Pediatric Fulminant Myocarditis in Japan: A Retrospective Nationwide Database Study of Hospital Volume, Management Practices, and Mortality.
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
OBJECTIVES:Pediatric fulminant myocarditis is a subset of pediatric acute myocarditis associated with critical illness. We aimed to compare mortality and other outcomes such as length of hospital stay between pediatric fulminant myocarditis and nonfulminant myocarditis. For the subgroup of patients with fulminant myocarditis, we also aimed to describe the current management practices and evaluate the impact of clinically relevant factors, including hospital case volume, on mortality. DESIGN:Retrospective observational study using the Diagnosis Procedure Combination database from April 2012 to March 2018. SETTING:Over 1,000 acute care hospitals in Japan. PATIENTS:Patients with acute myocarditis less than 18 years old, including patients with fulminant myocarditis (i.e., those who received at least one of the following by day 7 of hospitalization: inotropes/vasopressors, mechanical circulatory support, or cardiopulmonary resuscitation). INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Multivariable logistic regression analysis was conducted to investigate the association between clinically relevant factors and in-hospital mortality of patients with fulminant myocarditis. Furthermore, post hoc propensity score analyses (propensity score-adjusted, propensity score-matched, and inverse probability of treatment-weighted analyses) were performed to confirm the effect of hospital case volume on in-hospital mortality. In total, 866 pediatric patients with acute myocarditis were included, and 382 (44.1%) were categorized as fulminant myocarditis. In-hospital mortality for those with fulminant myocarditis was 24.1%. fulminant myocarditis was associated with 41.3-fold greater odds of mortality than nonfulminant myocarditis (95% CI, 14.7-115.9; p < 0.001). In the subgroup of patients with fulminant myocarditis, a higher in-hospital mortality was significantly associated with younger age (≤ 5 yr; odds ratio, 3.41; 95% CI, 1.75-6.64) and the need for either mechanical ventilation (odds ratio, 2.39; 95% CI, 1.03-5.57), cardiopulmonary resuscitation (odds ratio, 10.63; 95% CI, 5.52-20.49), or renal replacement therapy (odds ratio, 2.53; 95% CI, 1.09-5.87) by day 7. A lower in-hospital mortality rate was significantly associated with treatment at hospitals in the highest pediatric fulminant myocarditis case volume tertile (≥ 6 cases in 6 yr; odds ratio, 0.30; 95% CI, 0.13-0.68) compared with treatment at hospitals in the lowest tertile (1-2 cases in 6 yr). Post hoc propensity score analyses consistently supported the primary results. CONCLUSIONS:In-hospital mortality of pediatric fulminant myocarditis in Japan remains high. Treatment at hospitals in the highest pediatric fulminant myocarditis case volume tertile (≥ 6 cases in 6 yr) was associated with a 70% relative reduction in odds of in-hospital mortality compared with treatment at hospitals in the lowest tertile (1-2 cases in 6 yr). The reasons for such differences need further study.
10.1097/PCC.0000000000002692
Cardiovascular manifestations of monkeypox virus outbreak: An overview of the reported cases.
Heart & lung : the journal of critical care
BACKGROUND:Monkeypox (Mpox) is a zoonotic DNA virus related to the orthopoxvirus family that causes also smallpox infection. OBJECTIVES:In this paper, we aimed to study the cardiovascular manifestations of Mpox. METHOD:A literature databases search was conducted on 20th October 2022 and limited to 2022 (the new outbreak) to collect all the relevant papers that discussed cardiovascular manifestations in Mpox. RESULTS:The literature included 6 cases of myocarditis, one case of pericarditis, one case of myopericarditis and one case of atrial fibrillation. Of total 6 cases with completed data, ECG results and troponin levels were abnormal in 5 cases while only three cases had abnormal ECHO and CMR results. In the four cases who undergone chest X-rays, only one patient had non-specific retro-cardiac opacities. All patients (9 cases) recovered well from their cardiovascular manifestations with no deaths and only 3 of them required ICU admission. CONCLUSION:With the limited reported cases, we recommend performing cardiovascular examinations -in particular ECG and troponin levels- in order to exclude cardiovascular insult in patients with suspected Mpox -cardiovascular involvement. However, in our series the infection was mild in most patients with no mortality.
10.1016/j.hrtlng.2023.01.012
Anti-inflammatory treatment for carditis in acute rheumatic fever.
Cilliers Antoinette,Adler Alma J,Saloojee Haroon
The Cochrane database of systematic reviews
BACKGROUND:Rheumatic heart disease remains an important cause of acquired heart disease in developing countries. Although prevention of rheumatic fever and management of recurrences have been well established, optimal management of active rheumatic carditis remains unclear. This is an update of a review published in 2003, and previously updated in 2009 and 2012. OBJECTIVES:To assess the effects, both harmful and beneficial, of anti-inflammatory agents such as aspirin, corticosteroids and other drugs in preventing or reducing further valvular damage in patients with acute rheumatic fever. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (2013, Issue 9 of 12), MEDLINE (Ovid, 1948 to 2013 October Week 1), EMBASE (Ovid, 1980 to 2013 Week 41) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 17 October 2013). We last searched Index Medicus (1950 to April 2001) in 2001. We checked reference lists of identified studies and applied no language restrictions. SELECTION CRITERIA:Randomised controlled trials comparing anti-inflammatory agents (e.g. aspirin, steroids, immunoglobulins, pentoxifylline) versus placebo or controls, or comparing any of the anti-inflammatory agents versus one another, in adults and children with acute rheumatic fever diagnosed according to Jones, or modified Jones, criteria. The presence of cardiac disease one year after treatment was the major outcome criterion selected. DATA COLLECTION AND ANALYSIS:Two review authors extracted data and assessed risk of bias using the methodology outlined in the Cochrane Handbook of Systematic Reviews of Interventions. Standard methodological procedures as expected by The Cochrane Collaboration were used. MAIN RESULTS:No new studies were included in this update. Eight randomised controlled trials involving 996 people were selected for inclusion in the review. Researchers compared several steroidal agents such as corticotrophin, cortisone, hydrocortisone, dexamethasone, prednisone and intravenous immunoglobulin versus aspirin, placebo or no treatment. Six trials were conducted between 1950 and 1965; one was done in 1990 and the final study was published in 2001. Overall there were no observed significant differences in risk of cardiac disease at one year between corticosteroid-treated and aspirin-treated groups (six studies, 907 participants, risk ratio 0.87, 95% confidence interval 0.66 to 1.15). Similarly, use of prednisone (two studies, 212 participants, risk ratio 1.13, 95% confidence interval 0.52 to 2.45) compared with aspirin did not reduce the risk of heart disease after one year. Investigators in five studies did not report adverse events. The three studies reporting on adverse events reported substantial adverse events. However, all results should be interpreted with caution because of the age of the studies and the substantial risk of bias. AUTHORS' CONCLUSIONS:Little evidence of benefit was found when corticosteroids or intravenous immunoglobulins were used to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. In addition, risk of bias was substantial, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever are warranted to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone and the effects of other new anti-inflammatory agents. Advances in echocardiography will allow more objective and precise assessments of cardiac outcomes.
