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Jeab 200
Jeab 200
https://doi.org/10.1093/ehjci/jeab200
Received 26 April 2021; editorial decision 14 September 2021; accepted 18 September 2021; online publish-ahead-of-print 29 October 2021
See the editorial comment for this article ‘Muscle bundles in hypertrophic cardiomyopathy: wallflowers seem to gain in
importance’, by Claudia Stöllberger, https://doi.org/10.1093/ehjci/jeab232.
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 Two hundred fifty-six patients diagnosed with HCM were recruited. The morphologic characteristics of left ven-
and results 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.
C The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
Published on behalf of the European Society of Cardiology. All rights reserved. V
LV BMB in HCM: a risk factor for LVOTO 1019
Graphical Abstract
...
Introduction .. the interventricular septum (IVS) to the apex or papillary muscle,
.. namely IVS–apex, IVS–anterior papillary muscle (APM), and IVS–pos-
Hypertrophic cardiomyopathy (HCM) is a heterogeneous, inherited .. terior papillary muscle. And that mid-cavity muscle bundles might lead
..
cardiomyopathy with large clinical and phenotypic heterogeneity.1 .. to a middle left ventricular outflow tract (LVOT) or an apical obstruc-
The symptoms of HCM have been attributed to the development of
.. tion. During treatment of LVOTO, basal muscle bundle (BMB) was
..
left ventricular outflow tract obstruction (LVOTO), left ventricular .. resected without imaging analysis before the operation. Whether
..
(LV) diastolic dysfunction, arrhythmias, and mitral regurgitation, and .. BMB contributed to LVOTO in some of their patients was unknown.3
the focus of treating these patients is on the relief of LVOTO.2 .. Gruner et al.10 reported the detection of LV apical-BMB by cardiac
..
LVOTO is involved in a complex mechanism that depends on the LV .. magnetic resonance imaging (CMR) in 63% of patients with HCM and
morphology, loading conditions, contractility, and mitral apparatus.3–9 .. reported that BMB might be associated with LVOTO. To the best of
..
Wang et al. reported that 78.1% of patients had anomalous muscular .. our knowledge, there was no any other study using echocardiography
bundles by surgery. The anomalous muscle bundles extended from
.. to assess the prevalence of BMB in patients with HCM. The present
1020 M. Xiao et al.
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
Echocardiography
TTE was performed using a commercially available system (E9 ultra- Figure 1 Drawing of left ventricular basal muscle bundle that ori-
sound system, GE Healthcare, Horten, Norway). Standard two-di- ginated from the basal septum: ‹ the point of adhesion was the
mensional (2D) and Doppler echocardiographic images were apex and › the point of adhesion was the APM. AML, anterior mi-
acquired using an M5S phased-array transducer in the parasternal and tral leaflet; AO, ascending aorta; APM, anterior papillary muscle;
apical views, and the images were saved on a hard disc as archive files IVS, interventricular septum; PML, posterior mitral leaflet; PPM, pos-
for offline analysis using EchoPAC software version BT 201 (GE terior papillary muscle.
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- .. chamber or parasternal long-axis view. The maximal lengths of the anter-
mendations of the American Society of Echocardiography (ASE).12
..
.. ior mitral leaflet (AL) and posterior mitral leaflet were measured at end-
The LVOT gradient was estimated by using the simplified Bernoulli .. diastole in apical three-chamber view images from the base to the free
equation, avoiding contamination of the LVOT waveform by mitral re- ..
.. margin of A2 or P2. The distance between the mitral valve free margin
gurgitation. In patients with a resting LVOT gradient <50 mmHg, .. and the septum (or BMB when there was a significant muscle bundle; M-
exercise was used to provoke an LVOT gradient. Exercise echocardi- ..
ography was performed in 111 (50%) patients using a half-squat exer-
.. sept/bundle), the distance between the mitral valve coaptation and the
.. septum or BMB (C-sept/bundle), and the distance between the APM and
cise protocol in accordance with the European Association of ..
Echocardiography guidelines.13 An experienced operator performed .. the septum (APM-sept) were determined at end-diastole from the apical
.. three-chamber view (Figure 3).
all the tests using the same Vivid E9 machine. ..
..
..
Definition of LV BMB .. Reproducibility of BMB for echocardiography
On TTE, BMB was defined in parasternal long-axis, apical three-chamber .. Interobserver and intraobserver variabilities of the presence or absence
..
long-axis, apical four-chamber or LV short-axis cine images as a single .. of BMB were assessed from an HCM cohort including a random sample
band of muscle extending from the basal septum through the LV cavity to .. of 67 patients (the researchers were blinded to the previous results) by
the apex or papillary muscle without evidence of chordal attachment to
..
.. the primary (M.X. from Fuwai hospital) and second independent (J.W.
the mitral valve (Figure 1, Figure 2, and Supplementary data online, Figure .. from Fuwai hospital) observer, respectively.
S1). The description of CMR was shown in Supplementary data online ..
..
(Supplemental description of CMR). ..
