Cardiac Arrhythmias in Muscular Dystrophies Associated with Emerinopathy and Laminopathy: A Cohort Study.

Michał Marchel,Marcin Grabowski,Ewa Ostrowska,Agata Tymińska,Vincenzo Russo,Grzegorz Opolski,Agnieszka Madej-Pilarczyk,Roman Steckiewicz,Julia Wysińska

doi:10.3390/jcm10040732

Abstract

Introduction: Cardiac involvement in patients with muscular dystrophy associated with Lamin A/C mutations (LMNA) is characterized by atrioventricular conduction abnormalities and life-threatening cardiac arrhythmias. Little is known about cardiac involvement in patients with emerin mutation (EMD). The aim of our study was to describe and compare the prevalence and time distribution of cardiac arrhythmias at extended follow-up. Patients and methods: 45 consecutive patients affected by muscular dystrophy associated to laminopathy or emerinopathy were examined. All patients underwent clinical evaluation, 12-lead surface electrocardiogram (ECG), 24 h electrocardiographic monitoring, and cardiac implanted device interrogation. Results: At the end of 11 (5.0–16.6) years of follow-up, 89% of the patients showed cardiac arrhythmias. The most prevalent was atrial standstill (AS) (31%), followed by atrial fibrillation/flutter (AF/Afl) (29%) and ventricular tachycardia (22%). EMD patients presented more frequently AF/AFl compared to LMNA (50% vs. 20%, p = 0.06). Half of the EMD patients presented with AS, whilst there was no occurrence of such in the LMNA (p = 0.001). Ventricular arrhythmias were found in 60% of patients with laminopathy compared to 3% in patients with emerinopathy (p < 0.001). The age of AVB occurrence was higher in the LMNA group (32.8 +/− 10.6 vs. 25.1 +/− 9.1, p = 0.03). Conclusions: Atrial arrhythmias are common findings in patients with muscular dystrophy associated with EMD/LMNA mutations; however, they occurred earlier in EMD patients. Ventricular arrhythmias were very common (60%) in LMNA and occurred definitely earlier compared to the EMD group.

Highlights

Laminopathies and emerinopathies are genetic disorders caused by mutations in Lamin A/C mutations (LMNA) and EMD genes, respectively, encoding lamin A/C and emerin—ubiquitous proteins of the nuclear envelope
The study population included 30 patients with Emery–Dreifuss Muscular Dystrophy (EDMD1) and 15 patients with muscular dystrophy associated with mutations in LMNA gene encoding lamin A/C: 12 patients with EDMD2, 2 with LGMD, and 1 with LMNA-related congenital muscular dystrophy (L-CMD)
There were no significant differences in terms of baseline characteristics with the exception of gender, where 73% of LMNA patients were female and 80% of EMD were male (p < 0.001)

Summary

Introduction

Laminopathies and emerinopathies are genetic disorders caused by mutations in LMNA and EMD genes, respectively, encoding lamin A/C and emerin—ubiquitous proteins of the nuclear envelope. Both conditions show a heterogenous clinical presentation characterized by different neuromuscular and cardiac phenotypes. Cardiac involvement in patients with muscular dystrophy associated with laminopathy is typically characterized by atrioventricular conduction abnormalities, life-threatening cardiac arrhythmias, and heart remodeling towards dilated or restrictive cardiomyopathy [1]. The aim of our study was to describe and compare the prevalence and time distribution of cardiac arrhythmias in patients with muscular dystrophies associated with emerinopathy and laminopathy at extended follow-up

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