Left ventricular basal muscle bundle in hypertrophic cardiomyopathy: insights into the mechanism of left ventricular outflow tract obstruction

Abstract

Aims
Many factors cause left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM). Previous studies reported that left ventricular basal muscle bundle (BMB) may be associated with LVOTO. We aimed to evaluate the role of BMB in LVOTO by echocardiography.

Methods and results
Two hundred fifty-six patients diagnosed with HCM were recruited. The morphologic characteristics of left ventricular outflow tract (LVOT) were analysed. BMB was detected in 178 (69.5%) patients by echocardiography. Patients were separated by a resting or provocative LVOT gradient ≥30 mmHg or not. Compared to patients without LVOTO, patients with LVOTO had a significantly thicker basal septum, elongated anterior mitral leaflet (AML), shorter distance between the AML-free margin and the septum or BMB (M-sept/bundle), larger angle between the plane of the mitral valvular orifice and the ascending aorta (MV-AO angle), and higher prevalence of BMB (P < 0.05). According to multivariate analysis, the independent predictors of LVOTO were the presence of BMB, a large basal septum thickness, a short M-sept/bundle, a large MV-AO angle, and a large AML [odds ratio (95% confidence interval): 5.207 (1.381–19.633), 1.386(1.141–1.683), 0.615(0.499–0.756), 1.113(1.054–1.176), and 1.343(1.076–1.677), respectively, P < 0.05]. Of the 256 included patients, 139 underwent surgical myectomy. The transthoracic echocardiography, compared with surgical specimen, showed: sensitivity 98.3%, specificity 82.3%, positive predictive value 97.6%, negative predictive value 87.5%, and accuracy 96.4% to detect BMB.

Conclusions
BMB is common in HCM. BMB is a risk factor for LVOTO.

Full text

Left ventricular basal muscle bundle in
hypertrophic cardiomyopathy: insights into
the mechanism of left ventricular outflow
tract obstruction
Minghu Xiao
1
, Changrong Nie
2
, Jingjin Wang
1
, Changsheng Zhu
2
, Xin Sun
1
,
Zhenhui Zhu
1
, Hao Wang
1,
*
,†
, and Shuiyun Wang
2,
*
,†
1
Department of Echocardiography, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical
Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing 100037, China; and
2
Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular
Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Beijing
100037, China
Received 26 April 2021; editorial decision 14 September 2021; accepted 18 September 2021
Aims Many factors cause left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM).
Previous studies reported that left ventricular basal muscle bundle (BMB) may be associated with LVOTO. We
aimed to evaluate the role of BMB in LVOTO by echocardiography.
........................................................................ ............. ............. ............. .................. ..................................................................
Methods
and results
Two hundred fifty-six patients diagnosed with HCM were recruited. The morphologic characteristics of left ven-
tricular outflow tract (LVOT) were analysed. BMB was detected in 178 (69.5%) patients by echocardiography.
Patients were separated by a resting or provocative LVOT gradient >_30 mmHg or not. Compared to patients with-
out LVOTO, patients with LVOTO had a significantly thicker basal septum, elongated anterior mitral leaflet (AML),
shorter distance between the AML-free margin and the septum or BMB (M-sept/bundle), larger angle between the
plane of the mitral valvular orifice and the ascending aorta (MV-AO angle), and higher prevalence of BMB
(P< 0.05). According to multivariate analysis, the independent predictors of LVOTO were the presence of BMB, a
large basal septum thickness, a short M-sept/bundle, a large MV-AO angle, and a large AML [odds ratio (95% confi-
dence interval): 5.207 (1.381–19.633), 1.386(1.141–1.683), 0.615(0.499–0.756), 1.113(1.054–1.176), and
1.343(1.076–1.677), respectively, P< 0.05]. Of the 256 included patients, 139 underwent surgical myectomy. The
transthoracic echocardiography, compared with surgical specimen, showed: sensitivity 98.3%, specificity 82.3%,
positive predictive value 97.6%, negative predictive value 87.5%, and accuracy 96.4% to detect BMB.
........................................................................ ............. ............. ............. .................. ..................................................................
Conclusions BMB is common in HCM. BMB is a risk factor for LVOTO.
䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏䊏
* Corresponding authors. Tel: þ86 10 88396636; Fax: þ86 10 68330739. E-mail: fuwaiwanghao@163.com (H.W.); Tel: þ86 10 88396565. E-mail: wsymd@sina.com (S.W.)
†
These authors contributed equally to this work and are cocorresponding authors.
Published on behalf of the European Society of Cardiology. All rights reserved. V
CThe Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
European Heart Journal - Cardiovascular Imaging (2021) 00, 1–9 ORIGINAL PAPER
doi:10.1093/ehjci/jeab200
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Keywords hypertrophic cardiomyopathy •myectomy •echocardiography •left ventricular outflow tract obstruction
Introduction
Hypertrophic cardiomyopathy (HCM) is a heterogeneous, inherited
cardiomyopathy with large clinical and phenotypic heterogeneity.
1
The symptoms of HCM have been attributed to the development of
left ventricular outflow tract obstruction (LVOTO), left ventricular
(LV) diastolic dysfunction, arrhythmias, and mitral regurgitation, and
the focus of treating these patients is on the relief of LVOTO.
