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Current Opinion in Cardiology Jul 2024While pediatric myocarditis incidence has increased since the coronavirus disease 2019 (COVID-19) pandemic, there remain questions regarding diagnosis, risk... (Review)
Review
PURPOSE OF REVIEW
While pediatric myocarditis incidence has increased since the coronavirus disease 2019 (COVID-19) pandemic, there remain questions regarding diagnosis, risk stratification, and optimal therapy. This review highlights recent publications and continued unanswered questions related to myocarditis in children.
RECENT FINDINGS
Emergence from the COVID-19 era has allowed more accurate description of the incidence and prognosis of myocarditis adjacent to COVID-19 infection and vaccine administration as well that of multi-system inflammatory disease in children (MIS-C). As cardiac magnetic resonance technology has shown increased availability and evidence in pediatric myocarditis, it is important to understand conclusions from adult imaging studies and define the use of this imaging biomarker in children. Precision medicine has begun to allow real-time molecular evaluations to help diagnose and risk-stratify cardiovascular diseases, with emerging evidence of these modalities in myocarditis.
SUMMARY
Recent information regarding COVID-19 associated myocarditis, cardiac magnetic resonance, and molecular biomarkers may help clinicians caring for children with myocarditis and identify needs for future investigations.
Topics: Humans; Myocarditis; COVID-19; Child; SARS-CoV-2; Biomarkers; Magnetic Resonance Imaging; Prognosis; Systemic Inflammatory Response Syndrome
PubMed: 38661130
DOI: 10.1097/HCO.0000000000001151 -
Reviews in Medical Virology Nov 2023Myocarditis can result from various infectious and non-infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes,... (Review)
Review
Myocarditis can result from various infectious and non-infectious causes that can lead to dilated cardiomyopathy (DCM) and heart failure. Among the infectious causes, viruses are commonly suspected. But the challenge is our inability to demonstrate infectious viral particles during clinical presentations, partly because by that point, the viruses would have damaged the tissues and be cleared by the immune system. Therefore, viral signatures such as viral nucleic acids and virus-reactive antibodies may be the only readouts pointing to viruses as potential primary triggers of DCM. Thus, it becomes hard to explain persistent inflammatory infiltrates that might occur in individuals affected with chronic myocarditis/DCM manifesting myocardial dysfunctions. In these circumstances, autoimmunity is suspected, and antibodies to various autoantigens have been demonstrated, suggesting that immune therapies to suppress the autoimmune responses may be necessary. From this perspective, we endeavoured to determine whether or not the known viral causes are associated with development of autoimmune responses to cardiac antigens that include both cardiotropic and non-cardiotropic viruses. If so, what their nature and significance are in developing chronic myocarditis resulting from viruses as primary triggers.
Topics: Humans; Myocarditis; Autoimmunity; Cardiomyopathy, Dilated; Heart Failure; Virus Diseases
PubMed: 37658748
DOI: 10.1002/rmv.2478 -
European Heart Journal Dec 2023While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear.
BACKGROUND AND AIMS
While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear.
METHODS
Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders.
RESULTS
Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016).
CONCLUSIONS
Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.
Topics: Adult; Humans; Myocarditis; Biopsy; Heart Transplantation; Cardiac Catheterization; Magnetic Resonance Imaging; Retrospective Studies; Myocardium
PubMed: 37941449
DOI: 10.1093/eurheartj/ehad707 -
Rheumatology International Nov 2023To discuss what is currently known about myocarditis in the context of major connective tissue diseases, including Systemic lupus erythematosus, Rheumatoid Arthritis,... (Review)
Review
To discuss what is currently known about myocarditis in the context of major connective tissue diseases, including Systemic lupus erythematosus, Rheumatoid Arthritis, Sjogren, Dermato-myositis and Polymyositis, Systemic Sclerosis, and Mixed connective tissue disease. Variability exists between studies regarding the incidence of myocarditis in connective tissue diseases, which is hypothesized to be the result of its subclinical course in most cases. Extensive gaps of knowledge exist in the field of pathophysiology. Although endomyocardial biopsy remains to be the gold standard for diagnosis, the advancement in non-invasive modalities such as cardiac MRI, echocardiography, and nuclear medicine has allowed for earlier and more frequent detection of myocarditis. A lack of treatment guidelines was found across the different connective tissue diseases. Most of the literature available revolved around myocarditis in the context of Systemic lupus erythematosus. Numerous recent studies were published that contributed to advancements in diagnosis and treatment however, there remains a lack of diagnostic and treatment guidelines.
