Genetics and Clinical Destiny: Improving Care in Hypertrophic Cardiomyopathy

T he greatest opportunity afforded by discovering the genetic basis of human heart disease is accurate prediction and prevention of illness. Hypertrophic cardiomyopathy (HCM) provides a paradigm to fulfill this opportunity. Human genetics research has identified many gene mutations that result in cardiac hypertrophy, of which HCM is the most common and well-characterized. Sarcomere gene mutations in HCM result in left ventricular hypertrophy (LVH), myocardial fibrosis and disarray, diastolic dysfunction, and increased risk for arrhythmias, sudden death, and heart failure. Making the clinical diagnosis of HCM currently hinges on identifying unexplained hypertrophy, but LVH is a sign of established disease only. This finding cannot identify at-risk mutation carriers and cannot discriminate HCM from other forms of cardiac hypertrophy, either genetic or acquired.