Genetic Testing For Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is a disease that has grown more fascinating as new diagnostic and therapeutic tools have emerged over the last 50 years. In the early 20th century, HCM was a pathological entity. Subaortic obstruction was described at the outset but was only documented in patients after the advent of cardiac catheterization; it was first coined as "idiopathic hypertrophic subaortic stenosis" (IHSS) until the breakthrough of echocardiography revealed the broader phenotype. The nature of the outflow tract gradient as either dynamic or true mechanical obstruction was for years the subject of hot debate.Today HCM is considered a primary disease of the myocardium characterized by cardiac hypertrophy in the absence of a discernible clinical cause, such as hypertension or valvular heart disease.1 Typically, the left ventricle is hyperdynamic and has a small cavity size. The prevalence of HCM is at least 1:500 in the younger population,2 although it is likely to be higher in older individuals because of age-dependent expression of the disease. Early descriptions recognized sudden cardiac death (SCD) as a major clinical manifestation of HCM. While it remains the primary concern of physicians and patients, the development of internal defibrillators has provided a means to deal with this tragic event.The first series of surgeries for HCM were performed and refined about 40 years ago. The Moro procedure for septal myectomy became the standard surgical therapy for obstructive HCM. Advances in percutaneous techniques led to percutaneous septa! ablation, commonly performed by injecting alcohol into the main septal branches of the left anterior descending coronary artery. Its widespread use has led to ongoing debates about the superiority of surgical myectomy versus alcohol septal ablation, yet this debate remains unsettled due to the lack of large-scale randomized studies.While a familial form of HCM was recognized in the mid-20th century, the molecular genetic basis of HCM was revealed only in the last two decades with the development and application of modern molecular genetic techniques. Today, one of the most common questions asked by both physicians and patients centers around the availability and utility of genetic testing to diagnose and predict the risk of SCD.