10.1002/14651858.CD003176.pub3
Deep Learning-Based Medical Data Association Rules to Explore the Connectivity and Regulation Mechanism of miRNA-mRNA Network in Myocarditis.
Computational and mathematical methods in medicine
Acute, chronic myocarditis as myocardial localized or diffuse inflammation lesions is usually involving cardiac function in patients with severe adverse outcomes such as heart failure, sudden death, and no unified, but its pathogenesis clinical is mainly composed of a number of factors including infection and autoimmune defects, such as physical and chemical factors; therefore, it is of great significance to explore the regulation mechanism of myocarditis-related miRNA network connectivity and temperament for in-depth understanding of the pathogenesis of myocarditis and the direction of targeted therapy. Based on this, this study explored the miRNA network related to the pathogenesis of myocarditis through deep learning medical data association rules and analyzed its specific mechanism. The results showed that 39 upregulated miRNAs, 88 downregulated miRNAs, 109 upregulated differentially expressed miRNAs, and 589 downregulated mRNAs were obtained by data association through GSE126677 and GSE4172 databases. GO enrichment and KRGG enrichment analysis showed that the differentially expressed mRNAs were involved in the regulation of a variety of biological processes, cellular components, and molecular functions. At the same time, the miRNA with differentially expressed miRNAs and their corresponding mRNAs were connected to further clarify the specific molecular mechanism of the pathological changes of myocarditis by constructing miRNA-mRNA network. It provides effective potential molecular targets for subsequent treatment and diagnosis.
10.1155/2022/9272709
10-year survival outcome after clinically suspected acute myocarditis in adults: A nationwide study in the pre-COVID-19 era.
PloS one
BACKGROUND:Clinical courses of acute myocarditis are heterogeneous in populations and geographic regions. There is a dearth of long-term outcomes data for acute myocarditis prior to the coronavirus disease pandemic, particularly in the older and female population. This study aimed to provide the nationwide epidemiologic approximates of clinically suspected acute myocarditis across adults of all ages over the long term. METHODS:From the nationwide governmental health insurance database, a retrospective cohort comprised all patients aged 20-79 who were hospitalized for clinically suspected acute myocarditis without underlying cardiac diseases from 2006 to 2018. The complicated phenotype was defined as requiring hemodynamic or major organ support. Over 10 years, all-cause mortality and index event-driven excess mortality were evaluated according to young-adult (20-39 years), mid-life (40-59 years), and older-adult (60-79 years) age groups. RESULTS:Among 2,988 patients (51.0±16.9 years, 46.2% women), 362 (12.1%) were of complicated phenotype. Of these, 163 (45.0%) had died within 1 month. All-cause death at 30 days occurred in 40 (4.7%), 52 (4.8%), and 105 (10.0%) patients in the young-adult, mid-life, and older-adult groups, respectively. For 10 years of follow-up, all-cause death occurred in 762 (25.5%). Even in young adult patients with non-complicated phenotypes, excess mortality remained higher compared to the general population. CONCLUSION:In hospitalized patients with clinically suspected acute myocarditis, short-term mortality is high both in young and older adults, particularly those with comorbidities and severe clinical presentation. Furthermore, excess mortality remains high for at least 10 years after index hospitalization in young adults.
10.1371/journal.pone.0281296
Extracorporeal membrane oxygenation for the support of adults with acute myocarditis.
Diddle J Wesley,Almodovar Melvin C,Rajagopal Satish K,Rycus Peter T,Thiagarajan Ravi R
Critical care medicine
OBJECTIVES:To characterize survival outcomes for adult patients with acute myocarditis supported with extracorporeal membrane oxygenation and identify risk factors for in-hospital mortality. DESIGN:Retrospective review of Extracorporeal Life Support Organization registry database. SETTING:Data reported to Extracorporeal Life Support Organization by 230 extracorporeal membrane oxygenation centers. PATIENTS:Patients 16 years old or older supported with extracorporeal membrane oxygenation for myocarditis during 1995 to 2011. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:There were 150 separate runs of extracorporeal membrane oxygenation for 147 patients with a diagnosis of acute myocarditis in the Extracorporeal Life Support Organization database from 1995 through 2011. Survival to hospital discharge was 61%. Nine patients underwent heart transplantation, and transplant-free survival to discharge was 56%. Extracorporeal membrane oxygenation was deployed during extracorporeal cardiopulmonary resuscitation in 31 patients (21% of the cohort). In a multivariate model evaluating pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation support factors, pre-extracorporeal membrane oxygenation arrest (adjusted odds ratio, 2.4; 95% CI, 1.1-5.0) and need for higher extracorporeal membrane oxygenation flows at 4 hours post-extracorporeal membrane oxygenation cannulation (odds ratio, 2.8; 95% CI, 1.1-7.3) were associated with increased odds of in-hospital mortality. In a second multivariate model evaluating adverse events while on extracorporeal membrane oxygenation, central nervous system injury (odds ratio, 26.5; 95% CI, 7.3-96.6), renal failure (odds ratio, 3.6; 95% CI, 1.4-9.3), arrhythmia (odds ratio, 5.8; 95% CI, 2.2-15.1), and hyperbilirubinemia (odds ratio, 9.1; 95% CI, 2.6-31.8) were associated with increased odds of in-hospital mortality. CONCLUSIONS:Extracorporeal membrane oxygenation can be used effectively in adults with myocarditis to support the circulation while awaiting myocardial recovery. Early extracorporeal membrane oxygenation deployment prior to cardiac arrest may be associated with better outcomes.
10.1097/CCM.0000000000000920
Chagas Heart Disease: Beyond a Single Complication, from Asymptomatic Disease to Heart Failure.
