Detection of latent obstruction in patients with hypertrophic cardiomyopathy using parameters derived from resting echocardiography

Introduction

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disease, defined as left ventricular hypertrophy that cannot be explained by abnormal loading conditions (1,2). Left ventricular outflow tract (LVOT) obstruction is a crucial hallmark of HCM (3); latent obstruction is one of subtypes of obstructive HCM in which the obstruction is not observable under resting conditions but apparent after provocation (4). In patients with HCM, resting LVOT obstruction (LVOTO) has association with the rising rates of morbidity and mortality (5). Notably, latent obstruction can induce critical functional impairment and is associated with poor prognosis (6); LVOTO can be treated with drugs and invasive therapies (7-9).

Unlike fixed obstruction caused by aortic stenosis and subaortic membranes, LVOTO in HCM may be unstable (4). Additionally, LVOTO is influenced by preload and afterload conditions, ventricle and mitral apparatus morphology, and ventricular contractility (10). In several patients with resting-state HCM, LVOTO may not be exhibited unless provocation testing is conducted (11). Previous studies demonstrated that LVOTO affected approximately 75% of patients with HCM (3,12). Furthermore, among patients with HCM, 50% exhibited LVOTO under resting conditions (4); subpopulations of patients with HCM and latent LVOTO could have been underestimated.

The mechanisms underlying LVOTO involve various factors, and hypertrophy of the basal septum and systolic anterior motion (SAM) of the mitral valve (MV) are dominant. Septal hypertrophy may reduce the distance between the interventricular septum (IVS) and MV leaflets and alter blood flow towards the margin of the anterior leaflet, consequently inducing SAM and LVOTO (13). Owing to limited knowledge of the dynamic components of LVOTO and lack of experience with provocative manipulation in clinical practice, LVOTO is grossly underdiagnosed, and many patients do not receive optimal treatment (14). Therefore, simple and feasible echocardiographic parameters are vital to distinguish latent obstructive and nonobstructive HCM.

In our previous study, we proposed a new measurement method for quantitatively assessing the morphology of the basal IVS and demonstrated that the degree of basal IVS protrusion towards the LVOT, instead of the degree of hypertrophy, was associated with LVOTO (15); however, information regarding the relationship between basal IVS morphology and latent obstruction is limited. Thus, our objectives are (I) to identify the morphological characteristics of the basal IVS correlated with LVOTO and (II) to determine whether specific resting echocardiographic characteristics are crucial for detecting latent LVOTO. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2161/rc).

Methods

Patients selection

This retrospective study was conducted at Fuwai Hospital. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Institutional Review Board of Fuwai Hospital, and all patients provided informed written consent. A total of 278 patients diagnosed with HCM between September 2019 and January 2021 were enrolled. The diagnosis of HCM was established according to the following guidelines (12): left ventricular hypertrophy (maximal thickness ≥15 mm at the end-diastole, or ≥13 mm when present in family members, or a positive genetic test) indicated by echocardiography or cardiovascular magnetic resonance in the absence of other causes contributing to the hypertrophy. Patients with midventricular or apical hypertrophy (n=95), left ventricular ejection fraction (LVEF) <50% (n=9), a history of cardiac surgery (n=5), concomitant valvular disease or congenital heart disease (n=19), or poor image quality (n=12) were excluded. Finally, data from transthoracic echocardiography (TTE) of 138 patients were analyzed (Figure 1). The baseline data of all participants were provided by the hospital information system.

Figure 1 Flow diagram of patient selection. HCM, hypertrophic cardiomyopathy; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; PG, pressure gradient.

