Pathophysiology and Treatment of Hypertrophic Cardiomyopathy: New Perspectives

We provide a state of the art of therapeutic options in hypertrophic cardiomyopathy (HCM), focusing on recent advances in our understanding of the pathophysiology of sarcomeric disease.

A wealth of novel information regarding the molecular mechanisms associated with the clinical phenotype and natural history of HCM have been developed over the last two decades. Such advances have only recently led to a number of controlled randomized studies, often limited in size and fortune. Recently, however, the allosteric inhibitors of cardiac myosin adenosine triphosphatase, countering the main pathophysiological abnormality associated with HCM-causing mutations, i.e. hypercontractility, have opened new management perspectives. Mavacamten is the first drug specifically developed for HCM used in a successful phase 3 trial, with the promise to reach symptomatic obstructive patients in the near future. In addition, the fine characterization of cardiomyocyte electrophysiological remodelling has recently highlighted relevant therapeutic targets. Current therapies for HCM focus on late disease manifestations without addressing the intrinsic pathological mechanisms. However, novel evidence-based approaches have opened the way for agents targeting HCM molecular substrates. The impact of these targeted interventions will hopefully alter the natural history of the disease in the near future.