 |
|
Brief Reports Indian Pediatrics 2000;37: 1246-1251. |
||||||||
|
Prevalence and Patterns of Cardiac Involvement in Duchenne Muscular Dystrophy |
||||||||
|
V. Kalra A. Saxena* T. Dua
Duchenne muscular dystrophy, an X-linked recessive disorder, is the most common hereditary neuromuscular disease, with onset in early childhood and proximal distribution of weakness and a progressive course(1). Cardiac involvement in Duchenne’s muscular dystrophy is common(2-12), its onset is usually after the age of 10 years and increases in incidence with age, affecting almost all patients beyond the age of 18. The cardiomyopathy is usually latent initially without symptoms or overt clinical signs(9). Since a majority of patients have asymptomatic myocardial involvement for years, the recognition of cardiomyopathy in Duchenne patients require active cardiac investigation. An early diagnosis of cardiac involvement is essential to monitor the clinical progress of the patient and institute appropriate therapy. There is paucity of data regarding cardiac involvement as well as its pattern in Duchenne patients from India(5,12). The objectives of this study were to assess cardiac involvement in Duchenne muscular dystrophy (DMD) patients by clinical, radiographic, eletro-cardiographic, echocardiographic, and Holter monitoring and to further correlate clinical severity and duration of muscular disease with cardiac involvement.
Recruitment of Subjects This study was conducted on patients enrolled in the Muscle Clinic of Child Neurology Division of All India Institute of Medical Sciences. Children younger than 6 years were excluded from the study. The diagnostic criteria were typical history of proximal muscle weakness with onset in early childhood, objective signs of girdle weakness, calf pseudohypertrophy and elevated creatine kinase level. Confirmation of diagnosis was done by muscle biopsy. The clinical profile
included age of onset, course of disease, details of motor disability,
history of respiratory complaints, and developmental history. Cardiac
symptomatology was recorded including history of dyspnea, orthopnea,
exertional fatigue, paroxysmal nocturnal dyspnea and palpitations.
Family history of similar involvement especially in maternal uncles and
sibs was recorded. General physical examina-tion for myopathic facies,
pseudohypertrophy, pattern of muscle atrophy and systemic examination
with special reference to cardiovascular system was done. Motor handicap
was assessed using Swine-yard-Deaver criteria(13). The applicability of
this classification for evaluating cardiac status in patients with DMD
has been confirmed by previous reports(11,14).
Creatine kinase (CK) level and muscle biopsy was done for diagnosis. Cardiac investigations included 12 lead ECG, Chest X-ray for cardiomegaly, X-ray spine for kyphoscoliosis, echocardiography and 24-hour ambulatory ECG (Holter) monitoring. Electrocardiogram: All subjects had a 12-lead ECG recorded while recumbent. The characteristics of R waves, S waves, R/S ratios, Q waves, P-R interval, Q-T interval were measured manually in many ECG leads, and were interpreted on the basis of published standard age-matched normal values(15). Significant abnormalities were defined as those values that were outside the minimal or maximal limits for age. M-Mode Echocardiography: The models used were Hewlett Packard Sonos 1500 and Advanced Technology Laboratories model Ultramark 9. Either 2.25 MHz or 3.5 MHz transducer was used. The measurements of aorta, left atrium (end systole), left ventricular (end diastole and end systole), interventricular septum (end diastole), and posterior wall (end diastole) were done according to the recommendations of the American Society of Echocardiography(16). Fractional shortening (FS) was calculated by FS = LVed – LVes/LVed where LVed is Left Ventricular end-diastolic dimension and LVes is Left Ventricular end-systolic dimension. Ejection Fraction (EF) was calculated by the following formula (with the same abbreviations as above): EF = (LVed)3 – (LVes)3/(LVed)3 2D Echocardiography: Valve morphology was assessed and presence of mitral valve prolapse or any wall motion abnormality was looked for. The status of all chambers and pericardium was also examined. Doppler was also done to see any abnormal flow. Holter Monitoring: Each subject had a 24 hour ECG recording done. A diary was given to the attendant of the child to document any symptom of chest pain, palpitation, syncope, dizziness, and corresponding time and activity. The analysis of the record was done by a cardiologist using Marquette system. The maximum and minimum heart rates were recorded. Presence of any supraventricular or ventricular ectopics and longest RR interval were also documented.
The data were analyzed by Epi info- version 6. Means were calculated by the above program with their standard deviation. c2 tests were used for qualitative variables and Student-t test for quantitative variables. For multiple groups, ANOVA was used.
A total of 27 patients were enrolled out of which 26 were male and one was female. The mean age was 9.7 years (+ 2 years) with mean age of onset being 5.4 years (+ 2.4 years). Majority (85.2%) of patients were ambulatory and only 14.8% were wheelchair or bed bound at the time of enrollment in the study. Twenty patients were on oral prednisolone therapy (0.5-0.75 mg/kg) for 10 days in each month and 20 days drug holiday prior to cardiac investigation. The mean period of steroid therapy was 14.89 months (+ 11.59 mths.). Family history of sibling/relative affection was positive in 5 (18.5%) patients. The CK value was elevated in all patients with mean of 5320 + 4127 IU/L. No statistically significant differences were found in patients on basis of CK value with respect to R/S ratio in V1 >1, ejection fraction, isolated supraventricular ectopy and supraventricular couplets. The commonest reported symptom was exertional fatique (66.6%). No patient had any positive cardiac sign on physical examination. On skiagrams of chest and spine, 2 patients (7.4%) had cardiomegaly (by C/T ratio) and scoliosis respectively. Electrocardiographic abnormalities were present in 18 patients (66.7%). Sinus tachycardia (>100/min) was observed in 62.9% patients. PR interval was normal in all except one who had short PR interval. R/S ratio in V1 >1 was observed in 44.4% of patients. No patient exhibited ventricular hypertrophy, arrhythmia and ST-T changes. Q wave was seen in only one patient in lead V5 and Ve. There was no evidence of mitral valve prolapse, chamber hypertrophy or any wall motion abnormality. Only 1 patient (3.7%) had trivial tricuspid regurgitation on Doppler. All the chambers were normal with normal ventricular contractility. The ejection fraction was normal in all the patients. The ejection fraction was correlated with age, Swineyard stage, duration of disease and period of steroid intake. There was no significant association with any of the above factors. On Holter monitoring, all the patients had sinus rhythm without any evidence of sinus pauses, AV block or malignant ventricular arrhythmia. Three patients (11.1%) had isolated supraventricular ectopy and 7 patients (25.9%) had supraventricular couplets. Only one of them (3.7%) exceeded the frequency of more than 1/hour. Neither supraventricular ectopy nor couplets were related to age, steroid therapy or ejection fraction.
Death in Duchenne muscular dystrophy most commonly results from pulmonary insufficiency and respiratory infection. In about 10% of cases, death is due to cardiac dysfunction(4). The risk of dying from a cardiac complication increases with advancing age. The recognition of cardiomyopathy in Duchenne muscular dystrophy is thus important and requires active cardiac investigation. Our study confirms paucity of symptoms as well as abnormal physical findings of cardiac disease in DMD, despite evidence in some of significant cardiac involve-ment(6,8,17,18). A high proportion of DMD patients had ECG abnormalities (66.7%) and that is in accordance with others (2,3,6-8,12,19). Studies in Duchenne muscular dystrophy have shown that these abnormalities most likely originate in the posterobasal and inferior wall of the left ventricle(19,20). The percentage of children with particular type of ECG changes in our series is lower than reported by other authors except for sinus tachycardia(2,3,6,8,9,12,19). Sinus tachy-cardia an early manifestation, was thus found in higher percentage of patients due to younger age of our series of patients as compared to earlier reports(8,10,17). The pathogenesis of this persistent tachycardia in the absence of ventricular dysfunction raised the possibility of autonomic dysregulation. In a hypothesis proposed by Perloff, "dystrophic" sinoatrial node fibrosis and/or fatty infiltration causes not only abnormal sinus node automaticity but also sinus node re-entry and labile sinus tachy-cardia(21). Q-wave abnormalities indicate late, more progressive changes(4). Less frequent Q-wave abnormality could be due to younger age as well as less advanced disease of our patients. Others, however, have found that the Q-wave changes bear no relationship to age or disease severity(6,8). There was no relation of ECG changes with stage of disease, steroid therapy or ejection fraction. There was no evidence of any cardiac dysfunction on echocardiography in our set of patients. The reason for this difference could be their younger age. Supraventricular ectopy or couplets are reported to indicate increasing severity of arrhythmia with the progression of disease(11). Few patients who had supra-ventricular ectopy or couplets detected on Holter monitoring were not advanced. As the number of patients with these abnormalities was small, a large-scale study is needed to confirm this association. Ventricular arrhy-thmia was not observed in our study. It has been recommended that Holter monitoring should be prolonged to 48 hours, as some of the rare arrhythmias may not be picked by a single 24-hour recording(22). The degree of cardiac involvement and the extent of the skeletal muscle changes have been considered important clinical factors that affect prognosis in patients with DMD. As successful management of the skeletal and respiratory aspects has resulted in increasing the mobility and the life expectancy, cardiac pathology has become an increasingly important determinant of their functional capacity and survival. Cardiomyopathy of Duchenne muscular dystrophy is a unique entity that is charac-terized by lack of symptoms and few physical signs. Presence of subtle changes like sinus tachycardia may suggest early cardiac involvement, such patients need careful and frequent follow up for development of cardiomyopathy and an effort can be made to improve prognosis by institution of appropriate therapy. Contributors: RA, VK coordinated the study (particularly its design and interpretation); VK will act as the guarantor for the paper. AS participated in the cardiological inputs. TD drafted the paper. Funding:
None.
|
