with ischaemic MR seem to benefit from valve repair, using
undersized rigid ring annuloplasty,
120,121
except in the
most complex high-risk settings where survival after repair
or replacement is similar.
122
Finally, the presence of signifi-
cant myocardial viability is a predictor of good outcome
after repair combined with bypass surgery.
Most studies show that severe ischaemic MR is not usually
improved by revascularization alone.
123,124
There are
studies that suggest that there is improved survival with
valve surgery in patients with moderate ischaemic MR;
however, this is still debated since these studies are not con-
trolled and are of limited size.
125
Indications for surgery
Rupture of a papillary muscle necessitates urgent surgical
treatment after stabilization of the haemodynamic status,
using an intra-aortic balloon pump and vasodilators. In
addition to CABG, surgery consists of valve replacement in
most cases.
126
The limited data in the field of ischaemic MR result in less
evidence-based management (Table 9).
Severe MR should be corrected at the time of bypass
surgery. However, there is a continuing debate on the man-
agement of moderate ischaemic MR. In such cases, valve
repair is preferable and the decision must be made pre-
operatively, since intraoperative echocardiographic assess-
ment underestimates the severity of ischaemic MR. In
patients with low EF, surgery is more likely to be considered
if myocardial viability is present and if comorbidity is low.
There are no data to support surgically correcting mild MR
due to ischaemia when the patient is asymptomatic from the
point of view of MR and particularly when coronary revascu-
larization can be carried out by percutaneous coronary
intervention. However, these patients should be carefully
followed up to detect any later change in the degree and
the consequences of ischaemic MR.
Tabl e 9 Indications for surgery in chronic ischaemic mitral
regurgitation
Class
Patients with severe MR, LVEF .30% undergoing
CABG
IC
Patients with moderate MR undergoing CABG if
repair is feasible
IIaC
Symptomatic patients with severe MR, LVEF ,30%
and option for revascularization
IIaC
Patients with severe MR, LVEF .30%, no option
for revascularization, refractory to medical
therapy, and low comorbidity
IIbC
CABG ¼ coronary artery bypass grafting, MR ¼ mitral regurgitation,
LV ¼ left ventricular, EF ¼ ejection fraction.
246 ESC Guidelines
Functional mitral regurgitation
In this group, mitral valves are also structurally normal and
MR is secondary to the changes in LV geometry resulting from
impaired LV function. It includes MR observed in cardiomyo-
pathy and in ischaemic disease with severe LV dysfunction.
Evaluation is the same as in ischaemic MR.
The data on the natural history and results of surgery are
even more limited than in ischaemic MR. A precise analysis is
difficult because of the limited number of series including
small numbers of patients and mixing patients with or
without revascularization.
Several observational studies have shown the high preva-
lence of significant MR in chronic heart failure, as well as its
independent association with a poor prognosis.
127
However,
its true prevalence and its pathogenic contribution to prog-
nosis remain uncertain.
The main surgical technique is restrictive annulo-
plasty.
120,121,128,129
Other techniques can be combined
aiming at LV remodelling and are currently being evaluated.
Surgical treatment of MR in these patients was previously
avoided owing to concerns about the high operative risk
and the potential deleterious effect of increasing after-
load. Opinions have changed as a result of case series
from highly experienced centres reporting good
results.
120,121,128,129
Depending on the degree of urgency,
operative mortality has been reported between 5 and
18%. In patients with EF , 30%, a 2 year survival rate of
70% and a 5 year survival rate of 61% have been reported
with good functional results.
120,121
These data suggest
that valve surgery using stringent restrictive annuloplasty
combined with surgery of the LV may improve symptoms
at an acceptable risk. However, it is not clear if surgery
improves prognosis since more recent studies have shown
that valve surgery does not improve survival.
130,131
This
may be due to the fact that it may not influence LV remod-
elling, in particular, in patients with severe LV dilatation. In
addition, little information is available on the durability of
valve repair in this setting.
The limited data available suggest that isolated mitral
valve surgery in combination with LV reconstruction tech-
niques may be considered in selected patients with severe
functional MR and severely depressed LV function, including
those with coronary disease, where bypass surgery is not
indicated, who remain symptomatic despite optimal
medical therapy, and if comorbidity is low, the aim being
to avoid or postpone transplantation.
132,133
Ongoing trials
are expected to better define appropriate strategies. In
the other patients, medical therapy followed by transplan-
tation when this fails is probably the best option. However,
surgery on the regurgitant mitral valve should not be con-
sidered in ‘in extremis patients’ with low output, severe
right ventricular failure, and high comorbidity.
Medical therapy is the preferred treatment which should
be used before considering surgical correction of the func-
tionally regurgitant valve. ACE-inhibitors and beta-blockers,
which may reduce MR by progressive inverse LV remodelling,
are indicated. Nitrates and diuretics are useful for treating
acute dyspnoea, secondary to any dynamic component.
LV dilatation, distortion, and dyssynchrony are linked to
functional MR in patients with heart failure and LV dysfunc-
tion. Thus, in patients with increased QRS duration and
intra-ventricular asynchrony, cardiac resynchronization
therapy may reduce MR severity and improve LV function.
134
Defibrillators should be used according to the appropriate
recommendations.
Mitral stenosis
Introduction
Although the prevalence of rheumatic fever has greatly
decreased in industrialized countries, MS still results in sig-
nificant morbidity and mortality worldwide.
2,3
Since its
development 20 years ago, percutaneous mitral commissur-
otomy (PMC) has impacted significantly upon the manage-
ment of MS.
135
Evaluation
It may be difficult to evaluate precisely the functional dis-
ability in these patients who often present with a gradual
decrease in activity and may feel asymptomatic for years.
Physical examination, chest X-ray, and ECG establish the
diagnosis in most cases and allow for initial evaluation of
consequences such as atrial fibrillation and pulmonary
hypertension.
15
The general principles for the use of invasive and non-
invasive investigations follow the recommendations made
in the General comments section.
Specific issues in MS are as follows:
Echocardiography is the main method to assess the sever-
ity and consequences of MS, as well as the extent of ana-
tomic lesions. Severity of MS should be quantified using
two-dimensional planimetry and the pressure half-time
method, which are complementary approaches for measur-
ing valve area. Planimetry, when it is feasible, is the
method of choice, in particular, immediately after PMC.
Measurements of mean transvalvular gradient calculated
using Doppler velocities are highly rate- and flow-
dependent; however, they are useful to check consistency
of the assessment of severity, in particular, in patients in
sinus rhythm.
136
MS usually does not have clinical conse-
quences at rest when valve area is .1.5 cm
2
, except in
patients with particulary large body size.
The assessment of valve morphology is important for the
selection of candidates for PMC. Scoring systems have
been developed to assess suitability, taking into account
valve thickening, mobility, calcification, subvalvular
deformity, and commissural areas
135,137,138
(Tables 10,11).
Echocardiography also evaluates pulmonary artery press-
ures, the presence of associated MR, concomitant valve
disease, and the size of the left atrium.
The transthoracic approach usually provides sufficient
information for routine management. However, transoeso-
phageal examination should also be performed to exclude
left atrial thrombosis before PMC or after an embolic
episode or if transthoracic echocardiography provides sub-
optimal information on anatomy or associated MR.
In patients with no or doubtful symptoms, stress testing
aids decision-making by unmasking symptoms. Exercise
echocardiography provides other information by assessing
the evolution of mitral gradient and pulmonary pressures.
139
Its additional value for decision-making has to be further
defined.
ESC Guidelines 247
Echocardiography also plays an important role in monitor-
ing the results of PMC during the procedure and in evaluat-
ing the final results at least 24 h after its completion.
Natural history
Studies on natural history are old and non-controlled. In
asymptomatic patients, survival was good up to 10 years,
progression being highly variable with sudden deterioration,
precipitated by complications, such as atrial fibrillation or
embolism, in half of the patients.
140,141
Symptomatic
patients have a poor prognosis.
Results of intervention
Percutaneous balloon commissurotomy
PMC usually provides at least a 100% increase in valve area.
Good initial results are usually defined by a valve area
.1.5 cm
2
without more than mild MR. Technical success
and complications are related to the condition of the
patient and the team’s experience.
142
–
145
Failure rates
range from 1 to 15%. Major complications rates are as
follows: procedural mortality, 0.5
–
4%; haemopericardium,
0.5
–
10%; embolism, 0.5
–
5%; severe regurgitation, 2
–
10%.
Emergency surgery is seldom needed (, 1%).
Clinical follow-up data confirm the late efficacy of PMC
since event-free survival ranges from 35 to 70% after
10
–
15 years, depending on patient characteristics.
135,144,145
When the immediate results are unsatisfactory, surgery is
usually required in the following months. Conversely, after
successful PMC, long-term results are good in the majority
of cases. When functional deterioration occurs, it is late
and mainly related to re-stenosis. Successful PMC has also
been shown to reduce embolic risk. The prediction of long-
term results is related to preoperative anatomic and clinical
characteristics and to the quality of the immediate
results.
135,145
Identification of the variables linked to
outcome has enabled predictive models to be developed
with a high sensitivity; however, their specificity is low, indi-
cating insufficient prediction of poor immediate results.