2
LVOTO is involved in a complex mechanism that depends on the LV
morphology, loading conditions, contractility, and mitral apparatus.
3–9
Wang et al. reported that 78.1% of patients had anomalous muscular
bundles by surgery. The anomalous muscle bundles extended from
the interventricular septum (IVS) to the apex or papillary muscle,
namely IVS–apex, IVS–anterior papillary muscle (APM), and IVS–pos-
terior papillary muscle. And that mid-cavity muscle bundles might lead
to a middle left ventricular outflow tract (LVOT) or an apical obstruc-
tion. During treatment of LVOTO, basal muscle bundle (BMB) was
resected without imaging analysis before the operation. Whether
BMB contributed to LVOTO in some of their patients was unknown.
3
Gruner et al.
10
reported the detection of LV apical-BMB by cardiac
magnetic resonance imaging (CMR) in 63% of patients with HCM and
reported that BMB might be associated with LVOTO. To the best of
our knowledge, there was no any other study using echocardiography
to assess the prevalence of BMB in patients with HCM. The present
Graphical Abstract
Left ventricular basal muscle bundle in HCM: a risk factor for LVOTO. AF, atrial fibrillation; APM-sept, distance between the anterior papillary muscle and
the septum; BMB, left ventricular basal muscle bundle; C-sept/bundle, distance between the mitral valve coaptation and the septum or BMB; HCM, hyper-
trophic cardiomyopathy; LVH, left ventricular hypertrophy; LVOT, left ventricular outflow tract; M-sept/bundle, distance between the mitral valve free
margin and the septum or BMB; MV-AO angle, angle between the plane of the mitral valvular orifice and the ascending aorta; NSVT, non-sustained ven-
tricular tachycardia; SAM, systolic anterior motion; TTE, transthoracic echocardiography.
2M. Xiao et al.
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study aimed to investigate whether BMB played a vital role in the de-
velopment of LVOTO in HCM by transthoracic echocardiographic
(TTE) analysis.
Methods
Study population
This is a retrospective analysis of echocardiographic data from one
echocardiographic laboratory approved by the ethics committee of
Fuwai Hospital, and all patients provided written informed consent.
This study continuously included 256 patients with HCM at Fuwai
Hospital from April 2016 to November 2020. The diagnosis of HCM
was made by cardiologists on the basis of typical clinical, electrocar-
diographic, and echocardiographic features, with ventricular myocar-
dial hypertrophy (LV wall thickness > 15mm) occurring in the
absence of any other cardiac or systemic disease that could have
been responsible for the hypertrophy.
5
LVOTO was defined as an
LVOT gradient >_30mmHgatrestorafterbeingprovokedbyphysio-
logical exercise. The exclusion criteria were as follows: (i) mid-cavity
or apical obstruction; (ii) hypertensive heart disease of elderly
patients with concomitant LVOTO;
11
(iii) ejection fraction (EF)
<50%; (iv) more than mild aortic or mitral stenosis on initial echocar-
diography; and (v) competitive athletes. The evaluation of patients
included their complete medical history, a physical examination, 24-h
ambulatory electrocardiographic monitoring, and coronary
angiography.
Echocardiography
TTE was performed using a commercially available system (E9 ultra-
sound system, GE Healthcare, Horten, Norway). Standard two-di-
mensional (2D) and Doppler echocardiographic images were
acquired using an M5S phased-array transducer in the parasternal and
apical views, and the images were saved on a hard disc as archive files
for offline analysis using EchoPAC software version BT 201 (GE
Healthcare). Perioperative TTE data were collected during the
patients’ hospital stay. Postoperative TTE data were obtained during
the follow-up in outpatients. Maximal end-diastolic LV wall thickness,
LV diameter, volume, and EF were determined following the recom-
mendations of the American Society of Echocardiography (ASE).
12
The LVOT gradient was estimated by using the simplified Bernoulli
equation, avoiding contamination of the LVOT waveform by mitral re-
gurgitation. In patients with a resting LVOT gradient <50mmHg,
exercise was used to provoke an LVOT gradient. Exercise echocardi-
ography was performed in 111 (50%) patients using a half-squat exer-
cise protocol in accordance with the European Association of
Echocardiography guidelines.
13
An experienced operator performed
all the tests using the same Vivid E9 machine.
Definition of LV BMB
On TTE, BMB was defined in parasternal long-axis, apical three-chamber
long-axis, apical four-chamber or LV short-axis cine images as a single
band of muscle extending from the basalseptum through the LV cavity to
the apex or papillary muscle without evidence of chordal attachment to
the mitral valve (Figure 1, Figure 2,and Supplementary data online, Figure
S1). The description of CMR was shown in Supplementary data online
(Supplemental description of CMR).
Measurements of LV geometry
The angle between the plane of the mitral valvular orifice and the ascend-
ing aorta (MV-AO angle) was measured at end-diastole from the three-
chamber or parasternal long-axis view. The maximal lengths of the anter-
ior mitral leaflet (AL) and posterior mitral leaflet were measured at end-
diastole in apical three-chamber view images from the base to the free
margin of A2 or P2. The distance between the mitral valve free margin
and the septum (or BMB when there was a significant muscle bundle; M-
sept/bundle), the distance between the mitral valve coaptation and the
septum or BMB (C-sept/bundle), and the distance between the APM and
the septum (APM-sept) were determined at end-diastole from the apical
three-chamber view (Figure 3).
