Emery-Dreifuss muscular dystrophy Type 1 is associated with a high risk of malignant ventricular arrhythmias and end-stage heart failure

Background and Aims Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterize the cardiac complications of EMD variants.Methods Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidences in male and female variant-carriers were determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared with consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC).Results Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers [mean (SD) ages 33.4 (13.3) and 43.3 (16.8) years, respectively]. Nine (23.7%) males developed MVA and five (13.2%) developed ESHF during a median (inter-quartile range) follow-up of 65.0 (24.3-109.5) months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median (inter-quartile range) age of 58.6 (53.2-60.4) years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank P = .49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank P = .09).Conclusions Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease. Structured Graphical Abstract Graphic depiction of new cardiac disease features demonstrated by this study (top left) with arrows to relevant analyses. Kaplan Meier survival analysis for the primary malignant ventricular arrhythmia endpoint during follow-up for male EMD and male LMNA variant-carriers with a baseline cardiac phenotype (top right). Cardiac disease features at last evaluation for male LMNA, male EMD and female EMD variant-carriers (bottom left). Violin plots comparing age at cardiac diagnosis for male EMD, female EMD and male LMNA variant-carriers (bottom right). Abbreviations: AF, atrial fibrillation; EDMD1, Emery-Dreifuss muscular dystrophy Type 1; ESHF, end-stage heart failure; LVSD, left ventricular systolic dysfunction; MVA, malignant ventricular arrhythmia; NSVT, non-sustained ventricular tachycardia.