0210: Long term follow up of cardiomyopathy in Friedreich Ataxia

Abstract

Friedreich Ataxia (FRDA) is an autosomal recessive cerebellar ataxia, caused by GAA expansion in frataxin gene. Hypertrophic cardiomyopathy is usual in FRDA and cardiac complications are the first cause of death. From 1990 to 2012, we studied 141 patients with genetically confirmed FRDA. Mean age was 30±10y (mean±sd), 54% were female, age at onset 16±8y, disease duration 15±8y and 74% were wheelchair users.Mean length of short GAA expansion was 1,85±0,7Kb and of longer allele 2.6±0.7Kb.Each patient underwent clinical examination, electrocardiogram and echocardiography. 9% had chest pain, 2,8% dyspnea and 9% palpitations. ECG presented T wave abnormalities (88%). 3 patients had atrial fibrillation (AF).LV interventricular septal wall thickness (IVS) was 12±3mm, LV posterior wall thickness (PW) =11±2mm, LV diastolic diameter (EDD) = 43±5mm, LV systolic diameter (ESD) =25±5mm and indexed LV mass (LVMi) =103±31g/m², LV ejection fraction (EF) = 67±7%. News were obtained in 2013, no patient was lost of follow-up. After a median follow up of 12±5y, 16 deaths occurred and 1 patient was transplanted (38±10y). 26 patients (18%) experienced AF (34±10y), 14 (10%) heart failure (36±12y) and 15 (11%) had EF<50% (33±11y). In univariate analysis, the predictors of survival were: short GAA (p<0.0001), age of onset (p=0.0002), ESD (p=0.002), IVS (p=0.0087), EF (p=0.0001) and LVMi (p=0.01). In multivariate analysis, only short GAA (p=0.001), EF (p=0.01) and LVMi (p=0.008) were independent predictors of survival. Short GAA and LVMi remained independent predictors of the first cardiac events in multivariate analysis (p=0.0002, and p=0.0003 respectively). GAA repeats are the best predictors of survival and cardiac events in FRDA patients, but EF and LV mass are also predictors of long term evolution suggesting the importance of cardiac management in Friedreich ataxia.