Reproducibility of BMB for echocardiography
Interobserver and intraobserver variabilities of the presence or absence
of BMB were assessed from an HCM cohort including a random sample
of 67 patients (the researchers were blinded to the previous results) by
the primary (M.X. from Fuwai hospital) and second independent (J.W.
from Fuwai hospital) observer, respectively.
Extended septal myectomy
Patients with an LVOT gradient >_50mmHg at rest or after exercise and
the presence of severe limiting symptoms refractory to maximum
pharmacologic therapy underwent septal myectomy by one surgeon
Figure 1 Drawing of left ventricular basal muscle bundle that ori-
ginated from the basal septum: ‹the point of adhesion was the
apex and ›the point of adhesion was the APM. AML, anterior mi-
tral leaflet; AO, ascending aorta; APM, anterior papillary muscle;
IVS, interventricular septum; PML,posterior mitral leaflet; PPM, pos-
terior papillary muscle.
LV BMB in HCM: a risk factor for LVOTO 3
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(S.W.).
3
The surgeon recorded the detailed anatomic features of BMB:
Type I: IVS–apex and Type II: IVS–APM (Figure 1).
Statistical analysis
Data are expressed as the mean ± standard deviation, median [inter-
quartile range (IQR)] or number (percentages). A t-test was used to
compare continuous variables, and a v
2
test was used for categorical
variables. The paired samples t-test was used to compare the pre-
myectomy variables and latest review variables. Binary logistic regres-
sion analysis was performed to identify factors associated with
LVOTO. A backward: Logistic regression (LR) method was performed
with the models. We calculated the odds ratio as well as the confi-
dence interval for each association. Interobserver and intraobserver
agreement were assessed by means of the kappa test. To evaluate the
ability of TTE to identify BMB, sensitivity, specificity, the positive pre-
dictive value (PPV), the negative predictive value (NPV), and accuracy
were calculated and compared with those of the surgical findings. All
analyses were performed with SPSS 24.0 software (IBM Inc., Armonk,
NY, USA). P-value <0.05 was considered statistically significant.
Results
Patient characteristics
Two hundred fifty-six patients were recruited in the study after the
exclusion of those who met any of the exclusion criteria. The patients
in the cohort had a median age of 45.9 ± 14.9years, and 156 (60.9%)
were male. The patients were separated by a resting or provocative
LVOT gradient >_30 mmHg or not, with 176 (68.9%) patients in the
obstructive group. The baseline characteristics are summarized in
Table 1and Supplementary data online, Table S1.
Baseline echocardiographic and LVOT
morphologic characteristics
The echocardiographic characteristics at baseline and the morpho-
logic characteristics of LVOT are presented in Table 2.Themedian
BMB thickness was 5 mm (IQR 4–6). The median distance from the
origin point of BMB to the aortic annulus was 14 mm (IQR 11–16).
There were 178 (69.5%) patients with BMB detected by TTE. Of the
Figure 2 Representative images of the preoperative echocardiography (A), surgical specimens (B), and postoperative echocardiography (C)of
HCM patients without and with muscle bundles. (A1–3) No muscle bundle, BMB originating from the basal septum, and muscle bundle originating
from the mid-septum. (B1–3) Corresponding surgical specimen removed from IVS. (C1–3) Corresponding echocardiography demonstrating no BMB
postoperatively. The yellow arrows indicate muscle bundles; red arrow, origin point of the muscle bundles; green line, mitral valve tip plane; and red
box in C1–3, scope of surgical resection. AO, ascending aorta; LA, Left atrium; LV, left ventricle; RV, right ventricle.
4M. Xiao et al.
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.256 included patients, BMB was detected in 11 (78.6%) of the 14
patients who underwent previous alcohol septal ablation (ASA).
Compared to patients without BMB, patients with BMB had a higher
LVOT gradient [resting: 57 (IQR 17–89) vs. 9 (6–17) mmHg, P< 0.001;
provocative: 69 (IQR 56–93] vs. 16 (IQR 10–28) mmHg, P< 0.001]
and a smaller APM-sept (18.1 ± 3.4 vs. 19.7 ± 6.4, P= 0.007). Regarding
the LV loading conditions and contractility, there were no significant
differences in indexed LV end-diastolic volume by body surface area
and EF between the obstructive group and non-obstructive group.
The patients in the obstructive group had a significantly thicker basal
septum, elongated AL, smaller M-sept/bundle, smaller C-sept/bundle,
larger MV-AO angle, higher prevalence of BMB, and higher prevalence
of systolic anterior motion (SAM). The direction of the mitral valve
was more anterior in the obstructive group (the difference between
C-sept/bundle and M-sept/bundle was larger, P< 0.001).
Surgical findings
A total of 139 (54.3%) patients underwent septal myectomy by one
surgeon (S.W.), and BMB was identified in 120 (86.3%) patients during
surgery (Supplementary data online, Table S2). The LVOT gradient after
myectomy was 11.6 ± 7.1 mmHg (decrease from 79.3 ± 33.8 mmHg,
P< 0.001). The resected mass was 9.7 ± 4.8 g. There was no periproce-
dural mortality in the studied patient group. Ten (71.4%) of the 14
patients who received a previous ASA underwent septal myectomy,
and BMB was identified in 8 (80.0%) patients by the surgeon.
