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Cureus Jul 2023Novel cancer therapies have revolutionized the management of various cancers. An immune checkpoint inhibitor (ICI) is one of these antitumor medications. ICIs, which are... (Review)
Review
Novel cancer therapies have revolutionized the management of various cancers. An immune checkpoint inhibitor (ICI) is one of these antitumor medications. ICIs, which are immune therapies, enhance the immune system's capacity to fight cancer cells. Based on the receptors that they inhibit, such as PD-1, PD-L1, and CTLA-4, ICIs are subdivided. Although this class of drugs is extremely beneficial for cancer patients, their adverse effects can be fatal. Multiple organs, such as the cardiovascular system, may be impacted by immune-related adverse effects (irAEs). These cardiotoxic irAEs can occur at a rate of up to 1% and can be fatal. Myocarditis is the most prevalent of all cardiotoxicities. The purpose of this systematic review is to assess the seriousness of myocarditis, the most prevalent cardiotoxicity of ICIs, and the importance of screening. We chose studies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 criteria. Therefore, from 2018 to 2023, we gathered articles from databases such as PubMed, ScienceDirect, Web of Science, the Cochrane Library, and Google Scholar. Of the 665 studies identified based on various screening methods and quality assessment tools, 13 were selected for inclusion in the study. This study shows that although the risk of myocarditis in ICI therapy is low and the majority of cases are asymptomatic or mild, some cases can be deadly and disastrous, and physicians should be aware that if myocarditis is suspected based on clinical symptoms, troponin, electrocardiogram, and echocardiogram, treatment should be initiated accordingly.
PubMed: 37602125
DOI: 10.7759/cureus.42071 -
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 -
International Journal of Cardiology Apr 2023Myocarditis and inflammatory bowel diseases (IBD) are rare conditions, but may coexist. Myocarditis in IBD may be infective, immune-mediated, or due to mesalamine...
BACKGROUND
Myocarditis and inflammatory bowel diseases (IBD) are rare conditions, but may coexist. Myocarditis in IBD may be infective, immune-mediated, or due to mesalamine toxicity. A gap of knowledge exists on the clinical features of patients that present myocarditis in association with IBD, especially for endomyocardial biopsy-proven cases. Our aims are: 1) to describe the clinical characteristics of patients with an associated diagnosis of myocarditis and IBD in a single-center hospital, 2) to perform a systematic review of the literature of analogous cases.
METHODS
We retrospectively analyzed data of patients followed up at the outpatient Cardio-immunology and Gastroenterology Clinic of Padua University Hospital, to identify those with an associated diagnosis of myocarditis and IBD. In addition, a systematic review of the literature was conducted. We performed a qualitative analysis of the overall study population.
RESULTS
The study included 104 patients (21 from our single center cohort, 83 from the literature review). Myocarditis in IBD more frequently affects young (median age 31 years) males (72%), predominantly with infarct-like presentation (58%), within an acute phase of the IBD (67%) and with an overall benign clinical course (87%). Nevertheless, a not negligible quote of patients may present giant cell myocarditis, deserve immunosuppression and have a chronic, or even fatal course. Histological evidence of mesalamine hypersensitivity is scarce and its incidence may be overestimated.
CONCLUSIONS
Our study shows that myocarditis in association with IBD, if correctly managed, may have a spontaneous benign course, but predictors of worse prognosis must be promptly recognized.