Journal of clinical medicine
Chagas cardiomyopathy (CC), caused by the protozoan , is an important cause of cardiovascular morbidity and mortality in developing countries. It is estimated that 6 to 7 million people worldwide are infected, and it is predicted that it will be responsible for 200,000 deaths by 2025. The World Health Organization (WHO) considers Chagas disease (CD) as a Neglected Tropical Disease (NTD), which must be acknowledged and detected in time, as it remains a clinical and diagnostic challenge in both endemic and non-endemic regions and at different levels of care. The literature on CC was analyzed by searching different databases (Medline, Cochrane Central, EMBASE, PubMed, Google Scholar, EBSCO) from 1968 until October 2022. Multicenter and bioinformatics trials, systematic and bibliographic reviews, international guidelines, and clinical cases were included. The reference lists of the included papers were checked. No linguistic restrictions or study designs were applied. This review is intended to address the current incidence and prevalence of CD and to identify the main pathogenic mechanisms, clinical presentation, and diagnosis of CC.
10.3390/jcm11247262
Echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in adult patients: A systematic review and meta-analysis.
Echocardiography (Mount Kisco, N.Y.)
BACKGROUND:Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. METHODS:A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). RESULTS:Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. CONCLUSIONS:LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. HIGHTLIGHTS:What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.
10.1111/echo.15760
Multisystemic Inflammation Influences Prognosis in Fulminant Lymphocytic Myocarditis.
Circulation journal : official journal of the Japanese Circulation Society
BACKGROUND:Multisystem inflammatory syndrome (MIS) is a hyperinflammatory shock associated with cardiac dysfunction and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are no reports on using MIS criteria, such as multisystemic inflammation (MSI) in fulminant myocarditis, without SARS-CoV-2 infection. This study investigated the differences in clinical characteristics and course between patients with fulminant lymphocytic myocarditis (FLM) plus MSI and those without MSI.Methods and Results: This multicenter retrospective cohort study included 273 patients with FLM registered in the JROAD-DPC database between April 2014 and March 2017. We evaluated the presence of MSI using criteria modified from previously reported MIS criteria and compared the characteristics and risk of mortality or heart transplantation between FLM patients with MSI and without MSI. Of the 273 patients with FLM, 107 (39%) were diagnosed with MSI. The MSI group was younger (44 vs. 57 years; P<0.0001) and had more females (50% vs. 36%; P=0.0236), a higher incidence of pericardial effusion (58% vs. 40%; P=0.0073), and a lower 90-day mortality rate (19% vs. 33%; P=0.0185) than the non-MSI group. The risk of mortality at 90 days was lower in FLM patients aged <50 years with MSI aged <50 years than in those without MSI (P=0.0463). CONCLUSIONS:These results suggest that MSI may influence the prognosis of FLM, especially in patients aged <50 years.
10.1253/circj.CJ-23-0914
[Cardiac magnetic resonance imaging : Trends and developments].
Mayr A,Reiter G,Beitzke D
Der Radiologe
BACKGROUND:In its almost 25 years of clinical use, cardiac magnetic resonance imaging (CMR) has been developed for a wide range of indications due to the development of robust techniques and their comprehensive validation. CMR-based assessment of cardiac volumes and systolic ventricular function as well as the characterization of focal myocardial scars belongs today to standard cardiac imaging. More recently, the introduction of accelerated acquisition techniques, quantitative myocardial T1- and T2-mapping methods and 4‑dimensional (4D) flow measurements as well as new postprocessing techniques such as myocardial feature tracking have attracted attention. METHODS:This review is based on a comprehensive literature search in the PubMed database on new CMR techniques and their clinical application. RESULTS AND CONCLUSION:This article provides an overview of the latest technical developments in the field of CMR and their possible applications based on the most important clinical MR issues.
10.1007/s00117-020-00766-3
Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy.
Rheumatology (Oxford, England)
OBJECTIVES:Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify high-risk population. METHODS:We included EGPA patients hospitalized in our center from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac magnetic resonance imaging, and endomyocardial biopsy results, the patients were divided into 3 groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS:A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, p< 0.01), ANCA positivity decreased (41.33/31.82/14.86%, p< 0.01), and lung involvement reduced (73.33/72.73/43.24%, p= 0.02). In EGPA-EM, cardiac troponin further elevated (0.27 vs 6.00 ng/ml, p< 0.01), ejection fractions decreased (57.79 vs 33.20%, p< 0.01), while more ST-T abnormality was observed (41.89 vs 20.45%, p= 0.02). The prognosis of EGPA-EM was significantly worse, with 14.86% death rate, and 2-year event-free survival rate below 50%. Further, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [AUC 0.85 (95%CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS:We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given timely and anti-IL-5 antibodies be tested in trials.
10.1093/rheumatology/keae085
Early characteristics of fulminant myocarditis vs non-fulminant myocarditis: A meta-analysis.
Medicine
BACKGROUND:Fulminant myocarditis (FM) is a sub-category myocarditis. Its primary characteristic is a rapidly progressive clinical course that necessitates hemodynamic support. FM can be difficult to predict at the onset of myocarditis. The aim of this meta-analysis was to identify the early characteristics in FM compared to those of non-fulminant myocarditis (NFM). METHODS:We searched the databases of MEDLINE, EMBASE, CENTRAL, for studies comparing FM with acute NFM from January 1, 2000 to June 1, 2018. The baseline variables were compared in each study. Mean differences (MD) and relative ratios (RR) were calculated. RESULTS:Seven studies (158 FM patients and 388 NFM patients) were included in the analysis. The FM group had significantly lower systolic blood pressure (SBP), higher creatine kinase (CK), wider QRS duration, lower left ventricular ejection fraction (LVEF), thicker left ventricular posterior wall diameter (LVPWd), higher incidence of ST depression, ventricular tachycardia/ventricular fibrillation (Vt/Vf) and syncope, less incidence of chest pain than the NFM groups. There was no difference in terms of heart rate (HR), c-reactive protein (CRP), fever, dyspnea, white blood cells (WBC), atrioventricular block (AVB), Q waves, ST elevation, interventricular septum diameter (IVSd), or end-diastolic left ventricular diameter (LVEDd) between FM and NFM. CONCLUSION:We found that the lower SBP, higher CK, wider QRS duration, lower LVEF, thicker LVPWd, higher incidence of ST depression, Vt/Vf and syncope as well as lower incidence of chest pain were early characteristics of FM.
10.1097/MD.0000000000014697
The association between aspirin use and immune-related adverse events in specific cancer patients receiving ICIs therapy: analysis of the FAERS database.
