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Communicable Diseases Intelligence... Jun 2024This report summarises Australia's spontaneous (passive) surveillance data for adverse events following immunisation (AEFI) for coronavirus disease 2019 (COVID-19)...
This report summarises Australia's spontaneous (passive) surveillance data for adverse events following immunisation (AEFI) for coronavirus disease 2019 (COVID-19) vaccines in 2021 reported to the Therapeutic Goods Administration (TGA). The TGA strongly promoted and facilitated adverse event reporting in preparation for, and during, the COVID-19 vaccine rollout as a core component of the most intensive vaccine safety monitoring ever conducted in Australia. There were 111,348 AEFI reports for COVID-19 vaccines administered in 2021, an annual AEFI reporting rate of 271.4 per 100,000 doses of COVID-19 vaccines administered to people aged ≥ 12 years. The annual AEFI reporting rate for non-COVID-19 vaccines in 2021 was 30.6 per 100,000 doses administered to people of all ages. Overall, the most frequently reported symptoms were headache, adverse events classified as 'gastrointestinal nonspecific symptoms and therapeutic procedures', myalgia, pyrexia and fatigue, which were consistent with common expected adverse events following COVID-19 vaccines used in Australia. The most commonly reported adverse events of special interest were myocarditis and/or pericarditis, followed by thrombosis and thromboembolism, and anaphylaxis. Of all COVID-19 vaccine AEFI reports, 762 (0.7%) included a fatal outcome, of which over 80% were in people aged ≥ 60 years. Thirteen deaths reported in 2021 were assessed as likely to be causally linked to vaccination. This report confirms the value of spontaneous post-marketing vaccine pharmacovigilance, especially in the context of new vaccines using novel vaccine technologies and near whole-of-population pandemic vaccination programs. The most frequently reported AEFI for COVID-19 vaccines were common, mild and temporary (lasting 1 or 2 days), and consistent with clinical trial and active surveillance data. Ongoing safety monitoring detected rare, unexpected conditions, such as myocarditis/pericarditis and thrombosis with thrombocytopenia syndrome (TTS), which were investigated and confirmed as safety signals, resulting in changes to vaccine recommendations and product information. The outcomes of TGA monitoring were published in weekly vaccine safety reports. Overall, COVID-19 vaccine safety monitoring provided critical information on the risks of vaccine related adverse events that enabled decisionmakers to undertake informed risk-benefit assessments.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Young Adult; Adverse Drug Reaction Reporting Systems; Australia; COVID-19; COVID-19 Vaccines; Vaccination
PubMed: 38926650
DOI: 10.33321/cdi.2024.48.2 -
Proceedings of the National Academy of... Jul 2024Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T...
Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA-4 Ig 1) concomitantly with ICT or 2) after ICT completion. Concomitant treatment reduced antitumor efficacy, while post-ICT administration improved efficacy without affecting frequency and function of CD8 T cells. The improved response was independent of the ICT used, whether CTLA-4 or PD-1 blockade. The frequency of Tregs was significantly decreased with CTLA-4 Ig. The resulting increased CD8/Treg ratio potentially underlies the enhanced efficacy of ICT followed by CTLA-4 Ig. This paradoxical mechanism shows that a CTLA-4 Ig regimen shown to reduce irAE severity does not compromise antitumor efficacy.
Topics: Animals; Mice; Immunotherapy; CTLA-4 Antigen; Immune Checkpoint Inhibitors; CD8-Positive T-Lymphocytes; T-Lymphocytes, Regulatory; Cell Line, Tumor; Abatacept; Female; Humans; Mice, Inbred C57BL; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 38923991
DOI: 10.1073/pnas.2404661121 -
Toxins Jun 2024We encountered a case of mushroom intoxication complicated by "toxic-like" myocarditis. Because of the lack of systematized knowledge on this subject, we performed a... (Review)
Review
We encountered a case of mushroom intoxication complicated by "toxic-like" myocarditis. Because of the lack of systematized knowledge on this subject, we performed a systematic review of the literature on cardiac toxicity in mushroom poisoning (MP). The aim of this study was to identify and describe the severity, the causal relationship, and the mushroom species involved in other reported cardiac events associated with MP. We included 39 studies in our review. We found 106 cases of cardiac events associated with MP, including 18 deaths. A wide variety of cardiac manifestations were reported, ranging from the simple elevation of cardiac enzymes (n = 61) to ventricular tachycardia (n = 14), acute heart failure (n = 18), and myocarditis (n = 7). Causal relationship between cardiac manifestations and mushroom poisoning was assessed for 42 patients, applying the algorithm validated by the French Toxicovigilance Coordination Committee. Twenty-three cases (54.8%) had a "possible" causal relationship, eight cases (19%) a "probable" relationship, and ten cases (23.8%) a "very probable" relationship. Several fungal genera were involved in reported cases, including but also rarer ones like and . In conclusion, we showed that cases of cardiac toxicity following MP have been documented in the existing literature, and for some of them, we assessed a strong causal relationship.
