Immunosuppressive therapy in virus-negative inflammatory cardiomyopathy

Andrea Frustaci, Cristina Chimenti

Research output: Contribution to journalArticlepeer-review


While there is general agreement on the favorable impact of immunosuppression in eosinophilic, granulomatous, giant cell myocarditis, in lymphocytic myocarditis associated with connective tissue disorders and with rejection of the transplanted heart, its therapeutic role for lymphocytic inflammatory cardiomyopathy (ICM), is still debated. Previous retrospective studies reported a relevant (≥10% left ventricular ejection fraction; LVEF) clinical benefit in 90% of patients with virus-negative ICM and no response or cardiac impairment in 85% of patients with virus-positive ICM following immunosuppression. Other studies identified cardiomyocyte HLA upregulation as an additional indicator of ICM susceptibility to immunosuppressive therapy. Recently, in a single-center randomized prospective double-blind trial using a combination of prednisone (1 mg/kg a day for 4 weeks followed by 0.33 mg/kg a day for 5 months) and azathioprine (2 mg/kg a day for 6 months) in addition to supportive treatment in 85 virus-negative ICM patients, a significant improvement was reported in LVEF and a significant reduction in left ventricular dimensions in 88% of 43 treated patients compared with 42 patients receiving placebo who showed a cardiac impairment in 83% of cases (TIMIC study). These data confirm the efficacy of immunosuppression in virus-negative ICM. Lack of response in 12% of cases suggests the presence of viruses that were not screened for or mechanisms of damage and inflammation not susceptible to immunosuppression. Recovery of cardiac function in responders to immunosuppression was associated with inhibition of cardiomyocyte death, an increase in cell proliferation and with newly synthesized contractile material.

Original languageEnglish
Pages (from-to)18-21
Number of pages4
JournalHeart and Metabolism
Issue number62
Publication statusPublished - 2014


  • Heart failure
  • Immunosuppressive therapy
  • Myocarditis
  • Recovery of function
  • Viruses

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism


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