Evaluation of Left Ventricular Enlargement as a Marker of Early Disease in Familial Dilated Cardiomyopathy

Background-Echocardiographic screening of families with dilated cardiomyopathy has identified a subgroup of asymptomatic relatives with left ventricular enlargement (LVE). The prognostic significance of LVE in this setting is incompletely understood. Methods and Results-We evaluated 457 asymptomatic relatives in 128 dilated cardiomyopathy families and identified 110 individuals (24%) with LVE. Serial echocardiograms in 72 untreated LVE relatives showed that 9 individuals (13%) had development of dilated cardiomyopathy over 10 to 152 months (median, 52). Thirty LVE relatives and 30 age- and sex-matched healthy control subjects were evaluated using 2-dimensional and M-mode echocardiography, tissue Doppler imaging, noninvasive pressure-volume assessment, exercise stress echocardiography, and brain natriuretic peptide levels. LVE relatives showed mild defects of systolic and diastolic LV function, with normal filling pressures and exercise-induced increments in systolic contraction in most cases. LV dimensions and fractional shortening most effectively differentiated LVE relatives from control subjects, with other functional indices lacking additive discriminative value. In a receiver operating characteristics analysis, the area under the curve for LV end-diastolic diameter (% predicted) was 0.96 (P<0.001). LV end-diastolic diameter (% predicted) >116% or LV end-diastolic diameter (% predicted) 112% to 116% + fractional shortening <= 29% had high sensitivity (100%) and specificity (93%) for LVE relatives and identified 8 of 9 progressors. Conclusions-LVE is a common finding in asymptomatic relatives in dilated cardiomyopathy families and can be a marker of preclinical cardiomyopathy. Assessment of LV size and contractile function is required for differentiating between pathological and physiological causes of LVE and may help to identify those at risk of disease progression. (Circ Cardiovasc Genet. 2011;4:342-348.)