Frontiers in pharmacology
The promise of immune checkpoint inhibitors (ICIs) therapy in cancer treatment is tempered by the occurrence of immune-related adverse events (irAEs). Many patients undergoing ICIs also take aspirin, but the association between aspirin and irAEs is not well understood. This study analyzed adverse reaction data associated with the use of ICIs in the US Food and Drug Administration (FDA) Adverse Event Reporting System FDA Adverse Event Reporting System database, from the approval date of each drug until 1 October 2022. Multivariate logistic regression was employed to assess the association of aspirin use with irAEs in patients receiving ICIs. The results indicated that aspirin use was associated with an increased risk of irAEs in a pan-cancer analysis, with a more pronounced association in specific cancer types such as lung cancer, mesothelioma, and pancreatic cancer. However, in lymphoma, aspirin use was associated with a reduced risk of irAEs. Furthermore, aspirin use was associated with an increased risk of certain irAEs, such as anemia, colitis, myocarditis, myositis, pancreatitis, pericarditis, and pneumonia, while it was associated with a reduced risk of rash, Stevens-Johnson syndrome, and thyroiditis. This study has unveiled an association between aspirin use and irAEs in cancer patients receiving ICIs therapy, emphasizing the need for individualized consideration of patients' medication history when devising cancer treatment plans to enhance efficacy and reduce risks.
10.3389/fphar.2023.1259628
The utility of cardiac magnetic resonance imaging in the diagnosis of adult patients with acute myocarditis: a systematic review and meta-analysis.
International journal of cardiology
BACKGROUND:The presence of myocardial late gadolinium enhancement (LGE) indicates myocyte necrosis, and assists with the diagnosis of acute myocarditis (AM). Cardiac magnetic resonance (CMR) measures other than LGE i.e. tissue characterization and myocardial structural and functional parameters, play an important diagnostic role in assessment for inflammation, as seen in AM. The aim of this systematic review was to appraise the evidence for the use of quantitative CMR measures to identify myocardial inflammation in order to diagnose AM in adult patients. METHODS:A systematic literature search of medical databases was performed using PRISMA principles to identify relevant CMR studies on AM in adults (2005-2020; English; PROSPERO registration CRD42020180605). Data for a range of quantitative CMR measures were extracted. Continuous variables with low heterogeneity were meta-analyzed using a random-effects model for overall effect size measured as the standard mean difference (SMD). RESULTS:Available data from 25 studies reporting continuous quantitative 1.5-T CMR measures revealed that AM is most reliably differentiated from healthy controls using T1 mapping (SMD 1.80, p<0.01) and T2 mapping (SMD 1.63, p<0.01), respectively. All other measures examined including T2-weighted ratio, extracellular volume, early gadolinium enhancement ratio, right ventricular ejection fraction, and LV end-diastolic volume, mass, ejection fraction, longitudinal strain, circumferential strain, and radial strain also had discriminatory ability although with smaller standard mean difference values (|SMD| 0.32-0.96, p < 0.01 for all). CONCLUSIONS:Meta-analysis shows that myocardial tissue characterization (T1 mapping>T2 mapping) followed by measures of left ventricular structure and function demonstrate diagnostic discriminatory ability in AM.
10.1016/j.ijcard.2022.06.047
Identification of the communal pathogenesis and immune landscape between viral myocarditis and dilated cardiomyopathy.
ESC heart failure
AIMS:Studies have confirmed that viral myocarditis (VMC) is one of the risk factors for dilated cardiomyopathy (DCM). The molecular mechanisms underlying the progression from VMC to DCM remain unclear and require further investigation. METHODS AND RESULTS:The mRNA microarray datasets GSE57338 (DCM) and GSE1145 (VMC) were obtained from the Gene Expression Omnibus database. The candidate key genes were further screened using weighted correlation network analysis (WGCNA), protein-protein interaction and external dataset validation, and the correlation between the candidate key genes and immune cells and the signalling pathways of the candidate key genes were observed by enrichment analysis and immune infiltration analysis. The expression of key genes was validated in the external dataset GSE35182. The crosstalk genes between DCM and VMC were mainly enriched in 'transcriptional misregulation in cancer', 'FoxO signalling pathway', 'AGE-RAGE signalling pathway in diabetic complications', 'thyroid hormone signalling pathway', 'AMPK signalling pathway', and other signalling pathways. The immune infiltration analysis indicated that VMC was mainly associated with resting dendritic cells and M0 macrophages, while DCM was mainly associated with monocytes, M0 macrophages, CD8+ T cells, resting CD4 memory T cells, naive CD4+ T cells, and resting mast cells. In DCM-related dataset GSE57338 and VMC-related dataset GSE1145, a total of 18 candidate key genes were differentially expressed. BLC6, FOXO1, and UBE2M were identified as the key genes that lead to the progression from VMC to DCM by GSE35182. CONCLUSIONS:Three key genes (BLC6, FOXO1, and UBE2M) were identified and provided new insights into the diagnosis and treatment of VMC with DCM.
10.1002/ehf2.14585
Research focus and theme trend on fulminant myocarditis: A bibliometric analysis.
Frontiers in cardiovascular medicine
Aims:This study intends to explore the research focus and trends of fulminant myocarditis (FM) to have a better understanding of the topic. Materials and methods:The data were downloaded from the Web of Science (WoS) database using the topic (TS) advanced search strategy. Many instruments were used to extract, analyze, and visualize the data, such as Microsoft Excel, HistCite Pro, GunnMap, BibExcel, and VOSviewer. Results:From 1985 to 2022, 726 documents were indexed in the WoS. The United States and Columbia University were the most productive country and institutions. Keywords co-occurrence was carried out and four research themes were identified. In addition, the top three prolific authors, the first three highly cited authors, and the core authors of the author co-citation network were identified. The topics that they kept an eye on were analyzed, and the research areas of key authors were similar to the results of keyword co-occurrence. The hot topics of FM were related to the mechanical circulatory support, etiology, diagnosis, and the disease or therapy associated with FM. Conclusion:This study carried out a systematic analysis of the documents related to FM from 1985 to 2022, which can provide a guideline for researchers to understand the theme trend to promote future research to be carried out.
10.3389/fcvm.2022.935073
Meta-analysis of the Value of Cardiac Nuclear Magnetic Resonance in the Diagnosis of Viral Myocarditis.
