Real-world experience on the application of mavacamten therapy among patients with hypertrophic obstructive cardiomyopathy

Introduction

The use of cardiac myosin inhibitor therapy has brought a paradigm shift in the treatment of hypertrophic obstructive cardiomyopathy (HOCM) in accordance with the 2023 ESC Cardiomyopathy Guidelines, as a result of landmark trials.

Aims

To assess the effect of mavacamten therapy on the left ventricular outflow tract obstruction (LVOTO) and relevant clinical parameters in a real-world, consecutive HOCM patient cohort during a 6-month follow-up period (FUP).

Patients and methods: A retrospective observational study was conducted at a tertiary cardiology centre in a consecutive cohort of HOCM patients who were started on mavacamten therapy between 01.03.2025 and 30.06.2025 and followed for 6 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], N-terminal pro-B type natriuretic peptide [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%, atrial fibrillation: 41%). βB medication was administered in 100% of the cohort, and 43% had an ICD implanted. 24% of the patients were poor CYP2C19 metabolisers. Median dose of mavacamten was 5 [5-10] mg at 6 months of FUP.

Baseline (before mavacamten therapy), and 1-, 2-, 3- and 6-month FUP data were evaluated. LVOTO at rest and at provocation, and LVEF changes were assessed using the Friedman test. The effect of mavacamten therapy on clinical parameters (NT-proBNP and troponin T level, six-minute walking test [6MWT], NYHA functional class) were also investigated. Serious adverse events (all-cause mortality, cardiovascular rehospitalisation) were assessed as well.

Results

In the effect of mavacamten therapy, a remarkable reduction was observed in LVOTO at rest (73 [35-99] vs. 33 [26-61] vs. 22 [16-36] vs. 18 [14-39] vs. 17 [8-20] mm Hg, p<0.001; baseline vs. 1 vs. 2 vs. 3 vs. 6 months of FUP, respectively) and at provocation (80 [55-96] vs. 70 [50-98] vs. 52 [34-63] vs. 39 [32-69] vs. 21 [14-29] mm Hg, p<0.001). No significant changes of LVEF were detected (65 [62-69] vs. 65 [61-68] vs. 65 [59-68] vs. 64 [60-65] vs. 62 [58-64] %, p=0.775).

The median NT-proBNP values decreased during adjustment of mavacamten therapy as well (739 [415-1797] vs. 419 [206-858] vs. 247 [160-1007] vs. 284 [177-560] vs. 330 [213-470] pg/mL, p=0.034). In terms of functional capacity (6MWT) a favourable trend was observed (487 [357-556] vs. 525 [413-642] vs. 550 [435-600] vs. 550 [450-600] vs. 543 [431-591] m, p=0.961). NYHA functional class and troponin T levels did not change significantly during FUP. No serious adverse events occurred during FUP.

Conclusions

According to our real-world data, the implementation of mavacamten therapy among HOCM patients led to a remarkable beneficial effect on LVOTO and clinical status and it was detectable even within a short FUP, without any severe adverse event.