Echocardiography

The patients were kept in the left lateral position, and attachment to the electrocardiogram was conducted. TTE was performed by qualified sonographers using the Philips EPIQ 7C machine (Philips Medical Systems, Andover, MA, USA) equipped with a matrix array S5-1 probe. Qlab 13.0 (Philips Healthcare, Andover, MA, USA) was used to analyze conventional echocardiographic images collected when the patients were at rest. LVEF, left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were measured using biplane Simpson’s method; LVEDVi and LVESVi were obtained by indexing LVEDV and LVESV to the body surface area. Measurement for the maximum thickness of basal IVS was made at end-diastole in the parasternal long-axis view. The LVOT peak velocity was measured in apical three- or five-chamber views, followed by the calculation of pressure gradient (PG) by simplified Bernoulli equation. Patients with an LVOT PG <30 mmHg under resting condition were candidates for provocation testing (such as the Valsalva or stand-to-squat). Patients were divided into three groups based on LVOT PG: (I) obstructive, ≥30 mmHg at rest; (II) latent obstructive, <30 mmHg at rest, or ≥30 mmHg during provocation; (III) non-obstructive, <30 mmHg at rest and during provocation.

HCM-specific parameters

Mitral regurgitation was graded according to guidelines (16): 0, none or trace; 1, mild; 2, moderate; 3, moderate-to-severe; 4, severe. SAM was graded according to the degree of valve motion towards the septum and the duration of mitral-septal contact (17,18): 0, no motion and no contact; I (mild), brief motion but no contact; II (moderate), brief motion with contact in late systole; III (severe), prolonged motion with contact in early systole. The anterior and posterior mitral leaflet lengths (AML and PML) were obtained during diastole in an apical three-chamber view; the angle between the mitral valvular orifice and ascending aorta (MV-AO angle) was measured at end-diastole in the apical three-chamber view (Figure 2). Hypertrophied papillary muscles (PMs) were defined as the diameter of at least one of the PMs ≥11 mm (19). Muscle bundles (MBs) were defined as muscular bands extending from the basal septum to the apex/PM without any tendinous cords connected to the MV (19); MBs may be found in the parasternal long axis, left ventricular short axis, and apical three- or four-chamber views.

Figure 2 Method of measurements for MV-AO angle. (A) An example demonstrating the measurement of MV-AO angle. Green lines and the labeled angle (153.8°) in the image demonstrate the measurement of the MV-AO angle. This is a patient with HCM with resting LVOTO, and the angle is 153.8°. (B) Schematics of the measurement. The red dashed line represents the MV-AO angle. HCM, hypertrophic cardiomyopathy; LVOTO, left ventricular outflow tract obstruction; MV-AO angle, the angle between the mitral valvular orifice and ascending aorta.

Measurements of basal septal morphology

Measurement of the morphology of the basal IVS was performed in the parasternal long-axis view by RadiAnt DICOM Viewer (Medixant, Poland) at the end of systole (Figures 3,4) (15). Line A was defined as a line connecting the two points on the aortic annulus, and Line B was defined as a line perpendicular to the line A and passing through the anterior point of the annulus. The area of the basal septum beneath lines A and B was defined as the IVSa. L_A was defined as the IVSa projected on Line A, and L_B was defined as the IVSa projected on Line B. The IVSa was divided by L_B to obtain a standardized value (S-IVSa).

Figure 3 Method of measurements for basal septal morphology. Line A was defined as a line connecting the two points on the aortic annulus, and Line B was defined as a line perpendicular to the line A and passing through the anterior point of the annulus. The area of the basal septum beneath lines A and B was defined as the IVSa. LA was defined as the IVSa projected on Line A, and LB was defined as the IVSa projected on Line B. The IVSa was divided by LB to obtain a standardized value (S-IVSa). From reference (15) with permission. IVSa, the area of basal septum protruding into the left ventricular outflow tract.

Figure 4 Examples demonstrating the measurement of basal septal morphology and HCM-specific parameters in echocardiography in patients with HCM. The MBs (red arrows) in patients with HCM with resting obstruction (A1), latent obstruction (A2), and non-obstruction (A3). The S-IVSa in patients with resting obstruction (B1), latent obstruction (B2), and non-obstruction (B3) were 8.1, 7.7, and 6.1 mm², respectively. The lengths of AML and PML (green straight lines) in patients with resting obstruction (C1), latent obstruction (C2), and non-obstruction (C3) were 41.2 and 19.2 mm, 32.7 and 21.8 mm, 23.0 and 14.7 mm, respectively. AML, the length of anterior mitral leaflet; HCM, hypertrophic cardiomyopathy; IVSa, the area of basal septum protruding into the left ventricular outflow tract; LA, the depth of IVSa relative to the left ventricular outflow tract; LB, the length of IVSa in the direction of the left ventricular long axis; MBs, muscle bundles; PML, the length of posterior mitral leaflet; S-IVSa, IVSa divided by LB.

