ABSTRACT
Cardiomyopathies are primary disorders of the myocardium that are classified as dilated, hypertrophic, or restrictive, according to the changes produced in cardiac morphology and physiology. Cardiomyopathy is an important cause of heart failure, and the most common diagnosis in patients referred for cardiac transplantation. Both adverse clinical outcomes and diminished survival from cardiomyopathy have provided considerable anatomical and histopathological information about these disorders over the past several decades. In concert with hemodynamic profiling, investigations have defined profound structural remodeling and functional changes that reflect both adaptive and maladaptive responses to triggers of cardiomyopathy. While such studies have defined natural history and provided important insights that shape management, these data have yielded few insights into the causes of primary cardiomyopathies. However, with the recognition of familial incidence and the delineation of Mendelian patterns of transmission of primary cardiomyopathies, the strategies used to study these intriguing disorders shifted from pathophysiology to human molecular genetics. Definition of autosomal dominant, recessive and X-linked inheritance of cardiomyopathies has fostered genome-wide mapping studies and, more recently, the discovery of cardiomyopathy genes. This productive line of research has caused a fundamental change in conventional paradigms about human cardiomyopathies: these ‘idiopathic’ disorders are now recognized as resulting from heritable gene mutations.
