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Schizophrenia Research Jun 2024The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
BACKGROUND
The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
METHODS
Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC).
RESULTS
The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases.
CONCLUSIONS
Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration.
Topics: Humans; Pancreatitis; Clozapine; Pericarditis; Pharmacovigilance; Adolescent; Child; Antipsychotic Agents; Databases, Factual; Male; Female; Pericardial Effusion
PubMed: 37981478
DOI: 10.1016/j.schres.2023.10.027 -
Heart (British Cardiac Society) Apr 2024In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly...
OBJECTIVE
In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly recommended in guidelines. This systematic review aims to summarise current approaches in diagnosing and treating EM with a particular emphasis on the utilisation and value of alternative diagnostic methods.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using the keywords "eosinophilic myocarditis" from their inception to 10 September 2022.
RESULTS
We included 239 articles, including 8 observational studies and 274 cases, in this review. The median patient age was 45 years. Initial presentations were non-specific, including dyspnoea (50.0%) and chest pain (39.4%). The aetiologies of EM were variable with the most common being idiopathic (28.8%) and eosinophilic granulomatosis polyangiitis (19.3%); others included drug-induced (13.1%) and hypereosinophilic syndrome (12.8%). 82.4% received an EM diagnosis by EMB while 17.6% were diagnosed based on clinical reasoning and cardiac MRI (CMR). CMR-diagnosed patients exhibited a better risk profile at diagnosis, particularly higher left ventricular ejection fraction and less need for inotropic or mechanical circulatory supports. Glucocorticoids were the primary treatment with variability in dosages and regimens.
CONCLUSION
EMB is the mainstay for diagnostic testing for EM. CMR is potentially helpful for screening in appropriate clinical scenarios. Regarding treatment, there is no consensus regarding the optimal dosage of corticosteroids. Large clinical trials are warranted to further explore the utility of CMR in the diagnosis of EM and steroid regimen in treating EM.
Topics: Humans; Myocarditis; Eosinophilia; Biopsy; Myocardium
PubMed: 37963727
DOI: 10.1136/heartjnl-2023-323225 -
Heart, Lung & Circulation Nov 2023This study aimed to evaluate the medium-term prognostic implications of cardiac magnetic resonance (CMR) imaging in patients with myocardial infarction with... (Meta-Analysis)
Meta-Analysis
Medium-Term Prognostic Implications of Cardiac Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): A Systematic Review and Meta-Analysis.
BACKGROUND
This study aimed to evaluate the medium-term prognostic implications of cardiac magnetic resonance (CMR) imaging in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).
METHODS
A systematic literature search of Embase, PubMed, and The Cochrane Library was performed. Eligible studies reported outcomes of CMR-assessed MINOCA with a mean follow-up period of >6 months. The primary endpoint was all-cause death. Secondary endpoints included cardiac death, reinfarction, and cardiovascular rehospitalisation. The pooled effect sizes with 95% confidence interval (CIs) were estimated using a random effect model.
RESULTS
A total of 3,050 patients from twenty-one studies were included in the meta-analysis. The prevalence of myocarditis, "true" myocardial infarction, Takotsubo cardiomyopathy, and normal CMR imaging was 36%, 25%, 14%, and 19%, respectively. Pooled data showed that the annualised event rates for all-cause mortality, cardiac mortality, reinfarction, and cardiovascular rehospitalisation were 1.01% (95% CI 0.59%-1.51%), 0.06% (95% CI 0.00%-0.39%), 0.68% (95% CI 0.18%-1.38%), and 5.67% (95% CI 3.11%-8.85%), respectively. Compared with patients with a diagnosis of myocarditis on CMR, patients with Takotsubo cardiomyopathy (RR 7.11; 95% CI 3.04-16.66) and "true" myocardial infarction (RR 3.82; 95% CI 1.65-8.86) were associated with a significantly higher risk of all-cause mortality, whereas a similar risk of all-cause mortality was observed in patients with normal imaging (RR 1.01; 95% CI 0.28-3.59). No association was found between CMR diagnoses and the risk of secondary endpoints in MINOCA.
CONCLUSIONS
In patients with MINOCA assessed by CMR, the overall absolute incidence rates of mortality and reinfarction were low. However, certain imaging diagnoses were associated with a higher risk of all-cause mortality, with most deaths attributed to non-cardiac causes. Additionally, these patients experienced a high burden of cardiovascular rehospitalisation.
REGISTRATION
PROSPERO (CRD42022323615).
