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Nature Reviews. Clinical Oncology Jul 2023Immune-checkpoint-inhibitor-associated myocarditis has a high fatality rate, warranting the development of more-effective treatment strategies. Herein, we discuss a...
Immune-checkpoint-inhibitor-associated myocarditis has a high fatality rate, warranting the development of more-effective treatment strategies. Herein, we discuss a recent report of a series of patients who were managed using a novel approach that involved personalized abatacept dosing, ruxolitinib and close respiratory monitoring, which was associated with low mortality.
Topics: Humans; Immune Checkpoint Inhibitors; Myocarditis; Immunomodulation; Immunotherapy
PubMed: 37041273
DOI: 10.1038/s41571-023-00762-1 -
The Brazilian Journal of Infectious... 2024Chlamydia psittaci ‒ related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional...
Chlamydia psittaci ‒ related community-acquired pneumonia associated to acute myocarditis was diagnosed in a young man with no medical history, and a professional exposition to birds. The diagnosis was confirmed with positive specific polymerase chain reaction in bronchoalveolar lavage. The patient was treated with spiramycin for two weeks with anti-inflammatory treatment for myocarditis for three months. Clinical and biological improvement was rapidly observed followed by normalization of electrocardiogram and chest CT scan. No relapse was reported for over a two-year follow-up.
Topics: Humans; Male; Myocarditis; Psittacosis; Chlamydophila psittaci; Adult; Polymerase Chain Reaction; Community-Acquired Infections; Acute Disease; Young Adult
PubMed: 38679059
DOI: 10.1016/j.bjid.2024.103739 -
Frontiers in Immunology 2024Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced... (Review)
Review
Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, and lymphocyte activation gene-3 (LAG-3) have improved cancer patient outcomes by enhancing anti-tumor responses. However, some patients are unresponsive, and others experience immune-related adverse events (irAEs), affecting organs like the lung, liver, intestine, skin and now the cardiovascular system. These cardiac irAEs include conditions like myocarditis, atherosclerosis, pericarditis, arrhythmias, and cardiomyopathy. Ongoing clinical trials investigate promising alternative co-inhibitory receptor targets, including T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT). This review delves into the mechanisms of approved ICIs (CTLA-4, PD-1, PD-L1, and LAG-3) and upcoming options like Tim-3 and TIGIT. It explores the use of ICIs in cancer treatment, supported by both preclinical and clinical data. Additionally, it examines the mechanisms behind cardiac toxic irAEs, focusing on ICI-associated myocarditis and atherosclerosis. These insights are vital as ICIs continue to revolutionize cancer therapy, offering hope to patients, while also necessitating careful monitoring and management of potential side effects, including emerging cardiac complications.
Topics: Humans; CTLA-4 Antigen; Immune Checkpoint Inhibitors; B7-H1 Antigen; Hepatitis A Virus Cellular Receptor 2; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Myocarditis; Immunotherapy; Neoplasms; Antibodies, Monoclonal; Receptors, Immunologic; Lung; Cardiovascular System; Atherosclerosis
PubMed: 38375475
DOI: 10.3389/fimmu.2024.1340373 -
Current Cardiology Reports Jul 2023Myocarditis is an inflammation of the myocardium secondary to a variety of agents such as infectious pathogens, toxins, drugs, and autoimmune disorders. In our review,... (Review)
Review
PURPOSE OF REVIEW
Myocarditis is an inflammation of the myocardium secondary to a variety of agents such as infectious pathogens, toxins, drugs, and autoimmune disorders. In our review, we provide an overview of miRNA biogenesis and their role in the etiology and pathogenesis of myocarditis, evaluating future directions for myocarditis management.
RECENT FINDINGS
Advances in genetic manipulation techniques allowed to demonstrate the important role of RNA fragments, especially microRNAs (miRNAs), in cardiovascular pathogenesis. miRNAs are small non-coding RNA molecules that regulate the post-transcriptional gene expression. Advances in molecular techniques allowed to identify miRNA's role in pathogenesis of myocarditis. miRNAs are related to viral infection, inflammation, fibrosis, and apoptosis of cardiomyocytes, making them not only promising diagnostic markers but also prognostics and therapeutic targets in myocarditis. Of course, further real-world studies will be needed to assess the diagnostic accuracy and applicability of miRNA in the myocarditis diagnosis.
