Cardiac involvement, that often precedes the skeletal muscle one, occurs in 80% of DM1 patients and represents the second most common cause of death, after respiratory causes (17
). Endomyocardial biopsies performed on patients with DM1 have shown specific changes, such as perivascular interstitial fibrosis, fatty infiltration, hypertrophy of myocardiocites, and focal myocarditis (8
Mathieu et al. (9
), during a 10 year follow up study on 367 DM1 patients, reported a mortality 7.3 times higher than in an age-matched control population, with a mean age at death of 53 years; furthermore they showed a positive correlation between age at onset of DM1 and age of death. In their series, respiratory failure and cardiovascular disease were the most prevalent causes of death, accounting for about 40% and 30% of fatalities, respectively.
Cardiac mortality usually occurred because of progressive left ventricular dysfunction, ischaemic heart disease, pulmonary embolism, or as a result of unexpected sudden death (SD) (19
Relative contribution of sudden death ranges from about 2-30% in different published series (24
), according to selection criteria. The hypothesis that cardiac arrhythmias may represent the most prevalent cause of sudden death in DM1 patients is supported by the absence of other causes of sudden death at necropsy studies. Sudden cardiac death may be caused by ventricular asystole, degeneration of ventricular tachycardia (VT), ventricular fibrillation (VF) or electromechanical dissociation (27
Clinical and experimental studies suggested that the basis of the arrhythmic risk and subsequent sudden death could be a heterogeneity of regional and ventricular repolarization (20
), a substrate for life-threatening ventricular arrhythmias. Such a heterogeneity is expressed by an increase of QTc and JTc dispersion (29
), as reported in other diseases such as hypertrophic cardiomyopathy (24
), chronic heart failure (18
), myocardial ischemia (26
), beta thalassemia major (22
) and aortic coarctation (23
); however it is not expressed by other parameters such heart rate variability (HRV) or P dispersion (Pd), as it can be observed in other neuromuscular disorders presenting with cardiomyopathy and arrhythmias (28
The evidence of the degeneration of the conduction system in DM generated the hypothesis that bradyarrhythmias might represent the most prevalent mechanism of SD. However, ventricular tachy-arrhythmias are increasingly recognised as a common finding in these patients, possibly explaining some cases of sudden death after pacemaker implantation.
The cardiac manifestations that are seen in DM1 can be grouped into 3 distinct categories: 1) conduction defects; 2) tachyarrhythmias and 3) other manifestations (see ).
Cardiac Involvement in Myotonic Dystrophy (DM1).
1. Conduction defects
Conduction defects are the most prevalent cardiac abnormalities seen in patients with DM1, occurring in 40% of patients. These defects can affect any part of the conduction system; however, most commonly the His-Purkinje system is affected (8
). Minor conduction defects are commonly seen on standard electrocardiograms (ECG) and His-Bundle studies as prolongations of the PR, QRS and HV intervals, also in asymptomatic patients (21
). These minor defects can progress to more severe conduction defects often associated with breath shortness, dizziness, fainting, syncope, and sudden death (8
Because of the progressive nature of DM cardiac disease, a specific protocol for the follow-up of DM1 patients has been designed (40
) recommending at least an ECG every 6 months. There is no consensus on the rate of progression of conduction defects. While some authors report a slow progression of conduction defects, others correlate the rate of progression with the size of repeats. Among them, the study conducted by Clarke et al. (15
) showed that patients with repeats > 1000 CTG had a more rapid progression. This finding is significant because of risk to develop a complete heart block potentially leading to sudden death (30
A delayed impulse propagation, along the conduction system, can be associated with a long PR interval (prevalence 20-40% in different studies, depending on patient selection criteria) and/or a wide QRS complex (prevalence 5-25% in different studies, depending on patient selection criteria). Unfortunately, the presence of a long PR interval does not give any clue regarding the site of the conduction delay, as it may occur at any level, from the atrium to the His bundle, through the atrio-ventricular node. However, a wide QRS complex (for right or left bundle branch block), is frequently associated with an infrahissian (below the His bundle) conduction impairment. A prolongation of the HV interval has been observed in about 50% of unselected patients with DM1 (10
Late potentials are also expression of delayed myocardial activation, usually caused by abnormal tissue (fibrosis or necrosis), and are considered predictors of ventricular arrhythmias. In DM1 it seems that delayed myocardial activation is a consequence of delayed activation along the His-Purkinje system (42
) rather than an inhomogeneous conduction, through scattered areas of fibrosis. Abnormal late potentials are therefore expression of a conduction defect, and represent an important noninvasive clue for the presence of a long HV interval. QRS duration > 100 ms and low amplitude signals in the last 40 ms of QRS complex have been shown to predict a prolonged HV interval at the intracardiac electrophysiology study (EPS) with good sensitivity and specificity (80% and 83.3%, respectively) (42
In DM1 patients, supraventricular tachyarrhythmias are a common finding on 12 lead ECG or 24 hour Holter monitoring, often asymptomatic. Most common arrhythmias are atrial flutter or fibrillation, observed in up to 25% of patients both as un-sustained and sustained forms (44
). Atrial flutter, atrial fibrillation, and atrial tachycardia are also easily inducible at EPS even in the absence of previously documented spontaneous episodes, but the clinical implications of these findings are still uncertain.
Ventricular arrhythmias such as ventricular tachycardia (VT) and ventricular fibrillation may also occur in patients with DM1. The possible mechanisms that may lead to VT are bundle branch re-entry – the most typical cause of VT –, triggered activity, and re-entry around areas of fibro-fatty degeneration of the myocardium (26
). VT results from the delay of conduction along the Bundle of His, which presents as a prolonged HV interval. The identification of this cause of VT is important because it can be readily treated by a radiofrequency ablation (8
). Patients may also benefit from prophylactic pacing devices (40
). Because of the fatal risk of these arrhythmias as early as the second decade of life (41
), it has been suggested that any patient who presents with any clinical symptoms of VT such as presyncope, syncope, shortness of breath, or family history of sudden death should undergo EPS (8
). Inducible VT is most commonly represented by un-sustained polymorphic VT, but sustained polymorphic VT, VF, and both sustained and un-sustained monomorphic VT have also been reported. Given the risk of sudden death in these patients, the prognostic significance of inducible VTs, even when polymorphic and un-sustained, should be carefully considered, as risk stratification criteria used in other subsets of patients may not apply to DM1 (47
3. Other cardiac manifestations
Although conduction abnormalities and arrhythmias are the most common heart manifestations of DM1, many other cardiac symptoms have been reported (10
). A study performed by Bhakta et al (48
) showed that 1,8% of DM1 patients have clinical symptoms of congestive heart failure, maybe also under-represented as a result of their physical inactivity or inability to communicate secondary to mental retardation. Other DM1 associated cardiac manifestations include ischemic heart disease, in the form of stable angina, unstable angina, and myocardial infarction. Mitral valve prolaps because of papillary dysfunction is also found in 25% to 40% of patients and may often be detected on the physical examination.