Cardiac Involvement In Myotonic Dystrophy Research Articles

Echocardiographic Features of Cardiac Involvement in Myotonic Dystrophy 1: Prevalence and Prognostic Value

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. Cardiac involvement is reported in 80% of cases and includes conduction disturbances, arrhythmias, subclinical diastolic and systolic dysfunction in the early stage of the disease; in contrast, severe ventricular systolic dysfunction occurs in the late stage of the disease. Echocardiography is recommended at the time of diagnosis with periodic revaluation in DM1 patients, regardless of the presence or absence of symptoms. Data regarding the echocardiographic findings in DM1 patients are few and conflicting. This narrative review aimed to describe the echocardiographic features of DM1 patients and their prognostic role as predictors of cardiac arrhythmias and sudden death.

Cardiac involvement in myotonic dystrophy

BackgroundMyotonic dystrophy (DM) is an inherited progressive muscle disorder caused by defects in muscle proteins. As the incidence of this condition is low, not many are familiar with the multisystem involvement. At times, cardiac disease may even be the predominant manifestation in the form of arrhythmias, conduction defects, and cardiomyopathies. The progression of the disease can lead to sudden, unpredictable death. Thus, it is important to identify this subgroup and treat accordingly.ObjectiveTo identify patients with DM and assess their risk for sudden cardiac death.MethodsNine patients previously diagnosed with muscular dystrophy were evaluated by cardiologists for various reasons, from a general follow-up to cardiac arrest. All of them had electrocardiograms (EKG) and 2-D echocardiograms, and seven of them had further electrophysiological (EP) studies.ResultsOf the nine patients with DM, eight had EKG evidence of conduction abnormalities ranging from first-degree heart block to complete heart block. Of the seven who had EP studies, five had inducible ventricular tachycardia requiring immediate cardioversion and implantable cardioverter defibrillator (ICD) implant. Two of them underwent permanent pacemaker placement due to complete heart block and infra-Hissian block. The remaining two patients opted for a conservative approach with yearly EKG monitoring.ConclusionBecause one-third of the cardiac deaths in patients with DM are sudden, there is a strong need to identify these patients and intervene in those at high risk. Prophylactic pacemaker placement is recommended even in those with minimal conduction system abnormality. However, the common practice is to identify patients at high risk of conduction abnormalities by EP studies and then provide them with prophylactic invasive strategies.

Cardiac involvement in myotonic dystrophy: a nationwide cohort study.

To quantify the association between myotonic dystrophy (DM) and cardiac disease in a nationwide cohort. We identified a nationwide cohort of 1146 DM patients (period 1977-2011) using the National Patient Registry (NPR) and a subcohort of 485 patients who had undergone genetic testing for DM1. Information on incident cardiac diseases was obtained from the NPR. We estimated standardized incidence ratios (SIRs) of cardiac disease compared with the background population, overall and according to selected diagnostic subgroups (cardiomyopathy, heart failure, conduction disorders, arrhythmias, and device implantation). In the DM cohort, SIR for any cardiac disease was 3.42 [95% confidence interval (CI) 3.01-3.86]; for a cardiac disease belonging to the selected subgroups 6.91 (95% CI: 5.93-8.01) and for other cardiac disease 2.59 (95% CI: 2.03-3.25). For a cardiac disease belonging to the selected subgroups, the risk was particularly high in the first year after DM diagnosis [SIR 15.4 (95% CI: 10.9-21.3)] but remained significantly elevated in subsequent years [SIR 6.07 (95% CI: 5.11-7.16]). The risk was higher in young cohort members [e.g. 20-39 years: SIR 18.1 (95% CI: 12.3-25.8)] compared with older [e.g. 60-79 years: SIR 3.99 (95% CI: 2.98-5.23)] but remained significantly increased in all age categories. Results were similar in separate analyses of the genetically confirmed DM1 patients. Myotonic dystrophy is strongly associated with cardiac disease. The risk is pronounced in the young and remains elevated throughout life, stressing the importance of lifelong cardiac follow-up from time of DM diagnosis.

Subclinical cardiac involvement in myotonic dystrophy manifesting as decreased myocardial Doppler velocities

To assess subendocardial (long-axis) and mid-wall (short-axis) left ventricular (LV) function in patients with type 1 myotonic dystrophy (MD1), with no symptoms or clinical signs of heart disease, to investigate if they have subclinical cardiac involvement, 28 subjects (14 with MD1, and 14 age- and sex-matched normals) had conventional and tissue Doppler echocardiography. Myocardial velocities and timings to peak systolic contractions were measured. LV wall thickness, diameters, and ejection fraction were not different between the groups. 4/14 of the MD1 patients (29%) had global diastolic dysfunction. Both long-axis and short-axis systolic and early diastolic myocardial velocities were lower in patients with MD1, whereas time-to-peak myocardial contraction was longer; mean longitudinal systolic velocity was 5.5±1.7 cm/s in patients with MD1, compared with 7.8±1.3 cm/s in normal subjects ( P<0.001). 10/14 of the patients (71%) had reduced longitudinal systolic function. Longitudinal systolic and diastolic velocities were inversely related to the duration of the QRS complex ( r=−0.86 and r=−0.63, respectively, both P<0.01), but they did not correlate with the CTG-repeat size. Patients with MD1 have subclinical cardiac impairment revealed by measurement of myocardial velocities using tissue Doppler echocardiography.

Severity of cardiac conduction involvement and arrhythmias in myotonic dystrophy type 1 correlates with age and CTG repeat length.

Cardiac myopathy manifesting with conduction disturbances and arrhythmias is common in the neurologic disease myotonic dystrophy. We studied whether the severity of cardiac involvement in myotonic dystrophy correlates with the severity of the genetic abnormality cytosine-thymine-guanine (CTG) repeat expansion. History, physical examination, ECG evaluation, and genetic testing were performed in patients with a clinical diagnosis of myotonic dystrophy. In 342 of 385 patients, the diagnosis was confirmed by CTG repeat expansion. In these patients, the muscular disability severity correlated with age and CTG repeat length (r = 0.44, P < 0.001). An arrhythmia diagnosis was present in 19 (5.6%) patients with a likelihood of diagnosis correlating with age (relative risk [RR] 2.2 per decade, 95% confidence intervals [CI] 1.4 to 3.4, P = 0.001) and CTG repeat length (RR 2.9 per 500 repeats, 95% CI 1.5 to 5.4, P = 0.001). ECGs were abnormal in 222 (64.9%) of the patients. Age, CTG repeat length, and male gender were factors found to correlate with ECG conduction abnormalities quantitated by the PR interval (r = 0.43, P < 0.001) and QRS duration (r = 0.32, P < 0.001). A 24-hour ambulatory ECG was abnormal in 95 (29.6%) of 321 recordings. The presence of an abnormality correlated with age (RR 1.5 per decade, 95% CI 1.2 to 1.9, P < 0.001) and CTG repeat length (RR 1.6 per 500 repeats, 95% confidence intervals 1.1 to 2.2, P = 0.01). The severity of skeletal and cardiac myopathy in myotonic dystrophy correlates with age and CTG repeat length, suggesting a similar mechanism causing a time-dependent degenerative process.

Relation of cardiac abnormalities and CTG-repeat size in myotonic dystrophy.

It is unclear if the severity of cardiac involvement in patients with myotonic dystrophy (MD) is related to the size of the CTG-repeat expansion. This open, uncontrolled, observational, prospective study aimed to find out if there is a relation between the severity of cardiac involvement in MD and the CTG-repeat size. In 21 patients with MD, (8 women, 13 men, aged 11-88 years) a detailed cardiologic examination, including history, clinical examination, electrocardiography (ECG), transthoracic echocardiography and ambulatory 24-h ECG, was carried out and cardiac involvement was assessed according to a previously described scoring system. Additionally, the CTG-repeat size was determined from nuclear DNA of blood leukocytes. The correlation between the CTG-repeat size and the mean heart rate, PQ-interval, QTc-interval, fractional shortening, left ventricular enddiastolic diameter, septal thickness, posterior wall thickness, mean heart rate on 24-h ECG and cardiac involvement score was r=0.47, r=0.086, r=0.11, r=-0.27, r=-0.34, r=-0.06, r=-0.12, r=0.16 and r=0.09 (all p>0.05), respectively. In patients 21-30, 31-40 and 41-50 years of age, cardiac involvement increased with increasing CTG-repeat size. In younger patients, the number of CTG-repeats needed to develop a reasonable cardiac involvement was higher than in older patients. Depending on age, cardiac involvement increases with increasing CTG-repeat size obtained from blood leukocytes in patients with MD.

Natural history of cardiac involvement in myotonic dystrophy: correlation with CTG repeats.

The authors prospectively studied the natural course of cardiac involvement and its relationship to cytosine-thymine-guanine (CTG) expansion in 50 patients with myotonic dystrophy who were submitted to periodic cardiovascular EKG and EKG-Holter monitoring during a median follow-up of 56 months. Nineteen patients (38%) developed major EKG changes. CTG length was not correlated with the frequency of EKG abnormalities, but was inversely correlated with the age at onset of EKG abnormalities (p < 0.0001). CTG length influences the timing of cardiac complications in myotonic dystrophy.

Natural history of cardiac involvement in myotonic dystrophy (Steinert's disease): a 13-year follow-up study.