Surgery
Conservative surgery
In industrialized countries, closed mitral valve commissurot-
omy has been replaced by open-heart mitral commissurot-
omy using cardiopulmonary bypass, which not only
corrects commissural fusion but also acts on subvalvular
deformity. In selected series from experienced centres,
mostly including young patients, long-term results are
good: at 15 years, survival was 96%, and freedom from
valve-related complications 92%.
146
The recent Euro Heart
Survey shows that in current practice, open-heart commis-
surotomy is seldom performed.
3
Valve replacement
Operative mortality ranges between 3 and 10% and corre-
lates with age, functional class, pulmonary hypertension,
and presence of coronary artery disease. Long-term
survival is related to age, functional class, atrial fibrillation,
pulmonary hypertension, preoperative LV function, and
complications of the prosthetic valve, especially thrombo-
embolism and haemorrhage or structural deterioration.
147
Indications for intervention
Type of treatment, as well as its timing, should be decided on
the basis of clinical characteristics (including functional status
and predictors of operative risk and of the results of PMC),
Table 10 Anatomic scores predicting outcome after percutaneous mitral commissurotomy: Wilkins’ mitral valve morphology score
137
Grade Mobility Subvalvular thickening Thickening Calcification
1 Highly mobile valve with
only leaflet tips restricted
Minimal thickening just
below the mitral leaflets
Leaflets near normal in
thickness (4
–
5 mm)
A single area of increased
echo brightness
2 Leaflet mid and base
portions have normal
mobility
Thickening of chordal
structures extending to
one-third of the chordal
length
Mid-leaflets normal,
considerable thickening
of margins (5
–
8 mm)
Scattered areas of brightness
confined to leaflet margins
3 Valve continues to move
forward in diastole,
mainly from the base
Thickening extended to
distal third of the chords
Thickening extending
through the entire
leaflet (5
–
8 mm)
Brightness extending into the
mid-portions of the leaflets
4 No or minimal forward
movement of the leaflets
in diastole
Extensive thickening and
shortening of all chordal
structures extending
down to the papillary
muscles
Considerable thickening of
all leaflet tissue
(.8
–
10 mm)
Extensive brightness
throughout much of the
leaflet tissue
Table 11 Anatomic scores predicting outcome after percutan-
eous mitral commissurotomy: Cormier’s grading of mitral valve
anatomy
142
Echocardiographic
group
Mitral valve anatomy
Group 1 Pliable non-calcified anterior mitral
leaflet and mild subvalvular disease
(i.e. thin chordae 10 mm long)
Group 2 Pliable non-calcified anterior mitral
leaflet and severe subvalvular disease
(i.e. thickened chordae ,10 mm long)
Group 3 Calcification of mitral valve of any
extent, as assessed by fluoroscopy,
whatever the state of subvalvular
apparatus
248 ESC Guidelines
valve anatomy, and local expertise and availability in the
fields of PMC and surgery.
Indications for intervention are as follows (Table 12,
Figure 4):
Intervention should only be performed in patients with
clinically significant MS (valve area ,1.5 cm
2
or
,1.7
–
1.8 cm
2
in particular in cases of unusually large
patients).
5,13
Intervention should be performed in symptomatic
patients. In the PMC era, most symptomatic patients with
favourable valve anatomy undergo PMC. However, open
commissurotomy may be performed by experienced oper-
ators in young patients with no or mild calcification and
mild-to-moderate MR. PMC is the procedure of choice
when surgery is contraindicated or high risk, or for patients
with favourable characteristics. Indications are a matter of
debate for patients with unfavourable anatomy.
Decision-making in this heterogeneous group of patients
must take into account the multifactorial nature of result
prediction of PMC and the relative experience in PMC and
surgery of the treating centre.
135,144,145
In current practice
in Europe, surgery for MS is mostly valve replacement.
3
PMC can be offered as initial treatment for selected patients
with mild-to-moderate calcification or impairment of the
subvalvular apparatus, who have otherwise favourable clini-
cal characteristics, in particular, in young patients in whom
Figure 4 Management of severe mitral stenosis. Patients at high risk of embolism or haemodynamic decompensation are defined by previous history of
embolism, dense spontaneous contrast in the left atrium, recent or paroxysmal atrial fibrillation, systolic pulmo nary pressure .50 mmHg at rest, need for
major non-cardiac surgery, desire of pregnancy.
Table 12 Indications for percutaneous mitral commissurotomy
in mitral stenosis with valve area , 1.5 cm
2
Class
Symptomatic patients with favourable
characteristics
a
for PMC
IB
Symptomatic patients with contraindication or high
risk for surgery
IC
As initial treatment in symptomatic patients with
unfavourable anatomy but otherwise favourable
clinical characteristics
a
IIaC
Asymptomatic patients with favourable
characteristics
a
and high thrombo-embolic risk or
high risk of haemodynamic decompensation:
Previous history of embolism IIaC
Dense spontaneous contrast in the left atrium IIaC
Recent or paroxysmal atrial fibrillation IIaC
Systolic pulmonary pressure . 50 mmHg at rest IIaC
Need for major non-cardiac surgery IIaC
Desire of pregnancy IIaC
PMC ¼ percutaneous mitral commissurotomy.
a
Favourable characteristi cs for PMC can be defined by the absence of
several of the following:
- Clinical characteristics: old age, history of commissurotomy, NYHA
class IV, atrial fibrillation, severe pulmonary hypertension,
- Anatomic characteristics: echo score . 8, Cormier score 3 (Calcifica-
tion of mitral valve of any extent, as assessed by fluoroscopy), very small
mitral valve area, severe tricuspid regurgitation.
ESC Guidelines 249
postponing valve replacement is particularly attractive. In
the other patients, surgery is preferable.
Because of the small but definite risk inherent in PMC,
truly asymptomatic patients are not usually candidates for
the procedure, except in the cases where there is increased
risk of thrombo-embolism or of haemodynamic decompensa-
tion such as severe pulmonary hypertension or a desire for
pregnancy. In such patients, PMC should only be performed
if they have favourable characteristics and by experienced
operators.
In asymptomatic patients with MS, because of the
inherent risks, surgery is seldom considered and is limited
to the rare patients at high risk of complications and with
contraindications for PMC.
Surgery is the only alternative when PMC is contraindi-
cated (Table 13). The most important contraindication is
left atrial thrombosis. A contraindication is self-evident if
the thrombus is localized in the cavity. When the thrombus
is localized in the left atrial appendage, the indications
for PMC are limited to patients with contraindications to
surgery or those without urgent need for intervention
when oral anticoagulation can be given for a minimum of
2 months and a maximum of 6 months and provided a new
TEE examination shows the disappearance of the throm-
bus.
148
If the thrombus persists, surgery is preferred.
Intraoperative correction of AF can be combined with
valve surgery in selected cases; the benefit of this approach,
however, requires further validation.
Medical therapy
Diuretics or long-acting nitrates transiently ameliorate dys-
pnoea. Beta-blockers or heart-rate regulating calcium
channel blockers are useful to slow the heart rate and can
greatly improve exercise tolerance by prolonging diastole
and hence the time available for LV filling via the stenosed
valve. Anticoagulant therapy with a target INR in the
upper half of the range 2
–
3 is indicated in patients with
either permanent or paroxysmal AF.
108
In patients with
sinus rhythm, anticoagulation is mandatory when there has
been prior embolism or a thrombus is present in the left
atrium (Recommendation class I, Level of evidence C), and
recommended when TEE shows dense spontaneous echo
contrast or in patients who have an enlarged left atrium
(diameter .50 mm) (Recommendation class IIa, Level of
evidence C).
12,13
Cardioversion is not indicated before intervention in
patients with severe MS, as it does not usually restore
sinus rhythm in the medium or long term. If atrial fibrillation
is of recent onset and the left atrium only moderately
enlarged, cardioversion should be performed soon after suc-
cessful intervention. Sinus rhythm can be maintained with
the use of class IC or III anti-arrhythmic drugs.
Infective endocarditis prophylaxis is indicated.
10
In
countries with a high prevalence of rheumatic disease, rheu-
matic fever prophylaxis should be given to young patients
and be continued after conservative intervention until
adult age.
Serial testing
Asymptomatic patients with clinically significant MS who
have not undergone intervention should be followed up
yearly by means of clinical and echocardiographic examin-
ations and at longer intervals in cases with stenosis of a
lesser degree.
Management of patients after successful PMC is similar to
that of asymptomatic patients. When PMC is not successful
and symptoms persist, surgery should be considered early
unless there are definite contraindications.
Special patient populations
When re-stenosis with symptoms occurs after surgical com-
missurotomy, reoperation in most cases requires valve repla-
cement. PMC can be considered in such patients if they have
favourable characteristics and no contraindications and if
the predominant mechanism of re-stenosis is commissural
re-fusion.
149
Similarly, repeat PMC can be proposed in selected patients
with the same characteristics as mentioned earlier if reste-
nosis occurs several years after an initially successful PMC.
In patients who present with valve anatomy that is not
ideal for PMC but who are not surgical candidates, repeat
PMC may have a palliative role.
For information on MS during pregnancy, see Management
of pregnancy section.
In the elderly, when surgery is high risk or contraindi-
cated, PMC is a useful option, even if only palliative. In
patients with favourable anatomic characteristics, PMC
can be attempted first, resorting to surgery if results are
unsatisfactory. In other patients, surgery is preferable if
not contraindicated.
