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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 -
Physical Medicine and Rehabilitation... Aug 2023Cardiovascular complications associated with the severe acute respiratory syndrome coronavirus 2 infection are common and lead to high mortality in the acute phase and... (Review)
Review
Cardiovascular complications associated with the severe acute respiratory syndrome coronavirus 2 infection are common and lead to high mortality in the acute phase and high morbidity in the chronic phase impacting an individual's quality of life and health outcomes. Patients afflicted with coronavirus disease-2019 (COVID-19) infection display an increased risk for myocarditis, dysrhythmia, pericarditis, ischemic heart disease, heart failure, and thromboembolism. Although cardiovascular complications are reported across all patients with COVID-19, hospitalized patients with severe infection are most vulnerable. The underline pathobiology remains poorly defined albeit complex. Following current guidelines in decision-making for evaluation and management in addition to the beginning or returning exercise is recommended.
Topics: Humans; COVID-19; SARS-CoV-2; Quality of Life; Myocarditis; Cardiovascular Diseases
PubMed: 37419531
DOI: 10.1016/j.pmr.2023.03.003 -
Clinical Cardiology Jul 2023
Topics: Humans; Antipyretics; Myocarditis
PubMed: 37249254
DOI: 10.1002/clc.24026 -
Drug Safety Sep 2023Immune checkpoint inhibitors (ICIs) have revolutionized the treatment and care of patients with cancer owing to unique features, including the occurrence of the... (Review)
Review
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment and care of patients with cancer owing to unique features, including the occurrence of the so-called immune-related adverse events (irAEs). A multidisciplinary team, possibly including a cardio-oncology specialist, is warranted to achieve a favorable patient outcome. Cardiovascular toxicity, especially myocarditis, emerged as a life-threatening irAE in the real-word setting, and the European Society of Cardiology has recently published the first guideline on cardio-oncology to increase awareness and promote a standardized approach to tackle this complex multimodal issue, including diagnostic challenges, assessment, treatment, and surveillance of patients with cancer receiving ICIs. In this article, through a question & answer format made up of case vignettes, we offer a clinically oriented overview on the latest advancements of ICI-related cardiovascular toxicity, focusing on myocarditis and associated irAEs (myositis and myasthenia gravis within the so-called overlap syndrome), with the purpose of assisting clinicians and healthcare professionals in daily clinical practice.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Myocarditis; Neoplasms; Medical Oncology
PubMed: 37341925
DOI: 10.1007/s40264-023-01320-5 -
Journal of Clinical Medicine Jul 2023A minority of patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) develop cardiovascular complications, such as acute cardiac lesions with elevated... (Review)
Review
A minority of patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) develop cardiovascular complications, such as acute cardiac lesions with elevated troponins, de novo systolic heart failure, pericardial effusion and, rarely, acute myocarditis. The prevalence of COVID-19-related myocarditis ranges from 10 to 105 cases per 100,000 COVID-19-infected individuals, with a male predominance (58%) and a median age of 50 years. The etiopathogenetic mechanism is currently unclear, but may involve direct virus-mediated damage or an exaggerated immune response to the virus. Mortality is high, as fulminant myocarditis (FM) develops very often in the form of cardiogenic shock and ventricular arrhythmias. Hence, medical therapy with ACE inhibitors and beta-blockers may not always be sufficient, in which case inotropic and immunosuppressive drugs, most commonly corticosteroids, may be necessary. In this review we analyze the current data on COVID-19 myocarditis, management strategies and therapy, with a brief description of COVID-19 vaccine-associated myocarditis to help clinicians dealing with this peculiar form of myocarditis.
PubMed: 37510815
DOI: 10.3390/jcm12144700 -
Diagnostics (Basel, Switzerland) Sep 2023Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of... (Review)
Review
Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic methods. The multitude of different etiological factors, the diversity of the clinical picture, and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated with diseases that in their natural course can lead to myocardial involvement, as well as the iatrogenic cause of myocarditis, which is due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, such as changes in ECG and echocardiography readings, has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive and is the gold standard for diagnosis and clinical follow-up of these patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening cases with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support, and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.
PubMed: 37835816
DOI: 10.3390/diagnostics13193073 -
Current Oncology Reports Jul 2023Immune checkpoint inhibitors (ICIs) have improved the field of cancer, especially in patients with advanced malignancies. Nevertheless, cardiovascular immune-related... (Review)
Review
PURPOSE OF REVIEW
Immune checkpoint inhibitors (ICIs) have improved the field of cancer, especially in patients with advanced malignancies. Nevertheless, cardiovascular immune-related adverse events (irAEs) with high mortality and morbidity have been observed, including myocarditis, pericarditis, and vasculitis. To date, only a few clinical risk factors have been described and are currently being investigated.
