Non-invasive evaluation of left ventricular hemodynamic force abnormalities in hypertrophic cardiomyopathy: Implications for myosin inhibition

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by abnormal myocardial mechanics, with or without left ventricular outflow tract obstruction (LVOTO). Myosin inhibitors such as mavacamten have shown clinical efficacy in reducing obstruction, but their effects on left ventricular hemodynamic forces (HDF)-a novel marker of myocardial function-are not yet defined. This study aimed to characterize left ventricular HDF patterns in patients with obstructive (oHCM) and non-obstructive (noHCM) HCM compared to healthy controls, and to evaluate the impact of long-term mavacamten therapy on HDF parameters in oHCM. METHODS: We retrospectively analyzed 40 HCM patients (20 oHCM, 20 noHCM) and 20 age- and sex-matched healthy controls. HDF parameters were quantified using echocardiographic strain imaging software (Qstrain, Medis Medical Imaging Systems). Parameters included systolic and diastolic force amplitudes and time indices. Six oHCM patients receiving mavacamten were assessed at baseline and after three years of therapy. RESULTS: Compared to controls, HCM patients had significantly reduced systolic time to peak (p < 0.001) and diastolic-systolic transition time (p < 0.001), indicating premature systolic thrust and impaired relaxation. Diastolic force amplitude was significantly lower in oHCM than noHCM (p < 0.001). Mavacamten treatment in oHCM patients significantly prolonged diastolic-systolic transition (p = 0.030) and restored longitudinal force dynamics (p = 0.031), suggesting improved mechanical coordination and reduced LVOTO. CONCLUSIONS: HDF analysis identifies distinct mechanical impairments in HCM regardless of obstruction status. Mavacamten favorably modulates HDF, delaying systolic thrust initiation and normalizing force distribution, offering new mechanistic insights into its therapeutic action in HCM.