150,151
In patients with MS combined with severe aortic valve
disease, surgery is usually preferable. In cases of coexisting
MS and moderate aortic valve disease, PMC can be per-
formed as a means of postponing the surgical treatment of
both valves. PMC can be attempted in patients with severe
MS and severe functional tricuspid regurgitation (TR). In
the others, with severe organic disease of the tricuspid
valve, surgery on both valves may be preferred.
Tricuspid disease
Tricuspid stenosis
Tricuspid stenosis (TS), which is almost exclusively of
rheumatic origin, is rarely observed in developed countries,
although it is still seen in developing countries.
2,4
Detection requires careful evaluation, as it is almost
always associated with left-sided valve lesions that
dominate the presentation.
Tabl e 1 3 Contraindications to percutaneous mitral
commissurotomy
Mitral valve area . 1.5 cm
2
Left atrial thrombus
More than mild MR
Severe- or bicommissural calcification
Absence of commissural fusion
Severe concomitant aortic valve disease or severe combined TS
and TR
Concomitant coronary artery disease requiring bypass surgery
MR ¼ mitral regurgitation, TR ¼ tricuspid regurgitation, TS ¼ tricuspid
stenosis.
250 ESC Guidelines
Evaluation
Clinical signs are often masked by those of the associated
valvular lesions, especially MS.
15
Echocardiography provides
the most useful information. TS is often overlooked and
requires careful evaluation. The pressure half-time
method has never been validated for the tricuspid valve
and the continuity equation is rarely applicable because of
the frequency with which associated regurgitation is
present. Planimetry of the valve area is usually impossible
unless three-dimensional echocardiography is used. No
generally accepted grading of TS severity exists. A mean
gradient .5 mmHg is considered indicative of clinically
significant TS.
17
Echocardiography should also examine the
presence of commissural fusion, the anatomy of the valve
and its subvalvular apparatus, which are the most important
determinants of reparability, and the degree of concomitant
regurgitation.
Surgery
The lack of pliable leaflet tissue is the main limitation for
conservative techniques.
For valve replacement, even though this is still a matter
of debate, biological prostheses are usually preferred to
mechanical ones because of the higher risk of thrombosis
carried by the latter and the satisfactory long-term dura-
bility of the former in the tricuspid position.
152
–
154
Percutaneous intervention
Percutaneous balloon tricuspid dilatation has been per-
formed in a limited number of cases, either alone or along-
side PMC, but frequently induces significant regurgitation.
Data on evaluation of long-term results are lacking.
155,156
Indications for intervention
Intervention on the tricuspid valve is usually carried out at
the time of intervention on the other valves in patients
who are symptomatic despite medical therapy.
Conservative surgery or valve replacement, according to
anatomy and surgical expertise in valve repair, is preferred
to balloon commissurotomy, which can only be considered
as a first approach in the rare cases of isolated TS
76
(Table 14).
Medical therapy
In the presence of heart failure, diuretics are useful but of
limited efficacy. Endocarditis prophylaxis should be given
as appropriate.
10
Tricuspid regurgitation
Trivial TR is frequently detected by echocardiography in
normal subjects. Pathological TR is more often functional
rather than due to a primary valve lesion. Functional TR is
due to annular dilatation and secondary to right ventricular
pressure and/or volume overload. Pressure overload is most
often caused by pulmonary hypertension resulting from left-
sided heart disease or, more rarely, cor pulmonale, idio-
pathic pulmonary artery hypertension, and right ventricular
volume overload possibly relating to atrial septal defects or
intrinsic disease of the right ventricle.
157,158
Evaluation
Predominant symptoms are those of associated diseases and
even severe TR may be well tolerated for a long period of
time. Although they are load dependent, clinical signs of
right heart failure are of value in evaluating the severity
of TR.
15
Echocardiography is the ideal technique to evaluate TR. It
provides the following information:
.
Structural abnormalities of the valve distinguishing
between its functional and primary forms. In the latter
form, the aetiology can usually be identified from specific
abnormalities such as vegetations in endocarditis,
159
leaflet retraction in rheumatic and carcinoid, and flail
leaflet in myxomatous or post-traumatic disease. The
degree of dilatation of the annulus should also be
measured.
.
Semi-quantitative evaluation of TR severity should be
based on the proximal convergence zone, proximal jet
width, dilatation of the inferior vena cava, and reduction
or reversal of systolic blood flow in the hepatic veins
19,160
(Table 2). It is important that this assessment should inte-
grate the quantitative data and the parameters evaluating
the consequences of TR, taking into account the sensi-
tivity of the different indices to loading conditions.
19
The criteria for defining severe TR are described in
Table 2.
.
Evaluation of the right ventricle, despite existing limit-
ations of any assessment of right ventricular function.
.
Measurement of peak right ventricular systolic pressure as
an estimate of pulmonary pressure by measuring peak tri-
cuspid regurgitant velocity.
.
Assessment of the degree of the combined lesions, looking
carefully at the LV and the associated valve lesions, par-
ticularly on the left side, and LV function.
Table 14 Indications for intervention in tricuspid valve disease
Class
Severe TR in a patient undergoing left-sided valve
surgery
IC
Severe primary TR and symptoms despite medical
therapy without severe right ventricular dysfunction
IC
Severe TS (+TR), with symptoms despite medical
therapy
a
IC
Severe TS (+TR) in a patient undergoing
left-sided valve intervention
a
IC
Moderate organic TR in a patient
undergoing left-sided valve surgery
IIaC
Moderate secondary TR with dilated
annulus (.40 mm) in a patient undergoing
left-sided valve surgery
IIaC
Severe TR and symptoms, after left-sided valve
surgery, in the absence of left-sided myocardial,
valve, or right ventricular dysfunction and
without severe pulmonary hypertension
(systolic pulmonary artery pressure . 60 mmHg)
IIaC
Severe isolated TR with mild or no symptoms and
progessive dilation or deterioration of right
ventricular function
IIbC
TR ¼ tricuspid regurgitation, TS ¼ tricuspid stenosis.
a
Percutaneous technique can be attempted as a first approach if TS is
isolated.
ESC Guidelines 251
When available, MRI may provide additional useful infor-
mation on the size and function of the right ventricle,
which is difficult to evaluate using other imaging techniques.
Natural history
The limited data that are available on the natural history of
primary TR suggest that severe TR has a poor prognosis even
if it may be well tolerated functionally for years.
Functional TR may diminish or disappear as right ventricu-
lar failure improves following the treatment of its cause.
However, TR may persist even after successful correction
of left-sided lesions. Predicting the evolution of functional
TR after surgical treatment of mitral valve disease remains
difficult.
157
Pulmonary hypertension, increased right ventri-
cular pressure and dimension, reduced right ventricular
function, and the diameter of the tricuspid annulus are
important risk factors for persistence or late worsening of
TR.
161,162
However, TR may persist even after successful cor-
rection of left-sided lesions.
Results of surgery
Annuloplasty is key to conservative surgery. Better long-
term results are observed with prosthetic rings than with
the stitch technique, the incidence of residual TR being,
respectively, 10 and 20
–
35% at 5 years.
158,161,163
Valve
replacement carries a risk of operative mortality ranging
from 7 to 40%. Ten year survival ranges from 30 to 50%, the
predictors being preoperative functional class, LV function
and right ventricular function, and prosthetic compli-
cations.
152
–
154
The current experience favours the use of
large bioprostheses over mechanical valves.
Reoperation on the tricuspid valve in cases of persistent
TR after mitral valve surgery carries a high risk mostly due
to the clinical condition of the patients (including age and
the number of previous cardiac interventions) and may
well have poor long-term results related to the presence
of irreversible right ventricular dysfunction prior to
reoperation.
Indications for surgery
The timing of surgical intervention and the appropriate
technique remain controversial mostly due to the limited
data available and their heterogeneous nature (Table 14).
As general principles, we can say, if technically possible,
conservative surgery is preferable to valve replacement,
and surgery should be carried out early enough to avoid irre-
versible right ventricular dysfunction.
The possible need for correction of TR is usually con-
sidered at the time of surgical correction of left-sided valv-
ular lesions. In these circumstances, the relative simplicity
of tricuspid valve repair and the high risk of secondary sur-
gical correction are incentives to earlier indications for tri-
cuspid repair. In these circumstances, severe TR should be
corrected. In the other cases with lesser degree of TR, sur-
gical correction can be recommended when there is pulmon-
ary hypertension or severe dilatation of the annulus
161,162
(diameter .40 mm or .21 mm/m
2
BSA) and, even more
so, if TR is of organic origin. Finally, mild TR does not
warrant intervention.
Surgery limited to the tricuspid valve can be required in
patients with severe primary TR resulting from endocarditis
or trauma who remain symptomatic or in those with no or
mild symptoms who have objective signs of significant
impairment of right ventricular function.
In the particular circumstances of persistent or recurrent
severe TR despite medical therapy after mitral valve
surgery, isolated operation on the tricuspid valve should be
considered in the absence of left-sided valve, myocardial,
or severe right ventricular dysfunction.
Medical therapy
Diuretics improve signs of congestion. Specific therapy of
the underlying disease is warranted.