Xu Juan,Xu Yikai
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP
To evaluate the diagnostic value of cardiac magnetic resonance imaging (MRI) in viral myocarditis by meta-analysis. PubMed, EMbase, Cochrane, Web of Science, China National Knowledge Infrastructure (CNKI, China) Wanfang Databases were searched for clinical research literature on MRI diagnosis of viral myocarditis from the establishment of the database to March 1, 2020.The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR) and the summary receiver operating characteristic (SROC) were analysed by Stata 15.0. Eight articles were included in the end. The results showed that the sensitivity, specificity, DOR, and area under the curve (AUC) SROCs were 94%, 75%, 45.24 and 0.88, respectively. Existing research have confirmed that cardiac MRI has high sensitivity (94%) and moderate specificity (75%) for viral myocarditis. The positive ratio of test in myocarditis group is 45.24 times higher than that in non-myocarditis group indicating the outstanding effect of diagnosis and discrimination. Key Words: Cardiac magnetic resonance imaging, Viral myocarditis, Systematic review, Meta-analysis.
10.29271/jcpsp.2020.12.1326
Patients with fulminant myocarditis supported with veno-arterial extracorporeal membrane oxygenation: a systematic review and meta-analysis of short-term mortality and impact of risk factors.
Heart failure reviews
Fulminant myocarditis (FM) may lead to cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Results of effectiveness studies of VA-ECMO have been contradictory. We evaluated the aggregate short-term mortality after VA-ECMO and predictive factors in patients with FM. We systematically searched in electronic databases (February 2022) to identify studies evaluating short-term mortality (defined as mortality at 30 days or in-hospital) after VA-ECMO support for FM. We included studies with 5 or more patients published after 2009. We assessed the quality of the evidence using the QUIPS and GRADE tools. Mortality was pooled using random effect models. We performed meta-regression to explore heterogeneity based on a priori defined factors. We included 54 observational studies encompassing 2388 FM patients supported with VA-ECMO. Median age was 41 years (25th to 75th percentile 37-47), and 50% were female. The pooled short-term mortality was 35% (95% CI 29-40%, I = 69%; moderate certainty). By meta-regression, studies with younger populations showed lower mortality. Female sex, receiving a biopsy, cardiac arrest, left ventricular unloading, and earlier recruitment time frame, did not explain heterogeneity. These results remained consistent regardless of continent and the risk of bias category. In individual studies, low pH value, high lactate, absence of functional cardiac recovery on ECMO, increased burden of malignant arrhythmia, high peak coronary markers, and IVIG use were identified as independent predictors of mortality. When conventional therapies have failed, especially in younger patients, cardiopulmonary support with VA-ECMO should be considered in the treatment of severe FM.
10.1007/s10741-022-10277-z
Association of parvovirus B19 and myocarditis/dilated cardiomyopathy: A systematic review and meta-analysis.
Khatami Alireza,Razizadeh Mohammad Hossein,Ghadirali Monire,Yazdani Shahrooz,Bahadory Saeed,Soleimani Alireza
Microbial pathogenesis
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.
10.1016/j.micpath.2021.105207
Racial Disparities in Hospital Mortality Among Pediatric Cardiomyopathy and Myocarditis Patients.
Olsen Jillian,Tjoeng Yuen Lie,Friedland-Little Joshua,Chan Titus
Pediatric cardiology
Racially disparate health outcomes exist for a multitude of populations and illnesses. It is unknown how race and ethnicity impact mortality for children with cardiomyopathy or myocarditis. This retrospective cross-sectional study employed the Kids' Inpatient Database to analyze 34,617 hospital admissions for patients ≤ 18 years old with cardiomyopathy, myocarditis, or both, without concomitant congenital heart disease. Multivariate logistic regression models investigated the impact of race/ethnicity on in-hospital mortality adjusting for age, calendar year, sex, insurance type, diagnostic category, treatment at a pediatric hospital, and non-cardiac organ dysfunction. African American race and Hispanic ethnicity were independent risk factors for mortality (African American: odds ratio (OR) 1.25, 95% confidence interval (CI) 1.01-1.53 and Hispanic: OR 1.29, 95% CI 1.03-1.60). African American race was also found to be significantly associated with the use of extracorporeal membrane oxygenation (ECMO), mortality while on ECMO, and cardiac arrest. Adjusting the regression model for ECMO and arrest attenuated the impact of African American race on mortality, suggesting that these variables may indeed play a role in explaining the impact of race on mortality for African American patients with myocardial disease. Hispanic ethnicity remained associated with higher risk of mortality despite controlling for all mechanical circulatory support and transplant (OR 1.30, 95% CI 1.04-1.63). Children of racial and ethnic minorities hospitalized with cardiomyopathy or myocarditis are more likely to die than their white counterparts, a trend that may be due at least in part to in-hospital differences in care or response to therapy.
10.1007/s00246-020-02454-4
Machine Learning for Mortality Prediction in Pediatric Myocarditis.
Chou Fu-Sheng,Ghimire Laxmi V
Frontiers in pediatrics
Pediatric myocarditis is a rare disease. The etiologies are multiple. Mortality associated with the disease is 5-8%. Prognostic factors were identified with the use of national hospitalization databases. Applying these identified risk factors for mortality prediction has not been reported. We used the Kids' Inpatient Database for this project. We manually curated fourteen variables as predictors of mortality based on the current knowledge of the disease, and compared performance of mortality prediction between linear regression models and a machine learning (ML) model. For ML, the random forest algorithm was chosen because of the categorical nature of the variables. Based on variable importance scores, a reduced model was also developed for comparison. We identified 4,144 patients from the database for randomization into the primary (for model development) and testing (for external validation) datasets. We found that the conventional logistic regression model had low sensitivity (~50%) despite high specificity (>95%) or overall accuracy. On the other hand, the ML model struck a good balance between sensitivity (89.9%) and specificity (85.8%). The reduced ML model with top five variables (mechanical ventilation, cardiac arrest, ECMO, acute kidney injury, ventricular fibrillation) were sufficient to approximate the prediction performance of the full model. The ML algorithm performs superiorly when compared to the linear regression model for mortality prediction in pediatric myocarditis in this retrospective dataset. Prospective studies are warranted to further validate the applicability of our model in clinical settings.
10.3389/fped.2021.644922
Factors affecting in-hospital mortality among pediatric patients with myocarditis treated with mechanical circulatory support.