Reproducibility analysis

To analyze the reproducibility of the variables, two experienced echocardiographers performed measurements on a random sample of 20 patients. The intraobserver and interobserver reproducibilities of the MV-AO angle, L_A, IVSa, and L_B were assessed by intraclass correlation coefficient (ICC).

Statistical analysis

SPSS 25.0 (version 25.0; IBM Inc., Armonk, NY, USA) was used for the statistical tests. Variables were expressed as numbers (percentages), mean ± standard deviation (SD), and median (interquartile range [IQR]), as appropriate. Continuous variables between the groups were compared by one-way analysis of variance (ANOVA) with Bonferroni correction, Kruskal-Wallis test, or t-test. Categorical variables between groups were compared by chi-square test. The correlations between the echocardiographic parameters was analyzed by Pearson’s or Spearman’s correlation coefficient, and a correlation coefficient ≥0.60 or variance inflation factor >10 was considered to exhibit collinearity. Logistic regression analysis was conducted to evaluate the associations between variables and latent obstruction, and the results were described as odds ratios (ORs) with 95% confidence intervals (CIs). Univariate variables with a significance level of <0.1 in univariable analysis but without collinearity were included in the multivariable model. Diagnostic performance was determined by receiver operating characteristic (ROC) curve analyses using MedCalc Software (version 20.100, Ostend, Belgium). The area under the ROC curve (AUC) with 95% CI was calculated to assess the diagnostic accuracy of the models. Cutoff values with optimal sensitivity and specificity were determined using the AUC, and the positive predictive value (PPV) and negative predictive value (NPV) of these cutoffs were calculated. P<0.05 was considered statistically significant.

Results

Baseline characteristics

The baseline characteristics of the three groups are presented in Table 1. According to the grouping criteria, the patients were divided into a resting obstruction group (n=65), a latent obstruction group (n=38), and a non-obstruction group (n=35). The baseline characteristics of the three groups were comparable (P>0.05), except for the New York Heart Association (NYHA) class and symptoms of dyspnea. The number of patients with NYHA class I in the resting obstruction group was significantly lower than that in the latent and non-obstruction groups, but the opposite was true for patients with NYHA class IV (all P<0.05). Symptoms of dyspnea were more common in the resting obstruction group than in the non-obstruction and latent obstruction groups, and the differences were statistically significant (P<0.05).

Routinely echocardiographic parameters

The echocardiographic parameters of the three groups are presented in Table 2. The maximal basal septal thickness was comparable among the three groups (P=0.060), with a mean value of 21.6±5.0 mm. There was a statistically significant difference in LVESVi among the three groups (P=0.044), and the LVESVi in patients with latent obstruction was higher than that in patients with resting obstruction; however, no differences were observed between patients with and without latent obstruction (P>0.999). Resting PG was higher in patients with resting obstruction than in those with latent obstruction and non-obstruction (both P<0.001) and was higher in patients with latent obstruction than in those without obstruction (P=0.047). Provocable LVOT PG was significantly higher in patients with latent obstruction than those without latent obstruction (P<0.001). No differences were observed in LVEDVi and the presence of hypertrophied PMs among the three groups (P=0.180 and P=0.065, respectively).

