This single-center retrospective cohort study assessed whether there were any associations between BSWT, AML and PML lengths, sex, and outcomes in patients who received ASA treatment for HOCM. In general, patients with BSWT ≥ 23 mm had a significantly higher rate of remaining LVOTO at follow-up. Most patients had elongated MVLL; however, AML and PML lengths were not associated with remaining LVOTO at follow-up. In addition, the amount of alcohol injected during ASA was not associated with remaining LVOTO at follow-up. These results suggest that BSWT could be a possible predictive value for LVOTO reduction after ASA; however, further studies of the potential anatomical predictors for patients with HOCM to optimize treatments based on individual conditions are required.

At the 1-year follow-up, 14% of patients had remaining LVOTO, which is supported by a recent ASA review showing that 10%-20% of patients have a residual gradient > 30 mmHg after ASA [11]. In addition, considering that BSWT ≥ 23 mm had a significantly higher rate of remaining LVOTO at follow-up, it has previously been shown that BSWT is associated with LVOTO in patients with HOCM [11]. Jensen et al.’s study of 531 patients with HOCM using a follow-up time of 0.6 ± 0.6 years after ASA showed that patients with a thicker septum had a higher residual LVOTO on follow-up compared to patients with a thinner septum [12]. Their study used three cutoffs (i.e., < 20 mm, 20–24 mm, and ≥ 25 mm), where the ≥ 25 mm group showed a trend of higher residual gradients on follow-up, although this was not significant when compared with the other groups [12]. A study of 102 patients with HOCM by Lu et al. found that a septum thinner than 24.3 mm had a higher rate of LVOT gradient reduction, which was defined as a 50% reduction compared to the gradient before ASA, while patients with a septal thickness of ≥ 24.3 mm had more non-responders [13]. Lulu et al. suggested using 24.3 mm as a cutoff when considering treating patients with ASA because a significant number of patients with a septum thicker than 24.3 mm were non-responders and had worse outcomes in LVOT gradient reduction [13]. In contrast to our study, however, Lu et al. used a different definition for LVOT reduction, with a 50% reduction in LVOT gradient between pre-procedural examination and follow-up. In summary, BSWT seems to be a promising predictive value for LVOTO reduction after ASA. Given a non-prohibited surgical risk, septal myectomy could be a better suitable method for the treatment of severe LVOTO in patients with a very thick septum; however, this must be studied further.

In this study, the amount of alcohol injected during the procedure was not associated with remaining LVOTO at follow-up. The mean amount of alcohol injected during the ASA treatment in this study (1.6 ± 0.3 mL) was lower than in previous studies reporting mean alcohol doses of 2.1–2.2 mL [14]. However, the BSWT in this study was lower (mean, 19 mm) than in earlier studies (mean, 20.1–20.7 mm). Although the recommended dose of alcohol in ASA is 1 mL per 10 mm of BSWT [15], the amount of alcohol per 10 mm of BSWT in this study equaled 0.85 ± 0.2 mL/mm, which was lower than the recommended dose. This could explain some of the cases of remaining LVOTO after ASA. The reasons for using a lower dose of alcohol than 1 mL per 10 mm of BSWT included contrast uptake (indicating possible alcohol exposure) in the right ventricular (RV) myocardium, contrast bubbles in LV or RV lumen directly after alcohol injection, indicating possible endocardial alcohol exposure, or difficulty injecting alcohol into the septal branch due to catheter blockage after partial alcohol injection. At the 1-year follow-up, one patient had undergone surgical myectomy, and 13 (9%) patients had undergone reablation. Therefore, seven patients with remaining LVOTO after ASA did not undergo reintervention during the first year after ASA. However, some patients could have undergone reintervention later than 1 year after ASA or their symptoms might have been relieved, as the LVOT gradient could have been reduced.

