Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document
Open accessAbstract
Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.
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Cardiotropic viruses such as adenoviruses and enteroviruses can directly damage the heart, leading to the development of myocarditis.
“cardiotropic viruses such as adenoviruses and enteroviruses can directly damage the heart, leading to the development of myocarditis”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The ‘Virus-Induced and Immune-Mediated Lymphocytic AM and Infl-CMP’ section says enteroviral replication can directly injure cardiomyocytes and cause myocarditis. But ‘Definitions, Epidemiology, and Pathophysiology’ says it is not known which viruses other than enteroviruses directly damage human tissue, so the claim’s inclusion of adenoviruses as an established direct cause is not supported. Page numbers are unavailable in our copy. (LLM, conf=0.89)
Experimental — accuracy not yet measuredCertain viruses including HIV, hepatitis C virus, influenza A virus, and influenza B virus are thought to trigger myocarditis by activating the immune system.
“certain viruses including HIV, hepatitis C virus, influenza A virus, and influenza B virus are thought to trigger myocarditis by activating the immune system”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The section on virus-induced and immune-mediated myocarditis says influenza can trigger immune-mediated lymphocytic myocarditis and describes a suspected immune mechanism. It does not identify influenza A or B separately, or support the same mechanism for HIV or hepatitis C virus (searched those terms in our copy). (LLM, conf=0.87)
Experimental — accuracy not yet measuredUp to 20% of giant cell myocarditis cases are associated with existing autoimmune disorders such as inflammatory bowel disease, thyroiditis, and thymoma.
“with up to 20% of giant cell myocarditis cases associated with existing autoimmune disorders such as inflammatory bowel disease, thyroiditis, and thymoma.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The GCM > Etiology and Pathogenesis section reports associated autoimmune disorders in approximately 20% of giant cell myocarditis cases, particularly inflammatory bowel diseases and thyroid disorders. It does not specifically name thyroiditis or mention thymoma, so the full list of examples is not supported by our copy. No page number is available in the indexed passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGiant cell myocarditis and eosinophilic necrotizing myocarditis are traditionally classified as autoimmune myocarditis due to their strong association with existing autoimmune conditions.
“Giant cell myocarditis and eosinophilic necrotizing myocarditis are traditionally classified as autoimmune myocarditis due to their strong association with existing autoimmune conditions”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The GCM Etiology and Pathogenesis section reports associated autoimmune disorders in approximately 20% of cases. The Eosinophilic Myocarditis Etiology and Pathogenesis section lists autoimmune-related systemic conditions among several possible associations, but also describes drug hypersensitivity and parasitic infection. The Definitions section classifies these forms by infiltrating cell type; our copy does not say that both are traditionally classified as autoimmune because of a strong association with pre-existing autoimmune conditions. Page numbers were not available in the indexed passages. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn giant cell myocarditis and cardiac sarcoidosis, macrophages are a significant contributor to the formation of multinucleated giant cells or granulomas.
“In well-known forms of autoimmune myocarditis such as giant cell myocarditis and cardiac sarcoidosis, macrophages have been identified as a significant contributor to the formation of multinucleated giant cells or granulomas”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The Sarcoidotic Myocarditis, Etiology and Pathogenesis section says activated macrophages can lead to granulomas and that macrophages within them form multinucleated giant cells. The GCM, Etiology and Pathogenesis section lists macrophages and giant cells among the cells involved, but does not say macrophages contribute to giant-cell formation in GCM. Page numbers are not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured
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 [31]
The section on virus-induced and immune-mediated lymphocytic myocarditis (page unavailable) identifies autoimmune injury and drug toxicity as possible causes, including when no viral genome is detected. The paper discusses medication-related hypersensitivity in its eosinophilic myocarditis section, not as a cause of lymphocytic myocarditis; that part of the claim is unsupported. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLymphocytic myocarditis is primarily associated with viral infections, characterized by histological observations of myocardial infiltration predominantly by T lymphocytes.
“Lymphocytic myocarditis is primarily associated with viral infections, characterized by histological observations of myocardial infiltration predominantly by T lymphocytes”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The section on virus-induced and immune-mediated lymphocytic myocarditis says viruses are the main pathogens associated with lymphocytic acute myocarditis and describes T-cell infiltration in virus-triggered cases. The Definitions section classifies myocarditis by infiltrating cell type, but the available passages do not establish that T lymphocytes specifically predominate on histology. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn 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 [31]
The section on virus-induced and immune-mediated lymphocytic myocarditis (page unavailable) says lymphocytic myocarditis can occur without detectable viral genome in the myocardium. It describes autoreactive T cells, but does not report heart-specific autoantibodies in those virus-negative cases. The laboratory-tests section mentions autoantibodies only as possible tests for patients with suspected autoimmune disorders. (LLM, conf=0.85)
Experimental — accuracy not yet measuredChest pain in myocarditis can be pleuritic and positional or pressure-like mimicking acute coronary syndrome.
“which can be pleuritic and positional, similar to that of pericarditis, or pressure-like mimicking the pain of acute coronary syndrome.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The “AM - Symptoms and signs” section identifies chest pain as the most frequent symptom of acute myocarditis. “Differential diagnosis” says myocarditis and pericarditis can cause similar symptoms and that acute coronary syndrome may need to be ruled out. Neither section describes the pain as pleuritic, positional, or pressure-like. (LLM, conf=0.85)
Experimental — accuracy not yet measuredChest pain is the most commonly reported symptom in myocarditis, occurring in 82% to 95% of cases.