Accuracy of the detection of BMB,
compared with that of the surgical
specimens
For the diagnosis of BMB presence or absence, the sensitivity, PPV,
and accuracy of detection of BMB by TTE were optimal (sensitivity,
specificity, PPV, NPV, and accuracy were 98.3%, 82.3%, 97.6%, 87.5%,
and 96.4%, respectively); and the CMR showed accuracy: 95.9%. For
Type I BMB, the accuracy of TTE was much higher than CMR. For
Type II BMB, the accuracy of CMR was much higher than TTE
(Supplementary data online, Tables S3–S5). The interobserver and
Figure 3 Morphologic characteristics of LVOT (A)withoutor
(B)withBMB.(A1) A small MV-AO angle (green dotted line),
normal AML, large C-sept (blue arrow), and large M-sept (black
arrow), resulting in the normal direction of the mitral valve at
the isovolumic phase (grey arrow); (A2) no LVOTO (green
arrows). (B1) BMB integrated into an elongated AML, a large
MV-AO angle (green dotted line), small C-bundle (blue arrow),
and small M-bundle (black arrow), resulting in the anterior direc-
tion of the mitral valve at the isovolumic phase (grey arrow);
(B2) LVOTO (red arrows). APM-sept, distance between the an-
terior papillary muscle and the septum; C-sept/bundle, distance
between the mitral valve coaptation and the septum or BMB;
LVOTO, left ventricular outflow tract obstruction; M-sept/bun-
dle, distance between the mitral valve free margin and the sep-
tum or BMB; MV-AO angle, angle between the plane of the
mitral valvular orifice and the ascending aorta.
....................................................................................................................................................................................................................
Table 1 Baseline clinical characteristics
Parameters All patients (n5256) Obstructive (n5176) Non-obstructive (n580) P-value
Age (years) 45.9 ± 14.9 46.7 ± 14.9 44.1 ± 14.7 0.200
Sex: male 156 (60.9) 112 (63.6) 44 (55.0) 0.214
Body surface area (m
2
) 1.8 (1.7–1.9) 1.8 (1.7–1.9) 1.7 (1.6–1.9) 0.001
NYHA, III–IV 101 (39.5) 85 (48.3) 16 (20.0) <0.001
Hypertension 68 (26.6) 52 (32.9) 16 (22.5) 0.128
Hyperlipidaemia 64 (25.0) 49 (27.8) 15 (18.8) 0.161
Diabetes mellitus 11 (4.3) 9 (5.1) 2 (2.5) 0.732
Coronary artery disease 21 (8.2) 16 (9.0) 5 (6.3) 0.624
Previous alcohol septal ablation 14 (5.5) 13 (7.4) 1 (1.3) 0.071
b-blocker or Ca-blocker 235 (91.8) 158 (89.8) 77 (96.3) 0.090
Values are means ± SD, median (IQR), or n(%).
IQR, interquartile range; NYHA, New York Heart Association; SD, standard deviation.
LV BMB in HCM: a risk factor for LVOTO 5
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intraobserver variabilities showed excellent agreement for the identi-
fication of BMB (inter: Kappa = 0.815, and intra: Kappa = 0.897, re-
spectively, P<0.001).
Independent predictors of LVOTO
In the multivariate analysis, the independent predictors of
LVOTO were a large basal septum thickness, the presence of
BMB, a large AL, a short M-sept/bundle, and a large MV-AO
angle (Table 3).
Follow-up
Fifty-four of 139 patients underwent myectomy did not return
for follow-up TTE. The reasons were that (i) economic difficul-
ties (n= 30), (ii) traffic difficulties (n= 16), (iii) death (n= 2), and
(iv) loss of TTE data (n= 6). Eighty- five pa tients underwent out-
patient follow-up echocardiographic evaluations [6 months
(IQR) 3–12]; for these patients, we used the results of the last
follow-up.
Echocardiographic improvement
after myectomy
After myectomy, the morphologic characteristics of LVOT improved
significantly: the target anteroseptal thickness decreased, the MV-AO
angle decreased, and M-sept and C-sept increased (Table 4), which
resulted in a wider LVOT and a more posterior direction of the mi-
tral valve (the difference between C-sept and M-sept decreased dra-
matically). Fourteen (16.5%) patients underwent surgical mitral valve
procedures. LVOTO was observed in two patients (2.4%) (LVOT
gradient was 36 and 31mmHg, respectively). No significant BMB was
found by TTE during follow-up.
Discussion
In this study, we found that BMB was not uncommon in the cohort of
HCM. Compared to that of patients without BMB, patients with BMB
had a higher LVOT gradient. BMB may influence the morphologic
....................................................................................................................................................................................................................
