Current and emerging perspectives on pathophysiology, diagnosis, and management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetically inherited cardiomyopathy with an autosomal dominant inheritance pattern. A disease-causing gene is found between 34% and >60% of the times and the two most frequently mutated genes, which encode sarcomeric proteins, are MYBPC3 and MYH7. HCM is a diagnosis of exclusion since secondary causes of left ventricular hypertrophy should first be ruled out. These include hypertension, aortic stenosis, infiltrative disease, metabolic and endocrine disorders, mitochondrial cardiomyopathies, neuromuscular disorders, malformation syndromes and some chronic drug use. The disease is characterized by great heterogeneity of its clinical manifestations, however diastolic dysfunction and increased ventricular arrhythmogenesis are commonly seen. Current HCM therapies focus on symptom management and prevention of sudden cardiac death. Symptom management includes the use of pharmacological agents, elimination of medication promoting outflow track obstruction, control of comorbid conditions and invasive procedures, whereas in the prevention of sudden cardiac death, implantable cardiac defibrillators and antiarrhythmic drugs are used. A targeted therapy for LVOTO represented by allosteric cardiac myosin inhibitors has been developed. In terms of sport participation, a more liberal approach is recently recommended, after careful evaluation and common-shared decision. The application of the current therapies has lowered HCM mortality rates to <1.0%/year, however it appears to have shifted focus to heart failure and atrial fibrillation, as the predominant causes of disease-related morbidity and mortality and, therefore, unmet treatment need. With improved understanding of the genetic and molecular basis of HCM, the present decade will witness novel treatments for disease prevention and modification.