Combined and multiple valve diseases
The data on mixed and multiple valve diseases are lacking
and do not allow for evidence-based recommendations. In
addition, the large number of combinations possible leads
to the necessity of individualized decisions in this domain.
Significant stenosis and regurgitation can be found on the
same valve. Such combined VHDs are encountered in rheu-
matic valve disease and, less frequently, in degenerative
valve disease. When stenosis or regurgitation is largely pre-
dominant, the management follows the recommendations
concerning the predominant VHD. When the severity of
both stenosis and regurgitation is balanced, indications for
interventions should be based on how well the patient toler-
ates the combined VHD rather than indices of severity of
stenosis or regurgitation. Intervention can be considered
when a non-severe stenosis is combined with a non-severe
regurgitation in patients who have symptoms or in whom it
is clear the combined lesion is leading to LV impairment.
Intervention is nearly always prosthetic valve replacement
in this setting.
Disease of multiple valves may be encountered in several
conditions but particularly rheumatic heart disease. Besides
the separate assessment of each separate valve lesion, it is
necessary to take into account the interaction between the
different valve lesions. As an illustration, associated MS may
lead to underestimation of the severity of AS, since
decreased stroke volume due to MS lowers the flow across
the aortic valve and hence the aortic gradient. This under-
lines the need to combine different measurements, includ-
ing assessment of valve areas, if possible using methods
that are less dependent on loading conditions, such as
planimetry. Associated MR and AR can be encountered, in
particular, in Marfan’s syndrome. In these patients, besides
severity, the assessment of valve anatomy is of importance
to evaluate the possibility of conservative surgery on each
valve.
Indications for intervention are based on global assess-
ment of the consequences of the different valve lesions,
i.e. symptoms or consequences on LV dimensions and func-
tion. In addition, the decision to intervene on multiple
valves should take into account the extra surgical risk of
combined procedures. The choice of surgical technique
should take into account the presence of the other VHD.
For example, the desire to repair one valve may be
decreased if prosthetic valve replacement is needed on
another valve. The management of other specific associ-
ations of VHD is detailed in the individual sections.
252 ESC Guidelines
Prosthetic valves
Patients who have undergone previous valve surgery rep-
resent an important proportion of patients with VHD,
accounting for 28% of all patients with VHD in the Euro
Heart Survey.
3
The extent of prosthesis-related compli-
cations in patient outcome after surgery emphasizes the
importance of optimizing the choice of the valve substitute
as well as the subsequent management of patients with
prosthetic valves.
Choice of prosthet ic valve
There is no perfect valve substitute. All involve some com-
promise and all introduce new disease processes, whether
they are mechanical or biological. The latter include xeno-
grafts, homografts, and autografts. Autografts and homo-
grafts in the aortic position provide the best effective
orifice area (EOA). Stentless bioprostheses provide better
EOA than stented bioprostheses, which are relatively steno-
tic in the small sizes (annulus size 21 mm). Modern mech-
anical valves provide better haemodynamic performance
than stented bioprostheses.
All mechanical valves require long-term anticoagulation.
Biological valves are less thrombogenic and do not require
long-term anticoagulation unless there are other indi-
cations, e.g. persistent atrial fibrillation. However, all are
subject to structural valve deterioration (SVD) over time.
Two randomized trials, which began in the 1970s, compar-
ing now obsolete models of mechanical and bioprosthetic
valves found no significant difference in rates of valve
thrombosis and thrombo-embolism, in accordance with
numerous individual valve series in the literature. Long-
term survival was also very similar.
147,164
A recent
meta-analysis of mechanical and bioprosthetic valve series
found no difference in survival when age and risk factors
were taken into account.
165
Apart from haemodynamic considerations, choice between
a mechanical valve and a bioprosthesis in adults is thus deter-
mined primarily by assessing the risk of anticoagulant-related
bleeding with a mechanical valve vs. the risk of SVD with a
bioprosthesis.
166,167
The former is determined mainly by the
target INR chosen, the quality of anticoagulation control,
the concomitant use of aspirin, and the patient’s own risk
factors for bleeding.
168
The risk of SVD must take into
account the gradual deterioration in performance status
with increasing SVD, the risk of re-operation and length of
the recovery period after subsequent surgery.
Homografts and pulmonary autografts are mainly used in
the aortic position, though even here they together
account for less than 0.5% of aortic valve replacements in
most large databases. Like bioprostheses, homografts are
subject to SVD.
169
Besides technical concerns, limited avail-
ability and increased complexity of reoperation contribute
to restrict the use of homografts to complicated aortic
valve endocarditis.
Although the pulmonary autograft in the aortic position
(Ross operation) provides excellent haemodynamics, it
requires specific expertise and has several disadvantages:
the risk of SVD in the homograft in the pulmonary position,
the risk of moderate AR due to dilatation of the aortic root,
and the risk of rheumatic involvement. Apart from short-
term advantages in selected young adults, such as
professional athletes, the main advantage of the autograft
is in growing children, as the valve and new aortic annulus
appear to grow with the child.
170
However, the homograft
pulmonary valve replacement does not and, therefore,
usually needs replacement as the child gets bigger.
In practice, the choice is between mechanical prosthesis
and bioprosthesis in most patients. Rather than setting arbi-
trary age limits, prosthesis choice should be individua-
lized
167
and discussed in detail with the patient, taking
into account the following factors (Tables 15,16):
(1) Life expectancy should be estimated according to
country and patient’s age, and take into account
comorbidities.
(2) A mechanical valve should be recommended if a mech-
anical valve is implanted on another valve and should
Table 15 Choice of the prosthesis: in favour of mechanical
prosthesis
a
Class
Desire of the informed patient
and absence of contraindication for
long-term anticoagulation
IC
Patients at risk of accelerated SVD
b
IC
Patient already on anticoagulation because
of other mechanical prosthesis
IC
Patients already on anticoagulation because
at high risk for thrombo-embolism
c
IIaC
Age ,65
–
70 and long life expectancy
d
IIaC
Patients for whom future redo valve surgery
would be at high risk (due to LV dysfunction,
previous CABG, multiple valve prosthesis)
IIaC
CABG ¼ coronary artery bypass grafting, LV ¼ left ventricular, SVD ¼
structural valve deterioration.
a
The decision is based on the integration of several of the factors given
in the table.
b
Young age, hy perparathyroidism.
c
Risk factors for thrombo-embolism: severe LV dysfunction, atrial fibril-
lation, previous thrombo-embolism, hypercoagulable state.
d
According to age, gender, the presence of comorbidity, and country-
specific life expectancy.
Table 16 Choice of the prosthesis: in favour of bioprosthesis
a
Class
Desire of the informed patient IC
Unavailability of good-quality anticoagulation
(contraindication or high risk, unwillingness,
compliance problems, lifestyle, occupation)
IC
Re-operation for mechanical valve thrombosis in a
patient with proven poor anticoagulant control
IC
Patient for whom future redo valve surgery would
be at low risk
IIaC
Limited life expectancy
b
, severe comorbidity, or
age .65
–
70
IIaC
Young woman contemplating pregnancy IIbC
a
The decision is based on the integration of several of the factors given
in the table.
b
According to age, gender, the presence of comorbidity, and country-
specific life expectancy.
ESC Guidelines 253
be also considered if the patient is already on anticoagu-
lants for another reason.
(3) If there are definite contraindications to
anticoagulation or the patients’ lifestyle exposes them
to frequent injury, a biological substitute should be
recommended.
171,172
(4) SVD occurs more rapidly in young patients and in case of
hyperparathyroidism, including renal failure.
173
Bioprostheses should be avoided if possible before the
age of 40. SVD progresses more slowly in elderly patients
but this conclusion is based upon reports of lower rates
of re-operation, often without taking into account those
patients with SVD who are too frail to undergo
re-operation. Bioprostheses should be recommended in
patients whose life expectancy is lower than the pre-
sumed durability of the bioprosthesis, particularly if
comorbidities will necessitate other surgical procedures
in the future, and in those with increased bleeding risk.
Although SVD is accelerated in chronic renal failure,
poor long-term survival with either type of prosthesis
and an increased risk of complications with mechanical
valves may favour the choice of a bioprosthesis in this
situation.
174
(5) In women of childbearing age who wish to become preg-
nant, choice between mechanical and bioprosthetic
valves depends on a balance of risks, both for the
mother and the foetus. Using warfarin in a dose of
5 mg/day or less throughout pregnancy until the 36th
week minimizes the risk of both foetal malformation
and maternal valve thrombosis.
175
On the other hand,
although SVD occurs rapidly in this age group, the risk
of reoperation is relatively low (if surgery is not required
in an emergency during pregnancy) and compares
favourably with the risk of a pregnancy under anticoagu-
lant therapy.
(6) Quality of life issues must also be taken into account.
Inconvenience of oral anticoagulation can be minimized
by home monitoring and self-management of anticoagu-
lation.
176
Although bioprosthetic recipients can avoid
long-term anticoagulation, they face the possibility of
deterioration in functional status owing to SVD and the
prospect of reoperation if they live long enough.
Management after valve replacement
Thrombo-embolism and anticoagulant-related bleeding
together account for 75% of complications experienced
by prosthetic valve recipients and most space is therefore
devoted to this topic. Endocarditis prophylaxis and manage-
ment of prosthetic valve endocarditis are detailed in separ-
ate ESC Guidelines devoted to endocarditis.
