☆ 3.8 Review

Immune checkpoint inhibitor-associated myocarditis: from pathophysiology to rechallenge of therapy - a narrative review

FUTURE CARDIOLOGY (2023)

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Electrocardiographic Features of Immune Checkpoint Inhibitor-Associated Myocarditis

Wenhua Song et al.

Summary: Immune checkpoint inhibitors (ICIs) have both beneficial effects, improving cancer-related outcomes, and adverse effects, such as myocarditis. Identifying electrocardiographic manifestations of ICI-related myocarditis is important for clinical management. A review of clinical studies and case reports found that patients on ICIs can present with various arrhythmias, ST-T segment changes unrelated to coronary artery disease, and low voltages in multiple leads.

CURRENT PROBLEMS IN CARDIOLOGY (2023)

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ESC 2022 guidelines on cardio-oncology in collaboration with the European Hematology Association (EHA), European Society of Therapeutic Radiology and Oncology (ESTRO) and International Cardio-Oncology Society (IC- OS) developed by the Cardio-Oncology Task Force of the European Society of Cardiology (ESC)

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Article Oncology

Abatacept/Ruxolitinib and Screening for Concomitant Respiratory Muscle Failure to Mitigate Fatality of Immune-Checkpoint Inhibitor Myocarditis

Joe-Elie Salem et al.

Summary: ICI-associated myotoxicity is a life-threatening condition involving both myocarditis and myositis. This study reports a strategy involving the identification and management of severe ICI myocarditis, concomitant respiratory muscle involvement, and treatment with abatacept and ruxolitinib. The implementation of systematic screening and targeted treatment resulted in a significant decrease in myotoxicity-related fatality rates.

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Review Cardiac & Cardiovascular Systems

State-of-the-Art of Endomyocardial Biopsy on Acute Myocarditis and Chronic Inflammatory Cardiomyopathy

Enrico Ammirati et al.

Summary: This review discusses the application of endomyocardial biopsy (EMB) in the diagnosis of myocarditis, including the indications, strengths, and shortcomings of EMB techniques and the ongoing innovations in this field. EMB provides unique diagnostic and prognostic information for myocarditis. Recent technological advancements have improved the utility of EMB.

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Article Oncology

Biomarker Trends, Incidence, and Outcomes of Immune Checkpoint Inhibitor-Induced Myocarditis

Alexi Vasbinder et al.

Summary: This study aimed to determine the biomarker trends and their association with the incidence and outcomes of immune checkpoint inhibitor (ICI) myocarditis. The results showed that patients with ICI myocarditis had elevated levels of AST, ALT, and CPK. An increase in noncardiac biomarkers, especially CPK, during ICI treatment should prompt further evaluation for ICI myocarditis.

JACC: CARDIOONCOLOGY (2022)

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Article Cardiac & Cardiovascular Systems

2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC) Endorsed by the Association for European Paediatric and Congenital Cardiology (AEPC)

Katja Zeppenfeld et al.

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2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS) Developed by the task force on cardio-oncology of the European Society of Cardiology (ESC)

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Review Pharmacology & Pharmacy

Immune Checkpoint Inhibitor Cardiotoxicity: Understanding Basic Mechanisms and Clinical Characteristics and Finding a Cure

Sarah Waliany et al.

Summary: ICIs alter the immune system's response to cancerous tissues but can lead to varying degrees of autoimmunity, with cardiovascular complications such as myocarditis emerging as significant side effects. Understanding the mechanisms underlying these toxicities may help improve patient outcomes by reducing treatment-related morbidity.

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021 (2021)

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Clinical Pharmacology and Interplay of Immune Checkpoint Agents: A Yin-Yang Balance

Arthur Geraud et al.

Summary: T cells play a crucial role in immune system balance, and immune checkpoint proteins regulate their function. CTLA-4 agonists are used to treat rheumatologic immune disorders, while CTLA-4, PD-1, and PD-L1 antagonists are approved for multiple cancer types. However, immune checkpoint inhibitors may be associated with immune-related adverse events.