RECENT FINDINGS
In this review, we address the four most prevailing risk factors for cardiovascular irAEs. ICI combination therapy is a predominant risk factor for developing ICI-mediated myocarditis. Additionally, ICI combined with other anti-cancer treatments (e.g., tyrosine kinase inhibitors, radiation, chemotherapy) seems to increase the risk of developing cardiovascular irAEs. Other risk factors include female sex, pre-existing cardiovascular disease, and specific tumors, on which we will further elaborate in this review. An a priori risk strategy to determine who is at risk to develop these cardiovascular irAEs is needed. Insights into the impact of risk factors are therefore warranted to help clinicians improve care and disease management in these patients.
Topics: Humans; Female; Immune Checkpoint Inhibitors; Myocarditis; Antineoplastic Agents, Immunological; Cardiovascular System; Neoplasms; Risk Factors
PubMed: 37079251
DOI: 10.1007/s11912-023-01414-4 -
Biomedicines Mar 2024Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad... (Review)
Review
Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis.
PubMed: 38540269
DOI: 10.3390/biomedicines12030656 -
Oncology Reviews 2023Immune checkpoint inhibitors (ICIs) have reshaped and have become a well-established treatment modality for multiple advanced-stage malignancies. ICIs block the immune... (Review)
Review
Immune checkpoint inhibitors (ICIs) have reshaped and have become a well-established treatment modality for multiple advanced-stage malignancies. ICIs block the immune system regulatory checkpoints, namely CTLA-4 and PD-1/PDL1, which provokes excess immune response against self-antigens. Immune modulation with ICIs can result in diverse immune-related adverse events targeting organ systems. Several cases of ICI-related cardiotoxicity were reported, while the actual incidence was likely underestimated due to heterogeneous clinical presentation. These include, but are not limited to, myocarditis, pericarditis, atherosclerosis, and arrhythmia. EKG, Troponin, Echocardiogram (TTE), and Cardiac MRI (CMRI) are indispensable diagnostic tools to aid in the management of cardiac adverse effects. Herein, we review the ICI-mediated cardiovascular adverse events, diagnosis, treatment strategies, and reintroduction of ICIs post-cardiotoxicity.
PubMed: 38045806
DOI: 10.3389/or.2023.11456 -
Journal For Immunotherapy of Cancer Jan 2024Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can...
Immune checkpoint inhibitor (ICI) treatment has become an important therapeutic option for various cancer types. Although the treatment is effective, ICI can overstimulate the patient's immune system, leading to potentially severe immune-related adverse events (irAEs), including hepatitis, colitis, pneumonitis and myocarditis. The initial mainstay of treatments includes the administration of corticosteroids. There is little evidence how to treat steroid-resistant (sr) irAEs. It is mainly based on small case series or single case reports. This systematic review summarizes available evidence about sr-irAEs. We conducted a systematic literature search in PubMed. Additionally, we included European Society for Medical Oncology, Society for Immunotherapy of Cancer, National Comprehensive Cancer Network and American Society of Clinical Oncology Guidelines for irAEs in our assessment. The study population of all selected publications had to include patients with cancer who developed hepatitis, colitis, pneumonitis or myocarditis during or after an immunotherapy treatment and for whom corticosteroid therapy was not sufficient. Our literature search was not restricted to any specific cancer diagnosis. Case reports were also included. There is limited data regarding life-threatening sr-irAEs of colon/liver/lung/heart and the majority of publications are single case reports. Most publications investigated sr colitis (n=26), followed by hepatitis (n=21), pneumonitis (n=17) and myocarditis (n=15). There is most data for mycophenolate mofetil (MMF) to treat sr hepatitis and for infliximab, followed by vedolizumab, to treat sr colitis. Regarding sr pneumonitis there is most data for MMF and intravenous immunoglobulins (IVIG) while data regarding infliximab are conflicting. In sr myocarditis, most evidence is available for the use of abatacept or anti-thymocyte globulin (ATG) (both with or without MMF) or ruxolitinib with abatacept. This review highlights the need for prompt recognition and treatment of sr hepatitis, colitis, pneumonitis and myocarditis. Guideline recommendations for sr situations are not defined precisely. Based on our search, we recommend-as first line treatment-(1) MMF for sr hepatitis, (2) infliximab for sr colitis, followed by vedolizumab, (3) MMF and IVIG for sr pneumonitis and (4) abatacept or ATG (both with or without MMF) or ruxolitinib with abatacept for sr myocarditis. These additional immunosuppressive agents should be initiated promptly if there is no sufficient response to corticosteroids within 3 days.
Topics: Humans; Abatacept; Adrenal Cortex Hormones; Colitis; Hepatitis; Immunoglobulins, Intravenous; Infliximab; Mycophenolic Acid; Myocarditis; Neoplasms; Nitriles; Pneumonia; Pyrazoles; Pyrimidines
PubMed: 38233099
DOI: 10.1136/jitc-2023-007409