Immunosuppression may benefit long term in virus-negative inflammatory cardiomyopathy
Immunosuppressive therapy for virus-negative inflammatory cardiomyopathy was associated with reduced CV mortality and need for transplantation and persistent improvements in left ventricular function, researchers reported.
The 20-year results of the TIMIC trial have been published in the European Heart Journal.
“This is the first study on immunosuppression in inflammatory cardiomyopathy, describing the long-term efficacy of this treatment on cardiac dimension and function and on HF symptoms over a very long follow-up period (up to 20 years),” Cristina Chimenti, MD, PhD, of the department of clinical, internal, anesthesiology and cardiovascular sciences at Sapienza University of Rome, and the Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani in Rome, and colleagues wrote. “Of note, similar functional improvements persisted over time also in patients with severe left ventricular dilation and dysfunction at the time of diagnosis.”
A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases published in 2013 recommends individualized use of immunosuppression in patients with infection-negative lymphocytic myocarditis resistant to standard therapy and those with proven autoimmune forms of myocarditis.
A prior study in 2003 found that patients with a myocardial viral infection who were prescribed immunosuppressive treatment without preliminary viral genome search were unresponsive to the treatment. This trial led researchers to conduct the randomized, double-blind, placebo-controlled TIMIC trial, which evaluated the effects of 6 months of prednisone and azathioprine on biopsy-proven virus-negative chronic inflammatory cardiomyopathy. The trial demonstrated a positive impact of immunosuppression on LV function recovery in 88% of participants.
For the present analysis, researchers evaluated the 20-year outcomes among the 85 participants in the original TIMIC cohort with the primary outcome of CV death and heart transplantation. Participants were 1:2 matched to a cohort of untreated controls.
At 20 years, researchers observed lower risk for CV death (HR = 6.77; 95% CI, 2.36-19.45) and heart transplantation (HR = 7.92; 95% CI 1.8-34.88) among patients with virus-negative chronic inflammatory cardiomyopathy who underwent immunosuppression compared with controls.
Patients who underwent immunosuppression had persistent improvement in LVEF compared with the control group (HR = 7.24; 95% CI, 3.05-17.18).
In addition, patients in the control arm more often underwent implantable cardioverter defibrillator implantation compared with the treatment arm (42.4% vs. 10.6%; P < .001) and the incidence of recurrent myocarditis was similar between groups (control arm, 8.2% vs. treatment arm, 5.9%; P < .62).
Among patients in the control arm with evidence of recurrent cardiac inflammatory process, more than half promptly responded to the TIMIC protocol.
“The effectiveness of the TIMIC treatment was also demonstrated in patients who were initially allocated to the placebo arm of the trial and were subsequently switched to immunosuppressive therapy at study completion as a result of the documented superiority of immunosuppressive therapy,” the researchers wrote. “This observation is suggestive of a long-lasting persisting focal myocardial inflammation that does not resolve spontaneously or with supportive therapy alone.”
References:
- Caforia AL, et al. Eur Heart J. 2013;doi:10.1093/eurheartj/eht210.
- Frustaci A, et al. Circulation. 2003;doi:10.1161/01.CIR.0000048147.15962.31.
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