Comprehensive cardiovascular magnetic resonance for evaluating structural myocardial changes in patients with hypertrophic obstructive cardiomyopathy treated with the first myosin inhibitor

Background

Mavacamten is the first myosin inhibitor causally targeting pathogenesis in sarcomeric hypertrophic obstructive cardiomyopathy (HOCM), showing promising outcomes in reducing LVOT gradients and enhancing exercise capacity. Despite these functional improvements, results on its effects on myocardial structure assessed by cardiovascular magnetic resonance (CMR) are lacking. This study aims to evaluate the one-year structural effects of mavacamten assessed by comprehensive CMR examinations.

Methods

This ongoing prospective study investigates the treatment effects of mavacamten in HOCM patients at a tertiary centre, where all included participants undergo comprehensive contrast-enhanced 1.5 T-CMR at baseline and one-year follow-up. Patients are treated following current guideline recommendations with negative inotropic therapy as tolerable and in case of persistent symptoms and LVOT gradient with additional specific treatment with mavacamten. One-year changes in key parameters, including left and right ventricular ejection fraction (LVEF/RVEF), cardiac index (CI), LV mass, global longitudinal strain (GLS), late gadolinium enhancement (LGE, %), native T1 mapping, and extracellular volume (ECV) are compared between patients with and without (control group) mavacamten.

Results

To date, 19 patients have been enrolled (mean age 59.0 ± 12.0 years, 73.6% male). Mavacamten therapy was initiated in 11/19 patients (58%). Compared to the control group, patients treated with mavacamten showed a significantly greater reduction in LV mass index (-28.0 g/m² [95% CI -43.4 to -12.6] vs. +3.4 g/m² [95% CI -2.4 to +9.1], p=0.004) and in left atrial (LA) volume index (-15.5 mL/m² [95% CI -2.7 to -28.3] vs. +4.2 mL/m² [95% CI -6.4 to +14.8], p=0.008). Moreover, in the mavacamten group, there was a significant reduction in LVEF (79.3 ± 4.8% to 70.5 ± 8.8%, p=0.029), RVEF (48.3 ± 7.4% to 42.5 ± 6.0%, p=0.011), and CI (3.0 ± 0.8 to 2.5 ± 0.7 L/min/m², p=0.020) at follow-up. In contrast, the control group showed stable LVEF and RVEF and a significant increase in CI (LVEF: 76.1 ± 11.2% to 76.3 ± 12%, p=0.724; RVEF: 49.4 ± 6.8% to 52.1 ± 8.8%, p=0.192; CI: 2.0 ± 0.5 to 2.4 ± 0.6 L/min/m², p=0.012). GLS of both LV and RV showed no significant changes over time within or between groups (GLS LV: +3.34 [95% CI +10.0 to -3.3] vs. -0.8 [95% CI -2.4 to -0.8] %, p=0.457; GLS RV: +5.3 [95% CI +10.2 to +0.4] vs. +1.6 [95% CI +7 to -4.1] %, p=0.409).

Regarding parameters of myocardial fibrosis, the mavacamten group demonstrated a significant reduction in global myocardial native T1 (1040.1 ± 23.2ms vs. 1010.9 ± 36.0ms, p=0.016) and LGE extent (9.1 ± 6.0% to 8.8 ± 6.0%, p=0.017) while ECV remained unchanged (25.0 ± 2.9% vs. 28.2 ± 5.0%, p=0.151). In contrast, all parameters remained unaltered in the control group (T1 mean: 1009.2 ± 40.5ms vs. 997.0 ± 39.0ms, p=0.33; LGE: 18.1 ± 25.6% to 18.1 ± 25.5%, p=0.774; ECV: 27.7 ± 6.9% vs. 29.3 ± 6.9%, p=0.171).

Conclusion

Myosin inhibitor therapy favourably affects structural remodelling by reducing LV mass and left LA size. While LVEF and CI decrease, the preservation of GLS suggests maintained regional systolic performance during myosin inhibition. Additionally, our findings indicate the potential of a minor reduction in fibrosis, a finding which requires a larger cohort to validate these effects.