Immunosuppressive therapy in virus-negative inflammatory cardiomyopathy: 20-year follow-up of the TIMIC trial
Open accessAbstract
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.
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Recent long-term data support benefits of immunosuppressive therapies such as glucocorticoids for myocarditis.
“There has been some controversy regarding the effect of immunosuppressive therapies such as glucocorticoids for myocarditis, while recent long-term data support its benefits.”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [78]
The Introduction describes a six-month regimen of prednisone and azathioprine for virus-negative inflammatory cardiomyopathy, and the Long-term efficacy section reports sustained improvements over follow-up of up to 20 years. This supports long-term benefit for the studied patients, but the claim omits the virus-negative qualification and could be read as applying to myocarditis generally. (LLM, conf=0.86)
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COVID-19, Myocarditis and Pericarditis
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Evolution in the Diagnosis and Treatment of Myocarditis in Recent Years: State of the Art
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- Authors
- Chimenti, C., Russo, M. A., & Frustaci, A.
- Affiliations
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- San Raffaele University of Rome (IT)
- Corresponding author
- Frustaci, Andrea
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2022-07-14
- Volume
- 43
- Issue
- 36
- Pages
- 3463-3473
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- PMC
- PMC9492235
- OpenAlex
- W4285387202
- Cited by
- 108
- References
- 11
- Citations by year
- 2026: 28 · 2025: 27 · 2024: 31 · 2023: 16 · 2022: 6
- FWCI
- 13.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Heart Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- European Project ERA-CVD
- Italian Ministry of Health
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Takotsubo Cardiomyopathy and Associated Phenomena
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- immunosuppressive therapy, prednisone, azathioprine, long-term outcomes, cardiovascular mortality, heart transplantation, left ventricular ejection fraction, recurrent myocarditis, implantable cardioverter-defibrillator, endomyocardial biopsy
- MeSH terms
- Azathioprine, Follow-Up Studies, Humans, Immunosuppression Therapy, Myocarditis, Prednisone, Stroke Volume, Ventricular Function, Left, Treatment Outcome
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