Table 2 LV loading conditions, contractility characteristics, and LVOT morphologic characteristics
Parameters All patients
(n5256)
Obstructive
(n5176)
Non-obstructive
(n580)
P-value
LV loading conditions
LVEDVi (mL/m
2
) 43.1 ± 11.9 43.2 ± 10.5 42.9 ± 15.0 0.888
LVESVi (mL/m
2
) 12.3 ± 4.7 12.3 ± 4.5 12.3 ± 5.1 0.985
Contractility
Left ventricular ejection fraction (%) 71.7 ± 6.56 71.9 ± 6.5 71.4 ± 6.8 0.630
Haemodynamics
Resting LVOT gradient (mmHg) 27 (10–78) 61 (24–91) 8 (6–11) <0.001
Peak LVOT gradient (mmHg) 60 (21–87) 75 (59–96) 12 (10–20) <0.001
SAM of the anterior mitral leaflet 194 (75.8) 170 (96.6) 24 (30.0) <0.001
Moderate or severe mitral regurgitation 99 (38.6) 95 (53.9) 4 (5.0) <0.001
LV wall thickness
Interventricular septum thickness (mm) 18.5 ± 3.9 19.2 ± 3.8 16.9 ± 3.8 <0.001
Posterior wall thickness (mm) 12.2 ± 3.0 12.8 ± 3.0 10.9 ± 2.7 <0.001
Maximal wall thickness (mm) 19.7 ± 3.9 20.1 ± 3.9 18.8 ± 3.6 0.016
Morphologic characteristics of LVOT
BMB 178 (69.5) 154 (87.5) 24 (30.0) <0.001
Basal septum thickness (mm) 17.0 ± 3.6 18.0 ± 3.3 14.8 ± 3.4 <0.001
Mitral annulus diameter (mm) 29.8 ± 3.3 29.9 ± 3.4 29.6 ± 3.2 0.610
Length of the anterior mitral leaflet (mm) 27.9 ± 3.6 28.7 ± 3.7 26.1 ± 2.7 <0.001
Length of the anterior mitral leaflet >30 mm 79 (30.9) 73 (41.4) 6 (7.5) <0.001
Length of the posterior mitral leaflet (mm) 16.4 ± 2.9 16.9 ± 2.9 15.5 ± 2.8 <0.001
C-sept/bundle (mm) 18.0 ± 4.3 16.7 ± 3.4 21.3 ± 4.3 <0.001
M-sept/bundle (mm) 14.9± 5.3 12.3 ± 2.9 20.7 ± 4.8 <0.001
Difference between C-sept/bundle and M-sept/bundle (mm) 3.2 ± 3.2 4.4 ± 2.7 0.6 ± 2.7 <0.001
MV-AO angle () 147.9 ± 14.7 154.2 ± 10.7 134.0 ± 12.5 <0.001
APM-sept (mm) 18.6 ± 4.6 18.1 ± 3.4 19.7 ± 6.4 0.007
Values are means ± SD, median (IQR), or n(%).
APM-sept, distance between the anterior papillary muscle and the septum; BMB, basal muscle bundle; C-sept/bundle, distance between the mitral valve coaptation and the sep-
tum or BMB; IQR, interquartile range; LV, left ventricular; LVEDVi, indexed left ventricular end-diastolic volume by body surface area; LVESVi, indexed left ventricular end-sys-
tolic volume by body surface area; LVOT, left ventricular outflow tract; M-sept/bundle, distance between the mitral valve free margin and the septum or BMB; MV-AO angle,
angle between the plane of the mitral valvular orifice and the ascending aorta; SAM, systolic anterior motion; SD, standard deviation.
6M. Xiao et al.
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characteristics of LVOT (reduced distance between the septum/bun-
dle and AML) and integrate into an enlarged septum, a large MV-AO
angle and an elongated AL, resulting in a narrower LVOT and more
SAM. In the multivariate analysis, the presence of BMB, a large basal
septal thickness, a short M-sept/bundle, a large AL, and a large MV-
AO angle were independent predictors of LVOTO. After myectomy,
the morphologic characteristics of LVOT improved significantly,
which resulted in a larger LVOT and a more posterior direction of
the mitral valve to keep the AML away from the ejection flow, there-
by eliminating SAM.
Echocardiography in BMB detection
TTE could identify BMB. Compared with those of the surgical speci-
mens, the sensitivity, specificity, PPV, NPV, and accuracy for BMB for
TTE were optimal.
Regarding echocardiography, the first challenge was image quality.
The reason for false-negative echocardiographic diagnosis of BMB
was poor image quality. The second challenge was the lack of know-
ledge about BMB; more practice was needed. The reasons for false-
positive echocardiographic diagnosis of BMB were (i) accessory APM
directly inserted into anterior mitral leaflet; (ii) abnormal thickened
chordae tendineae; and (iii) ultrasonic artefact (Supplementary data
online, Figure S2). It was sometimes challenging to distinguish BMB
from abnormal chordae, especially for thin muscle bundles.
According to our experience, the better view for identifying BMB
was the parasternal long-axis view, and the transducer was slightly
adjusted to find the true BMB; it was easier to identify BMB one or
two frames after the onset of systole; at this time, BMB could be sep-
arated from IVS and was easier to identify. At the end-diastole phase,
BMB attached closely to the septum; thus, BMB might be ignored
(Supplementary data online, Videos S1 and S2).
CMR in the diagnosis of BMB
CMR could diagnose BMB. We found that CMR and TTE had their
own advantages and disadvantages in detecting BMB.
