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

Abstract

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.

Emery–Dreifuss muscular dystrophy: a closer look at cardiac complications

“…In this issue of the European Heart Journal , Cannie and colleagues perform a multi-centre study that aims to fill this gap by comparing the incidence of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF) in both male and female carriers of both EMD and LMNA variants. 5 The study demonstrates that, quite contrary to current thinking, males with pathogenic EMD variants face a risk of MVA comparable with those with pathogenic LMNA variants, with incidence rates of 4.8 and 6.6 per 100 person-years for EMD and LMNA variant carriers, respectively ( P = .49). This finding challenges the existing guidelines, which have primarily advocated for pacemaker implantation as a preventive measure for EMD variant carriers.…”

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Graphical Abstract A comparative overview of current guideline-recommended patient pathways vs. findings by Cannie et al . 5

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