Topics: Male; Humans; Adult; Myocarditis; Mesalamine; Retrospective Studies; Inflammatory Bowel Diseases; Prognosis
PubMed: 36738845
DOI: 10.1016/j.ijcard.2023.01.071 -
Brain and Behavior Aug 2021Among many of the autoimmune diseases observed in patients with myasthenia gravis (MG), myocarditis is one of the most critical. The goal of this review is to... (Review)
Review
Among many of the autoimmune diseases observed in patients with myasthenia gravis (MG), myocarditis is one of the most critical. The goal of this review is to systematically describe and investigate the characteristics of MG complicated with myocarditis. We identified 183 records in PubMed (MEDLINE), Web of Science, and EMBASE from 1948 to September 10, 2020. Studies were included if they presented clinical data on MG complicated with myocarditis. Of the 35 patients from 28 studies in this review, 57.14% (20/35) were males, with a mean age of 59.11 ± 15.87. Dyspnea was the most common cardiac symptom accounting for over 60% in the study. Among the 35 patients, 13 cases of myocarditis occurred concomitantly with MG and the longest interval between MG and myocarditis was 7 years. Forty percent of patients developed myocarditis caused by immune checkpoint inhibitors (ICI). Among the patients with myocarditis, over half of the patients were diagnosed by myocardial biopsy. After active immune regulation and symptomatic treatment, only 15 of 35 patients with MG complicated with myocarditis improved, 18 patients died during hospitalization, one patient died due to tumor progression and 1patient died 5 years later. The prognosis of patients with MG complicated with myocarditis is poor, and myocardial enzymes and other indexes need to be monitored for patients taking ICI drugs. Patients with dyspnea who are still not ideally treated by mechanical ventilation should be vigilant against the occurrence of MG complicated with myocarditis.
Topics: Humans; Immune Checkpoint Inhibitors; Male; Myasthenia Gravis; Myocarditis
PubMed: 34105901
DOI: 10.1002/brb3.2242 -
Systematic review and meta-analysis of rates of clozapine-associated myocarditis and cardiomyopathy.The Australian and New Zealand Journal... May 2020Clozapine is the most effective medication for treatment refractory schizophrenia, but is associated with cardiac adverse drug reactions. Myocarditis and cardiomyopathy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clozapine is the most effective medication for treatment refractory schizophrenia, but is associated with cardiac adverse drug reactions. Myocarditis and cardiomyopathy are the most serious cardiac adverse drug reactions although reported rates of these conditions vary in the literature. We systematically reviewed and meta-analysed the event rates, the absolute death rates and case fatality rates of myocarditis and cardiomyopathy associated with clozapine.
METHODS
PubMed, EMBASE and PsycINFO were searched for studies that reported on the incidence of cardiomyopathy or myocarditis in people exposed to clozapine. Data were meta-analysed using a random effects model, with subgroup analysis on study size, time frame, region, quality, retrospective vs prospective, and diagnostic criteria of myocarditis or cardiomyopathy.
RESULTS
28 studies of 258,961 people exposed to clozapine were included. The event rate of myocarditis was 0.007 (95% confidence interval [CI] = [0.003, 0.016]), absolute death rate was 0.0004 (95% CI = [0.0002, 0.0009]) and case fatality rate was 0.127 (95% CI = [0.034, 0.377]). The cardiomyopathy event rate was 0.006 (95% CI = [0.002, 0.023]), absolute death rate was 0.0003 (95% CI = [0.0001, 0.0012]) and case fatality rate was 0.078 (95% CI = [0.018, 0.285]). Few included studies provided information on criteria for diagnosis of myocarditis and cardiomyopathy. Event rates of cardiomyopathy and myocarditis were higher in Australia.
CONCLUSION
Clarity of diagnostic criteria for myocarditis remains a challenge. Observation bias may, in part, influence higher reported rates in Australia. Monitoring for myocarditis is warranted in the first 4 weeks, and treatment of comorbid metabolic syndrome and diabetes may reduce the risk of cardiomyopathy. The risks of myocarditis and cardiomyopathy are low and should not present a barrier to people with treatment refractory schizophrenia being offered a monitored trial of clozapine.
Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Humans; Myocarditis; Prospective Studies; Retrospective Studies
PubMed: 31957459
DOI: 10.1177/0004867419898760 -
Schizophrenia Research Nov 2023Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that... (Review)
Review
Antipsychotic drug-induced myocarditis is a serious and potentially fatal adverse drug reaction characterized by inflammation of the heart muscle (myocardium) that typically develops within the first month after commencing an antipsychotic drug. Although the precise mechanism of this severe adverse drug reaction is unknown, multiple theories have been proposed with varying levels of support from cellular or animal studies. We conducted a systematic review, in accordance with PRISMA guidelines, of published preclinical and clinical studies investigating the cellular mechanism by which antipsychotic drugs induce myocarditis. A literature search including all studies available before December 10, 2022, yielded 15 studies that met our inclusion criteria. Antipsychotics examined in the included studies included clozapine (n = 13), ziprasidone (n = 1), amisulpride (n = 1), haloperidol (n = 1), levomepromazine (n = 1), olanzapine (n = 1), and sertindole (n = 1). The evidence suggests several overlapping mechanistic cascades involving: (1) increased levels of catecholamines, (2) increased proinflammatory cytokines, (3) increased reactive oxygen species (ROS), (4) reduced antioxidant levels and activity, and (5) mitochondrial damage. Notable limitations such as, a focus on clozapine, sample heterogeneity, and use of supratherapeutic doses will need to be addressed in future studies. Discovery of the mechanism by which antipsychotic drugs induce myocarditis will allow the development of clinically-useful biomarkers to identify those patients at increased risk prior to drug exposure. The development or repurposing of therapeutics to prevent or treat drug-induced myocarditis will also be possible and this will enable increased and safe use of antipsychotics for those patients in need.