HCM-specific parameters in echocardiography

There are significant differences among the three groups in the AML and PML lengths and the MV-AO angle (all P<0.001). The AML length in patients with resting obstruction was longer than that in patients with latent obstruction and non-obstruction (P=0.001 and P<0.001, respectively,Figure 4), and no difference was observed between the latter two groups (P=0.334). The PML in patients with resting and latent obstruction was longer than that in those without obstruction (P<0.001 and P=0.034, respectively), and there was no statistical difference between patients with resting and latent obstruction (P=0.176). The MV-AO angle had similar patterns to those of PML length (P<0.001, P<0.001, and P=0.278, respectively). Abnormal MBs were more common in patients with resting and latent obstruction than in those without obstruction (all P<0.05); however, there was no significant difference between patients with resting and latent obstruction (P>0.05). The occurrence of mitral regurgitation grades ≥2 and SAM grades ≥2 were statistically different among the three groups (both P<0.001). More patients presented with mitral regurgitation grades ≥2 and SAM grades ≥2 in resting obstruction group than in latent obstruction and non-obstruction groups (P<0.05). Mitral regurgitation grades ≥2 were more common in patients with latent obstruction than those without obstruction (P=0.020).

Morphological parameters of basal IVS

The morphological parameters of the basal IVS are shown in Table 2. The IVSa, L_A, and S-IVSa were significantly different among the three groups (P=0.04, P<0.001, and P<0.001, respectively, Figure 4). L_A and S-IVSa were lower in patients without obstruction than in those with resting and latent obstructions (P=0.025 and P=0.001, respectively), and no differences were observed between patients with resting and latent obstructions.

Correlations among the AML length, MV-AO angle, L_A, and S-IVSa

The correlations between the AML length, MV-AO angle, L_A, and S-IVSa are shown in Table 3. The L_A and IVSa showed good correlations with the length of the PML (r=0.360, P<0.01, and r=0.421, P<0.01, respectively) and the MV-AO angle (r=0.292, P<0.05, and r=0.328, P<0.01, respectively). The correlation between the length of the PML and the MV-AO angle was weak (r=0.220, P>0.05). L_A showed an excellent correlation with the S-IVSa (r=0.892, P<0.01).

Echocardiographic parameters associated with latent obstruction

Further analyses were conducted on patients with and without latent obstruction. The results of the logistic regression analysis are shown in Table 4. In the univariate logistic regression analyses, dyspnea, mitral regurgitation grades ≥2, the length of PML, MV-AO angle, presence of abnormal MBs, L_A, and S-IVSa were associated with latent obstruction in patients with HCM. In multivariate logistic regression analyses, the MV-AO angle, presence of abnormal MBs, and S-IVSa were associated with latent obstruction [OR (95% CI): 0.831 (0.756–0.913), P<0.001; 7.922 (1.584–40.551), P=0.013; 0.439 (0.208–0.887), P=0.022].

Latent obstruction detected by echocardiographic parameters

The results of the ROC curve analysis are presented in Table 5 and Figure 5. Among the individual parameters, the MV-AO angle showed the strongest association with latent obstruction, with an AUC of 0.890 (95% CI: 0.795–0.951). The sensitivity, specificity, PPV, and NPV of an MV-AO angle >142.7° for detecting latent obstruction were 81.6%, 88.6%, 88.6%, and 81.6%, respectively. The AUC of S-IVSa to detect latent obstruction was 0.738 (95% CI: 0.621–0.834), and the sensitivity, specificity, PPV, and NPV of an S-IVSa >5.9 mm for detecting latent obstruction were 78.9%, 62.9%, 69.8%, and 73.3% respectively. The presence of abnormal MBs had a sensitivity, specificity, PPV, and NPV of 68.4%, 71.3%, 72.2%, and 67.6%, respectively. A new model consisting of the MV-AO angle, S-IVSa, and presence of abnormal MBs derived from multivariate logistic regression analysis showed a stronger association with latent obstruction, with an AUC of 0.954 (95% CI: 0.878–0.989). The combination of MV-AO angle >142.7°, S-IVSa >5.9 mm, and the presence of abnormal MBs showed a sensitivity of 92.1% and specificity of 91.4% for detecting latent obstruction.