Journal of cardiology
BACKGROUND:Mechanical circulatory support (MCS) is a common treatment modality for circulatory failure caused by pediatric myocarditis. Despite improvements in treatment strategy, the mortality rate of pediatric patients with myocarditis treated with MCS is still high. Identifying the factors associated with mortality among pediatric patients with myocarditis treated with MCS may help reduce the mortality rate. METHODS:This retrospective cohort study examined the data of patients aged <16 years who were admitted to a hospital between July 2010 and March 2018 for myocarditis; the data were collected from the Diagnosis Procedure Combination database, which is a national inpatient database in Japan. RESULTS:During the study period, 105 of the 598 patients with myocarditis were treated with MCS. We excluded seven patients who died within 24 h of admission, resulting in 98 eligible patients. The overall in-hospital mortality was 22 %. In-hospital mortality was higher among patients aged <2 years and those who received cardiopulmonary resuscitation (CPR). Multivariable logistic regression analysis showed significantly higher in-hospital mortality among patients aged <2 years old [odds ratio (OR), 6.57; 95 % confidence interval (CI), 1.89-22.87] and those who received CPR (OR, 4.70; 95 % CI, 1.51-14.63; p < 0.01). CONCLUSION:The in-hospital mortality of pediatric patients with myocarditis treated with MCS was high, particularly of children younger than 2 years and those who received CPR.
10.1016/j.jjcc.2023.03.009
Systemic Lupus Erythematosus and Cardiovascular Diseases: A Systematic Review.
Cureus
Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by multi-organ involvement. The clinical presentation often varies from mild to moderate to severe. The cardiovascular system may also be affected, often portending a poor prognosis for patients. Although the relationship between SLE and cardiovascular disorders has been extensively explored through case reports and literature reviews, few systematic reviews explicitly focusing on this association have been conducted. In light of this, this systematic review aims to analyze the extent of the association between SLE and cardiovascular diseases (CVDs), by exploring the risk of developing CVDs, including myocardial infarction (MI), atherosclerosis, myocarditis, pericarditis and arrhythmias, in SLE patients vs. non-SLE patients. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to perform the systematic review. A detailed search was done covering the period from March 2003 to March 2023 using three databases: PubMed, Google Scholar, and Cochrane. The PubMed search identified 597 articles, while Google Scholar and Cochrane searches yielded 559 and three articles, respectively. Of the 1159 articles retrieved, we chose eight for final consideration, after excluding papers that did not discuss the role of SLE in CVDs, papers published earlier than 2003, and papers with incomplete data. The eight studies chosen included two narrative reviews, two systematic reviews, and four observational studies. In this systematic review, SLE was proven to have a strong relationship with diverse CVDs, including rare ones scarcely discussed in the literature, such as vasculitis and aortic dissection. All eight of the final papers indicated a connection between SLE and CVDs, based on the systematic analysis of these articles, which revealed that most recent research supports a higher risk of peripheral arterial occlusive disease (PAOD), MI, pericarditis, myocarditis, and other cardiovascular disorders in individuals with SLE. These associations may have certain gray areas, as patient characteristics and comorbidities often affect the extent of illness and long-term prognosis. Larger-scale studies are required to probe this relationship further and research the etiopathogenesis involved in order to improve patient outcomes. The effects of SLE on the heart are, however, unequivocal.
10.7759/cureus.39284
Long-term Outcomes of Catheter Ablation for Ventricular Arrhythmias in Post-Myocarditis Patients: Insights from a Meta-Analysis of Current Data.
SN comprehensive clinical medicine
BACKGROUND:In the past decade, catheter ablation (CA) has become a rapidly expanding treatment option for ventricular tachycardia (VT); however it is not commonly utilised for patients with post-myocarditis VT. We aimed to systematically review up-to-date evidence regarding feasibility, effectiveness, and safety of CA, with a specific focus on long-term relapse rate and procedural complications. METHODS:A structured electronic database search (PubMed, Embase, Cochrane) of the scientific literature was performed according to PRISMA guidelines for studies describing outcomes at up to 7.3 years after CA. The primary outcome measured was VT recurrence post-ablation. Procedural success was defined as freedom of ventricular arrhythmias (at the end of follow-up after an ablation procedure). The secondary outcome was significant procedural complications which included procedural death, stroke, cardiac tamponade, acute myocardial infarction, major vascular complications, and major bleeding, assessed on a study-by-study basis. RESULTS:A total of 186 patients were included in analysis with most patients (88%) being male. Over the follow-up period, there was a 18% relapse rate ( = 34) (confidence interval (CI); 0.12-0.24, ≈0, = 0.77) with the majority of patients remaining VT free for the duration of follow-up. The overall procedural complication rate was 3.0% ( = 7) (CI; 0.01-0.07, ≈0, = 0.44), and of note, there were no peri-procedural deaths or heart transplant surgeries reported. However, a single study reported a mortality of 10% ( = 2) during the follow-up period. CONCLUSIONS:CA is an effective and durable long-term therapeutic strategy for post-myocarditis VT patients with limited relapse rate and very low complication rates based on these non-randomised data. Larger randomised-controlled trials with standardised treatment and long follow-up are required to compare CA versus conventional treatment in the post-acute myocardial phase. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1007/s42399-022-01137-w.
10.1007/s42399-022-01137-w
Myocarditis and intracardiac thrombus due to Henoch-Schönlein purpura: case report and literature review.
Yılmaz Neslihan,Yüksel Selçuk,Becerir Tülay,Girişgen İlknur,Ufuk Furkan,Gürses Dolunay,Yılmaz Münevver,Yalçın Nagihan
Clinical rheumatology
Cardiac involvement is very rare in patients with Henoch-Schönlein purpura (HSP). In this case study, we present an 8-year-old girl presenting with HSP-induced myocarditis and thrombus in the right atrium and HSP nephritis. To date, 15 cases of HSP-related cardiac involvement have been reported in the PubMed/MEDLINE, Scopus, and Google Scholar databases. These cases, together with our case, are included in this review. We excluded those patients with other rheumatologic diseases (acute rheumatic fever, acute post-streptococcal glomerulonephritis, Kawasaki disease) accompanied by HSP. Three were children and 13 were adults and all were male except our case. This review revealed tachyarrhythmia, chest pain, dyspnea, murmur, and heart failure as the major signs. Cardiac tests, electrocardiogram (ECG), and imaging methods (echocardiography in all patients, cardiac magnetic resonance imaging (MRI) in three, cardiac biopsy in one, and post-mortem necropsy in three) showed that the cardiac involvements were pericardial effusion, intra-atrial thrombus, myocarditis, coronary artery changes, myocardial ischemia, infarction and necrosis, subendocardial hemorrhage, and left ventricular dilatation. Kidney involvement was not observed in three patients. As the treatment, high-dose prednisolone and cyclophosphamide, oral corticosteroid, azathioprine, nadroparin calcium, ACE inhibitors, calcium antagonists, beta-blockers, and diuretics were used. Eleven patients (all three children and eight of the adults) had a complete cardiac recovery. Cardiac involvement in adults was more likely to be fatal. Death (three patients), ischemia, and infarct have been reported only in adults. We suggested that early and aggressive treatment can be life-saving. MRI examination is effective at identifying cardiac involvement.
