Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study

Eur Heart J. 2009 Aug;30(16):1995-2002. doi: 10.1093/eurheartj/ehp249. Epub 2009 Jun 25.


Aims: To evaluate the efficacy of immunosuppression in virus-negative inflammatory cardiomyopathy.

Methods and results: This randomized, double-blind, placebo-controlled study included 85 patients with myocarditis and chronic (>6 months) heart failure unresponsive to conventional therapy, with no evidence of myocardial viral genomes. Patients received either prednisone 1 mg kg(-1) day(-1) for 4 weeks followed by 0.33 mg kg(-1) day(-1) for 5 months and azathioprine 2 mg kg(-1) day(-1) for 6 months (43 patients, Group 1) or placebo (42 patients, Group 2) in addition to conventional therapy for heart failure. Primary outcome was the 6 month improvement in left-ventricular function. Group 1 showed a significant improvement of left-ventricular ejection fraction and a significant decrease in left-ventricular dimensions and volumes compared with baseline. None of Group 2 patients showed improvement of ejection fraction, that significantly worsened compared with baseline. No major adverse reaction was registered as a result of immunosuppression.

Conclusion: These data confirm the efficacy of immunosuppression in virus-negative inflammatory cardiomyopathy. Lack of response in 12% of cases suggests the presence of not screened viruses or mechanisms of damage and inflammation not susceptible to immunosuppression.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Azathioprine / therapeutic use*
  • Chronic Disease
  • Double-Blind Method
  • Heart Failure / drug therapy*
  • Heart Failure / physiopathology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Middle Aged
  • Myocarditis / drug therapy*
  • Myocarditis / physiopathology
  • Stroke Volume
  • Treatment Outcome
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / physiopathology
  • Young Adult


  • Immunosuppressive Agents
  • Azathioprine