The objective of this project is to better understand the familial occurrence and pathogenesis of idiopathic dilated cardiomyopathy (IDC). Specifically, the aims are 1) to determine the proportion of familial cases of IDC, 2) to determine if there is familial clustering of atrial natriuretic peptide (ANP) levels and/or echocardiographic indices that reflect cardiac structure and function, regardless of whether or not other family members have disease, and 3) to determine for those indices that cluster in families if genes or environment play a role in the observed familial clustering. Previous data in a retrospective study by the investigators suggest that greater than or equal to 6% of patients will have clinically evident familial disease. The index cases of the study population will consist of 100 patients, in whom the diagnosis has been made by echocardiography or cardiac catheterization. Medical histories of 1st degree relatives will be obtained; these relatives will be studied by electrocardiography and M-mode, 2-dimensional, and Doppler echocardiography and will have levels of ANP determined. Each of the 4 cardiac valves will be inspected by Doppler echocardiography. Severity of regurgitation will be estimated by standard Doppler techniques including spatial mapping and color-flow analysis. Statistical analysis of ANP levels and echocardiographic data (e.g., ejection fraction, left ventricular fractional shortening, ventricular septum excursion, posterior wall excursion) will provide estimates of the contribution to variability in these data of both measured (those reflecting or indexing an individual's characteristics and environment) and unmeasured sources of variability (genetic, environment shared by individuals and environment specific to individuals). First, the contribution of variability in age, sex, drug use, smoking, and other concomitants to variability in ANP and echocardiographic data will be estimated. After removing these sources of variability in age, sex, drug use, smoking, and other concomitants to variability in ANP and echocardiographic data will be estimated. After removing these sources of variability, the strength of similarity among family members will be assessed. Finally, the relative contributions of genes and shared environments to the similarity among family members will be estimated. Heterogeneity in the mean levels of echocardiographic indices and ANP levels, familial aggregation and etiology of aggregation will be assessed between families with familial IDC and families with nonfamilial IDC. Identification of the sources of variability of ANP levels and echocardiographic variables of cardiac structure and function will be relevant for cardiac diseases other than IDC.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Epidemiology and Disease Control Subcommittee 2 (EDC)
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Mayo Clinic, Rochester
United States
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Theis, Jeanne L; Sharpe, Katharine M; Matsumoto, Martha E et al. (2011) Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy. Circ Cardiovasc Genet 4:585-94
Michels, V V; Moll, P P; Rodeheffer, R J et al. (1994) Circulating heart autoantibodies in familial as compared with nonfamilial idiopathic dilated cardiomyopathy. Mayo Clin Proc 69:24-7
Michels, V V; Moll, P P; Miller, F A et al. (1992) The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med 326:77-82