Topics: Humans; MicroRNAs; Myocarditis; Myocardium; Myocytes, Cardiac; Inflammation
PubMed: 37269474
DOI: 10.1007/s11886-023-01888-5 -
Arquivos Brasileiros de Cardiologia Jul 2023The diagnosis of acute myocarditis is usually made with clinical and laboratory parameters. This can sometimes be mixed up with diseases that have similar clinical...
BACKGROUND
The diagnosis of acute myocarditis is usually made with clinical and laboratory parameters. This can sometimes be mixed up with diseases that have similar clinical features, making the diagnosis difficult. Therefore, the use of more specific biomarkers, in addition to the classically used biomarkers such as troponin, will accelerate the diagnosis. In addition, these biomarkers may help us to understand the mechanism of myocarditis development and thus predict unpredictable clinical outcomes.
OBJECTIVE
This study aims to reveal the possible relationship between intestinal permeability and acute myocarditis.
METHODS
In this study, we wanted to evaluate serum levels of zonulin and presepsin in 138 consecutive subjects, including 68 patients with myocarditis and another 70 as the control group, matched for age, gender, and cardiovascular risk factors. P-values <0.05 were considered to be statistically significant.
RESULTS
Compared to the control group, zonulin and presepsin were significantly higher in the patient group with myocarditis (p < 0.001, for all). Zonulin levels were positively correlated with presepsin, peak CK-MB, and peak troponin levels (r = 0.461, p < 0.001; r = 0.744, p < 0.001; r = 0.627, p < 0.001; respectively). In regression analysis, presepsin and zonulin were determined as independent predictors for myocarditis (OR 1.002, 95% CI 1.001-1.003, p = 0.025; OR 12.331, 95% CI 4.261-35.689; p < 0.001; respectively). The predictive value of acute myocarditis of presepsin and zonulin in ROC curve analysis was statistically significant (p < 0.001, for both).
CONCLUSION
This study showed that zonulin and presepsin could be biomarkers that can be used in the diagnosis of myocarditis, and they can also be therapeutic targets by shedding light on the developmental mechanism of myocarditis.
Topics: Humans; Myocarditis; Biomarkers; Protein Precursors; Troponin; Peptide Fragments; Lipopolysaccharide Receptors
PubMed: 37556677
DOI: 10.36660/abc.20230017 -
EBioMedicine Oct 2023Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury.... (Review)
Review
BACKGROUND
Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF.
METHODS
This retrospective autopsy study included cases from the São Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers.
FINDINGS
Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test.
INTERPRETATION
Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10.
FUNDING
This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Bill and Melinda Gates Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Topics: Humans; Middle Aged; Yellow Fever; Myocarditis; Chemokine CXCL10; Retrospective Studies; Brazil; Heart Injuries; RNA; Autopsy; Biomarkers; Necrosis
PubMed: 37757571
DOI: 10.1016/j.ebiom.2023.104810 -
Journal of the American Heart... Sep 2023Myocarditis is most recognized in patients with moderate to severe, recent-onset heart failure. However, less typical presentations including myocardial infarction with... (Review)
Review
Myocarditis is most recognized in patients with moderate to severe, recent-onset heart failure. However, less typical presentations including myocardial infarction with normal coronary arteries and arrhythmias are important manifestations but less commonly recognized to be caused by myocarditis. Most cases of myocarditis can be self-limiting without specific treatment; however, appropriate identification of risk during the diagnostic process of myocarditis and once a diagnosis is established is of primordial importance to identify patients in need for more specific follow-up and management. We propose a flexible, multitiered approach to the diagnostic process, allowing for capturing of the spectrum of myocarditis at an early time-point, individualized use of diagnostic resources through disease severity phenotyping, and providing structured follow-up care once myocarditis is confirmed. Such diagnostic processes allow for identification of specific etiologies with potential therapeutic consequences or allows for the comprehension of disease chronicity by understanding genetic contributions or elements of persistent immune dysregulation and degree of cardiac damage. The article highlights the evolving field of immunophenotyping in myocarditis, generating a potential for the development of targeted therapeutic approaches. Currently long-term follow-up should be titrated to the refined risk assessments of patients with a diagnosis of myocarditis and includes arrhythmia monitoring and imaging when the results will likely impact management. Genetic testing should be considered in selected cases, and histologic diagnosis may be considered in nonresponders even at later stages.
