Background
Prevention of sudden cardiac death is an essential aspect of HCM management. Current ESC/ACC/AHA guidelines recommend estimating 5-year risk with the HCM-SCD calculator and evaluating major clinical risk factors. Mavacamten, a cardiac myosin inhibitor, reduces LVOT gradients, improves exercise capacity, and decreases symptoms in obstructive HCM. Furthermore, a favorable cardiac remodeling was observed, that could potentially lead to reduced cardiovascular events, including ventricular arrhythmias and sudden cardiac death.
Objective
The aim of this study is to investigate the treatment effect of mavacamten on modifiable risk factors for SCD in oHCM and the resulting changes on estimated HCM-SCD risk.
Methods
This retrospective single-center study included adults with symptomatic LVOT obstruction (NYHA II–III), LVOT gradient ≥50 mmHg, and ≥3 months of stable mavacamten after dose titration. Exclusion criteria were ICD, prior septal reduction, therapy interruption, or follow-up at another facility. The following SCD risk factors were assessed at baseline and follow-up: maximal left ventricular wall thickness, left atrial diameter, maximal LVOT gradient and LVEF. The primary endpoint was the change in estimated 5-year HCM-SCD risk. Secondary endpoints included changes in the aforementioned individual risk factors.
Results
A total of 34 patients were included. Mean age was 62 years, 53% were men. All patients were symptomatic: 26 (76%) NYHA II and 8 (24%) NYHA III. At baseline, the mean provoked LVOT gradient was 102 ± 36.4 mmHg, LVEF 72 ± 8.5 %, maximal LV wall thickness 19.7 ± 2.5 mm and LA diameter 47 ± 7.5 mm. Mean estimated HCM-SCD risk at baseline was 2.99 ± 1.4 %, with n=10 (29.4%) patients classified as low risk, n=22 (64.7%) as moderate risk, and n=2 (5.9%) as high risk for SCD. After a mean follow-up of 41 ± 20 weeks, the following changes were observed: mean Δ-LVOT gradient -79 mmHg (102 vs. 21 mmHg, p<0.001), Δ-LVEF -2.47 % (71.6 % vs. 69.2 %, p=0.04), Δ-LV wall thickness -0.4 mm (19.7 vs. 19.2 mm, p = 0.08), and Δ-LA diameter -0.72 mm (47 vs. 46 mm, p = 0.04). Mean Δ-HCM-SCD risk score was -0.94 % (2.99 vs. 1.95 %, p<0.001). At follow-up, 21 (65.6%) patients were classified as low risk, 11 (34.4%) as moderate risk, and none as high risk. Thirteen (54%) initially moderate/high-risk patients shifted to a lower category. During follow-up, no arrhythmic complications, syncopal events, deaths, or ICD implantations for primary or secondary prevention were reported.
Conclusion
Treatment with mavacamten was associated with improvement in modifiable risk factors for SCD in oHCM and a reduction in estimated SCD risk. These findings suggest a potential role for myosin inhibitors in SCD risk modification. Longer treatment duration may reveal additional benefits related to interstitial fibrosis and ongoing reverse remodeling. There remains an unmet need for precise SCD prediction tools in patients treated with mavacamten. The potential antiarrhythmic benefit of cardiac myosin inhibitors should be assessed in larger cohorts with long-term follow-up and integrated rhythm monitoring, followed by external validation.