10
A more
comprehensive review of management after valve surgery
is available in a previous Special ESC article.
14
Baseline assessment and modalities of follow-up
A complete baseline assessment should be ideally performed
6
–
12 weeks after surgery. If for practical reasons this outpa-
tient evaluation cannot be organized, it could be done at
the end of the postoperative stay. This will include clinical
assessment, chest X-ray, ECG, transthoracic echocardiogra-
phy, and blood testing. This reference assessment is of
utmost importance to interpret subsequent changes in
murmur, prosthetic sounds, as well as ventricular function
and transprosthetic gradients as assessed by Doppler echo-
cardiography. This postoperative visit is also useful to
improve patient education on endocarditis prophylaxis
and, if needed, on anticoagulant therapy, as well as empha-
sizing that new symptoms should be reported as soon as they
occur.
All patients who have undergone valve surgery require
lifelong follow-up by a cardiologist in order to detect early
deterioration in prosthetic function or ventricular function,
or progression of disease in a further heart valve. Clinical
assessment should be performed yearly or as soon as poss-
ible if new cardiac symptoms occur. Transthoracic echocar-
diography should be performed if any new symptoms occur
after valve replacement or if complications are suspected.
Yearly echocardiographic examination is recommended
after the fifth year in patients with bioprosthesis.
Transprosthetic gradients during follow-up are best inter-
preted in comparison with the baseline values in the same
patient, rather than in comparison with theoretical values
for a given prosthesis, which lack reliability. TEE should be
considered if transthoracic echocardiography is of poor
quality and in all cases of suspected prosthetic dysfunction
or endocarditis. Cinefluoroscopy can provide useful
additional information if valve thrombus or pannus is
suspected.
14
Antithrombotic management
General management
Antithrombotic management should encompass the effec-
tive management of risk factors for thrombo-embolism in
addition to the prescription of antithrombotic drugs.
177,178
Oral anticoagulation is recommended for the following
situations:
.
Lifelong for all patients with mechanical valves.
5,14,178
.
Lifelong for patients with bioprostheses who have other
indications for anticoagulation, e.g. atrial fibrillation, or
with a lesser degree of evidence, e.g. heart failure,
impaired LV function (EF , 30%).
.
For the first 3 months after insertion in all patients with
bioprostheses with a target INR of 2.5. However, there is
widespread use of aspirin (low dose: 75
–
100 mg) as an
alternative to anticoagulation for the first 3 months, but
there are no randomized studies to support the safety of
this strategy.
179
Although there is no consensus regarding the initiation
of anticoagulant therapy immediately after valve
replacement, oral anticoagulation should be started during
the first postoperative days. Intravenous heparin enables
effective anticoagulation to be obtained before the INR
rises.
The first postoperative month is a particularly high-risk
period for thrombo-embolism, and anticoagulation should
avoid being lower than the target value during this
period.
180
In addition, anticoagulation should be monitored
more frequently during this period.
Target INR
The choice of optimum INR should take into account patient
risk factors and the thrombogenicity of the prosthesis as
determined by reported valve thrombosis rates for that
prosthesis in relation to specific INR levels (Table 17).
Reported thrombo-embolic rates do not provide sufficient
254 ESC Guidelines
guidance about individual prosthesis thrombogenicity, as
they are heavily influenced by so many other patient-related
factors and the methods of data collection. Unfortunately,
currently available randomized trials comparing different
INRs offer little general guidance owing to limitations
imposed by their selection criteria, small numbers of
patients with short follow-up, and varied methodologies,
making them unsuitable for meta-analysis.
181,182
In selecting the optimum INR, certain caveats apply:
.
Prostheses cannot be conveniently categorized by basic
design (e.g. bileaflet, tilting disc, etc.) or date of intro-
duction for the purpose of determining thrombogenicity.
.
For many currently available prostheses, particularly
newly introduced prostheses, sufficient data on valve
thrombosis rates at different levels of INR do not exist
to allow categorization. Until further data become avail-
able, they should be placed in the ‘medium thrombogeni-
city’ category.
.
INR recommendations in individual patients may need to
be revised downwards if recurrent bleeding occurs from
a source not amenable to treatment, or revised upwards
in case of embolism.
We chose to recommend a median INR value rather than a
range to avoid considering extreme values in the target
range as a valid target INR, since values at either end of a
range are not equally acceptable and effective.
The risk of major bleeding rises considerably when the INR
exceeds 4.5, and exponentially above an INR of 6.0. An INR
of 6.0 therefore requires reversal of anticoagulation.
However, in patients with prosthetic valves who are not
bleeding, intravenous vitamin K should not be used
because of the risk of valve thrombosis if the INR falls
rapidly. The patient should be admitted to hospital, the
oral anticoagulant stopped, and the INR allowed to fall gradu-
ally. Spontaneous fall in the INR after anticoagulant cessation
occurs more slowly in the elderly and in the presence of heart
failure.
183
It is permissible to use oral vitamin K, given in
increments of 1 mg, in patients who are treated using long
half-life vitamin K blockers such as phenprocoumon. If the
INR is .10.0, consideration should be given to the use of
fresh frozen plasma. Reversal of anticoagulation should be
more aggressive, using fresh frozen plasma and adapted
doses of intravenous vitamin K,
184
if there is active bleeding
not amenable to local control. Bleeding with a therapeutic
INR is often related to an underlying pathological cause and
it is important to identify and treat it.
High variability of the INR is the strongest independent
predictor of reduced survival after valve replacement.
168
Self-management of anticoagulation has been shown to
reduce INR variability and should therefore be rec-
ommended in all patients who, after education and training,
have the ability to control their own anticoagulation.
176
Antiplatelet drugs
In determining whether an antiplatelet agent should be
added to anticoagulation in patients with prosthetic
valves, it is important to distinguish between the possible
benefits in vascular disease and those specific to prosthetic
valves. Trials showing a benefit from antiplatelet drugs in
vascular disease
185
and in patients with prosthetic valves
and vascular disease
186
should not be taken as evidence
that patients with prosthetic valves and no vascular
disease will also benefit. When added to anticoagulation,
antiplatelet agents increase the risk of major bleed-
ing.
185
–
191
They should therefore not be prescribed for all
patients with prosthetic valves, but reserved for specific
indications, according to the analysis of the benefit and
the increased risk of major bleeding.
Indications for the addition of an antiplatelet agent to
anticoagulation include concomitant arterial disease, in par-
ticular, coronary disease and other significant atherosclero-
tic disease. Antiplatelet agents can also be added after
recurrent or one definite embolic episode with adequate
INR. Addition of antiplatelet agents should be associated
with a full investigation and treatment of identified risk
factors and optimization of anticoagulation management
(Recommendation class IIa, Level of evidence C).
Addition of aspirin and clopidogrel is necessary following
intracoronary stenting but increases bleeding risk.
192,193
The use of drug-eluting stents should be restricted in
patients with mechanical prostheses to shorten as much as
possible the use of triple antithrombotic therapy. During
this period, weekly monitoring of INR is advised and any
over-anticoagulation should be avoided.
Finally, there is no evidence to support the long-term use
of antiplatelet agents in patients with bioprosthesis who do
not have an indication other than the presence of the bio-
prosthesis itself.
Interruption of anticoagulant therapy
Although most instances of short-term anticoagulation
interruption do not lead to thrombo-embolism or valve
thrombosis, the corollary is that most cases of valve throm-
bosis occur following a period of anticoagulation interrup-
tion for bleeding or another operative procedure.
194
Anticoagulation management during subsequent non-cardiac
surgery therefore requires very careful management on the
basis of risk assessment.
177,195,196
Besides prosthesis- and
patient-related prothrombotic factors (Table 17), surgery
for malignant disease or an infective process carries a par-
ticular risk, due to the hypercoagulability associated with
these conditions. For very high-risk patients, anticoagula-
tion interruption should be avoided if at all possible. Many
minor surgical procedures (including dental extraction)
and those where bleeding is easily controlled do not
require anticoagulation interruption. The INR should be
Table 17 Target international normalized ratio for mechanical
prostheses
Prosthesis thrombogenicity
a
Patient-related risk factors
b
No risk factor 1 Risk factor
Low 2.5 3.0
Medium 3.0 3.5
High 3.5 4.0
LVEF ¼ left ventricular ejection fraction, MS = mitral stenosis.
a
Prosthesis thrombogenicity: Low ¼ Carbomedics (aortic position),
Medtronic Hall, St Jude Medical (without Silzone); Medium ¼ Bjork-Shiley,
other bileaflet valves; High ¼ Lillehei-Kaster, Omniscience, Starr-Edwards.
b
Patient-related risk factors: mitral, tricuspid, or pulmonary valve repla-
cement; previous thrombo-embolism; atrial fibrillation; left atrial diam-
eter .50 mm; left atrial dense spontaneous contrast; MS of any degree;
LV E F ,35%; hypercoagulable state.
ESC Guidelines 255
lowered to a target of 2.0.
197,198
(Recommendation class I,
Level of evidence B).
