title: Evaluation of left ventricular enlargement as a marker of early disease in familial dilated cardiomyopathy.
abstract: 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.
  
  
  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.
authors.affiliation: Molecular Cardiology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia. d.fatkin@victorchang.edu.au
authors.forename: Diane
authors.initials: D
authors.lastname: Fatkin
authors.forename: Thomas
authors.initials: T
authors.lastname: Yeoh
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hayward
authors.forename: Victoria
authors.initials: V
authors.lastname: Benson
authors.forename: Angela
authors.initials: A
authors.lastname: Sheu
authors.forename: Zara
authors.initials: Z
authors.lastname: Richmond
authors.forename: Michael P
authors.initials: MP
authors.lastname: Feneley
authors.forename: Anne M
authors.initials: AM
authors.lastname: Keogh
authors.forename: Peter S
authors.initials: PS
authors.lastname: Macdonald
mesh_terms: D000328:Adult; D015415:Biomarkers; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis*; D016022:Case-Control Studies; D003971:Diastole; D018450:Disease Progression; D042241:Early Diagnosis; D004562:Electrocardiography; D005190:Family; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers