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Brief Reports Indian Pediatrics 2000;37: 1242-1246. |
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Dilated Cardiomyopathy : Clinical Profile and Treatment |
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Kavita Chawla Anita Chakravarti
Cardiomyopathies constitute a group of diseases, often of unknown etiology, in which the dominant feature is the involvement of heart muscle itself(1). Three types are described - dilated, restrictive and hyper-trophic. Dilated cardiomyopathy (DCMP) represents a common expression of myocardial damage that has been produced by a variety of yet unestablished myocardial insults. It has been speculated that an episode of subclinical viral myocarditis initiates an auto-immune reaction that cultivates in the development of full blown DCMP(2). Abnormalities of both humoral and cellular immunity have been documented(3). Various studies have shown the association between cardiomyopathy and infection with Coxsackie B virus(4,5), cytomegalo virus (CMV)(6), human immuno-deficiency virus (HIV)(7), and Mumps virus(8). ACE-inhibitors have documented beneficial effects in such patients(9) and in adults with dilated cardiomyopathy. Beta blockers have also been found to be beneficial. In view of the paucity of relevant data in India, the present study was designed to evaluate the clinical profile and comparative efficacy of beta blockers and ACE-inhibitors in children with dilated cardiomyopathy.
Twenty five children of either sex in the age group of 0-12 years, who manifested with congestive cardiac failure and on echocardiographic examination were found to have dilated cardiomyopathy were included in the study. These children were enrolled prospectively after echocardiographic examination. Parenteral consent was obtained for procedures and drug trials. The subjects were followed-up for the next 9 months. Patients having evidence of congenital, valvular, rheumatic and hypertensive heart diseases or with any pulmonary or renal involvement were excluded. The subjects were divided into two groups by alternate randomization. All the patients were hospitalized, and were observed and followed-up over the next 9 months. Initially routine investigations, e.g., hemogram, skiagram chest and electrocardiogram and 24 hours ambulatory ECG monitoring were done. Serological tests were done for detection of antibodies to HIV, CMV, mumps and rubella by Elisa and antibodies to Coxsackie B virus was tested for by microneutralization test. The total levels of IgM and IgG were also estimated.
Group I comprised of 13 patients (Table I). The subjects were treated with digoxin, diuretics (furosemide) and Captopril – an ACE-inhibitor, starting with a dose of 0.05 mg/kg/day and increased upto 4 mg/kg/day depending upon the result. Group II consisted of 12 patients. They were treated with digoxin, diuretics (furosemide) and Propranolol – a beta-blocker at a dose of 1 mg/kg/day. During the study, 5 (20%) patients expired, one of refractory congestive heart failure (Group II) and the remaining 4 (Group I) expired due to arrhythmias. Electrocardiographic Findings Electocardiograms revealed tachycardia in all and 24 hours ambulatory electro-cardiograms showed some significant arrhythmias, which included supraventricular ectopics with 2:1 A.V. block and ventricular tachycardia (Table I).
Figures in parentheses denote percentages, none of the differences between the two groups were significant. Echocardiographic Profile The average heart rates of both the groups were high because they all presented with CHF but after treatment, the heart rate decreased in both the groups, but the fall was greater in those receiving propranolol. There was increase in LVDd and LVDs (left ventricular diameters in diastole and systole) and depression in fractional shortening (FS) in all the patients before treatment. (Table II) Table II__Comparison of the Outcome
Values depict mean + SDs. Except * (p = 0.019), none of the before and after comparisons in both the groups were statistically significant (p >0.05).
Following therapy – left ventricular func-tion improved in both the groups, though the improvement was noticeable in Group I (increase in ejection fraction was statistically significant). Serological Results IgM and IgG levels were estimated in all (Table III). IgM levels were elevated in 80%. IgM was positive for cytomegalovirus in 36% and IgG in 60%. Antibodies to Coxsackie B virus were present in 16%. No one had antibodies against HIV. Table III__Serological Results (n=25)
We compared the effects of Captopril (angiotensin converting enzyme inhibitor) and Propranolol (beta blocker) for treatment of DCMP in children. Both these drugs have been extensively studied in congestive heart failure in adults but the experience in children is less. A beneficial effect of ACE-inhibitors in DCMP in children, including survival, has been reported(9,10). The baseline clinical and echocardio-graphic characteristics of patients in group I were comparable to those of Group II, except for baseline stroke volume and ejection fraction (Table II). Captopril caused a significant improvement in symptoms and ejection fraction. This was an expected response as Captopril acts in congestive heart failure predominantly as a vasodilator resulting in reduction in the systemic vascular resistance and it is also an effective inotropic agent. Nine children of Group I are still being followed-up after 4 years, Captopril has been stopped in 5 (55%) in whom all the parameters of left ventricular function have reached normal levels. Patients put on propranolol also showed a significant improvement in clinical signs and symptoms of CHF. This paradoxical effect of betablocker with negative inotropic effect leading to clinical improvement in DCMP has been validated in several studies in adults(11-13). In this study also, there was no significant depression of systolic function of the left ventricle as assessed by left ventricular ejection fraction. In an earlier report in adults(12), a significant improvement in symptoms was found which was attributed to the effect on the left and right ventricular filing pressures. The total IgM was raised in 80% of our patients which was consistent with an earlier study and possibly reflects ongoing and persistent infection. In DCMP there is a reduction in CDB-suppressor cells which results in an increase in IgM response. Increased IgM levels could be due to unchecked production of antibodies by B cells(15). These antibodies may act as auto-antibodies and be cytotoxic to heart cells or may induce an antibody dependent lymphocyte mediated cytotoxicity or may activate the complement system. Alteration in the immunoglobulin levels may indicative an immune mediated injury secondary to viral infection in the pathogenesis of DCMP(2). Antibodies to Coxsackie B virus were found in 16% of our cases. Earlier studies(4,5) have also reported a high percentage of antibodies to Coxsackie B virus, which implicates this virus as a causative agent in DCMP. However, definite proof in the causation is only possible by isolating the virus from the heart tissue. IgM for both rubella and mumps were negative in our study. IgG antibodies for rubella were positive in only 1 patient which may indicate the normal seroprevalence of this infection in the population, whereas 7 patients had IgG antibodies for mumps. Mumps virus can result in myocarditis but definite diagnosis as a causative agent is only possible by biopsy. Though we had IgM-CMV positive in 36% and IgG for CMV in 60% of our patients, definite diagnosis as an etiological agent can only be made from cardiac biopsy estimates. Contributors: AK co-ordinated the study (its design, analysis and interpretation) and also drafted the article; she will act as the guarantor for the paper. KC was responsible for data collection. AC was responsible for estimation of serology and other microbiological parameters. Funding:
None.
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