Familial Dilated Cardiomyopathy: Cardiac Abnormalities Are Common in Asymptomatic Relatives and May Represent Early Disease

Objectives. This study sought to determine whether early disease is identifiable in asymptomatic relatives of patients with dilated cardiomyopathy (DCM) by means of noninvasive cardiologic assessment. Background. DCM is diagnosed on the basis of advanced heart failure, where cardiac dilation and impaired contractility are recognized in the absence of a recognized etiology (World Health Organization criteria). However, initial clinical presentation may be with severe complications: thromboembolism, arrhythmia or sudden death. DCM has recently been recognized to be familial, with autosomal dominant inheritance in many cases. Familial disease is present in 9% to 20% of patients with DCM, and the ability to identify early disease in such people may improve patient management and aid in the understanding of pathogenesis. Method. We prospectively assessed 408 asymptomatic relatives (mean [±SD] age 35 ± 15 years, 193 men) of 110 consecutive patients with DCM by means of history and physical examination, two-dimensional echocardiography, 12-lead and signal-averaged electrocardiography and metabolic exercise testing. We hypothesized that signs of lesser cardiac dysfunction in such relatives might indicate early disease. Results. Twenty-nine percent of relatives had abnormal results on the echocardiogram. Twenty percent (n = 45) had left ventricular enlargement (LVE), defined as LV end-diastolic diameter (LVEDD) ≥112% predicted; 6% (n = 13) had depressed fractional shortening (dFS), defined as FS ≤25%; and 3% (n = 7) had frank DCM, defined as LV dilation, impaired contractile performance and LVEDD ≥112% plus FS ≤25%. Other abnormalities of cardiac function were identified in relatives with LVE or dFS: A greater number with LVE had an abnormal metabolic exercise test result than normal relatives (9% vs. 1%, p < 0.05). Relatives with LVE and abnormal maximal oxygen consumption (Vo2max) (defined as Vo2max