.. Extended septal myectomy
Measurements of LV geometry .. Patients with an LVOT gradient >_50 mmHg at rest or after exercise and
..
The angle between the plane of the mitral valvular orifice and the ascend- .. the presence of severe limiting symptoms refractory to maximum
ing aorta (MV-AO angle) was measured at end-diastole from the three-
.. pharmacologic therapy underwent septal myectomy by one surgeon
LV BMB in HCM: a risk factor for LVOTO 1021
..
(S.W.).3 The surgeon recorded the detailed anatomic features of BMB: .. Results
Type I: IVS–apex and Type II: IVS–APM (Figure 1). ..
..
.. Patient characteristics
..
Statistical analysis .. Two hundred fifty-six patients were recruited in the study after the
Data are expressed as the mean ± standard deviation, median [inter-
.. exclusion of those who met any of the exclusion criteria. The patients
..
quartile range (IQR)] or number (percentages). A t-test was used to .. in the cohort had a median age of 45.9 ± 14.9 years, and 156 (60.9%)
compare continuous variables, and a v2 test was used for categorical
.. were male. The patients were separated by a resting or provocative
..
variables. The paired samples t-test was used to compare the pre- .. LVOT gradient >_30 mmHg or not, with 176 (68.9%) patients in the
myectomy variables and latest review variables. Binary logistic regres- ..
.. obstructive group. The baseline characteristics are summarized in
sion analysis was performed to identify factors associated with .. Table 1 and Supplementary data online, Table S1.
LVOTO. A backward: Logistic regression (LR) method was performed ..
..
with the models. We calculated the odds ratio as well as the confi- .. Baseline echocardiographic and LVOT
dence interval for each association. Interobserver and intraobserver ..
.. morphologic characteristics
agreement were assessed by means of the kappa test. To evaluate the ..
ability of TTE to identify BMB, sensitivity, specificity, the positive pre- .. The echocardiographic characteristics at baseline and the morpho-
.. logic characteristics of LVOT are presented in Table 2. The median
dictive value (PPV), the negative predictive value (NPV), and accuracy ..
were calculated and compared with those of the surgical findings. All .. BMB thickness was 5 mm (IQR 4–6). The median distance from the
analyses were performed with SPSS 24.0 software (IBM Inc., Armonk,
.. origin point of BMB to the aortic annulus was 14 mm (IQR 11–16).
..
NY, USA). P-value <0.05 was considered statistically significant. . There were 178 (69.5%) patients with BMB detected by TTE. Of the
1022 M. Xiao et al.
..
intraobserver variabilities showed excellent agreement for the identi- .. Echocardiographic improvement
fication of BMB (inter: Kappa = 0.815, and intra: Kappa = 0.897, re- ..
.. after myectomy
spectively, P < 0.001). .. After myectomy, the morphologic characteristics of LVOT improved
..
.. significantly: the target anteroseptal thickness decreased, the MV-AO
Independent predictors of LVOTO ..
In the multivariate analysis, the independent predictors of
.. 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-
LVOTO were a large basal septum thickness, the presence of ..
.. tral valve (the difference between C-sept and M-sept decreased dra-
BMB, a large AL, a short M-sept/bundle, and a large MV-AO .. matically). Fourteen (16.5%) patients underwent surgical mitral valve
angle (Table 3). ..
.. procedures. LVOTO was observed in two patients (2.4%) (LVOT
.. gradient was 36 and 31 mmHg, respectively). No significant BMB was
Follow-up ..
.. found by TTE during 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 ..
.. Discussion
(iv) loss of TTE data (n = 6). Eighty-five patients underwent out- ..
patient follow-up echocardiographic evaluations [6 months .. In this study, we found that BMB was not uncommon in the cohort of
..
(IQR) 3–12]; for these patients, we used the results of the last .. HCM. Compared to that of patients without BMB, patients with BMB
follow-up.
.. had a higher LVOT gradient. BMB may influence the morphologic
1024 M. Xiao et al.
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.
Wang et al.3 reported that anomalous mid-cavity muscle bundles ... and kept the AML away from the ejection flow, thereby eliminating
..
may lead to middle LVOT or apical obstruction. Wang’s study .. SAM. After myectomy, M-sept and C-sept increased significantly.
included patients with mid-cavity or apical obstructions. During treat- ..
..
ment of LVOTO, BMB was resected without imaging analysis before .. Clinical significance
the operation. Whether BMB contributed to LVOTO in some of
.. The presence of BMB may have implications for clinical management
..
their patients was unknown. In our study, patients with mid-cavity or .. strategies.3,10 With regard to surgical myectomy for the relief of
apical obstructions were excluded; we only evaluated the effect of
.. LVOTO, BMB can be identified by the surgeon intraoperatively and
..
