Familial dilated cardiomyopathy: Current challenges and future directions

1Molecular Cardiology Division, Victor Chang Cardiac Research Institute 2Cardiology Department, St Vincent’s Hospital, Darlinghurst 3Faculty of Medicine, University of New South Wales, Kensington; New South Wales, Australia *Corresponding address: Victor Chang Cardiac Research Institute, Darlinghurst, Australia. Email: [email protected] INTRODUCTION Heart failure is a highly prevalent and increasing health problem for the developed and developing worlds. At 40 years of age, the lifetime risk of heart failure is 1 in 5 for both men and women, and despite advances in heart failure therapies, 50% individuals diagnosed with heart failure will die within 5 years [1,2]. Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and is a major cause of heart failure [2]. DCM is a myocardial disorder defined by ventricular chamber enlargement and systolic dysfunction, that can occur as a primary cardiomyopathy or in association with other factors, such as coronary artery disease, infection, autoimmune disorders, alcohol excess, chemotherapeutic drugs or nutritional deficiencies. Like many common cardiovascular disorders, DCM is generally regarded as a complex trait with genetic and acquired (environmental) components [3]. Despite the enormous clinical importance of DCM, surprisingly little is known about its genetic basis. Studies of families in which DCM segregates as a Mendelian trait have been instrumental in deciphering fundamental molecular defects that cause impairment of cardiac contractile function. This group of patients with familial DCM is the subject of this review. Current perspectives on the insights gained from genetics studies of familial DCM, implications for clinical practice, and challenges for clinicians and for researchers will be discussed.