Topics: Humans; Prognosis; MINOCA; Myocarditis; Takotsubo Cardiomyopathy; Coronary Angiography; Myocardial Infarction; Magnetic Resonance Imaging; Coronary Vessels; Risk Factors; Coronary Artery Disease
PubMed: 37919116
DOI: 10.1016/j.hlc.2023.09.007 -
Frontiers in Immunology 2023Immune checkpoint inhibitors (ICIs) therapy can be complicated by their potential cardiovascular toxicities, including myocarditis. Nowadays, no prospective trials have...
BACKGROUND
Immune checkpoint inhibitors (ICIs) therapy can be complicated by their potential cardiovascular toxicities, including myocarditis. Nowadays, no prospective trials have focused on ICI-associated myocarditis optimized management. Available evidence only come from case reports or series. A systematic case reports analysis was conducted to collect and evaluate emerging evidence of ICI-associated myocarditis to provide more information to clinicians.
METHODS
We performed a literature search for eligible case reports or series published between January 2018 and May 2023 using the PubMed database. Then, we extracted interesting information via table form. Finally, this study included 113 publications on 106 patients with ICI-associated myocarditis.
RESULTS
Myocarditis was found to be a highly life-threatening disease, with 53.8% of cases. Over half of cases were life-threatening (G4, 23.6%) or severe (G3, 35.8%) and required glucocorticoids. Higher rates of improvement were associated with the best response to ICI for complete response/partial response (72.7% vs. 53.9%), glucocorticoid administration (30% vs. 22%), and discontinuation of ICI (58.8% vs. 32.1%). Consequently, ICI-associated G3-G4 myocarditis should be treated with a combination of discontinuation of ICIs, high-dose glucocorticoids, other drugs, chemical drugs, plasma exchange, and life support. For moderate G1 or G2 cases, discontinuation of ICIs and regular-dose glucocorticoids should be considered.
CONCLUSION
Once full recovery or improvement was achieved; glucocorticoids can be administered at low doses or stopped. Notably, re-challenge with ICIs appears feasible after resolution or meaningful improvement of myocarditis.
Topics: Humans; Glucocorticoids; Heart; Immune Checkpoint Inhibitors; Myocarditis
PubMed: 37876928
DOI: 10.3389/fimmu.2023.1275254 -
Pharmacotherapy Dec 2023Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring... (Review)
Review
Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: (i) the impact of clozapine on inflammatory markers, (ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and (iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4-8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.
Topics: Humans; Clozapine; Antipsychotic Agents; Myocarditis; Inflammation; Pneumonia
PubMed: 37842767
DOI: 10.1002/phar.2887 -
Risk Management and Healthcare Policy 2023Early studies showed that the risks of mRNA vaccine-associated myocarditis and pericarditis are low but with substantial variation across studies. Study characteristics,... (Review)
Review
PURPOSE
Early studies showed that the risks of mRNA vaccine-associated myocarditis and pericarditis are low but with substantial variation across studies. Study characteristics, ethnicity, vaccine types, dose intervals, and SARS-CoV-2 infection prevalence may influence the rates of myocarditis and pericarditis after mRNA vaccination in population-based studies.
METHODS
We comprehensively searched MEDLINE for relevant articles published before November 30, 2022. We also searched the websites of health authorities in several countries for unpublished surveillance data on myocarditis and pericarditis after mRNA vaccination. The outcome of interest was the incidence of myocarditis and pericarditis developed after mRNA vaccination for COVID-19.
RESULTS
A total of 17 studies form 10 countries were included for review. We noted that considerable heterogeneity in study characteristics, including surveillance method, case definition, and observation period, may partially be responsible for the widely varied reported rates. Studies from countries that adopted active surveillance reported higher rates than those using passive surveillance. Compared to BNT162b2 vaccine, mRNA-1273 may have a higher risk of myocarditis only in young men after the second dose. Our comparison of sex-, age-, vaccine type-, and dose-specific rates of myocarditis across countries did not support the hypothesis that individuals with recent SARS-CoV-2 infection and young Asian males were at higher risk. We also could not find sufficient evidence to conclude whether extending the between-dose interval could reduce myocarditis incidence following mRNA vaccination.
CONCLUSION
Differences in the study characteristics must be fully considered when comparing the risks of mRNA vaccine-related myocarditis and pericarditis in different countries.
PubMed: 37841076
DOI: 10.2147/RMHP.S422372 -
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 -
International Journal of Cardiology Jan 2024Previous literature suggests that both SARS-CoV-2 infection and COVID-19 mRNA vaccine are associated with myocarditis, in which the incidence is higher in the infection... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous literature suggests that both SARS-CoV-2 infection and COVID-19 mRNA vaccine are associated with myocarditis, in which the incidence is higher in the infection group. COVID-19 mRNA vaccine-related myocarditis is noted to have a more benign course. Despite these findings, there is a need for a larger population systematic review that compares the outcomes to pre-pandemic acute myocarditis to better understand the extent of the current post-COVID state.
