Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiomyopathy in both humans and cats, yet there are few preclinical pharmacological studies exploring interventions. Small-molecule sarcomere inhibitors present promising new therapeutic options for managing obstructive HCM (oHCM), demonstrating efficacy in alleviating left ventricular outflow tract obstruction (LVOTO). This study aimed to investigate the pharmacodynamic effects of the cardiac myosin inhibitor CK-586 at 6, 24, and 48 hours in six purpose-bred cats with naturally occurring oHCM. We conducted a blinded, randomized, crossover preclinical trial with five treatment groups to evaluate CK-586′s pharmacodynamic effects in this oHCM model. We assessed dose-response relationships and select echocardiographic variables five times over a 48-hour period. Oral administration of CK-586 safely reduced LVOTO in oHCM cats. Treatment resulted in a dose-dependent decrease in obstruction (lowered LVOTOmaxPG), an increase in systolic chamber size (LVIDs Sx), and a reduction in select heart function metrics (LV FS% and LV EF%) without affecting heart rate. At all administered doses, a single oral dose of CK-586 improved or resolved LVOTO, with well-tolerated, dose-dependent reductions in left ventricular systolic function. These findings suggest that CK-586 may have potential applications in both veterinary and human clinical settings.