“the most commonly reported symptom is chest pain (82% to 95% of cases)”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The “AM - Symptoms and signs” section says chest pain is the most frequent symptom of acute myocarditis, but gives a range of 85–95%, not 82–95%. The claim also says myocarditis generally, whereas the passage concerns acute myocarditis. No page number is supplied in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSarcoidosis is a systemic autoimmune syndrome characterized by nonnecrotizing granulomas in various organs including the lung and heart.
“Sarcoidosis is a systemic autoimmune syndrome characterized by the formation of nonnecrotizing granulomas, a histological hallmark, found in various organs including the lung and heart.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The Etiology and Pathogenesis section describes sarcoidosis as a multisystem granulomatous disease, with pulmonary involvement common and cardiac involvement possible; it also describes non-necrotizing granulomas in sarcoidotic myocarditis. It does not classify sarcoidosis as an autoimmune syndrome: it says the etiology is unknown and that evidence suggests an immunological response to an unidentified trigger. Page numbers are not supplied in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAn unnoticed history of viral infection may contribute to the migration and activation of autoreactive T cells in the heart.
“an unnoticed history of viral infection may contribute to the migration and activation of autoreactive T cells in the heart. 7,10,31,107”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
The section “Virus-Induced and Immune-Mediated Lymphocytic AM and Infl-CMP” (page not provided) says a viral trigger may lead to autoreactive T-cell infiltration of the myocardium through molecular mimicry. It does not say the preceding infection was unnoticed or specifically describe activation of those T cells. (LLM, conf=0.82)
Experimental — accuracy not yet measuredGiant cell myocarditis is a rare but rapidly progressing condition associated with a high risk of death or the necessity for heart transplantation.
“Giant cell myocarditis is a rare but rapidly progressing condition associated with a high risk of death or the necessity for heart transplantation.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
Giant cell myocarditis shows myocardial infiltration of multinucleated giant cells along with lymphocytes and eosinophils.
“Histopathologic observations reveal myocardial infiltration of multinucleated giant cells along with lymphocytes and eosinophils in this condition.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
Various conditions including infections, drugs, hypersensitivity, and autoimmune factors may be associated with the onset and progress of eosinophilic myocarditis.
“various conditions including infections, drugs, hypersensitivity, and autoimmune factors may be associated with the onset and progress of this disease.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [31]
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2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
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Self-citation2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure
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Self-citation2025 ESC Guidelines for the management of myocarditis and pericarditis
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Self-citationAcute myocarditis: aetiology, diagnosis and management
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JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis
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Viral Myocarditis—From Pathophysiology to Treatment
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Fulminant myocarditis proven by early biopsy and outcomes
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Myocarditis: Etiology, Pathogenesis, and Their Implications in Clinical Practice
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Pathogenic Variants Associated With Dilated Cardiomyopathy Predict Outcome in Pediatric Myocarditis
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Self-citationBiomarkers for Myocarditis and Inflammatory Cardiomyopathy
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Clinical Characteristics and Mechanisms of Acute Myocarditis
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Self-citationAutoimmune Myocarditis, Old Dogs and New Tricks.
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At the Heart of Eosinophilic Granulomatosis with Polyangiitis: into Cardiac and Vascular Involvement
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Gene therapy vector-related myocarditis
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Elevated Neutrophil-to-Lymphocyte Ratio Predicts Prognosis in Acute Myocarditis
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Diretriz Brasileira de Atendimento à Dor Torácica na Unidade de Emergência – 2025
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Current Treatment and Immunomodulation Strategies in Acute Myocarditis
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- Authors
- Ammirati, E., Frigerio, M., Adler, E. D., Basso, C., Birnie, D. H., Brambatti, M., Friedrich, M. G., Klingel, K., Lehtonen, J., Moslehi, J. J., Pedrotti, P., Rimoldi, O. E., Schultheiss, H.-P., Tschöpe, C., Cooper, L. T., & Camici, P. G.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- University of California San Diego (US)
- University of Padua (IT)
- Ottawa Heart Institute (CA)
- Ionis Pharmaceuticals (United States) (US)
- McGill University (CA)
- Universitätsklinikum Tübingen (DE)
- Helsinki University Hospital (FI)
- Vanderbilt University Medical Center (US)
- IBFM CNR, Segrate, Italy (O.E.R.).
- Institute for Cardiac Diagnostics and Therapy, Berlin, Germany (H.-P.S.).
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- Mayo Clinic (US)
- Corresponding author
- Ammirati, Enrico
- Camici, Paolo G.
- ORCID
- Venue
- Circulation: Heart Failure
- Published
- 2020-11
- Volume
- 13
- Issue
- 11
- Pages
- e007405-e007405
- ISSN
- 1941-3289 (ISSN-L)
- 1941-3297
- PMC
- PMC7673642
- OpenAlex
- W3103940138
- Semantic Scholar
- beb20d26bcaef45ecb6c5c865df17930929b84c5
- Cited by
- 811
- References
- 123
- Citations by year
- 2026: 122 · 2025: 155 · 2024: 185 · 2023: 150 · 2022: 137 · 2021: 60 · 2020: 1 · 2014: 1
- FWCI
- 53.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Heart Failure (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- Deutsches Zentrum für Herz-Kreislaufforschung
- Bundesministerium für Bildung und Forschung
- Regione del Veneto
- National Heart, Lung, and Blood Institute (R01HL141466, R01HL155990)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Pericarditis and Cardiac Tamponade
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Keywords
- acute myocarditis, dilated cardiomyopathy, myocarditis, cardiac magnetic resonance imaging, viral myocarditis, myocardial fibrosis, histopathology, prognosis, treatment guidelines, expert consensus
- MeSH terms
- Acute Disease, Cardiology, Chronic Disease, Humans, Myocarditis, Terminology as Topic, Predictive Value of Tests, Risk Factors, Treatment Outcome, Consensus
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