Hypertrophic cardiomyopathy: Perspectives of drug therapy

Background. Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. Aim. So far, no medical treatment has reliably shown to halt or reverse progression of HCM or to alleviate its symptoms. While the angiotensin receptor neprilysin inhibitor sacubitril/valsartan has shown to reduce mortality and hospitalization in heart failure with reduced ejection fraction, data on its effect on HCM are sparse. We sought to explore the effect of sacubitril/valsartan on exercise tolerance (ie, peak oxygen consumption) in patients with nonobstructive HCM compared to the optimal standard therapy (control group). Methods. The study presented is a part of SILICOFCM - a prospective, multicenter, open-label, randomized, controlled, three-arm clinical trial (NCT03832660) that will recruit 240 adult patients with a confirmed diagnosis of nonobstructive HCM. However, this study included only 41 patients from a single center. Eligible patients are randomized to sacubitril/valsartan, or optimal standard therapy alone (control group). The primary endpoint is the change in functional capacity (ie, peak oxygen consumption). Results. The study included 41 patients assigned to intervention group (29 patients) and control (12 patients). Mean age was 60.0±10.4 years, and majority of patients were male (73.2%). Left ventricular wall thickness measured at interventricular septum and posterolateral wall was 17.3±4.3 mm and 15.6±3.5 mm, respectively. Baseline peak VO2 was 14.0±4.4 ml/kg/min and VE/VCO2 28.1±6.4. After 4 months follow-up, the intervention group expressed an increase in VO2 from 14.4 ml/kg/min to 16.4 ml/kg/min (p=0.016). The value of VE/VCO2 decreased from 26.6 to 25.8 in the intervention group, while in the control group it changed from 26.0 to 30.9. The value of VE/VCO2 after 4 months follow-up was significantly lower in the intervention group (25.8±5.3 vs 30.9±4.9; p=0.050). Conclusion. The results of the present study suggest that, despite the relatively short treatment period of 4 months, sacubitril/valsartan treatment can have positive effects functional capacity in patients with HCM. These results, together with the rest of the SILICOFCM study outcomes, will hopefully contribute to the optimization of the HCM management.