ReviewCardiac manifestations of myotonic dystrophy type 1☆
Introduction
Myotonic dystrophy type 1 (MD1) is the most common muscular dystrophy with an incidence of approximately 1:8.000. MD1 is an autosomal dominant disorder with a highly variable phenotypic expression. The genetic basis of MD1 is an abnormal expansion of a CTG trinucleotide repeat on chromosome 19q21.3 [1], [2].
MD1 is a multisystem disorder associated with myotonia, progressive weakness and atrophy of the skeletal muscles, cataract and systemic manifestations. Cardiac involvement may present as asymptomatic electrocardiographic (ECG) abnormalities, e.g. prolongation of the PR-, QRS- and QT-intervals. Arrhythmic events may be due to sinus-node dysfunction, progressive heart block, atrial tachycardia, -flutter or -fibrillation or ventricular tachycardia or -fibrillation [2], [3].
The conduction abnormalities and the arrhythmia are thought to be due to myocardial fibrosis, which may lead to degeneration of the cardiac conduction system and compose a substrate for re-entrant arrhythmia, e.g. the development of atrioventricular block and ventricular arrhythmia. The myocardial fibrosis probably also relates to the observed systolic ventricular function [3], [4], [5], [6]. The symptomatic presentations include palpitations, pre-syncopes and syncopes, heart failure symptoms and sudden cardiac death (SCD), but the cardiac involvement in MD1 is often clinically asymptomatic.
In a 10-years follow-up study, Mathieu et al. report a mean age of death at 53.2 years in MD1-patients and a significantly increased number of observed versus expected deaths for cardiovascular diseases [5]. It has been demonstrated that certain ECG abnormalities, including atrial tachyarrhythmia, are independent predictors of sudden death in patients with MD1 [3].
There are no evidence-based recommendations for the timing of initiation, frequency and extent of cardiovascular screening to prevent or reduce cardiac morbidity and mortality in patients with MD1. We reviewed the literature to get an overview of the degree of cardiac involvement regarding left ventricular ejection fraction, conduction abnormalities, arrhythmia and the relations between cardiac involvement and CTG-repeat, neuromuscular involvement, age and gender in MD1-patients. We aimed to provide cardiologists with a unique and detailed overview of cardiac manifestations in MD1-patients based on the present literature and to provide suggestions for patient management.
Section snippets
Search strategy
A Pub-Med search was performed and included all studies published in English between 1980 and 2010, meeting the search terms myotonic dystrophy in combination with one of the following terms; cardiac abnormalities, cardiac involvement, arrhythmia, echocardiography, ECG, Holter, conduction disturbances, structural abnormalities, heart disease and sudden death, respectively. Studies from both cardiac and non-cardiac journals were included. The primary Pub-Med search resulted in 1617 hits.
Classification
Clinical
Results
Detailed information including the authorship, year of publication, number of included patients, mean age, gender, ECG-/24 hour Holter-parameters and LVEF in each study is shown in Tables 1 and 2.
Discussion
This review demonstrates that a substantial fraction of MD1-patients has major cardiac involvement, mainly conduction abnormalities and arrhythmia.
Our review reveals a high prevalence of AVB1-block (28%). According to a large prospective, community-based cohort including 7575 individuals from the Framingham Study (mean age 47 years; 54% women), 124 patients (1.6%) had PR interval > 200 ms at baseline. AVB1 was found to be associated with increased risk of atrial fibrillation, PM-implantation and
Conclusions
Cardiac involvement such as conduction disturbances, arrhythmia and cardiomyopathy is a common finding in MD1-patients and carries a raised risk of SCD. In the management of MD1-patients it is important to stay attentive to the variety of cardiac manifestations. Without pre-symptomatic cardiac screening, MD1-patients may be diagnosed later than other patients with a cardiac disease, because of the muscular dystrophy-related reduced physical abilities. A delayed diagnosis of cardiac involvement
Acknowledgment
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [43].
References (43)
- et al.
Ethnic distribution of myotonic dystrophy gene
Lancet
(Sep 7 1991) - et al.
Value of the electrocardiogram in determining cardiac events and mortality in myotonic dystrophy
Am J Cardiol
(Dec 1 1997) - et al.
Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community
J Am Coll Cardiol
(Sep 15 2004) - et al.
Ventricular dysfunction in type 1 myotonic dystrophy: electrical, mechanical, or both?
Int J Cardiol
(Sep 3 2010) - et al.
Correlation between cardiac involvement and CTG trinucleotide repeat length in myotonic dystrophy
J Am Coll Cardiol
(Jan 1995) - et al.
Usefulness of clinical and electrocardiographic data for predicting adverse cardiac events in patients with myotonic dystrophy
Can J Cardiol
(Feb 2009) - et al.
Cardiac abnormalities in myotonic dystrophy. Electrocardiographic and echocardiographic findings in 65 patients and 34 of their unaffected relatives. Relation with age and sex and relevance for gene detection
J Neurol Sci
(Sep 1987) - et al.
Sex-specific increase in the prevalence of atrial fibrillation (The Copenhagen City Heart Study)
Am J Cardiol
(Dec 15 2003) - et al.
Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing: a multicenter diagnostic pacemaker study
J Am Coll Cardiol
(Nov 6 2002) - et al.
QT interval variability and spontaneous ventricular tachycardia or fibrillation in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients
J Am Coll Cardiol
(Oct 6 2004)
Prevalence of structural cardiac abnormalities in patients with myotonic dystrophy type I
Am Heart J
Beneficial effects of beta-blockers and angiotensin-converting enzyme inhibitors in Duchenne muscular dystrophy
J Cardiol
Myotonic dystrophy and the heart
Heart
Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1
N Engl J Med
A 10-year study of mortality in a cohort of patients with myotonic dystrophy
Neurology
Cardiac disease in myotonic dystrophy
Cardiovasc Res
Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators
N Engl J Med
Risk of arrhythmia in type I myotonic dystrophy: the role of clinical and genetic variables
J Neurol Neurosurg Psychiatry
Increased mortality with left ventricular systolic dysfunction and heart failure in adults with myotonic dystrophy type 1
Am Heart J
Cardiac involvement in patients with myotonic dystrophy: characteristic features of magnetic resonance imaging
Eur Heart J
Relation of cardiac abnormalities and CTG-repeat size in myotonic dystrophy
Clin Genet
Cited by (122)
Genetic Abnormalities of the Sinoatrial Node and Atrioventricular Conduction
2023, Cardiology ClinicsEpidemiology and Outcomes Associated with PR Prolongation
2023, Cardiology ClinicsCardiac MR Imaging of Muscular Dystrophies
2022, Current Problems in Diagnostic Radiology
- ☆
Funding: this work was supported by the Research Foundation of Rigshospitalet.