Topics: Animals; Humans; Antipsychotic Agents; Clozapine; Myocarditis; Schizophrenia; Drug-Related Side Effects and Adverse Reactions
PubMed: 37797362
DOI: 10.1016/j.schres.2023.09.039 -
Cureus Nov 2021Myocarditis is being increasingly reported as a potential complication of both Pfizer-BioNTech and Moderna vaccines for COVID-19. One thousand five hundred and... (Review)
Review
BACKGROUND
Myocarditis is being increasingly reported as a potential complication of both Pfizer-BioNTech and Moderna vaccines for COVID-19. One thousand five hundred and twenty-two cases were reported as of September 02, 2021, as per CDC's (Centers for Disease Control) vaccine adverse event reporting system. Most of the published data is available in the form of case reports and series. There is a need to compile the demographic data, clinical features, and outcomes in these patients. Methods: A systematic search was conducted in PubMed, Embase, Web of science, and google scholar for published literature between January 01, 2020, and July 17, 2021. Individual data of 69 patients were pooled from 25 qualifying case reports and case series.
RESULTS
The median age of onset was 21 years. 92.7% of the patients were male. 76.8% of patients received the Pfizer-BioNTech vaccine, and 23.2% received the Moderna vaccine. 88.5% developed symptoms after the second dose. Patients were admitted to the hospital a median of three days post-vaccination. All the patients had chest pain and elevated troponin. The myocarditis was confirmed on cardiac MRI in 87% of the patients. Most of the patients had late gadolinium enhancement on MRI. The median length of stay was four days. All the reported patients recovered and were discharged.
CONCLUSION
Post-mRNA vaccination myocarditis is seen predominantly in young males within a few days after their second dose of vaccination. The pathophysiology of myocarditis is not well known. The prognosis is good as all the reported patients recovered. The presence of late gadolinium enhancement on cardiac MRI indicated myocardial necrosis/fibrosis and further studies are needed to establish the long-term prognosis of the condition.
PubMed: 34877217
DOI: 10.7759/cureus.19240 -
Heart, Lung & Circulation Jun 2022Reports of SARS-CoV-2 coronavirus (COVID-19) vaccine-related myocarditis, particularly after mRNA vaccines, have raised concerns amongst the general public. This review... (Review)
Review
INTRODUCTION
Reports of SARS-CoV-2 coronavirus (COVID-19) vaccine-related myocarditis, particularly after mRNA vaccines, have raised concerns amongst the general public. This review examined the literature regarding myocarditis post COVID-19 vaccination, drawing from vaccine safety surveillance databases and case reports.
METHODS
Combinations of search terms were used in PubMed and COVID-19-specific repositories - LitCovid and the Cochrane COVID-19 Study Register - between 1 October 2020 and 31 October 2021. Manual searches of GoogleScholar and screening of article bibliographies were also performed.
RESULTS
Information was obtained from five vaccine safety surveillance databases. Fifty-two (52) case reports totalling 200 cases of possible COVID-19 vaccine-related myocarditis were summarised. Vaccine surveillance databases differed in reporting formats and vaccination rates; however, gross estimates suggested low overall incidence rates of 2-5 per million mRNA vaccines. The incidence appeared to be higher in younger male populations, with onset of symptoms within a few days, usually after the second dose. Some with prior COVID-19 infections had onset after the first dose. Cases with prior unrelated myocarditis were also noted. Almost all presented with chest pain (98.0%). Troponin elevation was universally described and cardiac magnetic resonance imaging was commonly reported based on the updated Lake Louise criteria. Clinical course was mild in the majority, with response to anti-inflammatory treatment.