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021 (2021)

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Cardiovascular Toxicity of Immune Checkpoint Inhibitors: Clinical Risk Factors

Flora Pirozzi et al.

Summary: Immune checkpoint inhibitors have shown significant improvements in the outcomes of many malignancies, but also bring about serious immune-related cardiovascular adverse events. Understanding patients' risk factors is crucial for the proper management of these toxicities, which can include autoimmune myocarditis among others.

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Article Oncology

A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitors-Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention

Spencer C. Wei et al.

Summary: This study presents a robust preclinical model of ICI-associated myocarditis that recapitulates the clinical syndrome. Using this model, researchers demonstrate that CTLA4 and PD-1 (ICI targets) functionally interact in the development of myocarditis, and intervention with CTLA4-Ig (abatacept) attenuates myocarditis, providing mechanistic rationale and preclinical support for therapeutic clinical studies.

CANCER DISCOVERY (2021)

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Article Rheumatology

Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors

Jeffrey Aldrich et al.

Summary: The study found that ICI-myositis is rare but severe in cancer patients receiving immune checkpoint inhibitors, with over half of the patients presenting with overlap manifestations leading to worse outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies remain to be determined.

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Review Cardiac & Cardiovascular Systems

Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies

Shirley Xu et al.

Summary: The approval of immune checkpoint inhibitors has revolutionized cancer treatment, but also led to a wide range of immune-related adverse events, including severe cardiac effects. Challenges remain in diagnosing cardiac events and further research is needed in this expanding field of cancer immunotherapy.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2021)

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Review Cardiac & Cardiovascular Systems

Mechanisms of Cardiovascular Toxicities Associated With Immunotherapies

Alan H. Baik et al.

Summary: Immune-based therapies have transformed cancer treatments, but cardiovascular complications arising from these therapies present new challenges in cardio-oncology. Understanding the mechanisms of immune activation and associated cardiovascular toxicities is crucial for addressing the cardiovascular sequelae of immunotherapy.

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Article Pharmacology & Pharmacy

Case Series of Steroid-Resistant Immune Checkpoint Inhibitor Associated Myocarditis: A Comparative Analysis of Corticosteroid and Tofacitinib Treatment

Cong Wang et al.

Summary: By conducting a retrospective analysis of ICI-associated myocarditis, we identified two subgroups based on corticosteroid responsiveness: corticosteroid-sensitive and corticosteroid-resistant. Corticosteroid-resistant patients require larger doses and longer duration of corticosteroid treatment, with a higher mortality rate. The use of tofacitinib in corticosteroid-resistant patients may offer a new therapeutic option for ICI-associated myocarditis.

FRONTIERS IN PHARMACOLOGY (2021)

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Article Oncology

68Ga-DOTATOC PET/CT to detect immune checkpoint inhibitor-related myocarditis

Sarah Boughdad et al.

Summary: This study aimed to evaluate the value of Ga-68-DOTATOC PET/CT for the early detection and diagnosis of ICI-related myocarditis. The research found that Ga-68-DOTATOC PET/CT is a highly sensitive method that can effectively detect early myocardial inflammation, especially useful for patients with concomitant myositis.

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Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Walid Shalata et al.

Summary: This review discusses the toxic effects on the heart caused by immune checkpoint inhibitors used in cancer treatment. These effects tend to occur early in treatment and have significant implications for treating physicians.

CANCERS (2021)

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Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor-Associated Myocarditis

Paaladinesh Thavendiranathan et al.

Summary: Myocarditis as a complication of immune checkpoint inhibitor therapy can be fatal, and the utility of CMR T1 and T2 mapping in these patients is limited. This study found that abnormal T1 and T2 values were common among patients with ICI myocarditis, and some patients met the criteria for nonischemic myocardial injury and myocardial edema.

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Cardiotoxicity of Immune Checkpoint Inhibitors

Rushin P. Patel et al.

Summary: ICIs have improved survival in various cancers, but can lead to cardiovascular toxicity, especially myocarditis, with severe outcomes. Early recognition and prompt treatment are crucial for managing cardiovascular toxicity associated with ICIs.

