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

Recent reports have, however, suggested that the heterogeneous results might depend on improper selection of patients, including myocardial inflammation with and without myocardial viral agents and inhomogeneous presence of immune-mediated myocardial damage .

The present randomised, prospective, double blind, placebo-controlled study provides encouraging results on the use of IMT (prednisone + azathioprine for 6 months) in patients with active lymphocytic myocarditis, compromise of contractile function and negative myocardial polymerase chain reaction for the major cardiotropic viruses.

In the 43 treated patients, 88% improved (EF from 26.5±6.7 % to 45.6±9.6 %) compared with no improvement of 42 non-treated cohort patients, who had an impairment of left ventricular function in 83% of cases (EF from 27.7±5.6 to 21.3±5.3 %).

No major adverse reactions were documented as result of IMT. IMT appears as a safe and valuable therapeutic option in patients with virus-negative inflammatory cardiomyopathy.

Discussant report: Keren, Andre (Israel)

Inflammatory Dilated Cardiomyopathy (DCMi) is defined by the presence of chronic myocardial inflammation in association with left ventricular dilatation and reduced ejection fraction (LVEF). The diagnosis requires endomyocardial biopsy (EMB) for histological, immunohistochemical and viral genome evaluation. The chronic inflammatory process can be virus positive or negative. Slides available

Initial attempts of immunosuppression in patients with DCM were disappointing. More recently, improvement in LVEF and NYHA functional class were observed in selected subsets of patients with DCMi, following viral elimination (spontaneous or antiviral therapy induced) and after immunosuppression. In a prospective randomized trial, long lasting improvement occurred after immunosuppression in patients with persistent immune activation (HLA upregulation) on EMB. In a retrospective analysis, patients who benefited from immunosuppression had findings of chronic immune activation and were virus negative on EMB. Nevertheless, immunosuppression can be potentially harmful if administered to virus positive DCMi patients.

In the current prospective, single center, randomized study, immunosuppressive therapy was administered to patients with DCMi of at least 6 months duration, who were unresponsive to standard heart failure therapy and were virus negative. After 6 months, 88% of treated patients showed significant improvement in echocardiographic, histologic and immunohistologic parameters, whereas 83% of the control group deteriorated.

Conclusion: This is the first randomized trial in patients with proof of both persistent inflammation and virus negative DCMi in whom immunosuppression proved to be remarkably effective. The strength of evidence for implementing this therapeutic approachin clinical practice will hopefully be enhanced by positive  results of ongoing multicenter studies of immunomodulatory therapy.