Myotonic dystrophy (MD) is associated with a wide spectrum of cardiac abnormalities, but only a few longitudinal studies have investigated the natural course of heart disease in MD. To assess whether neuromuscular involvement significantly predicts cardiac disorders in MD, 83 patients with various grades of disease severity were enrolled in a 13-year follow-up study (mean, 60.6 +/- 37.8 months) that included periodic physical and instrumental cardiac examinations (standard and Holter electrocardiography, echocardiography). During follow-up, muscular disease worsened clinically in 9 patients (11%) whose baseline severity grade changed accordingly; only 3 of them demonstrated parallel worsening of cardiac disturbance, however, compared with a large number of patients who showed additional cardiac abnormalities. These included further worsening of pre-existing pathologic features (19/83) and the appearance de novo of serious arrhythmias and/or conduction defects (23/83). Pacemaker implantation was necessary in 11 of 83 patients (13.2%) who had symptomatic bradyarrhythmias, bifascicular block, and P-R prolongation with a His-to-ventricle interval exceeding 55 ms, as documented by electrophysiologic study. Eight (9.6%) patients died: 2 from noncardiac and 1 from unknown causes, 1 from heart failure, and 4 from sudden death closely related to documented ventricular tachycardia. The incidence and seriousness of arrhythmic and conduction disturbances correlated with the severity of the muscular involvement. Nevertheless, cardiac and muscular disease did not show a linear progression. Cardiac involvement generally worsened more rapidly than did skeletal muscle disease.

Cardiac critical events in myotonic dystrophy: relationship with the severity of neuromuscular disease

Background: Conduction and ventricular arrhythmic disturbances in myotonic dystrophy (MD) are the main causes of cardiac morbidity and mortality. Methods: To better define the natural history of cardiac involvement and the relationship with severity grade of neuromuscular disease, we followed up 83 MD patients (56 men and 27 women; mean age 37±14 years) for a mean period of 61±38 months (range 2–156 months). Pre-study evaluation included physical examination, 12-lead electrocardiogram, 24-h Holter monitoring, and echocardiography. Results: During the study, cardiac critical events (CCE) occurred in 20 patients (24%), five of whom died of sudden death related to documented ventricular tachycardia, 12 of whom had pacemaker implantation and three of whom experienced ventricular tachyarrhythmias. The incidence of CCE appeared to be related to disease severity; in fact, CCE progressively increased from class I to class III (2% vs. 17% vs. 78%, respectively, P<0.001). Moreover, 8% of the patients experienced CCE in spite of low-grade muscular involvement. Conclusions: Critical cardiac events are significantly associated with the more severe forms of neuromuscular disease, while in some patients cardiac involvement in MD worsens independently from skeletal muscle disease.

Cardiac Involvement in a Large Kindred With Myotonic Dystrophy

To evaluate and quantitate cardiac involvement in myotonic dystrophy and assess whether the size of the trinucleotide (cytosine-thymine-guanine [CTG]) repeat expansion is a significant predictor of cardiac abnormalities. Case-control study of a large kindred with myotonic dystrophy. Ninety-one bloodline members of the kindred underwent clinical and cardiac evaluation with electrocardiograms, echocardiography (with Doppler in the majority of cases), and genetic and neurologic evaluations. Affected individuals were age-matched to normal family members. Electrocardiographic conduction abnormalities, wall motion abnormalities, mitral valve prolapse, and global parameters of systolic and diastolic function were determined by an observer blinded to all clinical data and genetic analysis. Compared with age-matched normals, patients with myotonic dystrophy (n = 25) were more likely to have conduction abnormality (52% vs 9%), mitral valve prolapse (32% vs 9%), and wall motion abnormality (28% vs 0%) (all P < .05). Left ventricular ejection fraction and stroke volume were reduced compared with normals matched for age and heart rate (P < .05), whereas Doppler indexes of diastolic function were only marginally altered. Using multivariate analysis, the number of CTG repeats (range, 69 to 1367; normal, < or = 37) was the strongest predictor of abnormalities in wall motion and electrocardiographic conduction (odds ratio of 16.5 and 5.07 per 500 repeats, respectively). The relation of mitral valve prolapse to the size of the CTG repeat was of borderline significance. Patients with more extensive neurologic findings (n = 12) had a higher incidence of wall motion and/or electrocardiographic conduction abnormalities (83% vs 43%; P = .04). Cardiac involvement in myotonic dystrophy affects predominantly the conduction system and myocardial function. Alterations in myocardial relaxation and diastolic properties, in contrast to skeletal muscle myotonia, are minor. In this kindred, the number of CTG repeats was a significant predictor of cardiac dysfunction in myotonic dystrophy.

Cardiac involvement in myotonic dystrophy

Cardiac involvement in myotonic dystrophy

The natural history of cardiac involvement in myotonic dystrophy: an eight-year follow-up in 17 patients.

We evaluated the progression of conduction system and myocardial disease in 17 asymptomatic myotonic dystrophy patients by clinical evaluation, electrocardiography, vector cardiography, and echocardiography. An exercise test was done in 10 patients. After 8 years, a follow-up study of 12 of the 17 original patients was done with a similar protocol. During this period, 2 patients died: one of sudden death while the other had acute left ventricular failure. In our first control study, we found EKG abnormalities in 15 of our patients, consisting mostly of conduction defects or pseudonecrotic patterns. In our second control, all patients had conduction system disease and, in addition, 3 of them had premature ventricular beats. One patient developed dilated cardiomyopathy. In 6 patients, structural involvement of the right ventricle was found. We conclude that even in asymptomatic myotonic dystrophy patients a conduction system deficit is present and progresses, and cardiac death may occur in about 12% of these patients.