The effect of mavacamten therapy on the risk of sudden cardiac death among patients with hypertrophic obstructive cardiomyopathy

Introduction

Hypertrophic cardiomyopathy (HCM) accounts for an increased risk of sudden cardiac death (SCD); thus, the current 2023 ESC Cardiomyopathy Guidelines recommend the regular risk stratification of SCD by using HCM Risk-SCD score model. The effect of cardiac myosin inhibitor therapy on the risk of SCD in hypertrophic obstructive cardiomyopathy (HOCM) patients is not fully uncovered yet.

Aims

To assess the effect of mavacamten therapy on the value of HCM Risk-SCD score in a real-world, consecutive HOCM patient cohort after the initiation of cardiac myosin inhibitor therapy with a 3-month follow-up (FUP) period.

Patients and methods: A retrospective observational single-centre study was conducted in a real-world, consecutive cohort of HOCM patients who were initiated on mavacamten therapy after it became available in the country, between 01.03.2025 and 30.06.2025 and were followed for 3 months. The data of 23 patients were assessed (at baseline: male: 61%, age: 53 [49-67] years, left ventricular ejection fraction [LVEF]: 65 [62-69] %, New York Heart Association [NYHA] functional class: 2 [2-3], NT-proBNP: 739 [415-1797] pg/mL, troponin T: 12 [9-18] ng/L, eGFR ≤ 60 mL/min/1.73m2: 14%, coronary artery disease: 32%, hypertension: 82%, atrial fibrillation: 41%). 100% of the patients were on βB therapy. 24% of the cohort were poor CYP2C19 metabolizers, the median dosage of mavacamten was 5 [5-10] mg at 3 months of FUP. HCM Risk-SCD scores were calculated at baseline (before mavacamten therapy) and at 1-, 2- and 3-month FUP based on current clinical data and transthoracic echocardiographic parameters. The HCM Risk-SCD score values were compared using the Friedman test. The proportion of patients in the different SCD risk categories (low risk [5-year risk <4%], intermediate risk [5-year risk ≥4% and <6%], high risk [5-year risk ≥6%]) at baseline and 3-month FUP was evaluated.

Results

Mavacamten therapy resulted in a significant reduction of LVOTO at rest (73 [35-99] vs. 33 [26-61] vs. 22 [16-36] vs. 18 [14-39] mm Hg, p<0.001; baseline vs. 1 vs. 2 vs. 3 months of FUP, respectively) as well as at provocation (80 [55-96] vs. 70 [50-98] vs. 52 [34-63] vs. 39 [32-69] mm Hg, p<0.001).

The median value of the HCM Risk-SCD scores decreased from 5.0 [3.7-6.6] % before mavacamten therapy to 2.3 [1.7-3.8] % at 3 months on therapy (p<0.001). Before the initiation of mavacamten treatment, 30% of the patients belonged to low-risk-, 40% to intermediate-risk, and 30% to high-risk SCD categories. After 3 months of FUP, 83% of the patients were in the low-risk, 17% were in the intermediate-risk category, while no patients remained in the high-risk SCD category.

Conclusions

Our results suggest that mavacamten therapy can reduce the value of the HCM Risk-SCD scores in HOCM patients within a short, 3-month follow-up time, which might influence the decision-making regarding the primary prevention ICD implantation in light of modern pharmacotherapy in HOCM.For image description, please refer to the figure legend and surrounding text.