Figure 5 ROC curves for the new model, the MV-AO angle, S-IVSa, and the presence of abnormal MBs to detect latent obstruction. IVSa, the area of basal septum protruding into the left ventricular outflow tract; MBs, muscle bundles; MV-AO angle, the angle between mitral valve orifice and the ascending aorta; ROC, receiver operating characteristic; S-IVSa, the IVSa divided by LB (the length of IVSa in the direction of left ventricular long axis).

Reproducibility assessment

Measurements of the MV-AO angle, L_A, IVSa, and L_B showed favorable inter- and intra-observer variability. Intra-observer analysis showed the ICC for MV-AO angle, L_A, IVSa, and L_B were 0.88 (95% CI: 0.69–0.95), 0.91 (95% CI: 0.80–0.97), 0.94 (95% CI: 0.85–0.95), and 0.88 (95% CI: 0.67–0.96), respectively, with the ICC for the corresponding inter-observer analysis being 0.85 (95% CI: 0.63–0.94), 0.81 (95% CI: 0.60–0.92), 0.82 (95% CI: 0.60–0.92), and 0.80 (95% CI: 0.56–0.92), respectively.

Discussion

In our cohort of patients with HCM, we demonstrated several echocardiographic parameters associated with latent obstruction, including the L_A, S-IVSa, MV-AO angle, and the presence of abnormal MBs. The S-IVSa and MV-AO angles had high PPV and NPV for detecting latent LVOTO and could be obtained in the resting state. Furthermore, we established a new model consisting of S-IVSa, MV-AO angle, and the presence of abnormal MBs for detecting latent obstruction, which showed better diagnostic value than any single parameter alone.

Relevance of latent obstruction in HCM

Various physical and pharmacological maneuvers in patients with HCM or latent LVOTO may cause SAM and LVOTO. Researchers have revealed that in patients with HCM, the prognosis of patients with latent obstruction is better than that of patients with resting obstruction (20). However, symptoms associated with intermittent obstruction, including chest pain, dyspnea, and palpitations, may be disturbing. LVOTO and associated symptoms may achieve remission by pharmacotherapy and septal reduction therapies (4,8,9,21-23); therefore, detecting latent obstructions is crucial for treatment and prognosis. Since obstruction in patients with latent LVOTO may not be present in the resting state, it is necessary to conduct further provocative maneuvers based on routine TTE in patients with suspected obstruction; however, implementing provocative maneuvers is time-consuming, and the investigators must be experienced (10). Therefore, identifying latent obstruction using TTE without the discomfort, time consumption, or cost of provocative maneuvers would be practical. In this study, we investigated several echocardiographic parameters associated with latent obstruction at rest.

Mechanisms of LVOTO

Various factors contribute to LVOTO in patients with HCM, with severe hypertrophy of the basal septum and SAM as the primary factors (24). In recent years, the development of echocardiography has enabled a broader understanding of the morphological features of HCM. Researchers have identified an increasing number of factors other than septal hypertrophy and SAM associated with obstruction, including PM abnormalities (hypertrophy, bifurcation, displacement, etc.), tendinous chordae abnormalities, and the presence of abnormal MBs (19). In addition, an elongated mitral leaflet is associated with obstruction (25), consistent with our findings. Our results revealed that the AML and PML were longer in patients without obstruction than those with resting obstruction. A previous study revealed that a longer AML was an independent factor of LVOTO (15); however, its role in distinguishing patients with and without latent obstruction was weakened in this study.

Basal septal morphology in HCM

The LVOT is a composite structure of the left ventricle between the AML and the IVS. Considering the diverse factors contributing to LVOTO, it is difficult to assess obstruction using a single parameter. In our cohort, the basal septal thickness was comparable among patients with resting obstruction, latent obstruction, and no obstruction. We focused on assessing the relative relationship between the septum and LVOT and proposed a new method of measurement to assess the morphology of the basal IVS. Septal thickness was measured at the end of diastole, and the morphology of the basal IVS was obtained at the end of systole; measurement of these parameters during systole allows for a better assessment of LVOT morphology. We measured the IVSa (the area of the basal septum protruding into the LVOT), L_A (the depth of the IVSa relative to the LVOT), L_B (the length of the IVSa in the direction of the left ventricular long axis), and calculated the S-IVSa (the standardized IVSa: IVSa divided by L_B) (15). We discovered that the L_A and S-IVSa were significantly higher in patients with resting obstruction than those with latent and non-obstructed obstruction. In further differentiating the presence of latent obstruction in patients without obstruction at rest, we discovered that S-IVSa was independently correlated with latent obstruction and exhibited good PPV and NPV for differentiating latent obstruction. In addition, basal septum parameters were simple to measure and showed good reproducibility.