Topics: Humans; Cardiotoxicity; Mushroom Poisoning; Myocarditis
PubMed: 38922159
DOI: 10.3390/toxins16060265 -
Veterinary Sciences May 2024In the present case report, we describe the clinical course and postmortem findings of a 12-year-old Labrador retriever dog with a third-degree atrio-ventricular block...
In the present case report, we describe the clinical course and postmortem findings of a 12-year-old Labrador retriever dog with a third-degree atrio-ventricular block that developed a chronic cough, and later dyspnea and weakness as a result of massive pulmonary thromboembolism 3 years after implantation of a transvenous permanent pacemaker. A large soft tissue mass was seen in the right ventricular chamber around the pacing lead with echocardiography. Initially, this was thought to be caused by mural bacterial endocarditis based on hyperthermia, severe leukocytosis and the appearance of runs of ventricular tachycardia, the latter suggesting myocardial damage. While blood culture results were pending, antibiotics were administered without a positive effect. Due to clinical deterioration, the owner elected for euthanasia and a post-mortem examination confirmed a right ventricular thrombus and surrounding myocarditis, without signs of bacterial infection, and a massive pulmonary thromboembolism. We conclude that pulmonary thromboembolism should be considered in dogs with a cough that have an endocardial pacing lead implanted. Serial screening for proteinuria before and after implantation of an endocardial pacing lead would allow timely initiation of prophylactic antiplatelet therapy. Local myocarditis can develop secondary to an intracavitary thrombus, which can subsequently lead to runs of ventricular tachycardia.
PubMed: 38921984
DOI: 10.3390/vetsci11060237 -
Annals of the Academy of Medicine,... Oct 2023Although severe acute respiratory failure is the primary cause of morbidity and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this... (Review)
Review
INTRODUCTION
Although severe acute respiratory failure is the primary cause of morbidity and mortality in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this viral infection leads to cardiovascular disease in some individuals. Cardiac effects of the virus include myocarditis, pericarditis, arrhythmias, coronary aneurysms and cardiomyopathy, and can result in cardiogenic shock and multisystem organ failure.
METHOD
This review summarises cardiac manifesta-tions of SARS-CoV-2 in the paediatric population. We performed a scoping review of cardiovascular disease associated with acute coronavirus disease 2019 (COVID-19) infection, multisystem inflammatory syndrome in children (MIS-C), and mRNA COVID-19 vaccines. Also examined are special considerations for paediatric athletes and return to play following COVID-19 infection.
RESULTS
Children presenting with acute COVID-19 should be screened for cardiac dysfunction and a thorough history should be obtained. Further cardiovascular evaluation should be considered following any signs/symptoms of arrhythmias, low cardiac output, and/or myopericarditis. Patients admitted with severe acute COVID-19 should be monitored with continuous cardiac monitoring. Laboratory testing, as clinically indicated, includes tests for troponin and B-type natriuretic peptide or N-terminal pro-brain natriuretic peptide. Echocardiography with strain evaluation and/or cardiac magnetic resonance imaging should be considered to evaluate diastolic and systolic dysfunction, coronary anatomy, the pericardium and the myocardium. For patients with MIS-C, combination therapy with intravenous immunoglobulin and glucocorticoid therapy is safe and potentially disease altering. Treatment of MIS-C targets the hyperimmune response. Supportive care, including mechanical support, is needed in some cases.
CONCLUSION
Cardiovascular disease is a striking feature of SARS-CoV-2 infection. Most infants, children and adolescents with COVID-19 cardiac disease fully recover with no lasting cardiac dysfunction. However, long-term studies and further research are needed to assess cardiovascular risk with variants of SARS-CoV-2 and to understand the pathophysiology of cardiac dysfunction with COVID-19.
Topics: Humans; COVID-19; Child; Systemic Inflammatory Response Syndrome; Cardiovascular Diseases; COVID-19 Vaccines; SARS-CoV-2
PubMed: 38920204
DOI: 10.47102/annals-acadmedsg.202386 -
Annals of the Academy of Medicine,... Oct 2023
Topics: Humans; COVID-19; COVID-19 Vaccines; Child; SARS-CoV-2
PubMed: 38920200
DOI: 10.47102/annals-acadmedsg.2023335 -
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