Discussion
HCM, LVOTO, fibrosis, myocardial disarray, myosin, cardiac disease, heart failure, Hypertrophic cardiomyopathy
DISEASE, FIBROSIS, CARDIAC DISEASE, HEART FAILURE, HYPERTROPHIC CARDIOMYOPATHY
A research colony of mixed-breed Maine Coon cats with the A31P Hypertrophic cardiomyopathy is the most prevalent inherited cardiac disease in humans with an estimated incidence of up to 1:500 (0.2%) in the general populationThe identification and treatment of LVOTO is important in humans with oHCM as it likely contributes to symptoms and is an independent predictor of progression to severe symptoms of heart failure and deathThe development of novel cardiac myosin inhibitors is a unique and promising new frontier for targeted therapies in affected individuals and may improve clinical signs as well as prevent deleterious effects of abnormal actin and myosin interactions, leading to reduced histopathologic changes and delayed progression of disease. A study in mice with HCM demonstrated the ability of another small molecule inhibitor, mavacamten, to significantly reduce the hallmark histopathologic features of fibrosis and myocardial disarray when administered prior to the development of significant hypertrophySafety and tolerability of Our study also demonstrates the plasma concentrations of Several limitations to this study exist. There is the possibility of type II error given the small sample size of eight cats. The temperament of the colony cats and drug administration by oral gavage requires significant sedation which may impact functional parameters. To minimize these effects, a three-hour recovery period was allowed following sedation with alfaxalone for oral gavage and a standardized sedation protocol (butorphanol and acepromazine) that previously demonstrated minimal effects on echocardiographic variables was used for each echocardiographic evaluationThe development of novel small molecule inhibitors is an exciting frontier for the advancement of therapeutic options in the management of preclinical HCM; the current study further highlights the utility of this feline model in evaluation of novel therapies that may benefit the human population. Based on the current study, the optimal dose of 