Safety and efficacy of mavacamten compared to alcohol septal ablation in hypertrophic obstructive cardiomyopathy in a retrospective real-world cohort

Background

In hypertrophic obstructive cardiomyopathy (HOCM), the advent of new treatment options, such as the cardiac myosin-inhibitor mavacamten, on top of established invasive septal reduction therapies has altered guideline recommendations for the treatment of left ventricular outflow tract obstruction (LVOTO). So far, there is limited data comparing safety and efficacy of pharmacological therapy with mavacamten to alcohol septal ablation (ASA).

Purpose

In this retrospective single-center analysis of a real world HOCM cohort, we investigated safety and efficacy of mavacamten compared to ASA after 12 and 48 weeks.

Methods

We performed a single-center cross sectional analysis of patients with HOCM who were either treated with mavacamten or ASA in our university hospital between 2017 and 2025. Baseline characteristics and follow-up data including efficacy outcomes and safety events after 12 and 48 weeks were collected from medical chart review. Echocardiographic analyses were performed using the post-processing software TomTec.

Results

In the overall cohort of 49 HOCM patients, 24 were treated with mavacamten and 25 patients with ASA. Both cohorts were overall comparable in terms of baseline characteristics as gender (49% women in the mavacamten group; 36% in the ASA group), age (59 ± 13 vs. 60 ± 12 years), NT-proBNP (519 [283, 1462] vs. 729 [329, 2079] pg/mL), and LVOT gradients (resting 24 [17, 50] vs. 33 [20, 69]; provoked 89 [57, 109] vs. 86 [64, 124] mmHg) (Table 1).

In both treatment groups resting and provoked LVOT gradient and NT-proBNP decreased after 12 and 48 weeks. Absolute changes after 12 and 48 weeks were overall comparable between treatment groups (Table 2). One patient in the ASA group had to undergo a repeat ASA due to persistent LVOTO after the first intervention, and one patient in the mavacamten group was switched to treatment with myectomy due to drug incompliance.

In terms of safety, in the ASA cohort five patients suffered from complications (18%) with four patients receiving a pacemaker due to postinterventional complete atrioventricular block and one patient suffering from postinterventional pulmonary embolism despite anticoagulation. In comparison, in the mavacamten cohort only in one patient (0.4%) treatment had to be stopped due to an LVEF drop below 50% (p=0.091).

Additionally during the 48 weeks follow-up, two patients in the ASA group were diagnosed with new onset atrial fibrillation (AF), and two patients in the mavacamten group had to be hospitalized due to tachycardic episodes of AF.

Conclusions

In this single-center retrospective analysis, treatment with mavacamten was overall comparable to ASA in terms of efficacy, while there was a trend toward more common treatment-related complications in the ASA group, yet not reaching statistical significance. Future multi-center studies are warranted to confirm our results in larger HOCM cohorts and assess long term follow-up of those patients.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.