Heart failure is the only major cardiovascular diagnosis increasing in incidence and prevalence in the U.S., and it affects more than two million citizens. Heart failure causes a great deal of morbidity, carries a high mortality rate and consumes considerable health care resources. Heart failure is the single most expensive diagnosis related group (DRG 127) in the Health Care Financing Administration (HCFA) Medicare budget (1992 data), due in substantial part to the high incidence and prevalence of heart failure in aging Americans. Despite this accelerating and costly public health problem, two decades of intensive basic and clinical investigations have not yielded a unifying pathophysiological concept, and the underlying molecular mechanisms of heart failure are still unknown. The most common type of heart failure is dilated cardiomyopathy, and one common form is idiopathic dilated cardiomyopathy (IDC). It has recently been shown that 20-30% of patients with IDC have family members similarly affected. This condition, termed familial dilated cardiomyopathy (FDC), suggests that an underlying molecular mechanism may be involved. Indeed, four groups have recently reported linkage in large families with FDC, suggesting that FDC is likely a genetic disease. The application suggests that identification of a disease-associated gene could provide a significant improvement of understanding the mechanisms of heart failure. Since 1993, the Oregon Health Sciences University (OHSU) has prospectively identified numerous families with FDC. The application suggests that the selection of three large pedigrees would be useful for clinical and gene mapping studies. The Specific Aims of this project are to: 1) perform extensive clinical screening and characterization of OHSU FDC-3, a very large African-American family with dilated cardiomyopathy, using echocardiographically-derived left ventricular dimensions to classify members as affected or non-affected. To date, no other African-American family has been characterized with FDC. Black Americans demonstrate considerable excess cardiovascular mortality and have traditionally been underrepresented in clinical research; and 2) map the gene or genes responsible for FDC in OHSU families FDC-1, FDC-2 and FDC-3. Preliminary data suggest that OHSU FDC-1 links to neither of the recently reported cardiomyopathy chromosomal locations, suggesting that an additional locus for FDC is present.