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2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

Theresa A. McDonagh et al.

EUROPEAN HEART JOURNAL (2021)

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Article Cardiac & Cardiovascular Systems

Cardiotoxicity associated with immune checkpoint inhibitor therapy: a meta-analysis

Nestor Rubio-Infante et al.

Summary: This study estimated the incidence of cardiac irAEs in patients treated with ICIs, finding myocarditis to be the most frequent one. Despite the low incidence, the high mortality rate associated with cardiac irAEs is an important consideration. Dual ICI therapies seem to provoke higher rates of cardiac irAEs than monotherapies or ICIs plus chemotherapy.

EUROPEAN JOURNAL OF HEART FAILURE (2021)

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Article Cardiac & Cardiovascular Systems

Immune checkpoint inhibitor myocarditis: elucidating the spectrum of disease through endomyocardial biopsy

Nicolas L. Palaskas et al.

Summary: A grading system was developed for ICI myocarditis based on degree of inflammatory infiltrate, with some patients able to continue ICI without immunosuppressive therapy and have good cardiovascular outcomes. Further studies are needed to identify low-risk patients who can safely receive ICI therapy.

EUROPEAN JOURNAL OF HEART FAILURE (2021)

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Review Cardiac & Cardiovascular Systems

Clinical Strategy for the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Associated Myocarditis A Narrative Review

Lorenz H. Lehmann et al.

Summary: ICIs have become an important treatment option for various cancer types, but their use is associated with the risk of myocarditis. The diagnosis of ICI-associated myocarditis can be challenging and relies on a combination of clinical suspicion, cardiac biomarkers, imaging, and endomyocardial biopsy. Combining different types of ICIs may increase the risk of developing myocarditis.

JAMA CARDIOLOGY (2021)

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Letter Oncology

Myocarditis Surveillance With High-Sensitivity Troponin I During Cancer Treatment With Immune Checkpoint Inhibitors

Sarah Waliany et al.

JACC: CARDIOONCOLOGY (2021)

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The Evolving Immunotherapy Landscape and the Epidemiology, Diagnosis, and Management of Cardiotoxicity JACC: CardioOncology Primer

Lili Zhang et al.

Summary: ICIs are newer therapies being increasingly applied to cancer patients, but the complexity in diagnosing ICI-related cardiotoxicity is increasing. Research and continued collaborations are urgently needed to provide evidence-based cardiovascular care for this rapidly expanding and vulnerable cohort of patients.

JACC: CARDIOONCOLOGY (2021)

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Article Cardiac & Cardiovascular Systems

Recognition and Initial Management of Fulminant Myocarditis A Scientific Statement From the American Heart Association

Robb D. Kociol et al.

CIRCULATION (2020)

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Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis

Magid Awadalla et al.

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Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

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Tocilizumab for refractory severe immune checkpoint inhibitor-associated myocarditis

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Article Medical Laboratory Technology

Histopathologic Characterization of Myocarditis Associated With Immune Checkpoint Inhibitor Therapy

Irina Sobol et al.

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Programmed Cell Death-1: Programmed Cell Death-Ligand 1 Interaction Protects Human Cardiomyocytes Against T-Cell Mediated Inflammation and Apoptosis Response In Vitro

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer

Charles Dolladille et al.

JAMA ONCOLOGY (2020)

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Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis

Lili Zhang et al.

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Immune checkpoint inhibitor-induced myositis, the earliest and most lethal complication among rheumatic and musculoskeletal toxicities

Yves Allenbach et al.

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Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy An Expert Consensus Document

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Acute autoimmune myocarditis and hepatitis due to ipilimumab monotherapy for malignant melanoma

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Jiun-Ruey Hu et al.

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Myocarditis Surveillance in Patients with Advanced Melanoma on Combination Immune Checkpoint Inhibitor Therapy: The Memorial Sloan Kettering Cancer Center Experience

Katherine Lee Chuy et al.

ONCOLOGIST (2019)

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Richeek Pradhan et al.

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Khashayar Esfahani et al.

NEW ENGLAND JOURNAL OF MEDICINE (2019)

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Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis

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