scholarly journals Paradoxical Cardiac Conduction during Exercise Stress Testing in Myotonic Dystrophy Type 1: A Case Report

2021 ◽  
Author(s):  
Suliman Ahmad ◽  
Peter Kabunga
Keyword(s):  
Myotonic Dystrophy ◽  
Stress Testing ◽  
Exercise Stress ◽  
Cardiac Conduction ◽  
Exercise Stress Testing ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Conduction Abnormalities ◽  
Asymptomatic Patients

Abstract Background Exercise stress testing identifies functional abnormalities that may manifest only during physiologic stress to the heart. This may have significant prognostic value in identifying latent conduction abnormalities in asymptomatic patients with Myotonic dystrophy type 1, who may benefit from prophylactic PPM implantation. Case report We report the case of a patient with Myotonic dystrophy type 1 with a 5-month history of atypical left sided chest pain. Her baseline ECG showed sinus rhythm and variable PR interval prolongation (206 to 220 ms) without symptoms of cardiac conduction disease. Routine blood tests and cardiac investigations including a 24-hour ECG monitoring, echocardiogram and a cardiac MRI scan, revealed no abnormalities. To investigate her chest pain and to determine the need for prophylactic permanent pacemaker implantation, exercise stress testing and an electrophysiological study were performed. Exercise testing revealed minimal PR shortening (PR = 200ms) at peak exercise and paradoxical PR prolongation (PR = 280ms) during the early recovery period. A prophylactic DDDR permanent pacemaker was implanted following an electrophysiological study that revealed a prolonged HV interval of 84 ms. Discussion and Conclusion The current use of annual ECG and 24 Holter monitoring may not adequately detect abnormal cardiac conduction in asymptomatic patients with Myotonic dystrophy type 1. The invasive nature of electrophysiology studies limits its use as a screening tool for conduction abnormalities in asymptomatic patients. Thus, exercise stress testing could be used to identify underlying conduction abnormalities in Myotonic dystrophy type 1 patients without any specific symptoms of bradycardia, which warrant further invasive electrophysiological studies.

scholarly journals Author response: Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1

2019 ◽  
Author(s):  
Emilie Auxerre-Plantié ◽  
Masayuki Nakamori ◽  
Yoan Renaud ◽  
Aline Huguet ◽  
Caroline Choquet ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Cardiac Conduction ◽  
Author Response ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

scholarly journals Mexiletine in myotonic dystrophy type-1

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011002
Author(s):  
Chad Heatwole ◽  
Elizabeth Luebbe ◽  
Spencer Rosero ◽  
Katy Eichinger ◽  
William Martens ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Cardiac Conduction ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Walk Distance ◽  
Hand Grip ◽  
Minute Walk Distance ◽  
Minute Walk

ObjectiveTo assess mexiletine's long-term safety and effect on 6 minute walk distance in a well-defined cohort of myotonic dystrophy type-1 (DM1) patients.MethodsWe performed a randomized, double-blind, placebo-controlled trial of mexiletine (150 mg 3 times daily) to evaluate its efficacy and safety in a homogenous cohort of adult ambulatory DM1 patients. The primary outcome was change in 6-minute walk distance at 6 months. Secondary outcomes included changes in hand grip myotonia, strength, swallowing, forced vital capacity, lean muscle mass, Myotonic Dystrophy Health Index scores, and 24-hour Holter and EKG results at 3 and 6 months.ResultsForty-two participants were randomized and 40 completed the 6-month follow-up (n = 20 in both groups). No significant effects of mexiletine were observed on 6-minute walk distance, but hand grip myotonia was improved with mexiletine treatment. There were no differences between the mexiletine and placebo groups with respect to the frequency or type of adverse events. Changes in PR, QRS, and QTc intervals were similar in mexiletine and placebo-treated participants.ConclusionsThere was no benefit of mexiletine on six-minute walk distance at 6 months. Although mexiletine had a sustained positive effect on objectively measured hand grip myotonia, this was not seen in measures reflecting participants' perceptions of their myotonia. No effects of mexiletine on cardiac conduction parameters were seen over the 6-month follow-up period.Classification of evidenceThis study provides Class I evidence that for ambulatory patients with DM1 mexiletine does not significantly change six-minute walk distance at 6 months.

scholarly journals Cardiac Conduction Disorders as Markers of Cardiac Events in Myotonic Dystrophy Type 1

2020 ◽  
Vol 9 (17) ◽  
Author(s):  
Hideki Itoh ◽  
Takashi Hisamatsu ◽  
Takuhisa Tamura ◽  
Kazuhiko Segawa ◽  
Toshiaki Takahashi ◽  
...  
Keyword(s):  
Sudden Death ◽  
Myotonic Dystrophy ◽  
Cardiac Conduction ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Cardiac Events ◽  
Conduction Disorders ◽  
Qrs Duration

Background Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1. Methods and Results This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine‐thymine‐guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow‐up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow‐up period of 87 months (Q1–Q3, 37–138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22–15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9–7.19, P <0.05) or QRS duration ≥120 ms (HR, 9.41; 95% CI, 2.62–33.77, P < 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval <240 ms or QRS duration <120 ms; these cardiac conduction parameters were not related to sudden death. Conclusions Cardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted.