Topics: Humans; Myocarditis; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Polymyositis; Mixed Connective Tissue Disease
PubMed: 37587233
DOI: 10.1007/s00296-023-05428-w -
European Heart Journal Dec 2023Cardiac magnetic resonance offers multiple facets in the diagnosis, risk stratification, and management of patients with myocardial diseases. Particularly, its feature... (Review)
Review
Cardiac magnetic resonance offers multiple facets in the diagnosis, risk stratification, and management of patients with myocardial diseases. Particularly, its feature to precisely monitor disease activity lends itself to quantify response to novel therapeutics. This review critically appraises the value of cardiac magnetic resonance imaging biomarkers as surrogate endpoints for prospective clinical trials. The primary focus is to comprehensively outline the value of established cardiac magnetic resonance parameters in myocardial diseases. These include heart failure, cardiac amyloidosis, iron overload cardiomyopathy, hypertrophic cardiomyopathy, cardio-oncology, and inflammatory cardiomyopathies like myocarditis and sarcoidosis.
Topics: Humans; Prospective Studies; Cardiomyopathies; Magnetic Resonance Imaging; Myocarditis; Magnetic Resonance Spectroscopy; Biomarkers
PubMed: 37700499
DOI: 10.1093/eurheartj/ehad510 -
Circulation Research Jun 2024Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus... (Review)
Review
Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.
Topics: Myocarditis; Humans; Autoimmune Diseases; Animals; Autoantibodies; Autoimmunity; T-Lymphocytes; Autoantigens; Cardiac Myosins
PubMed: 38843292
DOI: 10.1161/CIRCRESAHA.124.323816 -
Journal of the American Heart... Oct 2023Background Sarcoidosis is an inflammatory, granulomatous disease of unknown cause affecting multiple organs, including the heart. Untreated, unresolved granulomatous...
Background Sarcoidosis is an inflammatory, granulomatous disease of unknown cause affecting multiple organs, including the heart. Untreated, unresolved granulomatous inflammation can lead to cardiac fibrosis, arrhythmias, and eventually heart failure. Here we characterize the cardiac phenotype of mice with chronic activation of mammalian target of rapamycin (mTOR) complex 1 signaling in myeloid cells known to cause spontaneous pulmonary sarcoid-like granulomas. Methods and Results The cardiac phenotype of mice with conditional deletion of the () gene in CD11c cells (TSC2CD11c-Cre; termed ) and controls () was determined by histological and immunological stains. Transthoracic echocardiography and invasive hemodynamic measurements were performed to assess myocardial function. animals were treated with either everolimus, an mTOR inhibitor, or Bay11-7082, a nuclear factor-kB inhibitor. Activation of mTOR signaling was evaluated on myocardial samples from sudden cardiac death victims with a postmortem diagnosis of cardiac sarcoidosis. Chronic activation of mTORC1 signaling in CD11c cells was sufficient to initiate progressive accumulation of granulomatous infiltrates in the heart, which was associated with increased fibrosis, impaired cardiac function, decreased plakoglobin expression, and abnormal connexin 43 distribution, a substrate for life-threatening arrhythmias. Mice treated with the mTOR inhibitor everolimus resolved granulomatous infiltrates, prevented fibrosis, and improved cardiac dysfunction. In line, activation of mTOR signaling in CD68 macrophages was detected in the hearts of sudden cardiac death victims who suffered from cardiac sarcoidosis. Conclusions To our best knowledge this is the first animal model of cardiac sarcoidosis that recapitulates major pathological hallmarks of human disease. mTOR inhibition may be a therapeutic option for patients with cardiac sarcoidosis.
Topics: Animals; Humans; Mice; Death, Sudden, Cardiac; Disease Models, Animal; Everolimus; Fibrosis; Mammals; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes; Myocarditis; Sarcoidosis; Sirolimus; TOR Serine-Threonine Kinases; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins; Cardiomyopathies
PubMed: 37750561
DOI: 10.1161/JAHA.123.030478 -
Heart (British Cardiac Society) Apr 2024In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly...
