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Frontiers in Cardiovascular Medicine 2024Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be...
BACKGROUND
Immune checkpoint inhibitor (ICI)-induced myocarditis is a rare immune-related adverse event (irAE) with a fatality rate of 40%-46%. However, irMyocarditis can be asymptomatic. Thus, improved monitoring, detection and therapy are needed. This study aims to generate knowledge on pathogenesis and assess outcomes in cancer centers with intensified patient management.
METHODS
Patients with cardiac irAEs from the SERIO registry (www.serio-registry.org) were analyzed for demographics, ICI-related information (type of ICI, therapy line, combination with other drugs, onset of irAE, and tumor response), examination results, irAE treatment and outcome, as well as oncological endpoints. Cardiac biopsies of irMyocarditis cases ( = 12) were analyzed by Nanostring and compared to healthy heart muscle ( = 5) and longitudinal blood sampling was performed for immunophenotyping of irMyocarditis-patients ( = 4 baseline and = 8 during irAE) in comparison to patients without toxicity under ICI-therapy ( = 4 baseline and = 7 during ICI-therapy) using flow cytometry.
RESULTS
A total of 51 patients with 53 cardiac irAEs induced by 4 different ICIs (anti-PD1, anti-PD-L1, anti-CTLA4) were included from 12 centers in 3 countries. Altogether, 83.0% of cardiac irAEs were graded as severe or life-threatening, and 11.3% were fatal (6/53). Thus, in centers with established consequent troponin monitoring, work-up upon the rise in troponin and consequent treatment of irMyocarditis with corticosteroids and -if required-second-line therapy mortality rate is much lower than previously reported. The median time to irMyocarditis was 36 days (range 4-1,074 days) after ICI initiation, whereas other cardiotoxicities, e.g. asystolia or myocardiopathy, occurred much later. The cytokine-mediated signaling pathway was differentially regulated in myocardial biopsies as compared to healthy heart based on enrichment Gene Ontology analysis. Additionally, longitudinal peripheral blood mononuclear cell (PBMC) samples from irMyocarditis-patients indicated ICI-driven enhanced CD4+ Treg cells and reduced CD4+ T cells. Immunophenotypes, particularly effector memory T cells of irMyocarditis-patients differed from those of ICI-treated patients without side effects. LAG3 expression on T cells and PD-L1 expression on dendritic cells could serve as predictive indicators for the development of irMyocarditis.
CONCLUSION
Interestingly, our cohort shows a very low mortality rate of irMyocarditis-patients. Our data indicate so far unknown local and systemic immunological patterns in cardiotoxicity.
PubMed: 38915743
DOI: 10.3389/fcvm.2024.1408586 -
Journal of Korean Medical Science Jun 2024Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the...
BACKGROUND
Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea.
METHODS
We conducted a self-controlled case series study using the K-COV-N cohort (2018-2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0-28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI).
RESULTS
Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90-1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95-1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83-1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68-1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88-23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis.
CONCLUSION
For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.
Topics: Humans; Male; Female; Neoplasms; Republic of Korea; COVID-19 Vaccines; COVID-19; Middle Aged; Aged; SARS-CoV-2; Adult; Myocardial Infarction; Cardiovascular Diseases; Vaccination; Myocarditis; ChAdOx1 nCoV-19; Venous Thromboembolism; Stroke; Young Adult; Adolescent; Pericarditis
PubMed: 38915282
DOI: 10.3346/jkms.2024.39.e190 -
Frontiers in Immunology 2024Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic...
INTRODUCTION
Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management.
CASE PRESENTATION
A 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation.
DISCUSSION
EM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition.
CONCLUSION
Advancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM.
Topics: Humans; Hypereosinophilic Syndrome; Myocarditis; Female; Middle Aged; Heart Transplantation; Heart Failure; Eosinophilia
PubMed: 38911849
DOI: 10.3389/fimmu.2024.1418665 -
Frontiers in Cardiovascular Medicine 2024Cardio-oncology is a new field of interest in cardiology focusing on the detection and treatment of cardiovascular diseases, such as arrhythmias, myocarditis, and heart...