scholarly journals Cardiac Pathology in Myotonic Dystrophy Type 1

2021 ◽  
Vol 22 (21) ◽  
pp. 11874
Author(s):  
Mani S. Mahadevan ◽  
Ramesh S. Yadava ◽  
Mahua Mandal
Keyword(s):  
Myotonic Dystrophy ◽  
Smooth Muscles ◽  
Clinical Manifestations ◽  
Cardiac Conduction ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Cardiac Pathology ◽  
Systemic Disorder ◽  
Cardiac Manifestations

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.

scholarly journals Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in Myotonic Dystrophy type 1

2018 ◽  
Author(s):  
Emilie Plantié ◽  
Masayuki Nakamori ◽  
Yoan Renaud ◽  
Aline Huguet ◽  
Caroline Choquet ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Rna Binding ◽  
Cardiac Cells ◽  
Cardiac Conduction ◽  
Regulatory Subunit ◽  
Conduction Delay ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Intraventricular Conduction

ABSTRACTCardiac conduction defects decrease life expectancy in myotonic dystrophy type 1 (DM1), a complex toxic CTG repeat disorder involving misbalance between two RNA- binding factors, MBNL1 and CELF1. How this pathogenic DM1 condition translates into cardiac conduction disorders remains poorly understood. Here, we simulated MBNL1 and CELF1 misbalance in the Drosophila heart and identified associated gene deregulations using TU-tagging based transcriptional profiling of cardiac cells. We detected deregulations of several genes controlling cellular calcium levels and among them increased expression of straightjacket/α2δ3 that encodes a regulatory subunit of a voltage-gated calcium channel. Straightjacket overexpression in the fly heart leads to asynchronous heart beating, a hallmark of affected conduction, whereas cardiac straightjacket knockdown improves these symptoms in DM1 fly models. We also show that ventricular α2δ3 expression is low in healthy mice and humans but significantly elevated in ventricular muscles from DM1 patients with conduction defects. Taken together, this suggests that reducing the straightjacket/α2δ3 transcript levels in ventricular cardiomyocytes could represent a strategy to prevent conduction defects and in particular intraventricular conduction delay associated with DM1 pathology.

scholarly journals Straightjacket/α2δ3 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Emilie Auxerre-Plantié ◽  
Masayuki Nakamori ◽  
Yoan Renaud ◽  
Aline Huguet ◽  
Caroline Choquet ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Rna Binding ◽  
Cardiac Cells ◽  
Cardiac Conduction ◽  
Regulatory Subunit ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Conduction Disorders ◽  
Decrease Life Expectancy

Cardiac conduction defects decrease life expectancy in myotonic dystrophy type 1 (DM1), a CTG repeat disorder involving misbalance between two RNA binding factors, MBNL1 and CELF1. However, how DM1 condition translates into conduction disorders remains poorly understood. Here we simulated MBNL1 and CELF1 misbalance in the Drosophila heart and performed TU-tagging-based RNAseq of cardiac cells. We detected deregulations of several genes controlling cellular calcium levels, including increased expression of straightjacket/α2δ3, which encodes a regulatory subunit of a voltage-gated calcium channel. Straightjacket overexpression in the fly heart leads to asynchronous heartbeat, a hallmark of abnormal conduction, whereas cardiac straightjacket knockdown improves these symptoms in DM1 fly models. We also show that ventricular α2δ3 expression is low in healthy mice and humans, but significantly elevated in ventricular muscles from DM1 patients with conduction defects. These findings suggest that reducing ventricular straightjacket/α2δ3 levels could offer a strategy to prevent conduction defects in DM1.

scholarly journals Enhanced serum immunoglobulin G clearance in myotonic dystrophy-associated hypogammaglobulinemia: a case series and review of the literature

2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Sarah C. Sasson ◽  
Alastair Corbett ◽  
Andrew J. McLachlan ◽  
R. Chen ◽  
S. A. Adelstein ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Myotonic Dystrophy ◽  
Immunoglobulin G ◽  
Genomic Medicine ◽  
Case Series ◽  
Cardiac Conduction ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Protein Loss

Abstract Background Myotonic dystrophy type 1 is an autosomal dominant disorder characterized by muscle weakness, myotonia, cataracts, and cardiac conduction defects; it is associated with expansions of cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase. Hypogammaglobulinemia is a lesser known association of myotonic dystrophy type 1 and the underlying pathogenesis of immunoglobulin G depletion remains unclear. Case presentation Here we report a kindred of two members (a 62-year-old white woman and a 30-year-old white man; mother and son) with myotonic dystrophy type 1-associated hypogammaglobulinemia associated with altered intravenous immunoglobulin elimination kinetics and reduced half-life. There was no history of systemic immunosuppression or renal or gastrointestinal protein loss in either patient, and no underlying case for a secondary immunodeficiency could be found. One patient required fortnightly intravenous immunoglobulin to maintain adequate trough immunoglobulin G levels. Conclusions Ongoing study of myotonic dystrophy type 1-associated hypogammaglobulinemia using contemporary tools of genomic medicine may help to further delineate the pathogenesis of this entity.

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