10.1007/s10067-020-05317-8
Positive Predictive Value of ICD-10-CM Codes for Myocarditis in Claims Data: A Multi-Institutional Study in Taiwan.
Clinical epidemiology
Purpose:The validity of the diagnosis codes to identify myocarditis cases in healthcare databases research remains unclear, and this study aimed to determine the coding accuracy of myocarditis in Taiwan. Methods:We conducted a cross-sectional study based on Taiwan's largest multi-institutional healthcare system to identify inpatients newly diagnosed with ICD-10-CM myocarditis codes at discharge between January 1st, 2017 and March 31st, 2022. We ascertained the myocarditis diagnosis by a gold standard biopsy or by review of electronic medical records, and the positive predictive values (PPV) with 95% confidence intervals (CI) of the ICD-10-CM codes for myocarditis were determined. Results:We included a total of 498 inpatients (mean age: 33.8 years old; female: 38.8%) with new myocarditis diagnosis at discharge. Codes I409 (30.1%) and I514 (45.4%) constituted the majority of myocarditis diagnostic codes in any coding position, and the overall PPV of the myocarditis codes was 73.5% (95% CI: 69.6-77.4%). However, the highest PPV (96.6%) for myocarditis diagnosis was noted with code I409 as the primary diagnosis. We found 132 inpatients (26.5%) who were false-positive myocarditis cases, identified by the ICD-10-CM codes, and potential reasons for misclassification included other inflammation diseases (n=35, 26.5%), pre-existing heart failure (n= 25, 18.9%) and acute myocardial infarction (n=16, 12.1%). Conclusion:The PPV of ICD-10-CM codes for myocarditis in Taiwan was acceptable, but some other inflammation diseases and pre-existing heart diseases may be falsely coded as myocarditis. Our results may serve future secondary database studies as a fundamental reference on the validity of myocarditis diagnosis codes.
10.2147/CLEP.S405660
Evaluation of the Efficacy and Safety of Chinese Herbal Injection Combined With Trimetazidine for Viral Myocarditis: A Network Meta-Analysis.
Frontiers in pharmacology
Viral myocarditis (VMC) is a common emergency of cardiovascular disease. Current treatment for VMC includes the prohibition of exercise plus supportive and symptomatic treatment, given the lack of specific antiviral therapeutic options and insufficient evidence for the use of novel immunosuppressive therapies. Trimetazidine, a drug used to improve myocardial energy metabolism, is frequently used for the treatment of viral myocarditis. In China, Chinese herbal injections (CHIs) are often used in combination with trimetazidine. Therefore, we evaluate the efficacy and safety of CHI combined with trimetazidine in the treatment of VMC through the method of network meta-analysis. We searched PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Full-text Database (VIP), and China Biology Medicine Database (CBM) databases from inception to September 1, 2020, to identify eligible randomized controlled trials. The Cochrane risk of bias tool was used to assess the risk of bias among selected studies and the Stata 16.0 software was used to perform the network meta-analysis. A total of 29 studies were included, representing data from 2,687 patients. The effectiveness rate, level of myocardial injury marker, and the adverse reaction rate were evaluated. Compared with conventional treatment or conventional treatment combined with trimetazidine, CHIs combined with trimetazidine appeared to have a better therapeutic effect, with higher effectiveness rate and better reduction of the levels of creatine kinase, creatine kinase-MB, and lactate dehydrogenase. Based on surface under the cumulative ranking, Shenmai injection combined with trimetazidine appeared to be superior in terms of effective rate, while injection or and injection combined with trimetazidine appeared most effective in reducing myocardial injury markers. There was no significant difference in safety between the interventions. However, a lack of safety monitoring in some selected studies meant that the safety of some interventions could not be fully evaluated. CHIs combined with trimetazidine may have therapeutic value in the treatment of viral myocarditis, and Shenmai injection, injection, and and injection may represent the most effective CHIs. Further clinical investigation is required to confirm these results.
10.3389/fphar.2021.630896
Clinical outcome and risk factors for acute fulminant myocarditis supported by venoarterial extracorporeal membrane oxygenation: An analysis of nationwide CSECLS database in China.
International journal of cardiology
BACKGROUND:To assess the outcomes and risk factors for adult patients with acute fulminant myocarditis (AFM) supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) in China mainland. METHODS:Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Data from adult patients who were diagnosed with AFM and needed VA ECMO in the database were retrospectively analyzed. The primary outcome was 90-day mortality after ECMO initiation in patients with AFM supported with VA ECMO. Cox proportional hazard regression model was used to examine the risk factors associated with 90-day mortality. RESULTS:Among 221 patients enrolled and followed up to 90 days, 186 (84.2%) patients weaned from ECMO and 159 (71.9%) patients survived and discharged home. The median age was 38 years (IQR 29-49) and males (n = 115) represented 52.0% of the total accounted patients. The median ECMO duration was 134 h (IQR 96-177 h). The main adverse event during ECMO course was bleeding (16.3%), followed by infection (15.4%). In the multivariate Cox model analysis, cardiac arrest prior to ECMO initiation (adjusted HR 2.529; 95%CI: 1.341-4.767, p = 0.004), lower pH value (adjusted HR 0.016; 95%CI: 0.010-0.059, p < 0.001) and higher lactate concentration at 24 h after ECMO initiation (adjusted HR 1.146; 95%CI: 1.075-1.221, p < 0.001) were associated with 90-day mortality. CONCLUSIONS:71.9% patients with AFM (clinical diagnosed) supported with VA ECMO survived. Cardiac arrest prior to ECMO, lower pH and higher lactate concentration at 24 h after ECMO initiation were correlated with 90-day mortality of AFM patients supported with VA ECMO.
10.1016/j.ijcard.2022.09.055
Trends in Acute Myocarditis Related Pediatric Hospitalizations in the United States, 2007-2016.
