Favorable effects of immunosuppressive therapy in children with dilated cardiomyopathy and active myocarditis

Abstract

Among 68 children with severe dilated cardiomyopathy, 43 (aged 10 months to 15 years) presented with active myocarditis, diagnosed by endomyocardial biopsy. They were divided into four treatment groups: I, controls: 9 patients submitted to conventional treatment (digitalis, diuretics, and vasodilators) for 8.1 +/- 0.7 (SD) months; II, prednisone: 12 patients received conventional therapy plus prednisone; III, azathioprine: 16 patients submitted to conventional therapy plus prednisone and azathioprine; IV, cyclosporine: 13 patients treated with conventional therapy plus prednisone and cyclosporine. Immunosuppressive therapy was maintained for a mean of 8.4 +/- 1.2 months. They were submitted to noninvasive (electrocardiogram, chest radiograph, Doppler echocardiogram, and radioisotopic scintigraphy) and invasive (hemodynamic) studies. In the control group only 2 of 9 patients showed clinical and hemodynamic improvement and 1 of 4, histologic regression of the myocarditis. Among patients submitted to conventional therapy plus prednisone, 3 of 12 presented clinical and hemodynamic improvement; 2 of 5 also showed histologic regression of inflammatory process. By contrast, patients treated with azathioprine or cyclosporine associated with prednisone had significantly better results: 13 of 16 and 10 of 13 patients, respectively, had clinical and hemodynamic improvement; all 6 patients in the azathioprine group and all 4 patients in the cyclosporine group had histologic regression of the myocarditis. Two patients in the prednisone group, one in the azathioprine group, and one in the cyclosporine group died during treatment, in cardiogenic shock. In our experience immunosuppressive therapy with azathioprine or cyclosporine associated with prednisone improves the prognosis of children with active myocarditis and severe ventricular dysfunction.

Immunosuppressive Treatment for Inflammatory Cardiomyopathy: Meta-Analysis of Randomized Controlled Trials

“…Five papers were excluded for the following reasons: duplication (two studies), 9,10) trial did not use biopsy proven diagnosis (one study), 11) and participants with mixed conditions and unable to extract data (two studies). 12,13) Details of the 5 trials included can be found in the Table. Immunosuppressive agents: Five types of immunosuppressive therapy were used in the randomized control studies: prednisone, 8,14) prednisone combined with azathioprine, 7,15,16) prednisone combined with cyclosporine, 7,16) intravenous immune globulin, 13) and immunoadsorption. 12) None showed a beneficial effect on improving mortality and heart transplantation.…”

“…LVEF: LVEF for inflammatory cardiomyopathy was reported in 4 trials. 7,8,15,16) In the short-term (≤ 28 weeks), there was evidence of heterogeneity between the studies (P = 0.14, I 2 = 48.7%). This could not be explained in terms of the clinical characteristics at baseline or methodological quality.…”

“…In light of its lower methodological quality (it used admission sequence for randomization) and the limitation of the number of the participants, the results should be interpreted with caution. LVEDD: Four trials 7,8,15,16) provided outcome data on LVEDD. For the same reason mentioned above, the subgroup of child participants was not combined together, however, the published outcome data showed the similar result on the outcome of LVEF as previously described.…”

Myocarditis in Childhood: An Update on Etiology, Diagnosis and Management

“…Although a few uncontrolled studies showed benefit with several immune suppressive agents, meta analysis of adult studies did not confirm a significant favourable effect of immunosuppression (Garg et al, 1998, Maisch et al, 1998. There were also investigations to evaluate the results of immune suppressive regime in children with acute myocarditis (Chan et al, 1991, Camargo et al, 1995. However, studies in children are inadequate and yet, no randomized controlled trials are present.…”

“…However, studies in children are inadequate and yet, no randomized controlled trials are present. In a study (Camargo et al, 1995) conducted among 68 children with severe dilated cardiomyopathy, patients were classified into either conventional treatment or given one of three immune suppressive agents, prednisolone, prednisolone plus azathioprine and prednisolone with cyclosporine. Children taking immunosuppression treatment with a second agent, demonstrated enhanced hemodynamic parameters, as well as histological improvement in inflammation.…”