External validation of risk factors for malignant ventricular arrhythmias in lamin a/c mutation carriers

Abstract

International recommendations state that implantable cardiovertor defibrillator should be considered early in patients with a confirmed disease-causing LMNA mutation with clinical risk factors, especially in the presence of non-sustained ventricular tachycardia, LVEF < 45%, male sex or non-missense mutations. The prognostic model derived from these recommendations hasn’t been validated on a separate external sample of patients. To evaluate the performance of the 4 prognosis factors on a separate external cohort of LMNA patients. We identified 101 consecutive LMNA mutation carriers who have been managed and genotyped in our center between 2004 and 2015. We recorded for all patients the values of the 4 previous identified predictive factors and whether they experienced a malignant ventricular aarhythmia (MVA) or not. The mean follow-up was 4.7 years. MVA was oberserved in 16 patients. Four risk groups were defined from the four previous predictive factors and log-rank test showed statistical significance ( P < 0,001) of MVA occurrence rates between groups (See Fig. 1 ). The 4 risk factors (non-sustained ventricular tachycardia, LVEF < 45%, male sex and non-missense mutations) derived from a previous work showed good performance on predicting malignant ventricular arrhythmia on an external cohort. Further studies are needed to identify other potential risk factors that could be even more accurate to predict sudden cardiac death.