The development of familial hypertrophic cardiomyopathy: from mutation to bedside

Hypertrophic cardiomyopathy (HCM) is a familial disorder characterized by left ventricular hypertrophy in the absence of other cardiac or systemic disease likely to cause this hypertrophy. HCM is considered a disease of the sarcomere as most causal mutations are identified in genes encoding sarcomeric proteins, although several other disorders have also been linked to the HCM phenotype. The clinical course of HCM is characterized by a large inter- and intrafamilial variability, ranging from severe symptomatic HCM to asymptomatic individuals. The general picture emerges that the underlying pathophysiology of HCM is complex and still scarcely clarified. Recent findings indicated that both functional and morphological (macroscopic and microscopic) changes of the HCM muscle are present before the occurrence of HCM phenotype. This review aims to provide an overview of the myocardial alterations that occur during the gradual process of wall thickening in HCM on a myofilament level, as well as the structural and functional abnormalities that can be observed in genetically affected individuals prior to the development of HCM with state of the art imaging techniques, such as tissue Doppler echocardiography and cardiovascular magnetic resonance imaging. Additionally, present and future therapeutic options will be briefly discussed.