BMB on LVOTO. Gruner et al.10 reported that there was no differ- .. be resected during the operation (Supplementary data online, Figure
.. S3). However, ASA cannot remove BMB.20 In the present study,
ence regarding the presence of LVOTO among HCM patients with ..
or without BMB. One reason for this finding was that, in their study, .. BMB was identified during surgical myectomy in 8 (80.0%) patients
.. who underwent a previous ASA. We assume that BMB may be one
LVOTO was defined under resting conditions. It was interesting that ..
in Gruner’s study, during the follow-up period, 33 patients under- .. of the reasons for the failure of ASA, and we suggest that before mak-
.. ing an operation decision, BMB must be considered.
went surgical myectomy to relieve LVOTO, of whom 67% had an ac- ..
cessory BMB identified during the preoperative CMR study. They
..
.. Study limitations
provided an interesting pathophysiological hypothesis to explain the ..
contribution of BMB to LVOTO: fusion of the apical portion of BMB
.. This study has several limitations. First, the study population was
..
and APM could position the APM closer to the septum and limit its .. recruited from a single centre. Second, the size of our study popula-
.. tion was relatively small, which means that this study may have lacked
ability to move away from the septum during systole (Supplementary ..
data online, Figure S1A3–4). In the present study, the smaller APM- .. the statistical power necessary to identify all significant differences
.. and associations. Third, we excluded patients with mid-cavity or ap-
sept was found in patients with BMB. ..
Maron et al. reported the main reason for obstruction was due pri- .. ical obstructions if BMB also contributed to the mid-cavity or apical
.. obstructions or not was also unclear. Fourth, the characterization of
marily to an elongated MV.14 An elongated AL may be related to ..
early systolic flow, which impacts the posterior surfaces of the pro- .. the patients did not include their genotype, and whether BMB was an
.. independent and primary component of HCM disease expression
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
.. was unclear. Fifth, there was no healthy control group, and the preva-
.. lence of BMB in healthy patients with normal hearts was unclear.
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 ..
.. Conclusions
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 .. BMB is not uncommon in HCM patients, and 2D TTE is capable of re-
..
the septum than the coaptation margin. Previous studies assume that .. liably detecting this particular structural abnormality. Patients with
the aorto-mitral angle may play a role in causing SAM.4,15 A larger .. BMB have higher LVOT gradients. LVOTO can develop due to vari-
..
MV-AO angle may displace the mitral leaflets anteriorly.20 Successful .. ous geometric changes, e.g. an enlarged septum, an elongated AML, a
septal myectomy with BMB resection increased M-sept and C-sept
.. larger MV-AO angle, and a smaller M-sept/bundle, but patients with a
1026 M. Xiao et al.
..
prominent BMB have distinct characteristics suggestive of LVOTO. .. 7. Dimitrow PP, Bober M, Michałowska J, Sorysz D. Left ventricular outflow tract
BMB could be identified by the surgeon intraoperatively and resected .. gradient provoked by upright position or exercise in treated patients with hyper-
.. trophic cardiomyopathy without obstruction at rest. Echocardiography 2009;26:
during the operation. After myectomy, an enlarged M-sept and C- .. 513–20.
sept and a smaller MV-AO angle were obtained to keep the AML
.. 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
away from the ejection flow, thereby eliminating LVOTO. .. patients with non-obstructive hypertrophic cardiomyopathy. Heart 2007;94:
..
.. 1288–94.
.. 9. Ommen SR, Shah PM, Tajik AJ. Left ventricular outflow tract obstruction in
Supplementary data .. 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-
Supplementary data are available at European Heart Journal - Cardiovascular .. ic resonance imaging in patients with hypertrophic cardiomyopathy. Eur Heart J
Imaging online. .. 2014;35:2706–13.
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.. 11. Binder J, Ommen SR, Gersh BJ, Van Driest SL, Tajik AJ, Nishimura RA et al.
Acknowledgements .. Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal
This work was supported by the Capital’s Funds for Health Major Project .. European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015;28:
.. 1–39.e14.
(2020-2-4036) of the Beijing Municipal Commission of Health. .. 13. Sicari R, Nihoyannopoulos P, Evangelista A, Kasprzak J, Lancellotti P, Poldermans
.. D et al.; European Association of Echocardiography. Stress echocardiography ex-
Conflict of interest: none declared. .. pert consensus statement: European Association of Echocardiography (EAE) (a
.. registered branch of the ESC). Eur J Echocardiogr 2008;9:415–37.
Data availability .. 14. Rowin EJ, Maron BJ, Chokshi A, Kannappan M, Arkun K, Wang W et al. Clinical
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The datasets generated and/or analysed during the current study are .. spectrum and management implications of left ventricular outflow obstruction
.. with mild ventricular septal thickness in hypertrophic cardiomyopathy. Am J
not publicly available due to Fuwai Hospital system, but data can be .. Cardiol 2018;122:1409–20.
obtained from the corresponding author under reasonable request .. 15. Varghese R, Itagaki S, Anyanwu AC, Trigo P, Fischer G, Adams DH. Predicting
.. systolic anterior motion after mitral valve reconstruction: using intraoperative
and with the permission of the Ethics Committee of Fuwai Hospital. .. transoesophageal echocardiography to identify those at greatest risk. Eur J
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