METHODS
We performed a literature search with PubMed and EMBASE and identified studies investigating COVID-19 and its vaccinated population, and the population prior to the pandemic (control group) who had myocarditis. We performed a one-group meta-analysis of the incidence, baseline demographics, and outcomes of myocarditis for each group.
RESULTS
The incidence in the SARS-CoV-2 infection group was 2.76 per thousand (95% CI, 0.85-8.92), 19.7 per million (95% CI, 12.3-31.6) in the vaccine group, and 0.861 per million (95% CI, 0.04-16.7) in the control group. The majority of patients were male, with the highest proportion in the vaccine group. The mean age was the youngest in the vaccine group (24.8, 95% CI, 19.1-30.6). The vaccine group had the lowest mortality (2.0%, 95% CI, 1.3-2.7) followed by the control and the SARS-CoV-2 infection group. The vaccine group had the lowest proportion of immunoglobulin and glucocorticoid use, mechanical circulatory support, and cardiogenic shock.
CONCLUSION
Our study showed favorable outcomes of myocarditis in patients with COVID-19 mRNA vaccination, despite a higher incidence than pre-COVID controls. Further studies with standardized myocarditis diagnostic criteria assessing long-term outcomes are necessary.
Topics: Humans; Male; Female; COVID-19 Vaccines; COVID-19; mRNA Vaccines; Myocarditis; SARS-CoV-2; Vaccines; Vaccination
PubMed: 37774926
DOI: 10.1016/j.ijcard.2023.131401 -
The American Journal of Cardiology Nov 2023Recurrence of cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) after heart transplant is rare, with rates of 5% in CS and 8% in GCM. We aim to identify all... (Review)
Review
Recurrence of cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) after heart transplant is rare, with rates of 5% in CS and 8% in GCM. We aim to identify all reported cases of recurrence in the literature and to assess clinical course, treatments, and outcomes to improve understanding of the conditions. A systematic review, utilizing Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, was conducted by searching MEDLINE/PubMed and Embase of all available literature describing post-transplant recurrent granulomatous myocarditis, CS, or GCM. Data on demographics, transplant, recurrence, management, and outcomes data were collected from each publication. Comparison between the 2 groups were made using standard statistical approaches. Post-transplant GM recurrence was identified in 39 patients in 33 total publications. Reported cases included 24 GCM, 12 CS, and 3 suspected cases. Case reports were the most frequent form of publication. Mean age of patients experiencing recurrence was 42 years for GCM and 48 years for CS and favored males (62%). Time to recurrence ranged from 2 weeks to 9 years post-transplant, occurring earlier in GCM (mean 1.8 vs 3.0 years). Endomyocardial biopsies (89%) were the most utilized diagnostic method over cardiac magnetic resonance and positron emission tomography. Recurrence treatment regimens involved only steroids in 40% of CS, whereas other immunomodulatory regimens were utilized in 70% of GCM. In conclusion, GCM and CS recurrence after cardiac transplantation holds associated risks including concurrent acute cellular rejection, a higher therapeutic demand for GCM recurrence compared with CS, and mortality. New noninvasive screening techniques may help modify post-transplant monitoring regimens to increase both early detection and treatment of recurrence.
Topics: Adult; Humans; Male; Biopsy; Cardiomyopathies; Giant Cells; Heart Transplantation; Myocarditis; Sarcoidosis
PubMed: 37769570
DOI: 10.1016/j.amjcard.2023.08.005 -
European Cardiology 2023As vaccination against COVID-19 became more widespread, side-effects that were not initially detected during clinical trials became more prominent. The aim of this... (Review)
Review
As vaccination against COVID-19 became more widespread, side-effects that were not initially detected during clinical trials became more prominent. The aim of this systematic review is to discuss reports of adverse cardiovascular events associated with COVID-19 vaccination. Databases were searched from inception up to August 2022 to identify case reports and case series reporting on patients with cardiovascular disease after COVID-19 vaccination. This study assessed 150 published cases. Of these, 109 were case reports and 41 were case series. The majority of patients were male (n=302, 86.6%), with a mean age of 27.6 ± 16.7 years. Of the included patients, 268 (76.6%) had myocarditis, 50 (14.6%) had myopericarditis, 8 (2.3%) had pericarditis, and only 4 (1.1%) had stress-induced cardiomyopathy. Moreover, 30 (8.6%) and 11 (3.1%) were diagnosed with arrhythmia and ischaemic heart disease, respectively. Ultimately, cardiovascular complications after COVID-19 vaccination include myocarditis, myopericarditis, ischaemic heart disease and arrhythmia. The young population, especially young male patients, could be more vulnerable to myocarditis.
PubMed: 37745168
DOI: 10.15420/ecr.2023.01