Cardio-oncology is a new field of interest in cardiology focusing on the detection and treatment of cardiovascular diseases, such as arrhythmias, myocarditis, and heart failure, as side-effects of chemotherapy and radiotherapy. The association between chemotherapeutic agents and arrhythmias has previously been established. Atrial tachyarrhythmias, particularly atrial fibrillation, are most common, but ventricular arrhythmias, including those related to treatment-induced QT prolongation, and bradyarrhythmias can also occur. However, the association between chemotherapeutic agents and atrioventricular re-entrant tachycardia (AVRT)/atrioventricular node re-entrant tachycardia (AVNRT) remains poorly understood. Here, we report a patient with new-onset AVRT/AVNRT and lung cancer who underwent chemotherapy. We considered that chemotherapy or cancer itself may have been a trigger for the initiation of paroxysmal AVRT/AVNRT, and that radiofrequency catheter ablation was effective in treating this type of tachycardia. Here, possible mechanisms and potential genes (mostly ion channels) involved in AVRT/AVNRT are summarized and the mechanisms underlying the possible regulatory patterns of cancer cells and chemotherapy on ion channels are reviewed. Finally, we considered that ion channel abnormalities may link cancer or chemotherapy to the onset of AVRT/AVNRT. The aim of the present study was to highlight the association between chemotherapeutic agents and AVRT/AVNRT and to provide new insights for future research. Understanding the intermediate mechanisms between chemotherapeutic agents and AVRT/AVNRT may be beneficial in preventing chemotherapy-evoked AVRT/AVNRT (and/or other arrhythmias) in future.
PubMed: 38911514
DOI: 10.3389/fcvm.2024.1367893 -
Cureus May 2024Myocarditis is an inflammatory disease of the cardiac muscle that manifests as chest pain, dyspnea, and other signs of heart failure. ST segment changes with elevated...
Myocarditis is an inflammatory disease of the cardiac muscle that manifests as chest pain, dyspnea, and other signs of heart failure. ST segment changes with elevated cardiac biomarkers mimic acute coronary syndromes. It is most commonly caused by viruses like the Epstein-Barr virus (EBV) and Coxsackie B virus, but it can also be due to cardiotoxic drugs like cyclophosphamide and cocaine or caused by a systemic infiltrative process like sarcoidosis or collagen vascular diseases. One relatively common bacterial cause of myocarditis is beta-hemolytic Group A , which is well known to lead, two to three weeks later, to rheumatic fever and pancarditis. Less commonly, it can cause non-rheumatic myocarditis, which occurs faster, with the pathogenesis not very well understood. We will be reporting a case series of two brothers suffering at the same time from non-rheumatic streptococcal A-isolated myocarditis, questioning the possibility of bacterial toxin-mediated myocarditis or inter-linked genetic predisposition.
PubMed: 38910751
DOI: 10.7759/cureus.60990 -
International Journal of Infectious... Jun 2024To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety.
OBJECTIVES
To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety.
METHODS
This target trial emulation study included individuals aged ≥ 12 during 2022. Propensity score matching was applied to ensure group balance. The Cox proportional hazard model was used to compare the effectiveness outcomes including COVID-19 infection, severity, 28-day hospitalization and 28-day mortality after infection. Poisson regression was used for safety outcomes including 32 adverse events of special interests between groups.
RESULTS
639,818 and 1,804,388 individuals were identified for the 2-dose and 3-dose comparison, respectively. In 2-dose and 3-dose comparison, the hazard ratios (HRs) (95% confidence intervals [CI]) were 0.844 [0.833-0.856] and 0.749 [0.743-0.755] for COVID-19 infection, 0.692 [0.656-0.731] and 0.582 [0.559-0.605] for hospitalization, 0.566 [0.417-0.769] and 0.590 [0.458-0.76] for severe COVID-19, and 0.563 [0.456-0.697] and 0.457 [0.372-0.561] for mortality for BNT162b2 recipients versus CoronaVac recipients, respectively. Regarding safety, 2-dose BNT162b2 recipients had a significantly higher incidence of myocarditis (Incidence rate ratio[IRR][95% CI]: 8.999 [1.14-71.017]) versus CoronaVac recipients, but the difference was insignificant in 3-dose comparison (IRR [95% CI]: 2.000 [0.500-7.996]).