Topics: Humans; Myocarditis; Heart; Genetic Testing; Immunophenotyping; Reference Standards
PubMed: 37589159
DOI: 10.1161/JAHA.123.031454 -
Global Heart 2023
Topics: Humans; COVID-19 Vaccines; Myocarditis; COVID-19; Pericarditis; Risk Factors
PubMed: 38533475
DOI: 10.5334/gh.1252 -
Redox Biology Feb 2024Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3...
M2 macrophage exosome-derived lncRNA AK083884 protects mice from CVB3-induced viral myocarditis through regulating PKM2/HIF-1α axis mediated metabolic reprogramming of macrophages.
Viral myocarditis (VM) is a clinically common inflammatory disease. Accumulating literature has indicated that M2 macrophages protect mice from Coxsackievirus B3 (CVB3)-induced VM. However, mechanisms that underlie M2 macrophages alleviating myocardial inflammation remain largely undefined. We found that M2 macrophage-derived exosomes (M2-Exo) can effectively attenuate VM. The long non-coding RNA (lncRNA) AK083884 in M2-Exo was found to be involved in the regulation of macrophage polarization by exosome lncRNA sequencing combined with in vitro functional assays. M2-Exo-derived AK083884 promotes macrophage M2 polarization and protects mice from CVB3-induced VM. Furthermore, we identified pyruvate kinase M2 (PKM2) as a protein target binding to AK083884 and found that PKM2 knockdown could promote macrophages to polarize to M2 phenotype. Intriguingly, functional assay revealed that downregulation of AK083884 promotes metabolic reprogramming in macrophages. In addition, co-immunoprecipitation was performed to reveal AK083884 could interact with PKM2 and inhibition of AK083884 can facilitate the binding of PKM2 and HIF-1α. Collectively, our findings uncovered an important role of M2-Exo-derived AK083884 in the regulation of macrophage polarization through metabolic reprogramming, identified a new participant in the development of VM and provided a potential clinically important therapeutic target.
Topics: Animals; Humans; Mice; Exosomes; Macrophages; Metabolic Reprogramming; Myocarditis; RNA, Long Noncoding; Virus Diseases
PubMed: 38160539
DOI: 10.1016/j.redox.2023.103016 -
Minerva Cardiology and Angiology Aug 2023Eosinophilic myocarditis (EM) is a rare, potentially life-threatening, form of inflammatory heart disease characterized by eosinophilic infiltration of the myocardium....
Eosinophilic myocarditis (EM) is a rare, potentially life-threatening, form of inflammatory heart disease characterized by eosinophilic infiltration of the myocardium. Different diseases are involved in its etiopathogeneses, such as eosinophilic granulomatosis with polyangiitis (or Churg-Strauss Syndrome), hypereosinophilic syndromes, parasitic infections, drug reactions, paraneoplastic syndromes and primary immunodeficiencies (e.g. Omenn Syndrome). There is a wide spectrum of clinical pictures at presentation ranging from chronic restrictive cardiomyopathy (Loeffler cardiomyopathy) to acute necrotizing myocarditis with cardiogenic shock. The genetic contribution and the environmental interplay, such as SARS-CoV-2 infection and related vaccines, are fields not well studied yet. Many non-invasive tools, mainly echocardiography and cardiac magnetic resonance imaging, along with invasive procedures, such as endomyocardial biopsy, are the crucial steps in the diagnostic workup. The correct diagnosis is a challenge but mandatory for timely and appropriate immunosuppressive therapy.
PubMed: 37545195
DOI: 10.23736/S2724-5683.23.06297-X