For major surgical procedures, in which anticoagulant
interruption is considered essential (INR ,1.5), patients
should be admitted to hospital in advance and transferred
to intravenous unfractionated heparin (Recommendation
class IIa, Level of evidence C). Heparin is stopped 6 h
before surgery and resumed 6
–
12 h after. Low molecular
weight heparin (LMWH) can be given subcutaneously as
an alternative preoperative preparation for surgery
(Recommendation class IIb, Level of evidence C).
However, despite their wide use and the positive results
of observational studies,
199
–
201
the safety of LMWHs in
this situation has not been widely established and their
efficacy has not been proved by controlled studies, particu-
larly in patients at high risk of valve thrombosis. When
LMWHs are used, they should be administered twice a
day, using therapeutic rather than prophylactic doses,
adapted to body weight and if possible according to moni-
toring of anti-Xa activity. LMWHs are contraindicated in
case of renal failure.
Despite the low level of evidence for both strategies, the
committee favours the use of unfractionated intravenous
heparin.
Effective anticoagulation should be resumed as soon as
possible after the surgical procedure and maintained until
the INR is once again in the therapeutic range.
If required, after a careful risk
–
benefit assessment, com-
bined aspirin therapy should be discontinued 1 week before
a non-cardiac procedure.
Oral anticoagulation can be continued at modified
doses in the majority of patients who undergo cardiac
catheterization. Percutaneous arterial puncture is safe
with an INR , 2.0. If a higher target INR is needed, radial
approach may be recommended if the appropriate expertise
is available. In the rare patients who require transseptal
catheterization, direct LV puncture, or pericardiocentesis,
the INR should be , 1.2 and bridging anticoagulation is
needed as described previously.
14
Management of valve thrombosis
Obstructive valve thrombosis should be suspected promptly
in any patient with any type of prosthetic valve who pre-
sents with a recent increase in shortness of breath or
embolic event. Suspicion should be higher if there has
been recent inadequate anticoagulation or a cause for
increased coagulability (e.g. dehydration, infection, etc.).
The diagnosis should be confirmed by transthoracic echocar-
diography and/or TEE or cinefluoroscopy.
202,203
The management of prosthetic thrombosis is high risk
whatever the option taken. Surgery is high risk because it
is most often performed in emergency conditions and is
reintervention. On the other hand, fibrinolysis carries
risks of bleeding, systemic embolism, and recurrent
thrombosis.
The analysis of risk and benefits of fibrinolysis should be
adapted to patient characteristics and local resources.
Indications for surgery or antithrombotic therapy are as
follows (Figure 5):
Urgent or emergency valve replacement is the treatment
of choice for obstructive thrombosis in critically ill patients
without serious comorbidity (Recommendation class I, Level
of evidence C). If the thrombogenicity of the prosthesis is an
Figure 5 Management of left-sided obstructive prosthetic thrombosis.
256 ESC Guidelines
important factor, it should be replaced with a less thrombo-
genic prosthesis.
Fibrinolysis should be considered in:
.
Critically ill patients unlikely to survive surgery because of
comorbidities or severely impaired cardiac function prior
to developing valve thrombosis.
.
Situations in which surgery is not immediately available
and the patient cannot be transferred.
.
Thrombosis of tricuspid or pulmonary valve replacements,
because of the higher success rate and low incidence of
embolism.
Fibrinolysis is less likely to be successful in mitral
prostheses, in chronic thrombosis, or in the presence of
pannus, which can be difficult to distinguish from
thrombus.
204
–
206
Management of left-sided non-obstructive prosthetic
thrombosis is as follows (Figure 6):
Non-obstructive prosthetic thrombosis is diagnosed using
TEE performed after an embolic event, or systematically fol-
lowing mitral valve replacement with a mechanical prosthe-
sis. The management depends mainly on the occurrence of a
thrombo-embolic event and the size of the thrombus. Close
monitoring by echocardiography and/or cinefluoroscopy is
mandatory. The prognosis is favourable with medical
therapy in most cases of small thrombus (,10 mm). A
good response with gradual resolution of the thrombus
obviates the need for either surgery or fibrinolysis.
Conversely, surgery is recommended for large (10 mm)
non-obstructive prosthetic thrombus complicated by
embolism (Recommendation class IIa, Level of evidence C)
or which persists despite optimal anticoagulation.
207,208
Fibrinolysis may be considered as an alternative if surgery
is at high risk. However, the use of fibrinolysis for non-
obstructive prosthetic thrombosis raises serious concerns
regarding the risk of bleeding and thrombo-embolism and
should therefore be very limited.
Figure 6 Management of left-sided non-obstructive prosthetic thrombosis.
ESC Guidelines 257
Management of thrombo-embolism
Thrombo-embolism after valve surgery is multifactoral both
in its aetiology and its origin.
209
Although many
thrombo-embolic events will have originated from thrombus
or a vegetation on a prosthesis or as the result of the abnor-
mal flow conditions created by a prosthesis, many others
will have arisen from other sources as the result of other
pathogenic mechanisms and be part of the background inci-
dence of stroke and transient ischaemic attack in the
general population.
Thorough investigation of each episode of thrombo-
embolism is therefore essential (including cardiac and non-
cardiac imaging when appropriate) to allow for appropriate
management (Figure 6), rather than simply increasing the
target INR or adding an antiplatelet agent.
Prevention of further thrombo-embolic events involves:
.
Treatment or reversal of remediable risk factors such as
AF, hypertension, hypercholesterolaemia, diabetes,
smoking, chronic infection, and prothrombotic blood test
abnormalities.
.
Optimization of anticoagulation control, if possible with
patient self-management, on the basis that better
control is more effective than simply increasing the
target INR. This should be discussed with the neurologist
in case of recent stroke.
.
Aspirin should be added, if it was not prescribed before,
after a careful analysis of the risk
–
benefit ratio. Aspirin
should be prescribed in a low-dose formulation (100 mg
daily) and any over-anticoagulation should be avoided.
Management of haemolysis and paravalvular leak
Blood tests for haemolysis should be part of routine
follow-up. Haptoglobin measurement is too sensitive and
lactate dehydrogenase, although non-specific, is better
related to the severity of haemolysis. The diagnosis of hae-
molytic anaemia requires TEE to detect a paravalvular leak
(PVL). Only limited data are available regarding therapeutic
options. There is a consensus to recommend reoperation if
PVL is related to endocarditis or if PVL causes haemolysis
needing repeated blood transfusions or leading to severe
symptoms (Recommendation class I, Level of evidence C).
In patients with haemolytic anaemia and PVL, where
surgery is contraindicated, or those unwilling to undergo
re-operation, medical therapy includes iron supplemen-
tation, beta-blockers, and erythropoietin if haemolysis is
severe.
210,211
Percutaneous closure of PVL has only been
the subject of isolated case reports and could not be con-
sidered so far as a validated alternative to surgery.
Management of bioprosthetic failure
SVD occurs in all bioprostheses and homografts if they
remain in situ long enough. After the first 5 years from
implantation, yearly echocardiography is required to
detect early signs of SVD: leaflet stiffening, calcification,
reduced EOA and/or regurgitation. Auscultatory and echo-
cardiographic findings should be carefully compared with
previous examinations in the same patient. Reoperation is
advised in symptomatic patients with significant prosthetic
dysfunction (significant increase in trans-prosthetic gradient
or severe regurgitation) (Recommendation class I, Level of
evidence C) and in asymptomatic patients with any signifi-
cant prosthetic dysfunction, if they are at low risk for
reoperation (Recommendation class IIa, Level of evidence
C). Prophylactic replacement of a bioprosthesis implanted
.10 years ago, without structural deterioration, could be
considered during an intervention on another valve or coron-
ary artery.
The decision to reoperate should take into account the
risk of reoperation, which increases with older age, high
functional class, LV dysfunction, comorbidities, and, above
all, the emergency situation. This underlines the need for
careful follow-up to allow for reoperation at an early
stage, in particular, in patients who are at low risk for
reoperation.
212,213
Percutaneous balloon interventions should be avoided in
the treatment of stenotic left-sided bioprostheses and
have a limited short-term efficacy in right-sided prosthetic
valves.
Heart failure
Heart failure after valve surgery should lead to a search for
prosthetic-related complications, deterioration of repair, LV
dysfunction (in particular after correction of regurgitation),
or progression of another valve disease. Non-valvular-
related causes such as coronary disease, hypertension, or
sustained arrhythmias should also be considered.
The management of patients with persistent LV systolic
dysfunction should follow the guidelines on the management
of chronic heart failure.
16
Management during non-cardiac surgery
There is a significant risk of cardiovascular morbidity and
mortality in patients with VHD undergoing non-cardiac
surgery, especially in patients with severe AS, which is the
most common type of valve disease seen in Europe
3
and it
is particularly common in the elderly.
The problem of valvular patients undergoing non-cardiac
surgery is only partially addressed in the literature. The
existing guidelines for perioperative cardiovascular evalu-
ation for non-cardiac surgery
214
are mainly devoted to the
field of ischaemic heart disease.
The present recommendations arise from extrapolation
from studies concerning cardiovascular risk in other
instances, personal experience, and clinical judgement.
Clinical predictors of increased perioperative
cardiovascular risk
The major predictors of cardiovascular risk during non-
cardiac surgery are unstable coronary syndromes, decom-
pensated heart failure, significant arrhythmias (including
high-grade atrio-ventricular block, ventricular arrhythmias,
or supraventricular arrhythmias with uncontrolled ventricu-
lar rate), and severe valvular disease.
