Abstract 15318: Arrhythmogenic Left Ventricular Cardiomyopathy: Familial versus Sporadic Forms
BACKGROUND: Genetically proven arrhythmogenic left ventricular cardiomyopathy (ALVC) has been rarely reported. We further investigated the pathogenesis and the clinico-genetic profile of ALVC in a consecutive series of probands and their relatives.
METHODS: The study population included 80 individuals: 27 index cases with ventricular arrhythmias of LV origin and 53 family members. Besides routine cardiovascular evaluation, all probands underwent contrast enhanced-cardiac magnetic resonance (CE-CMR), electrophysiologic study, cardiac catheterization and endomyocardial biopsy (EMB) for histologic and immunohistochemical analysis of desmosomal proteins, and screening for desmosomal gene (PKP2, DSP, DSG-2, DSC-2, JUP) mutations.
RESULTS: The 27 probands (18 males; age 39±12 yrs) showed T-wave inversion in inferior (n=4), lateral (n=9) or infero-lateral leads (n= 14) and ventricular arrhythmias with a right bundle branch block morphology such as sustained ventricular tachycardia (VT) (n=11), nonsustained VT (n=7) or frequent isolated/coupled premature ventricular beats (n=9).Low QRS voltages on frontal leads and late potentials were recorded in 14 cases (52%). Echocardiography showed wall motion abnormality of the LV infero-lateral wall, with no or mild global LV dilatation and dysfunction (LVEDV=71±4ml/m2 and LVEF=52±4%). In all probands, CE-CMR demonstrated a large (≥3 segments) LV myocardial scar as subepicardial late gadolinium enhancement (LGE), which distinctively involved the mid-apical, infero-lateral LV. On EMB, neither histologic evidence of myocarditis and sarcoidosis nor immunohistochemical abnormality of desmosomal proteins were found. The disease phenotype was non-familial and unrelated to desmosomal gene defects in all but 4 probands, who had positive family screening and plakophilin-2 gene mutation. Over a follow-up of 35±7 months, 6 probands (25%) received an implantable defibrillator, because of aborted sudden death in 2.
CONCLUSIONS: ALVC is an emerging cause of arrhythmic cardiac arrest in young people with LV arrhythmias and distinctive infero-lateral LV LGE. Phenotype of familial ALVC overlaps with that of more common (85%) sporadic variants featuring an acquired inflammatory heart disease.
- © 2011 by American Heart Association, Inc.