CONCLUSIONS
BNT162b2 has higher effectiveness among individuals aged ≥ 12 against COVID-19-related outcomes for SARS-CoV-2 omicron compared to CoronaVac, with almost 50% lower mortality risk. (200 words).
PubMed: 38909928
DOI: 10.1016/j.ijid.2024.107149 -
Pathology, Research and Practice Jun 2024The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and...
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues.
MATERIALS AND METHODS
The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated.
RESULTS
In our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD.
DISCUSSION
The autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging.
CONCLUSION
Post-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.
PubMed: 38901140
DOI: 10.1016/j.prp.2024.155373 -
Cancer Medicine Jun 2024Severe immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective...
INTRODUCTION
Severe immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective study, we determined the incidence, treatment patterns and survival outcomes of this patient population at a comprehensive cancer center.
METHODS
All patients admitted to the ICU due to irAEs from ICI treatment between January 2015 and July 2022 were included. Descriptive statistics were reported on patient characteristics and treatment patterns during hospital admission. Overall survival (OS) from the time of ICU discharge to death was estimated using the Kaplan-Meier method.
RESULTS
Over the study period, 5561 patients received at least one ICI administration, of which 32 patients (0.6%) were admitted to the ICU due to irAEs. Twenty patients were treated with anti-PD-1 plus anti-CTLA-4 treatment, whereas 12 patients were treated with ICI monotherapy. The type of irAEs were de novo diabetes-related ketoacidosis (n = 8), immune-related gastrointestinal toxicity (n = 8), myocarditis or myositis (n = 10), nephritis (n = 3), pneumonitis (n = 2), and myelitis (n = 1). The median duration of ICU admission was 3 days (interquartile range: 2-6 days). Three patients died during ICU admission. The median OS of the patients who were discharged from the ICU was 18 months (95% confidence interval, 5.0-NA).
CONCLUSION
The incidence of irAEs leading to ICU admission in patients treated with ICI was low in this study. ICU mortality due to irAEs was low and a subset of this patient population even had long-term survival.
Topics: Humans; Immune Checkpoint Inhibitors; Male; Female; Intensive Care Units; Retrospective Studies; Middle Aged; Aged; Neoplasms; Adult; Incidence; Drug-Related Side Effects and Adverse Reactions; Aged, 80 and over; CTLA-4 Antigen
PubMed: 38899457
DOI: 10.1002/cam4.7302 -
Cureus May 2024Influenza, typically recognized as a respiratory ailment, can manifest severe cardiac complications, notably, myocarditis and pericarditis, with potential fatal... (Review)
Review
Influenza, typically recognized as a respiratory ailment, can manifest severe cardiac complications, notably, myocarditis and pericarditis, with potential fatal outcomes. Interestingly, influenza B demonstrates a reduced occurrence of troponin I elevation despite the risk of cardiac issues, such as isolated pericarditis. Interpreting the absence of troponin elevation as an indication of no cardiac involvement in cases of influenza B-related pericarditis may be contributing to poorer clinical outcomes. This trend may stem from the cellular tropism and unique affinity of certain influenza strains for pericardial cells rather than myocardiocytes. A thorough grasp of troponin dynamics in influenza is pivotal for customizing approaches aimed at improving clinical outcomes in myopericarditis cases.
PubMed: 38899234
DOI: 10.7759/cureus.60672 -
Molecular Medicine (Cambridge, Mass.) Jun 2024COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an... (Review)
Review
BACKGROUND
COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction.
PURPOSE
This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention.
METHODS
An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized.
RESULTS
The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection.
CONCLUSIONS
Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.
Topics: Humans; COVID-19; SARS-CoV-2; Cardiovascular Diseases; Pandemics; Pneumonia, Viral; Coronavirus Infections; Betacoronavirus; Myocarditis
PubMed: 38898389
DOI: 10.1186/s10020-024-00855-2