Long-term follow up of patients with dilated heart muscle disease treated with human leucocytic interferon alpha or thymic hormones initial results.

OBJECTIVE: To determine whether giving interferon-alpha or thymomodulin in addition to conventional treatment improves cardiac function in patients with idiopathic myocarditis and idiopathic dilated cardiomyopathy. DESIGN: Single-centre, randomised, open label, parallel group comparison of conventional treatment plus interferon-alpha, conventional treatment plus thymomodulin, and conventional treatment alone. PATIENTS: 38 patients aged 19-54 years (23 men) with biopsy-proven myocarditis or dilated cardiomyopathy. 12 were treated with conventional treatment alone, 13 were treated with interferon-alpha and conventional treatment, and 13 with thymomodulin and conventional treatment. SETTING: Tertiary cardiac referral centre. MAIN OUTCOME MEASURES: Clinical evaluation, echocardiography, and Holter monitoring at baseline, 6 months, and 1 and 2 years. Radionuclide ventriculography at rest and during exercise after 2 years. Endomyocardial biopsy at baseline and after a year if the initial diagnosis was myocarditis. RESULTS: Left ventricular ejection fraction was improved in 21 (81%) of 26 patients after interferon-alpha or thymomodulin administration and in 8 (66%) of 12 conventionally treated patients (P < 0.05) at 2 year follow up. The maximum exercise time was significantly longer at 2-year follow up in patients treated with immunomodulators (mean (SEM) 5.1 (0.6) minutes for interferon-alpha and 5.0 (0.4) minutes for thymomodulin) than in conventionally treated patients (3.3 (0.4) minutes). Left ventricular ejection fraction during exercise (assessed by radionuclide ventriculography) improved in 9 of 12 patients treated with interferon-alpha, 10 of 12 patients treated with thymomodulin, and 3 of 9 conventionally treated patients at 2 year follow up. The electrocardiogram was normal in 21 (88%) of 24 patients after interferon-alpha or thymomodulin treatment and 2 (22%) of 9 conventionally treated patients. At 2 year follow up, 19 (73%) of 26 patients treated with immunomodulators and 4 (25%) of 12 conventionally treated patients had improved their functional class. CONCLUSIONS: The results suggest that treatment of idiopathic myocarditis and/or idiopathic dilated cardiomyopathy with interferon-alpha or thymomodulin induces an earlier and significantly superior clinical improvement than conventional treatment alone.

Interferon and thymic hormones in the therapy of human myocarditis and idiopathic dilated cardiomyopathy.

It is becoming increasingly apparent that idiopathic dilated cardiomyopathy (IDC) probably results from an acute viral myocarditis. One reasonable hypothesis is that persistent viral infection causes myocardial destruction leading to left ventricular dilatation and heart failure. The aim of this study was to evaluate the efficacy of interferon-alpha (IFN) and thymomodulin in the treatment of idiopathic myocarditis and IDC. Clinical, immunological, haemodynamic and histological evaluation was performed in 40 patients before inclusion in the study. Patients were randomized into three treatment groups: (a) conventional therapy plus IFN, (b) conventional therapy plus thymomodulin and (c) conventional therapy alone. Two-year follow-up included repeated endomyocardial biopsy, echocardiographic evaluation, treadmill exercise test, Holter monitoring study and radionuclide assessment of left ventricular function during exercise. Left ventricular ejection fraction increased during follow-up in most of the IFN-and thymomodulin-treated patients, and only in a few of conventionally treated patients. Left ventricular reserve was significantly higher at 2-year follow-up in patients treated with immunomodulators. No serious adverse effects were noticed during treatment. Our results suggest that treatment of myocarditis and/or IDC with IFN or thymomodulin induces an earlier and significantly superior clinical improvement than conventional therapy alone.

Long-term follow-up of patients with myocarditis and idiopathic dilated cardiomyopathy after immunomodulatory therapy.

The randomized clinical trial with interferon-alpha (IFN) or thymic hormones versus conventional therapy was conducted in patients with myocarditis and idiopathic dilated cardiomyopathy (IDC). We enrolled 180 patients to receive IFN (3-5 million units per day) for 3 months, thymomodulin (10 mg three times per week) for 2 months, or conventional therapy alone. Patients were followed-up for 7 years after the end of treatment. Left ventricular function, exercise tolerance and survival rate were significantly better at long-term follow-up in patients treated with IFN or thymomodulin, than in conventionally treated patients. These results implicate that immune modulating therapy might represent important contribution in the treatment of myocarditis and IDC.