Cardiac Pathology in Myotonic Dystrophy Type 1

Abstract

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy affecting adults and children, is a multi-systemic disorder affecting skeletal, cardiac, and smooth muscles as well as neurologic, endocrine and other systems. This review is on the cardiac pathology associated with DM1. The heart is one of the primary organs affected in DM1. Cardiac conduction defects are seen in up to 75% of adult DM1 cases and sudden death due to cardiac arrhythmias is one of the most common causes of death in DM1. Unfortunately, the pathogenesis of cardiac manifestations in DM1 is ill defined. In this review, we provide an overview of the history of cardiac studies in DM1, clinical manifestations, and pathology of the heart in DM1. This is followed by a discussion of emerging data about the utility of cardiac magnetic resonance imaging (CMR) as a biomarker for cardiac disease in DM1, and ends with a discussion on models of cardiac RNA toxicity in DM1 and recent clinical guidelines for cardiologic management of individuals with DM1.

Case report: A rare complication after the implantation of a cardiac implantable electronic device: Contralateral pneumothorax with pneumopericardium and pneumomediastinum

“…As a result, these active fixation leads should be implanted cautiously. Anatomic variations, such as multilobed or a thin-walled atrial appendage, fatty infiltration of the myocardium due to myotonic dystrophy, ischemic and dilated cardiomyopathy, are variables that increase the likelihood of atrial perforation ( 10 , 11 , 13 , 15 , 20 , 23 – 29 ).…”

Recent Progress and Challenges in the Development of Antisense Therapies for Myotonic Dystrophy Type 1

“…Indeed, heart diseases are a major cause of sudden death in patients with DM1. First-degree atrioventricular block is the most common conduction disorder and other defects, including bundle branch blocks and prolongation of the QRS interval on surface electrocardiogram (ECG), are frequent with increased disease duration or severity [ 108 ]. Cardiac histopathology features fibrosis, fatty infiltration, and cardiomyocyte hypertrophy.…”

Myotonic Dystrophy: From Molecular Pathogenesis to Therapeutics

“…They include the CRISPR/Cas approach [ 5 , 6 ], as well as the application of small molecules, restoring MBNL1 and CUGBP1 activities or correcting splicing via other RNA-binding proteins [ 7 , 8 , 9 , 10 ]. Although indirectly, several review papers referred to the use of AONs as a potential therapy for DM1 [ 5 , 7 , 8 , 10 , 11 , 12 ].…”

“…While the first attempt to reduce DM1 pathology with the DMPK1 -specific AON in a clinical trial for adult DM1 was not successful due to the low penetration of AON in skeletal muscle, studies on the improvement of this approach continue. More importantly, preclinical studies in DM1 showed that AONs were beneficial not only for the skeletal muscle pathology, but that they could also reduce cognitive defects and reverse cardiac phenotypes [ 12 , 14 , 15 ]. As described in Dr. Mahadevan’s review, which focused on cardiac pathology in DM [ 12 ], the application of the DMPK -specific AON in the preclinical study using a tet-inducible DM1 mouse model, expressing the 3′UTR of DMPK with 200 CUG repeats, reduced skeletal and cardiac muscle deficiencies [ 12 , 15 ].…”

“…More importantly, preclinical studies in DM1 showed that AONs were beneficial not only for the skeletal muscle pathology, but that they could also reduce cognitive defects and reverse cardiac phenotypes [ 12 , 14 , 15 ]. As described in Dr. Mahadevan’s review, which focused on cardiac pathology in DM [ 12 ], the application of the DMPK -specific AON in the preclinical study using a tet-inducible DM1 mouse model, expressing the 3′UTR of DMPK with 200 CUG repeats, reduced skeletal and cardiac muscle deficiencies [ 12 , 15 ]. This paper provides a comprehensive discussion in regard to the cardiac phenotype in DM1 patients, the possible molecular pathogenesis in DM1 hearts and in vivo models to study DM1-linked cardiac deficiency.…”