For the diagnosis of BMB presence or absence, compared with
those of the surgical specimens, the accuracy of detection of BMB by
TTE and CMR were both optimal.
For the diagnosis of Type I BMB, the accuracy of TTE was much
higher than CMR. The reason was that the thinner BMB may be
ignored on CMR.
For the diagnosis of Type II BMB, the accuracy of CMR was much
higher than TTE. For CMR, especially in the short-axis cines from the
atrioventricular ring to apex (Supplementary data online, Figure S1), it
is easier to detect the distal part of BMB which fused with APM body
(Supplementary data online, Figure S1A3–4). For TTE, the distal part
of the BMB may extent backward or forward, and the main direction
of BMB was not always parallel with ultrasonic sound beam. So, for
most of the BMB, 2D TTE can diagnose the origin of the BMB [the
better view for identifying BMB was the parasternal long-axis view
(Supplementary data online, Figure 1B1)], but there is some difficulty
to show the distal part of the BMB. According to our experience, the
best view to diagnose Type I BMB is the apical three-chamber view
(Supplementary data online, Figure 1B5) and the best view to diag-
nose Type II BMB is the LV short-axis view (papillary muscle level)
(Supplementary data online, Figure S1B3).
Morphologic characteristics of LVOT and
mechanism of LVOTO
Previous studies have found that the independent predictors of SAM
are a smaller LV, an enlarged septum, an elongated mitral leaflet, a
short C-sept, and a large MV-AO angle.
4,14–19
In the present study,
the independent predictors of LVOTO were the presence of BMB, a
large basal septal thickness, a short M-sept/bundle, a large AL, and a
large MV-AO angle. There was no significant difference in the LV
loading condition or contractility between the obstructive group and
the non-obstructive group. To the best of our knowledge, this is the
first study to report that BMB is an independent predictor of
LVOTO.
.............................. ............................. ..........................................................
....................................................................................................................................................................................................................
Table 3 Independent predictors of LVOTO
Parameters Univariate analysis Multivariate analysis
OR (95%CI) P-value OR (95%CI) P-value
Age (years) 1.002 (0.986–1.019) 0.790 0.943
Sex: male 1.038 (0.628–1.715) 0.885 0.233
Basal septum thickness (mm) 1.391 (1.249–1.549) <0.001 1.386 (1.141–1.683) 0.001
LVEDVi (mL/m
2
) 1.026 (1.001–1.052) 0.044 0.218
Eject fraction (%) 1.010 (0.969–1.053) 0.629 0.422
Mitral annulus diameter (mm) 1.025 (0.946–1.111) 0.545 0.623
Length of the anterior mitral leaflet (mm) 1.266 (1.154–1.388) <0.001 1.343 (1.076–1.677) 0.009
Length of the posterior mitral leaflet (mm) 1.209 (1.085–1.347) 0.001 0.535
The presence of BMB 16.333 (8.499–31.425) <0.001 5.207 (1.381–19.633) 0.015
M-sept/bundle (mm) 0.575 (0.501–0.660) <0.001 0.615 (0.499–0.756) <0.001
MV-AO angle () 1.146 (1.108–1.185) <0.001 1.113 (1.054–1.176) <0.001
BMB, basal muscle bundle; CI, confidence interval; LVEDVi, indexed left ventricular end-diastolic volume by body surface area; LVOTO, left ventricular outflow tract obstruc-
tion; M-sept/bundle, distance between the mitral valve free margin and the septum or BMB; MV-AO angle, angle between the plane of the mitral valvular orifice and the ascend-
ing aorta; OR, odds ratio.
LV BMB in HCM: a risk factor for LVOTO 7
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Wang et al.
3
reported that anomalous mid-cavity muscle bundles
may lead to middle LVOT or apical obstruction. Wang’s study
included patients with mid-cavity or apical obstructions. During treat-
ment of LVOTO, BMB was resected without imaging analysis before
the operation. Whether BMB contributed to LVOTO in some of
their patients was unknown. In our study, patients with mid-cavity or
apical obstructions were excluded; we only evaluated the effect of
BMB on LVOTO. Gruner et al.
10
reported that there was no differ-
ence regarding the presence of LVOTO among HCM patients with
or without BMB. One reason for this finding was that, in their study,
LVOTO was defined under resting conditions. It was interesting that
in Gruner’s study, during the follow-up period, 33 patients under-
went surgical myectomy to relieve LVOTO, of whom 67% had an ac-
cessory BMB identified during the preoperative CMR study. They
provided an interesting pathophysiological hypothesis to explain the
contribution of BMB to LVOTO: fusion of the apical portion of BMB
and APM could position the APM closer to the septum and limit its
ability to move away from the septum during systole (Supplementary
data online, Figure S1A3–4). In the present study, the smaller APM-
sept was found in patients with BMB.
Maron et al. reported the main reason for obstruction was due pri-
marily to an elongated MV.
14
An elongated AL may be related to
early systolic flow, which impacts the posterior surfaces of the pro-
truding AML.
14,16,20
Deng et al.
21
found that C-sept was a factor for
the initiation of SAM. When C-sept was short, the AML was caught
in the path of the ejection flow stream and swept anteriorly.