Elongation of the AML and PML (compared to normal reference range [10]) was observed in most patients in this study, in line with previous studies of patients with HOCM suggesting elongated MVLs as being part of the innate HCM phenotype [10, 16,17,18]. Moreover, we found that BSA-indexed MVLL was significantly longer in women, highlighting a possible persistent functional difference that must be studied further. The pathophysiology of SAM in HOCM comprises an interaction between the hypertrophic morphology, abnormalities in the MV anatomy, and labile hemodynamic derangements, which cause drag forces that are responsible for SAM [2]. As MV abnormalities contribute to LVOT obstruction, septal myectomy may be combined with concomitant MV surgery to reduce SAM or SAM-mediated mitral regurgitation [19]. Several methods have been described, such as AML extension using bovine pericardium, stiffening the leaflet, and enhancing coaptation posteriorly, the “resect-plicate-release” procedure, AML extension, surgical edge-to-edge MV repair, AML retention plasty, or secondary chordal cutting [2, 19]. Septal myectomy with concomitant MV surgery has been shown to be equally safe and successful as isolated myectomy for the treatment of HOCM [20]. Hence, concomitant MV surgery is a possible advantage for surgical approaches during ASA. Freedom from reintervention as well as early and late reduction of LVOT gradient are superior in patients undergoing septal myectomy, although survival is equal in patients undergoing myectomy and ASA [21]. To our knowledge, the correlation between MVLL and outcome after ASA has not yet been shown. In our study, MVLL was not associated with remaining LVOTO at follow-up. AML length was not associated with SAM or mitral regurgitation (at both pre-procedural and follow-up), while patients with elongated AML (> 24 mm) did not have higher invasively measured peak systolic LVOT gradient (either pre- or post-procedural) than patients with AML < 24 mm. This could indicate that the patients in our study would maybe not have benefited from concomitant MV surgery, although this conclusion does not include other possible MV abnormalities. However, interventional treatment options for patients with symptomatic HOCM, with or without mitral regurgitation and/or MVL elongation, should be evaluated carefully to enable the best outcomes for individual patients.

There was no difference in the prevalence of remaining LVOTO at follow-up between women and men; however, the LVOT gradient at the pre-procedural ECHO was significantly higher among women. In addition, women were significantly older at the time of ASA and had a higher prevalence of postoperative complications (i.e., AV blocks) compared with men. This finding was supported by the results of a study by Saravanabavanandan et al., which showed that women were older at the time of intervention, had higher short-term all-cause mortality, as well as a higher incidence of atrioventricular block, permanent PM implantation, and hospital stay after ASA or myectomy, compared to men [22]. These findings suggest that women might be experiencing a more severe disease stage than men at the time of intervention, where they may have a higher risk for postoperative complications due to their late age and advanced disease. Nevertheless, this must be studied further.

This study was performed as a retrospective cohort study among patients diagnosed with HOCM undergoing ASA. One of the strengths of this study was the amount of data collected and reported for all included patients, which facilitated an evaluation with few excluded data points. In addition, the study population had an equal gender distribution, and the number of patients (n = 154) was satisfactory. The study-specific variables (i.e., AML and PML lengths) were measured by two observers according to a previously described methodology and were discussed with the team when necessary. The measurement methodology corresponded with previous studies [7, 9, 17]. A potential limitation could be that the examinations were performed by different examiners which may affect the repeatability of the results. In this study, two patients (equal to 1%) were excluded from the MV-specific measurements due to inadequate ECHO quality. In the pre- and post-procedural examinations, a total of 14 patients (9%) were measured in PLAX view instead of A3C view due to poor visualization, which could have only a limited impact on the results. The ICC values indicated good reliability for BSWT and PML length measurements; however, they showed a more moderate reliability for AML length. AML length can sometimes be problematic to measure, as it can be difficult to identify the transition between leaflet and chordae.

We have also shown that patients with a basal interventricular septum ≥ 23 mm had a lesser reduction of LVOTO after ASA; therefore, they may need a longer follow-up for reevaluation.