The MV-AO angle in patients with latent obstruction

Researchers have demonstrated that a steeper aorta-basal septum or aorta-left ventricle angle was an independent predictor of LVOTO (26,27). A steeper angle may remodel the LVOT by increasing turbulence and intraventricular pressure. Notably, different thickness of hypertrophied IVS and accurate identification of the LV long axis may be challenging when measuring the angles. Previous studies have explored the angle between the mitral annulus and the ascending aorta, which reduced potential confounding factors (15,28). The results showed that a larger MV-AO angle was independently associated with LVOTO; however, their cohort of patients was not subgrouped (based on whether the obstruction was present at rest or after provocation) for the analysis (15). In our study, we investigated the role of the MV-AO angle in latent obstruction; the MV-AO angle in patients without obstruction was lesser than that in patients with resting and latent obstruction and was independently associated with latent obstruction in patients without obstruction in the resting state. An MV-AO angle >142.7° yielded PPV and NPV of 88.6% and 81.6%, respectively, appropriate for detecting latent LVOTO among these patients. We hypothesized that, in patients with a high MV-AO angle, the MV leaflets would be more perpendicular to the long axis of the LVOT and more susceptible to LVOT flow. Additionally, researchers have demonstrated that a higher MV-AO angle contributes to the anterior shift of the MV towards the IVS, consequently producing SAM [37, 38].

Abnormal MBs

Abnormal MBs have attracted attention in recent years. Researchers have reported that the presence of an abnormal MB may induce SAM facilitation by decreasing the distance between the AML and MB/IVS (28). Additionally, studies have suggested that abnormal MBs are independent predictors of LVOTO (28). In this study, the presence of abnormal MBs was demonstrated an related factor for latent obstruction in patients without obstruction at rest. However, the sensitivity and specificity of abnormal MBs for detecting latent obstructions were not optimal (68.4% and 71.3%, respectively). In addition, the detection of MBs is crucial for determining surgical strategy. Consequently, the presence of abnormal MBs may provide clues for the diagnosis of latent obstruction and reference values for clinical treatment.

Potential clinical implications

TTE and Doppler echocardiography play vital roles in assessing LVOT PG in patients with HCM. Although no obstruction is observed in patients under resting conditions, traditional resting TTE parameters cannot exclude the existence of an obstruction after provocation. In such cases, a stress test is required; however, it may cause exhaustion, and the test may fail in a certain group of patients. To explore the resting parameters related to provocable obstruction, we proposed parameters of basal septal morphology that can provide information about the role of the basal septum in generating obstruction and serve as resting parameters to predict the existence of provocable obstruction. By combining the S-IVSa with other factors associated with obstruction demonstrated in previous studies (MV-AO angle and presence of abnormal MBs), we developed a new model with the potential to diagnose latent obstruction effectively (with an AUC of 0.954); this model provides diagnostic value for patients in whom the provocation tests are challenging or insensitive and provide additional information to provocation tests, improving the detection rate of latent obstruction and benefitting more patients.

Limitations

This study had some limitations. This was a retrospective study conducted at a single center, and further multicenter studies with larger sample sizes are needed to assess the cutoff values of echocardiographic parameters for LVOTO more accurately. Because the maximal thickness of the IVS in the majority of this sample was >18 mm, the role of basal septal morphology and the new model in patients with mild septal hypertrophy remains unclear. In our cohort, only a few patients with LVOTO who underwent surgery developed residual obstruction; therefore, we failed to evaluate basal septal morphology or the value of this model in residual obstruction. Among the enrolled patients, the distribution of the resting PG difference was non-normal. We anticipate supplementing the data in the future and using continuous PG data to study its correlation with the morphology of the basal septum and the new model.