Consistent with the findings of Deng’s study, in our study, the C-sept/
bundle was short, while the M-sept/bundle was also short. In our
study, the difference between C-sept/bundle and M-sept/bundle was
large in the LVOTO group. Thus, the AML-free margin was closer to
the septum than the coaptation margin. Previous studies assume that
the aorto-mitral angle may play a role in causing SAM.
4,15
Alarger
MV-AO angle may displace the mitral leaflets anteriorly.
20
Successful
septal myectomy with BMB resection increased M-sept and C-sept
and kept the AML away from the ejection flow, thereby eliminating
SAM. After myectomy, M-sept and C-sept increased significantly.
Clinical significance
The presence of BMB may have implications for clinical management
strategies.
3,10
With regard to surgical myectomy for the relief of
LVOTO, BMB can be identified by the surgeon intraoperatively and
be resected during the operation (Supplementary data online, Figure
S3). However, ASA cannot remove BMB.
20
In the present study,
BMB was identified during surgical myectomy in 8 (80.0%) patients
who underwent a previous ASA. We assume that BMB may be one
of the reasons for the failure of ASA, and we suggest that before mak-
ing an operation decision, BMB must be considered.
Study limitations
This study has several limitations. First, the study population was
recruited from a single centre. Second, the size of our study popula-
tion was relatively small, which means that this study may have lacked
the statistical power necessary to identify all significant differences
and associations. Third, we excluded patients with mid-cavity or ap-
ical obstructions if BMB also contributed to the mid-cavity or apical
obstructions or not was also unclear. Fourth, the characterization of
the patients did not include their genotype, and whether BMB was an
independent and primary component of HCM disease expression
was unclear. Fifth, there was no healthycontrol group, and the preva-
lence of BMB in healthy patients with normal hearts was unclear.
Conclusions
BMB is not uncommon in HCM patients, and 2DTTE is capable of re-
liably detecting this particular structural abnormality. Patients with
BMB have higher LVOT gradients. LVOTO can develop due to vari-
ous geometric changes, e.g. an enlarged septum, an elongated AML, a
larger MV-AO angle, and a smaller M-sept/bundle, but patients with a
....................................................................................................................................................................................................................
Table 4 Echocardiographic improvement after myectomy
Parameters Pre-myectomy (n585) Post-myectomy (n585) P-value
Peak LVOT gradient (mmHg) 80 (57–98) 10 (7–14) <0.001
Basal septum thickness (mm) 18.0 ± 3.1 11.1 ± 2.2 <0.001
LVEDVi (mL/m
2
) 43.3 ± 9.7 46.6 ± 10.5 0.008
LVESVi (mL/m
2
) 12.6 ± 4.3 15.6 ± 6.0 <0.001
Left ventricular ejection fraction (%) 71.7 ± 6.2 68.4 ± 7.1 0.001
C-sept/bundle (mm) 16.3 ± 3.6 18.5 ± 3.0 <0.001
M-sept/bundle (mm) 12.8 ± 3.4 19.1 ± 3.7 <0.001
Difference between C-sept/bundle and M-sept/bundle (mm) 3.6 ± 2.9 -0.6± 2.3 <0.001
MV-AO angle () 153.8 ± 12.4 132.8 ± 11.1 <0.001
SAM 69 (81.2) 4 (4.7) <0.001
Moderate or severe mitral regurgitation 63 (74.1) 5 (5.9) <0.001
BMB 74 (87.1) 0 (0) <0.001
Values are means ± SD, median (IQR), or n(%).
BMB, basal muscle bundle; C-sept/bundle, distance between the mitral valve coaptation and the septum or BMB; IQR, interquartile range; LVEDVi, indexed left ventricular end-
diastolic volume by body surface area; LVESVi, indexed left ventricular end-systolic volume by body surface area; LVOT, left ventricular outflow tract; M-sept/bundle, distance
between the mitral valve free margin and the septum or BMB; MV-AO angle, angle between the plane of the mitral valvular orifice and the ascending aorta; SAM, systolic anter-
ior motion; SD, standard deviation.
8M. Xiao et al.
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prominent BMB have distinct characteristics suggestive of LVOTO.
BMB could be identified by the surgeon intraoperatively and resected
during the operation. After myectomy, an enlarged M-sept and C-
sept and a smaller MV-AO angle were obtained to keep the AML
away from the ejection flow, thereby eliminating LVOTO.
Supplementary data
Supplementary data are available at European Heart Journal - Cardiovascular
Imaging online.
Acknowledgements
The authors thank Guimin Huang for revising the manuscript for stat-
istical analysis.
Funding
This work was supported by the Capital’s Funds for Health Major Project
(2020-2-4036) of the Beijing Municipal Commission of Health.
Conflict of interest: none declared.
Data availability
The datasets generated and/or analysed during the current study are
not publicly available due to Fuwai Hospital system, but data can be
obtained from the corresponding author under reasonable request
and with the permission of the Ethics Committee of Fuwai Hospital.
References
1. Pozios I, Corona-Villalobos C, Sorensen LL, Bravo PE, Canepa M, Pisanello C et
al. Comparison of outcomes in patients with nonobstructive, labile-obstructive,
and chronically obstructive hypertrophic cardiomyopathy. Am J Cardiol 2015;116:
938–44.