OBJECTIVE
In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly recommended in guidelines. This systematic review aims to summarise current approaches in diagnosing and treating EM with a particular emphasis on the utilisation and value of alternative diagnostic methods.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using the keywords "eosinophilic myocarditis" from their inception to 10 September 2022.
RESULTS
We included 239 articles, including 8 observational studies and 274 cases, in this review. The median patient age was 45 years. Initial presentations were non-specific, including dyspnoea (50.0%) and chest pain (39.4%). The aetiologies of EM were variable with the most common being idiopathic (28.8%) and eosinophilic granulomatosis polyangiitis (19.3%); others included drug-induced (13.1%) and hypereosinophilic syndrome (12.8%). 82.4% received an EM diagnosis by EMB while 17.6% were diagnosed based on clinical reasoning and cardiac MRI (CMR). CMR-diagnosed patients exhibited a better risk profile at diagnosis, particularly higher left ventricular ejection fraction and less need for inotropic or mechanical circulatory supports. Glucocorticoids were the primary treatment with variability in dosages and regimens.
CONCLUSION
EMB is the mainstay for diagnostic testing for EM. CMR is potentially helpful for screening in appropriate clinical scenarios. Regarding treatment, there is no consensus regarding the optimal dosage of corticosteroids. Large clinical trials are warranted to further explore the utility of CMR in the diagnosis of EM and steroid regimen in treating EM.
Topics: Humans; Myocarditis; Eosinophilia; Biopsy; Myocardium
PubMed: 37963727
DOI: 10.1136/heartjnl-2023-323225 -
Cardiovascular Toxicity Associated With Immune Checkpoint Inhibitor Therapy: A Comprehensive Review.Critical Pathways in Cardiology Sep 2023Immune checkpoint inhibitors (ICIs), a significant breakthrough treatment of cancer, exert their function through enhancing the immune system's ability to recognize and... (Review)
Review
Immune checkpoint inhibitors (ICIs), a significant breakthrough treatment of cancer, exert their function through enhancing the immune system's ability to recognize and attack cancer cells. However, these revolutionary cancer treatments have been associated with a range of immune-related adverse effects, including cardiovascular toxicity. The most commonly reported cardiovascular toxicities associated with ICIs are myocarditis, pericarditis, arrhythmias, and vasculitis. These cardiovascular manifestations are often severe and can lead to life-threatening complications. Therefore, prompt identification and management of these toxicities is critical, and a multidisciplinary teamwork by cardiologists and oncologists are required to ensure optimal patient outcomes. In this review, we summarize the current knowledge on the mechanisms underlying ICI-associated cardiovascular toxicity, clinical presentations of these toxicities, potential risk factors, diagnosis, management, and surveillance strategies during ICI therapy. While ICIs have already transformed cancer treatment, further research is needed to better understand and manage their immune-related cardiovascular effects, and possibly, to identify biomarkers which can predict the occurrence of these cardiovascular complications.
Topics: Humans; Immune Checkpoint Inhibitors; Myocarditis; Risk Factors; Neoplasms; Pericarditis
PubMed: 37363862
DOI: 10.1097/HPC.0000000000000327 -
International Journal of Cardiology Jun 2024Acute myocarditis is an acute inflammatory cardiomyopathy associated with cardiac damage triggered by a virus or a pathological immune activation. It may present with a... (Review)
Review
Acute myocarditis is an acute inflammatory cardiomyopathy associated with cardiac damage triggered by a virus or a pathological immune activation. It may present with a wide range of clinical presentations, ranging from mild symptoms to severe forms like fulminant myocarditis, characterized by hemodynamic compromise and cardiogenic shock. The immune system plays a central role in the pathogenesis of myocarditis. In fact, while its function is primarily protective, aberrant responses can be detrimental. In this context, both innate and adaptive immunity play pivotal roles; notably, the innate system offers a non-specific and immediate defense, while the adaptive provides specialized protection with immunological memory. However, dysregulation in these systems can misidentify cardiac tissue, triggering autoimmune reactions and possibly leading to significant cardiac tissue damage. This review highlights the importance of innate and adaptive immune responses in the progression and treatment of acute myocarditis.
Topics: Humans; Myocarditis; Heart; Shock, Cardiogenic; Adaptive Immunity; Immunity, Innate
PubMed: 38403204
DOI: 10.1016/j.ijcard.2024.131901