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. 1996 Jun;75(6):596–601. doi: 10.1136/hrt.75.6.596

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

M Mirić 1, J Vasiljević 1, M Bojić 1, Z Popović 1, N Keserović 1, M Pesić 1
PMCID: PMC484384  PMID: 8697164

Abstract

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.

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Selected References

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  1. Benczur M., Petrányl G. G., Pálffy G., Varga M., Tálas M., Kotsy B., Földes I., Hollán S. R. Dysfunction of natural killer cells in multiple sclerosis: a possible pathogenetic factor. Clin Exp Immunol. 1980 Mar;39(3):657–662. [PMC free article] [PubMed] [Google Scholar]
  2. Bowles N. E., Richardson P. J., Olsen E. G., Archard L. C. Detection of Coxsackie-B-virus-specific RNA sequences in myocardial biopsy samples from patients with myocarditis and dilated cardiomyopathy. Lancet. 1986 May 17;1(8490):1120–1123. doi: 10.1016/s0140-6736(86)91837-4. [DOI] [PubMed] [Google Scholar]
  3. Cohen M. C., Huberman M. S., Nesto R. W. Recombinant alpha 2 interferon-related cardiomyopathy. Am J Med. 1988 Oct;85(4):549–551. doi: 10.1016/s0002-9343(88)80094-9. [DOI] [PubMed] [Google Scholar]
  4. Deyton L. R., Walker R. E., Kovacs J. A., Herpin B., Parker M., Masur H., Fauci A. S., Lane H. C. Reversible cardiac dysfunction associated with interferon alfa therapy in AIDS patients with Kaposi's sarcoma. N Engl J Med. 1989 Nov 2;321(18):1246–1249. doi: 10.1056/NEJM198911023211806. [DOI] [PubMed] [Google Scholar]
  5. Disis M. L., McDonald T. L., Colombo J. L., Kobayashi R. H., Angle C. R., Murray S. Circulating immune complexes in cystic fibrosis and their correlation to clinical parameters. Pediatr Res. 1986 May;20(5):385–390. doi: 10.1203/00006450-198605000-00002. [DOI] [PubMed] [Google Scholar]
  6. Hirsch R. L., Johnson K. P. The effects of long-term administration of recombinant alpha-2 interferon on lymphocyte subsets, proliferation, and suppressor cell function in multiple sclerosis. J Interferon Res. 1986 Apr;6(2):171–177. doi: 10.1089/jir.1986.6.171. [DOI] [PubMed] [Google Scholar]
  7. Huber S. A. Viral myocarditis--a tale of two diseases. Lab Invest. 1992 Jan;66(1):1–3. [PubMed] [Google Scholar]
  8. Kandolf R., Ameis D., Kirschner P., Canu A., Hofschneider P. H. In situ detection of enteroviral genomes in myocardial cells by nucleic acid hybridization: an approach to the diagnosis of viral heart disease. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6272–6276. doi: 10.1073/pnas.84.17.6272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kay H. D., Fagnani R., Bonnard G. D. Cytotoxicity against the K562 erythroleukemia cell line by human natural killer (NK) cells which do not bear free Fc receptors for IgG. Int J Cancer. 1979 Aug;24(2):141–150. doi: 10.1002/ijc.2910240204. [DOI] [PubMed] [Google Scholar]
  10. Klingel K., Hohenadl C., Canu A., Albrecht M., Seemann M., Mall G., Kandolf R. Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):314–318. doi: 10.1073/pnas.89.1.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kristensson K., Orvell C., Leestma J., Norrby E. Sendai virus infection in the brains of mice: distribution of viral antigens studied with monoclonal antibodies. J Infect Dis. 1983 Feb;147(2):297–301. doi: 10.1093/infdis/147.2.297. [DOI] [PubMed] [Google Scholar]
  12. Maisch B., Trostel-Soeder R., Stechemesser E., Berg P. A., Kochsiek K. Diagnostic relevance of humoral and cell-mediated immune reactions in patients with acute viral myocarditis. Clin Exp Immunol. 1982 Jun;48(3):533–545. [PMC free article] [PubMed] [Google Scholar]
  13. Mason J. W., O'Connell J. B., Herskowitz A., Rose N. R., McManus B. M., Billingham M. E., Moon T. E. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. 1995 Aug 3;333(5):269–275. doi: 10.1056/NEJM199508033330501. [DOI] [PubMed] [Google Scholar]
  14. Oldstone M. B., Buchmeier M. J. Restricted expression of viral glycoprotein in cells of persistently infected mice. Nature. 1982 Nov 25;300(5890):360–362. doi: 10.1038/300360a0. [DOI] [PubMed] [Google Scholar]
  15. Oldstone M. B., Fujinami R. S., Lampert P. W. Membrane and cytoplasmic changes in virus-infected cells induced by interactions of antiviral antibody with surface viral antigen. Prog Med Virol. 1980;26:45–93. [PubMed] [Google Scholar]
  16. Santoli D., Hall W., Kastrukoff L., Lisak R. P., Perussia B., Trinchieri G., Koprowski H. Cytotoxic activity and interferon production by lymphocytes from patients with multiple sclerosis. J Immunol. 1981 Apr;126(4):1274–1278. [PubMed] [Google Scholar]
  17. Sonnenblick M., Rosenmann D., Rosin A. Reversible cardiomyopathy induced by interferon. BMJ. 1990 May 5;300(6733):1174–1175. doi: 10.1136/bmj.300.6733.1174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Weiss L. M., Liu X. F., Chang K. L., Billingham M. E. Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissues. J Clin Invest. 1992 Jul;90(1):156–159. doi: 10.1172/JCI115830. [DOI] [PMC free article] [PubMed] [Google Scholar]

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