2. Ball W, Ivanov J, Rakowski H, Wigle ED, Linghorne M, Ralph -Edwards A et al.
Long-term survival in patients with resting obstructive hypertrophic cardiomyop-
athy. J Am Coll Cardiol 2011;58:2313–21.
3. Wang S, Cui H, Yu Q, Chen H, Zhu C, Wang J et al. Excision of anomalous
muscle bundles as an important addition to extended septal myectomy for treat-
ment of left ventricular outflow tract obstruction. J Thorac Cardiovasc Surg 2016;
152:461–8.
4. Cha JJ, Chung H, Yoon YW, Yoon JH, Kim JY, Min PK et al. Diverse geometric
changes related to dynamic left ventricular outflow tract obstruction without
overt hypertrophic cardiomyopathy. Cardiovasc Ultrasound 2014;12:23.
5. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS et al. 2011
ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomy-
opathy: executive summary: a report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines. JAm
Coll Cardiol 2011;58:2703–38.
6. Dimitrow PP, Michałowska J, Sorysz D. The effect of hemodialysis on left ven-
tricular outflow tract gradient. Echocardiography 2010;27:603–7.
7. Dimitrow PP, Bober M, Michałowska J, Sorysz D. Left ventricular outflow tract
gradient provoked by upright position or exercise in treated patients with hyper-
trophic cardiomyopathy without obstruction at rest. Echocardiography 2009;26:
513–20.
8. Shah JS, Esteban MTT, Thaman R, Sharma R, Mist B, Pantazis A et al. Prevalence
of exercise-induced left ventricular outflow tract obstruction in symptomatic
patients with non-obstructive hypertrophic cardiomyopathy. Heart 2007;94:
1288–94.
9. Ommen SR, Shah PM, Tajik AJ. Left ventricular outflow tract obstruction in
hypertrophic cardiomyopathy: past, present and future. Heart 2008;94:1276–81.
10. Gruner C, Chan RH, Crean A, Rakowski H, Rowin EJ, Care M et al. Significance
of left ventricular apical-basal muscle bundle identified by cardiovascular magnet-
ic resonance imaging in patients with hypertrophic cardiomyopathy. Eur Heart J
2014;35:2706–13.
11. Binder J, Ommen SR, Gersh BJ, Van Driest SL, Tajik AJ, Nishimura RA et al.
Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal
morphological features predict the presence of myofilament mutations. Mayo
Clin Proc 2006;81:459–67.
12. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L et al.
Recommendations for cardiac chamber quantification by echocardiography in
adults: an update from the American Society of Echocardiography and the
European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015;28:
1–39.e14.
13. Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans
Det al.; European Association of Echocardiography. Stress echocardiography ex-
pert consensus statement: European Association of Echocardiography (EAE) (a
registered branch of the ESC). Eur J Echocardiogr 2008;9:415–37.
14. Rowin EJ, Maron BJ, Chokshi A, Kannappan M, Arkun K, Wang W et al. Clinical
spectrum and management implications of left ventricular outflow obstruction
with mild ventricular septal thickness in hypertrophic cardiomyopathy. Am J
Cardiol 2018;122:1409–20.
15. Varghese R, Itagaki S, Anyanwu AC, Trigo P, Fischer G, Adams DH. Predicting
systolic anterior motion after mitral valve reconstruction: using intraoperative
transoesophageal echocardiography to identify those at greatest risk. Eur J
Cardiothorac Surg 2014;45:132–7.
16. Ro R, Halpern D, Sahn DJ, Homel P, Arabadjian M, Lopresto C et al. Vector flow
mapping in obstructive hypertrophic cardiomyopathy to assess the relationship
of early systolic left ventricular flow and the mitral valve. J Am Coll Cardiol 2014;
64:1984–95.
17. Authors/Task Force Members, Elliott PM, Anastasakis A, Borger MA, Borggrefe
M, Cecchi F et al. 2014 ESC Guidelines on diagnosis and management of hyper-
trophic cardiomyopathy: the Task Force for the diagnosis and management of
hypertrophic cardiomyopathy of the European Society of Cardiology (ESC). Eur
Heart J 2014;35:2733–79.
18. Maslow AD, Regan MM, Haering JM, Johnson RG, Levine RA. Echocardiographic
predictors of left ventricular outflow tract obstruction and systolic anterior mo-
tion of the mitral valve after mitral valve reconstruction for myxomatous valve
disease. J Am Coll Cardiol 1999;34:2096–104.
19. Jiang L, Levine RA, King ME, Weyman AE. An integrated mechanism for systolic
anterior motion of the mitral valve in hypertrophic cardiomyopathy based on
echocardiographic observations. Am Heart J 1987;113:633–44.
20. Desai MY, Smedira NG, Bhonsale A, Thamilarasan M, Lytle BW, Lever HM.
Symptom assessment and exercise impairment in surgical decision making in
hypertrophic obstructive cardiomyopathy: relationship to outcomes. J Thorac
Cardiovasc Surg 2015;150:928–35.e1.
21. Deng L, Huang X, Yang C, Lyu B, Duan F, Tang D et al. Numerical simulation
study on systolic anterior motion of the mitral valve in hypertrophic obstructive
cardiomyopathy. Int J Cardiol 2018;266:167–73.
LV BMB in HCM: a risk factor for LVOTO 9
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