Conclusions

L_A and S-IVSa, the new morphological parameters of the basal septum, are more valuable for detecting the presence of obstruction than thickness alone, and the measurements are simple and reproducible. Combining S-IVSa with the MV-AO angle and abnormal MBs can effectively identify patients with latent obstruction and is superior to using either alone; this makes the new model a noninvasive assessment tool for clinicians in the diagnosis and provides additional information for the intervention of patients with latent obstruction.

Acknowledgments

We would like to thank Editage (www.editage.cn) for English language editing.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-2161/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-24-2161/dss

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2161/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Institutional Review Board of Fuwai Hospital, and all patients provided informed written consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Veselka J, Anavekar NS, Charron P. Hypertrophic obstructive cardiomyopathy. Lancet 2017;389:1253-67. [Crossref] [PubMed]
2. Nagueh SF, Phelan D, Abraham T, Armour A, Desai MY, Dragulescu A, Gilliland Y, Lester SJ, Maldonado Y, Mohiddin S, Nieman K, Sperry BW, Woo A. Recommendations for Multimodality Cardiovascular Imaging of Patients with Hypertrophic Cardiomyopathy: An Update from the American Society of Echocardiography, in Collaboration with the American Society of Nuclear Cardiology, the Society for Cardiovascular Magnetic Resonance, and the Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr 2022;35:533-69. [Crossref] [PubMed]
3. Affronti A, Pruna-Guillen R, Sandoval E, Pereda D, Alcocer J, Castellà M, Quintana E. Surgery for Hypertrophic Obstructive Cardiomyopathy: Comprehensive LVOT Management beyond Septal Myectomy. J Clin Med 2021;10:4397. [Crossref] [PubMed]
4. Cui H, Schaff HV, Nishimura RA, Dearani JA, Geske JB, Ommen SR. Latent outflow tract obstruction in hypertrophic cardiomyopathy: Clinical characteristics and outcomes of septal myectomy. J Thorac Cardiovasc Surg 2022;164:1863-1869.e1. [Crossref] [PubMed]
5. Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003;348:295-303. [Crossref] [PubMed]
6. Ji Q, Wang Y, Liu F, Yang Y, Xia L, Ding W, Lai H, Wang C. Hypertrophic cardiomyopathy with latent obstruction: Clinical characteristics and surgical results. J Cardiol 2022;79:42-9. [Crossref] [PubMed]
7. Maron BJ, Desai MY, Nishimura RA, Spirito P, Rakowski H, Towbin JA, Dearani JA, Rowin EJ, Maron MS, Sherrid MV. Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol 2022;79:390-414. [Crossref] [PubMed]
8. Dybro AM, Rasmussen TB, Nielsen RR, Andersen MJ, Jensen MK, Poulsen SH. Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol 2021;78:2505-17. [Crossref] [PubMed]
9. Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2020;396:759-69. [Crossref] [PubMed]
10. Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT, Nistri S, Cecchi F, Udelson JE, Maron BJ. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation 2006;114:2232-9. [Crossref] [PubMed]
11. Jain CC, Miranda WR, Geske JB, Schaff HV, Nishimura RA. Echocardiographic Characteristics of Severe Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy. J Am Soc Echocardiogr 2021;34:798-801. [Crossref] [PubMed]
12. Ommen SR, Mital S, Burke MA, Day SM, Deswal A, Elliott P, Evanovich LL, Hung J, Joglar JA, Kantor P, Kimmelstiel C, Kittleson M, Link MS, Maron MS, Martinez MW, Miyake CY, Schaff HV, Semsarian C, Sorajja P. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2020;142:e558-631. [PubMed]
