Mavacamten prolonged the time-to-peak of cardiac contraction (237.7 vs 221.0 ms, p=0.004) and functional refractory period in living myocardial slices from patients with HCM.
Does mavacamten alter the biomechanical response of living myocardial slices from patients with hypertrophic cardiomyopathy compared to verapamil?
Mavacamten reduces hypercontractility and prolongs the functional refractory period in HCM myocardial tissue, suggesting potential benefits in reducing wall stress and protecting against ventricular tachyarrhythmias.
Absolute Event Rate: 237.7% vs 221%
p-value: p=0.004
Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disorder of the heart, but effective treatment options remain limited. Mavacamten, a direct myosin modulator, has been presented as novel pharmacological therapy for HCM. The aim of this study was to analyze the biomechanical response of HCM tissue to Mavacamten using living myocardial slices (LMS). LMS (n = 58) from patients with HCM (n = 10) were cultured under electromechanical stimulation, and Verapamil and Mavacamten were administered on consecutive days to evaluate their effects on cardiac biomechanics. Mavacamten and Verapamil reduced contractile force and dF/dt and increased time-to-relaxation in a similar manner. Yet, the time-to-peak of the cardiac contraction was prolonged after administration of Mavacamten (221.0 ms (208.8 - 236.3) vs. 237.7 (221.0 - 254.7), p = 0.004). In addition, Mavacamten prolonged the functional refractory period (FRP) (330 ms (304 - 351) vs. 355 ms (313 - 370), p = 0.023) and better preserved twitch force with increasing stimulation frequencies, compared to Verapamil. As such, Mavacamten reduced (hyper-)contractility and prolonged contraction duration of HCM LMS, suggesting a reduction in cardiac wall stress. Also, Mavacamten might protect against the development of ventricular tachyarrhythmias due to prolongation of the FRP, and improve toleration of tachycardia due to better preservation of twitch force at tachycardiac stimulation frequencies.
Amesz et al. (Thu,) conducted a other in Hypertrophic cardiomyopathy (HCM) (n=10). Mavacamten vs. Verapamil was evaluated on Time-to-peak of cardiac contraction (p=0.004). Mavacamten prolonged the time-to-peak of cardiac contraction (237.7 vs 221.0 ms, p=0.004) and functional refractory period in living myocardial slices from patients with HCM.