214
Among patients with valvular disease, risk assessment
should incorporate symptomatic status, presence or not of
arrhythmias, severity of the valvular lesion, LV function,
and level of pulmonary pressure and comorbidities, includ-
ing ischaemic heart disease.
Cardiovascular risk can also be stratified according to the
different non-cardiac surgical procedures.
214
258 ESC Guidelines
Preoperative clinical evaluation
Before non-cardiac surgery, severe VHD should be identified
and the clinical status of the patient carefully evaluated.
The presence of symptoms, that is, dyspnoea, angina,
syncope, or heart failure, as well as the presence of arrhyth-
mias, like atrial fibrillation, should be recorded. Physical
examination and the ECG should focus on identification of
VHD. In patients with a murmur, an echocardiographic
study should be done to rule out the diagnosis of significant
valve disease. This is particularly important in aged
patients, because a mild systolic murmur can be the only
physical sign of significant AS.
The severity of the valve lesion, ventricular function, and
pulmonary pressure should be carefully evaluated by echo-
cardiography before surgery.
Each case should be individualized and agreement
reached after a full discussion with cardiologists, anaesthe-
siologists, ideally with a particular skill in cardiology, and
surgeons.
Specific valve lesions
Aortic stenosis
Several studies
215
–
219
have clearly shown that severe AS
(aortic valve area ,1cm
2
or 0.6 cm
2
/m
2
BSA) increases
the risk of non-cardiac surgery, and among patients with
valve disease undergoing non-cardiac surgery, those with
significant AS have the highest risk.
Recommendations for management are as follows:
In patients with significant AS who need urgent non-
cardiac surgery, surgical procedures should be performed
under careful haemodynamic monitoring.
When elective non-cardiac surgery is needed in a
patient with AS, the risk of cardiac complications during
surgery should be balanced with the risk and benefits
of having the valve replaced before non-cardiac surgery.
The severity of the valvular lesion and the presence of
clinical symptoms as well as the risk and the urgency of
non-cardiac surgery itself should be considered. It is also
important to re-evaluate whether non-cardiac surgery is
essential. A decision algorithm is proposed for patients
with significant AS facing elective non-cardiac surgery
(Figure 7).
In asymptomatic patients with severe AS, a non-cardiac
procedure of low or moderate risk can be performed
safely. If high-risk non-cardiac surgery is needed, the
patient should be carefully evaluated for aortic valve repla-
cement before non-cardiac surgery including coronary
angiography to rule out coexistent coronary artery disease.
Factors influencing the preference for valve replacement
performed before non-cardiac surgery would be the
degree of severity of AS, the likelihood of early symptom
development (high degree of valve calcification or abnormal
exercise test), as well as the overall status of the patient
(low comorbidity and long-life expectancy). In these
patients, a bioprosthesis is the preferred valve substitute,
Figure 7 Management of severe aortic stenosis and elective non-cardiac surgery. *Assessment of the risk of cardiac complications for non-cardiac surge ry (from
Eagle et al.
214
). High risk (.5%): emergent major operations, particularly in the elderly, aortic and other major vascular surgery, peripheral vascular surgery,
anticipated prolonged surgical procedures associated with large fluid shifts and/or blood loss. Intermediate risk (1 to 5%): carotid endarterectomy, head and
neck surgery, intraperitoneal and intrathoracic surgery, orthopedic surgery, prostate surgery. Low risk (,1%): endoscopic procedures; superficial procedure;
cataract surgery; breast surgery.
ESC Guidelines 259
in order to avoid anticoagulation problems during the sub-
sequent non-cardiac surgery.
In asymptomatic patients who are poor candidates for
valve replacement because of severe comorbidities as
assessed by a high Euroscore
39
or poor life expectancy, non-
cardiac surgery should be carefully discussed and, if really
needed, performed under strict haemodynamic monitoring.
In symptomatic patients with severe AS facing non-cardiac
surgery, valve replacement should always be considered
even before non-cardiac surgery at low-to-moderate risk.
If valve replacement is contraindicated, non-cardiac
surgery should be performed only if absolutely necessary.
Although its practice has not been rigorously evaluated, per-
cutaneous aortic valvuloplasty to create a time window of
reduced cardiac risk during which the non-cardiac surgery
can be performed has been considered
76
and could have a
role depending on local expertise.
Mitral stenosis
In non-significant MS (valve area . 1.5 cm
2
), non-cardiac
surgical procedures can be performed at low risk.
In asymptomatic patients with significant MS and a systolic
pulmonary artery pressure ,50 mmHg, non-cardiac surgery
can also be performed at low risk, although it should be
remembered that the onset of atrial fibrillation may
produce a sharp deterioration.
In symptomatic patients or in patients with systolic pul-
monary artery pressure . 50 mmHg, correction of MS, by
means of PMC whenever possible, should be attempted
before non-cardiac surgery.
This recommendation is stronger before high-risk non-
cardiac procedures. If surgery, in particular, valve replace-
ment, is needed, the decision to proceed before non-cardiac
surgery should be taken with caution and based on strict
individual considerations.
Aortic regurgitation and mitral regurgitation
In non-significant AR or MR, non-cardiac procedures can be
performed at low risk.
In asymptomatic patients with preserved LV function and
severe MR or AR, non-cardiac surgery can be performed at
low risk.
In symptomatic patients or in patients with depressed LV
function (EF ,30%), non-cardiac surgery should be per-
formed only if strictly needed. The medical therapy of
heart failure should be optimized before surgery and vasodi-
lators are particularly useful in this context.
220
Prosthetic valves
In patients with prosthetic valves, valvular disease has
already been corrected and non-cardiac surgery can be
safely performed from the haemodynamic point of view,
providing that there are no symptoms or signs of prosthetic
dysfunction and recent echocardiographic assessment has
been satisfactory. However, there is a high risk, mostly
related to the changes in anticoagulation regimen, in
patients with mechanical valves. Thus, the management
of anticoagulation is of utmost importance in these
circumstances (see Interruption of anticoagulant therapy
section).
Endocarditis prophylaxis
In valve disease patients, all surgical procedures, even
minor, require scrupulous asepsis and avoidance of wound
haematoma formation.
Antibiotic prophylaxis should be prescribed for those
patients undergoing non-cardiac procedures at high bactere-
mic risk.
10
Perioperative monitoring
Valvular patients submitted to moderate or high-risk non-
surgical procedures need particular perioperative care,
especially ensuring that systemic hypotension or volume
depletion or overload is avoided. Particular attention
should be paid to avoid hypotension in patients with AS.
In patients with moderate-to-severe AS or MS, beta-
blockers or amiodarone can be used prophylactically in
order to maintain sinus rhythm in the postoperative
period.
221
Whether the beneficial role of beta-blockers on
cardiovascular mortality before major vascular surgery
222
applies to valvular patients is not known.
It is prudent to electively admit such patients to intensive
care postoperatively even if they appear to be doing well.
Management during pregnancy
Haemodynamic changes that normally occur during preg-
nancy may worsen tolerance of underlying heart disease.
Native VHD is the most frequently acquired heart disease
encountered during pregnancy even in developed countries.
Certain native VHDs carry a poor prognosis for the mother
and foetus. In patients with a valve prosthesis, the modal-
ities of anticoagulant therapy are problematic.
Cardiac risk of pregnancy
The main cardiovascular changes are increase in blood
volume, decrease in systemic vascular resistance, and
increase in heart rate. Cardiac output increases from 30 to
50% after the fifth month, increases further during labour
and delivery, and normalizes within 3 days of delivery.
223
Pregnancy also induces changes in haemostasis, all of
which contribute to increased coagulability and thrombo-
embolic risk.
224
The risk of maternal cardiac complications is high in cases
of severe stenotic valvular disease, in particular, MS with
pulmonary hypertension, severe regurgitation complicated
by LV dysfunction, and Marfan’s syndrome with aneurysm
of the ascending aorta.
223
–
227
The risk is increased in
women with a history of cardiac events, arrhythmias, or
who are in NYHA class III or IV.
225
Thus, such patients must
undergo intervention to correct their valve lesions and, if
present, their aortic problems before considering preg-
nancy. However, pregnancy is often already present when
the patient presents.
Evaluation of the pregnant patient with heart
valve disease
Ideally, valve disease should be evaluated before pregnancy
and treated if necessary. Although dyspnoea may be difficult
to interpret in pregnant women, its occurrence after the
first trimester should lead to suspicion of underlying heart
disease. In women with mechanical valve prostheses, it is
260 ESC Guidelines
necessary to assess the effective adherence to anticoagulant
therapy and to check for previous complications. Cardiac
auscultation during pregnancy is mandatory to detect
native valve disease or prosthesis dysfunction.
Echocardiographic examination should be performed in
any pregnant patient presenting with a more than trivial
heart murmur, dyspnoea, or who has a prosthetic valve.
Valve stenosis should be quantified using the measurement
of valve area. Gradients are modified because of the
increase in cardiac output and are not reliable markers of
the severity of stenosis; however, they have a prognostic
value. Quantitation of regurgitation should combine differ-
ent measurements and take into account loading conditions.
