Long-term immunosuppressive therapy in virus-negative inflammatory cardiomyopathy significantly reduced the risk of cardiovascular death compared to untreated controls (control HR 6.77; 95% CI 2.36-19.45).
RCT (n=255)
double-blind
randomized
Does a 6-month course of immunosuppressive therapy (prednisone and azathioprine) reduce cardiovascular death and heart transplantation in patients with virus-negative inflammatory cardiomyopathy?
A 6-month course of immunosuppressive therapy with prednisone and azathioprine provides sustained long-term benefits, reducing cardiovascular death and heart transplantation up to 20 years in patients with virus-negative inflammatory cardiomyopathy.
Hazard Ratio: 6.77 (95% CI 2.36–19.45)
AIMS: Long-term results of the Tailored IMmunosuppression in virus-negative Inflammatory Cardiomyopathy (TIMIC) trial protocol have been evaluated. METHODS AND RESULTS: Eighty-five patients with endomyocardial biopsy-proven virus-negative chronic inflammatory cardiomyopathy were enrolled in the randomized, double-blind, placebo-controlled TIMIC trial and received prednisone and azathioprine (n = 43) vs. placebo (n = 42) for 6 months. Immunosuppressive treatment promoted an improvement in cardiac function in 88% of the cases compared with none of the patients in the placebo group, which were switched to a 6-month immunosuppressive therapy at the end of the 6-month study period. Long-term (up to 20 years) clinical outcomes of the whole cohort of 85 patients originally enrolled in the TIMIC trial (Group A) were compared with those of a 1:2 propensity score-matched control cohort of patients untreated with the TIMIC protocol (Group B) and followed for a comparable period of time. The primary outcome was a composite of cardiovascular death and heart transplantation. At long-term follow-up, the risk of cardiovascular death hazard ratio (HR) 6.77; 95% confidence interval (CI) 2.36-19.45 and heart transplantation (HR 7.92; 95% CI 1.80-34.88) was significantly higher in Group B patients. Group A showed a persistent improvement in the left ventricular ejection fraction compared with Group B (HR 7.24; 95% CI 3.05-17.18). A higher number of Group B patients underwent implantable cardioverter defibrillator implantation. The incidence of recurrent myocarditis was similar between groups, and patients with evidence of a recurrent cardiac inflammatory process promptly responded to a TIMIC protocol application. CONCLUSION: Virus-negative inflammatory cardiomyopathy benefits from immunosuppressive therapy even after long-term follow-up. Recurrence appears to respond to a new TIMIC protocol application.
“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). Of note, similar functional improvements persisted over time also in patients with severe left ventricular dilation and dysfunction at the time of diagnosis.”
Chimenti et al. (2022) conducted an RCT in virus-negative chronic inflammatory cardiomyopathy (n=255). prednisone and azathioprine vs. placebo (initially) and untreated propensity-matched cohort (long-term) was evaluated on composite of cardiovascular death and heart transplantation (HR 6.77, 95% CI 2.36-19.45). Long-term immunosuppressive therapy in virus-negative inflammatory cardiomyopathy significantly reduced the risk of cardiovascular death compared to untreated controls (control HR 6.77; 95% CI 2.36-19.45).