Idiopathic Dilated Cardiomyopathy

BACKGROUND:

In 1987 idiopathic dilated cardiomyopathy was a disorder of unknown cause that directly affected one or both cardiac ventricles in a diffuse or multifactorial fashion, and that produced heart failure, at least in some patients. Although a viral etiology had been proposed, dilated cardiomyopathy could be associated with numerous genetic and non-genetic diseases. However in 1987, the role of genetic factors was not known in humans. Although the condition was usually dismissed as sporadic, numerous families with multiple affected members have been observed.

The role of atrial natriuretic peptide levels in the pathogenesis or progression of idiopathic dilated cardiomyopathy was just beginning to be explored in 1987. Although Syrian hamster studies did not suggest a genetic deficiency as the primary cause of dilated cardiomyopathy in that model, it was thought possible that ANP production or levels were somehow involved in how the myocardium responds in idiopathic dilated cardiomyopathy patients.

DESIGN NARRATIVE:

Eligible patients were interviewed and asked whether any first-degree relatives were willing to participate. If family members participated, a three generation pedigree was constructed and first-degree relatives contacted. The relatives were interviewed for a medical history and medical records from other institutions were reviewed. Each family member had a brief cardiovascular examination, a 12-lead electrocardiogram and 2-dimensional, M-mode, and Doppler echocardiogram. Blood was drawn for determination of atrial natriuretic peptide (ANP) levels. The contributions of variability in age, sex, drug use, smoking, and other concomitants to variability in ANP and echocardiographic data were estimated. After removing these sources of variability, the strength of similarity among family members was assessed. The relative contributions of genes and shared environments to the similarity among family members were estimated.