Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study
Abstract
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.
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Regimens based on corticosteroids in combination with azathioprine or mycophenolate mofetil have long been used in the treatment of autoimmune myocarditis and inflammatory dilated cardiomyopathy by improving left ventricular systolic function and reducing VA burden.
“Regimens based on corticosteroids in combination with azathioprine or mycophenolate mofetil have long been used in the treatment of autoimmune myocarditis and inflammatory dilated cardiomyopathy by improving left ventricular systolic function and reducing VA burden [107,111].”
From A Paradigm Shift: Arrhythmogenic Cardiomyopathy Is an Inflammatory Disease (2026) · cites this paper as [111]
Non-selective suppression may partly explain why steroid therapy does not uniformly improve outcomes across all forms of myocarditis, with benefit primarily in virus-negative inflammatory cardiomyopathy and uncertain efficacy in virus-positive disease.
“This non-selective suppression may partly explain why steroid therapy does not uniformly improve outcomes across all forms of myocarditis—with benefit demonstrated primarily in virus-negative inflammatory cardiomyopathy [41], while efficacy remains uncertain in virus-positive disease [42].”
From Cardiac Macrophages Exhibit Dynamic Heterogeneity and Functional Specialization During Experimental Autoimmune Myocarditis. (2026) · cites this paper as [41]
In some cases of lymphocytic myocarditis, viruses test negative while heart-specific autoantibodies are present.
“Notably, in some cases of lymphocytic myocarditis, these viruses tested negative, while autoantibodies specific to the heart were present”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [151]
Virus-negative lymphocytic myocarditis may have alternative pathogenesis such as autoimmunity, hypersensitivity, or medication usage.
“suggesting potential alternative pathogenesis such as autoimmunity, hypersensitivity, or medication usage.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [151]
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- Authors
- Frustaci, A., Russo, M. A., & Chimenti, C.
- Affiliations
- Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT)
- IRCCS San Raffaele Roma (IT)
- Corresponding author
- Frustaci, A.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-06-25
- Volume
- 30
- Issue
- 16
- Pages
- 1995-2002
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W1991445486
- Cited by
- 604
- References
- 1
- Citations by year
- 2026: 39 · 2025: 38 · 2024: 46 · 2023: 39 · 2022: 44 · 2021: 48 · 2020: 48 · 2019: 37 · 2018: 22 · 2017: 47 · 2016: 31 · 2015: 23 · 2014: 27 · 2013: 35 · 2012: 35
- FWCI
- 16.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- myocarditis, immunosuppressive therapy, prednisone, azathioprine, heart failure, left ventricular ejection fraction, left ventricular function, chronic heart failure
- MeSH terms
- Adolescent, Adult, Aged, Azathioprine, Chronic Disease, Double-Blind Method, Heart Failure, Humans, Immunosuppressive Agents, Middle Aged, Myocarditis, Stroke Volume, Treatment Outcome, Ventricular Dysfunction, Left, Young Adult
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