Transcriptomic Biomarkers for the Accurate Diagnosis of Myocarditis
Open accessAbstract
Background—: Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures. Methods and Results—: Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (n=32) to develop accurate diagnostic transcriptome-based biomarkers using multiple classification algorithms. We identified 9878 differentially expressed genes in lymphocytic myocarditis versus idiopathic dilated cardiomyopathy (fold change >1.2; false discovery rate <5%) from which a transcriptome-based biomarker containing 62 genes was identified that distinguished myocarditis with 100% sensitivity (95% confidence interval, 46 to 100) and 100% specificity (95% confidence interval, 66 to 100) and was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8), and the normal heart (n=11). Multiple classification algorithms and quantitative real-time reverse-transcription polymerase chain reaction analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy. Conclusions—: Together, these findings demonstrate that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.
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IL-1β increases serum and cardiac IL-6 levels that are needed to drive Th17 responses, which promote fibrosis and progression to DCM and heart failure in patients with myocarditis and in animal models.
“IL-1 β also increases serum and cardiac IL-6 levels that are needed to drive Th17 responses, which also promote fibrosis and progression to DCM and heart failure in patients with myocarditis and in animal models. 36,165,172-174”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [174]
The Discussion (page not available) reports gene-expression differences between myocarditis and idiopathic dilated cardiomyopathy, but does not describe the claimed IL-1β–IL-6–Th17 pathway. Searches for IL-1β, IL-6, Th17, fibrosis, and progression to DCM or heart failure found no passage addressing that causal chain in patients or animal models. (LLM, conf=0.72)
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- Authors
- Heidecker, B., Kittleson, M. M., Kasper, E. K., Wittstein, I. S., Champion, H. C., Russell, S. D., Hruban, R. H., Rodriguez, E. R., Baughman, K. L., & Hare, J. M.
- Affiliations
- Brigham and Women's Hospital (US)
- From the University of Miami, Miller School of Medicine, Miami, FL (B.H., J.M.H.); Johns Hopkins Hospital, Baltimore, MD (E.K.K., I.S.W., S.D.R., R.H.H.); University of Pittsburgh, PA (H.C.C.); Cleveland Clinic Foundation, Cleveland, OH (E.R.R.); Department of Medicine, Division of Cardiology, University of California, Los Angeles (M.M.K.); and Brigham and Women's Hospital, Boston, MA (K.L.B.).
- ORCID
- Venue
- Circulation
- Published
- 2011-03-22
- Volume
- 123
- Issue
- 11
- Pages
- 1174-1184
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC3408077
- OpenAlex
- W2167297686
- Cited by
- 97
- References
- 41
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 7 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 12 · 2019: 8 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 19
- FWCI
- 7.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Johns Hopkins University
- Myocarditis Foundation
- National Institutes of Health
- National Institute on Aging (R01AG025017)
- National Heart, Lung, and Blood Institute (R01HL094849, R01HL084275, R01HL065455, U54HL081028)
- 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
- lymphocytic myocarditis, transcriptomic biomarkers, endomyocardial biopsy, idiopathic dilated cardiomyopathy, differentially expressed genes, gene expression signatures, inflammatory cardiomyopathy, ischemic cardiomyopathy, cardiac inflammation
- MeSH terms
- Adult, Algorithms, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Cardiomyopathies, Myocarditis, Phenotype, Biomarkers, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling
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