13. Silbiger JJ. Abnormalities of the Mitral Apparatus in Hypertrophic Cardiomyopathy: Echocardiographic, Pathophysiologic, and Surgical Insights. J Am Soc Echocardiogr 2016;29:622-39. [Crossref] [PubMed]
14. Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol 2016;117:1651-4. [Crossref] [PubMed]
15. Tao J, Li H, Yang P, Meng Q, Duan F, Wang H. Morphology of hypertrophied basal septum contributes to left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy: a retrospective case-control study. Quant Imaging Med Surg 2023;13:4117-29. [Crossref] [PubMed]
16. Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, Hahn RT, Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan S, Thavendiranathan P, Thomas JD, Weissman NJ. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr 2017;30:303-71. [Crossref] [PubMed]
17. Verheyen N, Batzner A, Zach D, Zirlik A, Gerull B, Frantz S, Maack C, Störk S, Seggewiss H, Morbach C. Spatial relationship between mitral valve and ventricular septum assessed by resting echocardiography to diagnose left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Eur Heart J Cardiovasc Imaging 2023;24:710-8. [Crossref] [PubMed]
18. Gilbert BW, Pollick C, Adelman AG, Wigle ED. Hypertrophic cardiomyopathy: subclassification by m mode echocardiography. Am J Cardiol 1980;45:861-72. [Crossref] [PubMed]
19. Tao J, Duan F, Long J, Meng Q, Zhang B, Zhu Z, Wang H. The Role of the Submitral Apparatus in Hypertrophic Obstructive Cardiomyopathy. J Am Soc Echocardiogr 2023;36:133-45. [Crossref] [PubMed]
20. Rowin EJ, Maron BJ, Chokshi A, Kannappan M, Arkun K, Wang W, Rastegar H, Maron MS. 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. [Crossref] [PubMed]
21. 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. [Crossref] [PubMed]
22. Hong JH, Schaff HV, Nishimura RA, Abel MD, Dearani JA, Li Z, Ommen SR. Mitral Regurgitation in Patients With Hypertrophic Obstructive Cardiomyopathy: Implications for Concomitant Valve Procedures. J Am Coll Cardiol 2016;68:1497-504. [Crossref] [PubMed]
23. Cui B, Wang S, Xu J, Wang W, Song Y, Sun H, Zheng Z, Lv F, Xiong H. The surgical management of hypertrophic obstructive cardiomyopathy with the concomitant mitral valve abnormalities. Interact Cardiovasc Thorac Surg 2015;21:722-6. [Crossref] [PubMed]
24. Dulguerov F, Marcacci C, Alexandrescu C, Chan KM, Dreyfus GD. Hypertrophic obstructive cardiomyopathy: the mitral valve could be the key. Eur J Cardiothorac Surg 2016;50:61-5. [Crossref] [PubMed]
25. Sakellaropoulos S, Svab S, Mohammed M, Dimitra L, Mitsis A. The Role of Mitral Valve in Hypertrophic Obstructive Cardiomyopathy: An Updated Review. Curr Probl Cardiol 2021;46:100641. [Crossref] [PubMed]
26. Critoph CH, Pantazis A, Tome Esteban MT, Salazar-Mendiguchía J, Pagourelias ED, Moon JC, Elliott PM. The influence of aortoseptal angulation on provocable left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. Open Heart 2014;1:e000176. [Crossref] [PubMed]
27. Kwon DH, Smedira NG, Popovic ZB, Lytle BW, Setser RM, Thamilarasan M, Schoenhagen P, Flamm SD, Lever HM, Desai MY. Steep left ventricle to aortic root angle and hypertrophic obstructive cardiomyopathy: study of a novel association using three-dimensional multimodality imaging. Heart 2009;95:1784-91. [Crossref] [PubMed]
28. Xiao M, Nie C, Wang J, Zhu C, Sun X, Zhu Z, Wang H, Wang S. Left ventricular basal muscle bundle in hypertrophic cardiomyopathy: insights into the mechanism of left ventricular outflow tract obstruction. Eur Heart J Cardiovasc Imaging 2022;23:1018-26. [Crossref] [PubMed]