CONCLUSION
COVID-19 vaccine-related myocarditis is an important but rare adverse event. More research is needed into its pathogenesis and reasons for its predominance in young males, while gaps in data exist in those aged <16 years, as well as those with prior COVID-19 infections and prior myocarditis.
Topics: BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Humans; Male; Myocarditis; SARS-CoV-2; Vaccination; mRNA Vaccines
PubMed: 35227610
DOI: 10.1016/j.hlc.2022.02.002 -
Microbial Pathogenesis Jan 2022The potential association between Parvovirus B19 and heart disease has been controversial. The aim of the present study was to report the prevalence of B19 in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The potential association between Parvovirus B19 and heart disease has been controversial. The aim of the present study was to report the prevalence of B19 in myocarditis and dilated cardiomyopathy (DCM) as well as measure the statistical association between them.
METHODS
Our systematic search was carried out to retrieve published articles between January 2000 and March 2021 using three major databases: PubMed, Scopus, and Web of Science, as well as the Google Scholar search engine. The overall prevalence of HAV, pooled odds ratio, and heterogeneity were estimated by comprehensive meta-analysis (V2.2, Biostat) software.
RESULTS
The overall prevalence results in myocarditis and DCM were 23.7% (95% CI: 18.7%-29.5%) and 34.1% (95% CI: 23.8%-46.1%) respectively; in addition, the overall OR for B19 and myocarditis was 4.317 (95% CI, 1.831-10.180) versus 1.163 (95% CI: 0.706-1.916) for B19 and DCM.
CONCLUSION
Our findings have shown a significant association between Parvovirus B19 and myocarditis with a high prevalence. In the case of DCM, no significant association was found while the prevalence of the virus was relatively high.
Topics: Cardiomyopathy, Dilated; Humans; Myocarditis; Parvoviridae Infections; Parvovirus B19, Human; Prevalence
PubMed: 34563612
DOI: 10.1016/j.micpath.2021.105207 -
QJM : Monthly Journal of the... Feb 2023Variable clinical criteria taken by medical professionals across the world for myocarditis following coronavirus disease 2019 (COVID-19) vaccination along with wide...
Variable clinical criteria taken by medical professionals across the world for myocarditis following coronavirus disease 2019 (COVID-19) vaccination along with wide variation in treatment necessitates understanding and reviewing the same. A systematic review was conducted to elucidate the clinical findings, laboratory parameters, treatment and outcomes of individuals with myocarditis after COVID-19 vaccination after registering with PROSPERO. Electronic databases including MEDLINE, EMBASE, PubMed, LitCovid, Scopus, ScienceDirect, Cochrane Library, Google Scholar and Web of Science were searched. A total of 85 articles encompassing 2184 patients were analysed. It was a predominantly male (73.4%) and young population (mean age: 25.5 ± 14.2 years) with most having taken an mRNA-based vaccine (99.4%). The mean duration from vaccination to symptom onset was 4.01 ± 6.99 days. Chest pain (90.1%), dyspnoea (25.7%) and fever (11.9%) were the most common symptoms. Only 2.3% had comorbidities. CRP was elevated in 83.3% and cardiac troponin in 97.6% patients. An abnormal ECG was reported in 979/1313 (74.6%) patients with ST-segment elevation being most common (34.9%). Echocardiographic data were available for 1243 patients (56.9%), of whom 288 (23.2%) had reduced left ventricular ejection fraction. Non-steroidal antiinflammatory drugs (76.5%), steroids (14.1%) followed by colchicine (7.3%) were used for treatment. Only 6 patients died among 1317 of whom data were available. Myocarditis following COVID-19 vaccination is often mild, seen more commonly in young healthy males and is followed by rapid recovery with conservative treatment. The emergence of this adverse event calls for harmonizing case definitions and definite treatment guidelines, which require wider research.
Topics: Humans; Male; Child; Adolescent; Young Adult; Adult; Female; COVID-19; COVID-19 Vaccines; Myocarditis; SARS-CoV-2; Stroke Volume; Ventricular Function, Left
PubMed: 35238384
DOI: 10.1093/qjmed/hcac064