0454: Long-term cardiac prognosis and risk stratification in 260 adults presenting with mitochondrial diseases

Aims To assess the long-term cardiac prognosis of adults with mitochondrial diseases. Methods and results Between January 2000 and May 2014, we retrospectively included in this study 260 consecutive patients (60% women) ≥18 years of age, (interquartile range [IQR]; 31 to 54), with genetically proven mitochondrial diseases, including 109 with mitochondrial DNA (mtDNA) single large-scale deletions, 64 with the m.3243A>G mutation in MT-TL1, 51 with other mtDNA point mutations, and 36 patients with nuclear genes mutations. Cardiac involvement was present at baseline in 81 patients (30%). Single and multiple variable analyses were performed in search of predictors of major adverse cardiac event (MACE), and hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Over a median follow-up of 7 years [3.6 to 11.7], 27 patients (10%) suffered a MACE, defined as sudden death, death due to heart failure (HF), resuscitated cardiac arrest, 3 rd degree atrioventricular block, sinus node dysfunction, cardiac transplantation, or hospitalization for management of HF. Patients with single large-scale mtDNA deletions or m.3243A>G mutations had the highest incidence of MACE. By multiple variable analysis, intraventricular conduction block (HR=16.9; 95% CI: 7.2 to 39.4), diabetes (HR=7.0; 95% CI: 2.9 to 16.7), premature ventricular complexes (HR=3.6; 95% CI: 1.4 to 9.2) and left ventricular (LV) hypertrophy (HR=2.5; 95% CI: 1.1 to 5.8) were independent predictors of MACE. In patients with 0, 1, and ≥2 risk factors, the incidence of MACE was 1.7, 15 and 42% respectively. Conclusions Patients with mitochondrial diseases are at high risk of MACE, independently predicted by intraventricular conduction block, diabetes, ventricular prematurity and LV hypertrophy.