Effect of Mavacamten on reducing sudden cardiac death risk in patients with Obstructive Hypertrophic Cardiomyopathy: an evaluation using the HCM-SCD Risk Score

Abstract Background Hypertrophic Cardiomyopathy (HCM) is a prevalent genetic heart disease associated with heart failure, atrial fibrillation, and sudden cardiac death (SCD) (1). It affects approximately 1 in 500 individuals, with two-thirds of patients experiencing left ventricular outflow tract (LVOT) obstruction, a key determinant of symptoms and clinical outcomes (2). Risk assessment for SCD, commonly using the HCM Risk-SCD Score, is vital for managing the condition (3). Recently, Mavacamten, a selective myosin inhibitor, emerged as the first treatment aimed at addressing HCM’s underlying mechanisms. Clinical trials such as VALOR-HCM and EXPLORER-HCM have demonstrated Mavacamten's efficacy in alleviating symptoms, reducing LVOT obstruction, and minimizing the need for invasive interventions (1). However, its effect on SCD risk remains underexplored. Purpose This study aims to assess changes in the SCD risk as determined by the HCM Risk-SCD Score in patients with hypertrophic cardiomyopathy before and after Mavacamten administration. Methods and Results This investigation was conducted at a high-volume university center specializing in cardiomyopathies in Italy. The study involved nine patients (five males and four females; mean age 61 years) diagnosed with obstructive hypertrophic cardiomyopathy (HCM) according to the ESC guidelines. All participants underwent a comprehensive baseline evaluation, including echocardiography and 24-hour ECG Holter monitoring, followed by reassessments every 4 weeks. The baseline HCM Risk-SCD Score was 2.9±1.6. After a mean treatment duration of 23±2 weeks, the mean HCM Risk-SCD Score decreased to 1.9±1.2, reflecting a significant absolute reduction of 1.0 points (95% CI, 1.13-1.83; p = 0.027) and a relative reduction of 34.14% (95% CI, 12.3-44.78%; p = 0.027) (Figure 1). This improvement was largely attributed to a marked reduction in LVOT obstruction, which showed an absolute decrease of 79.7 mmHg (95% CI, 39.9-119.4; p<0.001) and a relative reduction of 58.76% (95% CI, 34.8-83.7%; p<0.001) (Figure 2). Conclusion Mavacamten therapy is associated with a significant reduction in the HCM Risk-SCD Score in patients with obstructive hypertrophic cardiomyopathy. However, it remains uncertain whether this reduction correlates with a decrease in the 5-year risk of sudden cardiac death. Long-term studies are required to determine whether the observed reduction in the risk score translates into a reduced incidence of mortality events.Figure 1. Figure 2.