According to the type of valve disease, echocardiographic
examination should also assess mitral valve anatomy or
size of the ascending aorta. The assessment of LV dimensions
and EF, as well as systolic pulmonary artery pressure, indi-
cates the tolerance of the valvular disease.
The use of chest X-rays should be limited and, when absol-
utely required, accompanied by appropriate shielding of the
abdomen. CT is contraindicated because of the radiation
dose, but MRI can be performed during pregnancy. The use
of cardiac catheterization is restricted to the performance
of interventional procedures and again abdominal shielding
should be used.
Specific risks related to pregnancy
Native valve disease
MS, which is the most frequent VHD encountered during
pregnancy, is often poorly tolerated when valve area is
,1.5 cm
2
, even in previously asymptomatic patients.
226
Dyspnoea worsens between the third and fifth months,
which corresponds to the increase in cardiac output. The
persistence of dyspnoea or pulmonary hypertension is
associated with a high risk of complications at delivery,
thereby threatening the life of both the mother and
foetus.
223
Severe AS is less frequently encountered during preg-
nancy. Complications occur mainly in patients who were
symptomatic before pregnancy.
225
The risk of heart failure
during pregnancy or at delivery is low when mean aortic gra-
dient is ,50 mmHg.
224
Foetal prognosis is also impaired in the case of stenotic
heart valve disease, due to growth retardation, preterm
delivery, and low birth weight.
226,227
For these reasons, patients with severe MS or AS should be
treated before pregnancy if possible, even in asymptomatic
patients.
Chronic AR and MR are well tolerated during pregnancy,
even when severe, provided LV systolic function is pre-
served.
224
However, the risk of complications is high when
LVEF is ,40%, the prognosis being close to that of cardio-
myopathy. Conversely, acute regurgitation is poorly tolerated.
In patients with Marfan’s syndrome, the risk of
aortic-related complications including dissection during
pregnancy increases markedly when AR is more than mild
or when maximum aortic diameter is . 40 mm.
228
In these
cases, pregnancy should be preceded by replacement of
the ascending aorta, in particular, when the native aortic
valve can be preserved. Aortic complications should be con-
sidered in any patient presenting with chest pain or pain in
the posterior thorax.
Patients with prosthetic valves
Maternal mortality is estimated between 1 and 4% and is
mostly related to thombo-embolism.
229,230
The risks are particularly high in patients with mitral valve
prostheses. Therefore, these patients should be informed of
the risks and they require careful risk assessment and very
close monitoring of anticoagulant therapy if pregnancy
occurs.
Vitamin K antagonists increase the risk of miscarriage,
prematurity, and embryopathy, the latter in 5% of cases,
in particular, when used between the sixth and 12th
weeks. The risk is lower when Warfarin dose is 5 mg/
day.
224
Vitamin K antagonists are contraindicated during
labour and delivery because of the risk of cerebral bleeding
in the foetus. Unfractionated heparin therapy is safe for the
foetus, but it is associated with a considerable increase in
the thrombo-embolic risk for the mother, including occlusive
prosthetic thrombosis. Experience with LMWHs remains
limited and controversial, with uncertainties in dose
remaining.
229
Treatment
All strategies (Table 18) should be discussed and approved
between obstetricians, cardiologists, and the patient and
her family.
Table 18 Recommendations on the management of pregnant
women with valvular heart disease
Class
Patients with severe stenotic heart valve disease
should be treated before pregnancy, if possible using
percutaneous techniques in MS
IC
Echocardiographic examination should be performed in
any pregnant patient with a murmur or unexplained
dyspnoea
IC
Patients with Marfan’s syndrome and aortic
diameter .40 mm should be treated before
pregnancy
IC
Medical therapy is favoured in most patients with
regurgitant heart valve disease, even in
symptomatic patients
IC
Surgery under extracorporeal circulation should be
performed during pregnancy only in situations that
threaten the mother’s life and are not amenable to
percutaneous treatment.
IC
Vaginal delivery can be performed safely in patients
with heart valve disease who are in stable
haemodynamic condition.
IC
Warfarin is the favoured anticoagulant therapy during
the second and third trimesters until the 36th week
a
IC
Close monitoring of anticoagulation is advised when
unfractionated heparin used.
IC
PMC should be considered in pregnant patients who
have severe symptoms or pulmonary artery
pressure .50 mmHg owing to MS despite medical
therapy
IIaC
Warfarin is favoured during the first trimester if dose is
5 mg/24 h, after patient information
IIaC
MS ¼ mitral stenosis, PMC ¼ percutaneous mitral commissurotomy.
a
Data are lacking on other vitamin K antagonists.
ESC Guidelines 261
Aims
The treatment should relieve symptoms and avoid maternal
complications until the end of pregnancy and during deliv-
ery, without compromising foetal prognosis and subsequent
growth. Strategies whose unique purpose is to improve long-
term prognosis of the mother can be postponed until after
delivery.
Methods
The use of medical therapy should always take into account
foetal hazards. Beta-blockers are safe but may induce neo-
natal bradycardia and possible growth retardation.
Diuretics can be used at the lowest dose possible to avoid
impairing foetal perfusion. The use of vasodilators should
take into account the contraindication of ACE-inhibitors
and angiotensin receptor blockers.
Valvular surgery under cardiopulmonary bypass is associ-
ated with a foetal mortality between 20 and 30%.
231
Percutaneous valvular dilatation can be performed during
pregnancy after the 20th week. It should be performed in
experienced centres and associated with specific precau-
tions to shorten the procedure and reduce the hazards of
radiation, in particular, using abdominal shield protec-
tion.
232
TEE guidance is useful in addition to, but not
instead of fluoroscopy.
Management strategy
When the first visit occurs during pregnancy, early termin-
ation may be considered in the following situations:
.
Severe LV dysfunction (EF , 40%).
.
Marfan’s syndrome with aneurysm of ascending aorta
.40 mm.
.
Severe symptomatic stenotic valve disease, which cannot
be treated using percutaneous procedures.
The Task Force did not reach a full agreement on the
choice of prosthesis. However, the majority favours the
use of a bioprosthesis if valve replacement is necessary
during pregnancy.
During pregnancy, clinical and echocardiographic
follow-up should be performed at 3 and 5 months, and
every month thereafter in pregnant patients with severe
valve stenosis. Symptomatic MS should be treated using
bed rest, beta-blockers, favouring atenolol or metoprolol,
possibly associated with diuretics. Doses are adapted
according to symptoms and pulmonary artery pressure.
Beta-agonist agents are contraindicated. In the case of per-
sistent dyspnoea or pulmonary artery hypertension despite
medical therapy, PMC should be considered, in particular,
when anatomical conditions are favourable or in case of
uncertainty regarding follow-up.
In patients with severe AS who remain symptomatic
despite diuretics, balloon aortic valvuloplasty can be con-
sidered during pregnancy. The experience with this pro-
cedure during pregnancy is, however, much more limited
than that of PMC.
Patients with AR or MR who become symptomatic during
pregnancy should be treated medically using diuretics and
vasodilators. In most cases, surgery can be postponed until
the postoperative period.
Beta-blockers should be used throughout pregnancy in
patients with Marfan’s syndrome to avoid aortic dissection.
In patients with a mechanical prosthesis, vitamin K antag-
onists are favoured during the second and third trimesters
until the 36th week when they are replaced by unfractio-
nated heparin. During the first trimester, the choice should
take into account patient wishes after information, adher-
ence to treatment, and the possibility to use low-dose war-
farin; the use of warfarin is the safest regimen for the
mother.
224,229
The use of warfarin throughout pregnancy
until the 36th week is recommended when warfarin dose is
5 mg/day during the first trimester.
14
The target INR is
the same as before pregnancy. There are no data regarding
the use of other anticoagulant therapies. If unfractionated
heparin is used, we strongly recommend frequent control
of the target-activated partial thromboplastin time, which
should be between 2 and 3
14
. The use of LMWH cannot be
recommended on the basis of the information currently
available.
Delivery
Vaginal delivery is recommended whenever possible if the
haemodynamic condition is stable at the end of pregnancy.
Haemodynamic monitoring is recommended in women with
severe MS or LV dysfunction. The use of epidural analgesia
and obstetric procedures to shorten extraction time are
recommended to reduce the total duration of labour, dimin-
ishing haemodynamic consequences. Caesarean section has
the advantage of avoiding the haemodynamic consequences
of labour, but it is associated with other consequences
related to anaesthesia, blood volume shift, and assisted ven-
tilation, which can be harmful from a haemodynamic point
of view. It requires close haemodynamic monitoring and
should be ideally performed in specialized centres. It is
mainly considered in patients who have Marfan’s syndrome,
with an aortic diameter .40 mm, those in whom haemo-
dynamic conditions are unstable, in particular, in the pre-
sence of AS, or in case of premature delivery under oral
anticoagulation. Prophylactic antibiotic therapy can be
given at the beginning of labour and during delivery in
patients at high risk, i.e. with previous endocarditis or
heart valve prosthesis.
When valvular surgery is required during pregnancy,
caesarean section should be performed first if the foetus
is viable. In the other cases, the mode of delivery should
be discussed and planned by cardiologists, obstetricians,
anaesthetists, and the patient before delivery, even
more so for the patients who need to interrupt oral
anticoagulation.
262 ESC Guidelines
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268 ESC Guidelines