Vasudeva Rhythm,Bhatt Parth,Lilje Christian,Desai Pooja,Amponsah Jason,Umscheid Jacob,Parmar Narendrasinh,Bhatt Neel,Adupa Reshmi,Pagad Sukrut,Agrawal Prerna,Donda Keyur,Dapaah-Siakwan Fredrick,Yagnik Priyank
The American journal of cardiology
There has been little exploration of acute myocarditis trends in children despite notable advancements in care over the past decade. We explored trends in pediatric hospitalizations for acute myocarditis from 2007 to 2016 in the United States (US). This was a retrospective, serial cross-sectional study of the National Inpatient Sample database from 2007 to 2016, identifying patients ≤18 years hospitalized with acute myocarditis. Patient demographics and incidence trends were examined. Other relevant clinical and resource utilization outcomes were also explored. Out of 60,390,000 weighted pediatric hospitalizations, 6371 were related to myocarditis. The incidence of myocarditis increased from 0.7 to 0.9 per 100,000 children (p <0.0001) over the study period. The mortality decreased from 7.5% to 6.1% (p = 0.02). A significant inflation-adjusted increase by $4,574 in the median hospitalization cost was noted (p = 0.02) while length of stay remained stable (median 6.1 days). Tachyarrhythmias were identified as the most common type of associated arrhythmia. The occurrence of congestive heart failure remained steady at 27%. In conclusion, in-hospital mortality associated with pediatric acute myocarditis has decreased in the United States over years 2007 to 2016 with a concurrent rise in incidence. Despite steady length of stay, hospitalization costs have increased. Future studies investigating long-term outcomes relating to acute myocarditis are warranted.
10.1016/j.amjcard.2021.03.019
The Incidence of Myocarditis Following an Influenza Vaccination: A Population-Based Observational Study.
Drugs & aging
BACKGROUND AND OBJECTIVE:Recently, studies have pointed to a link between coronavirus disease 2019 vaccinations and myocarditis. Myocarditis following an influenza vaccine has been sporadically reported. However, it is not known whether this adverse event occurs among elderly individuals who have received influenza vaccines. We used a population-based database and a self-controlled case-series design to estimate the incidence of myocarditis following an influenza vaccination. METHODS:Data were extracted from Taiwan's National Health Insurance Research Database. The study population consisted of elderly people aged ≥ 65 years who had de novo myocarditis, which required hospitalization, within 6 months after receiving an influenza vaccination between 2003 and 2017. The first 1-7, 1-14, and 1-42 days after vaccination were defined as risk intervals, and the other periods were defined as control intervals. Poisson regression was used to calculate the incidence rate ratio for myocarditis between the risk and control periods. RESULTS:Within 180 days following a vaccination, 191 people were hospitalized for myocarditis among 19,678,904 people. In comparison with control intervals, the incidence rate ratios of an admission for myocarditis for days 1-7, 1-14, and 1-42 were 0.80 (95% confidence interval 0.36-1.81), 0.72 (95% confidence interval 0.39-1.32), and 0.73 (95% confidence interval 0.50-1.05), respectively. Subgroup analyses by sex, age, Charlson Comorbidity Index scores, and comorbidities did not yield significant differences in the incidence rate ratio. CONCLUSIONS:Regardless of the post-vaccination time and underlying baseline characteristics, the incidence risk of myocarditis is not significantly increased in the elderly following an influenza vaccination.
10.1007/s40266-022-00997-0
A Narrative Review of Preclinical In Vitro Studies Investigating microRNAs in Myocarditis.
Current issues in molecular biology
According to the World Health Organization's statement, myocarditis is an inflammatory myocardium disease. Although an endometrial biopsy remains the diagnostic gold standard, it is an invasive procedure, and thus, cardiac magnetic resonance imaging has become more widely used and is called a non-invasive diagnostic gold standard. Myocarditis treatment is challenging, with primarily symptomatic therapies. An increasing number of studies are searching for novel diagnostic biomarkers and potential therapeutic targets. Microribonucleic acids (miRNAs) are small, non-coding RNA molecules that decrease gene expression by inhibiting the translation or promoting the degradation of complementary mRNAs. Their role in different fields of medicine has been recently extensively studied. This review discusses all relevant preclinical in vitro studies regarding microRNAs in myocarditis. We searched the PubMed database, and after excluding unsuitable studies and clinical and preclinical in vivo trials, we included and discussed 22 preclinical in vitro studies in this narrative review. Several microRNAs presented altered levels in myocarditis patients in comparison to healthy controls. Moreover, microRNAs influenced inflammation, cell apoptosis, and viral replication. Finally, microRNAs were also found to determine the level of myocardial damage. Further studies may show the vital role of microRNAs as novel therapeutic agents or diagnostic/prognostic biomarkers in myocarditis management.
10.3390/cimb46020091
Outcomes of Heart Block in Myocarditis: A Review of 31,760 Patients.
Ogunbayo Gbolahan O,Elayi Samy-Claude,Ha Le Dung,Olorunfemi Odunayo,Elbadawi Ayman,Saheed Deola,Sorrell Vincent L
Heart, lung & circulation
BACKGROUND:Various electrocardiographic abnormalities, including atrioventricular conduction block, have been reported in patients with myocarditis. We performed an observation study to describe the characteristics and outcomes of inpatients diagnosed with myocarditis complicated by heart block (HB) in a large national cohort. METHODS:We identified patients with primary ICD-9 codes for myocarditis HB from the Nationwide Inpatient Sample (NIS) Database from 1998 to 2013. We compared the baseline characteristics and compared clinical outcomes between patients with and without HB, and in patients with/without high degree atrioventricular block (HDAVB). RESULTS:From the NIS database, 31,760 patients had a principal diagnosis of myocarditis and HB was reported in 1.7% of these patients (n=540). Female gender and Asian race were independently associated with HB. Out of 540 patients, 363 patients had HDAVB (67.2%) and 177 patients had not advanced HB (32.8%). Not advanced HB was not associated with an increased mortality rate compared to patients without HB (0% vs. 2.7%, p=0.315). On the other hand, the incidence of cardiogenic shock, respiratory failure and renal failure were higher in patients with HDAVB (26.2% vs. 5.0%, 33.9% vs. 5.9% and 29.2% vs. 5.5%, p<0.001 respectively). Patients with HDAVB required more procedural support (incidence of intra-aortic balloon pump 17.8% vs. 3.3%). They also had significantly longer lengths of hospital stay (9.4±9.4 vs. 4.3±8.4, p<0.001) and higher mortality (15.5% vs. 2.7%, p<0.001). Compared to myocarditis patients without HB, the odds for mortality in myocarditis patients with HDAVB 1.58 (95% CI=1.03-2.49, p=0.039). CONCLUSIONS:The incidence of HB and HDAVB among patients with acute myocarditis was 1.7% and 1.1% respectively. Female gender and Asian race were both independently associated with significant odds for the occurrence of HB and HDAVB. High degree atrioventricular block was independently associated with increased morbidity and mortality.
10.1016/j.hlc.2017.12.005
Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block.
Open medicine (Warsaw, Poland)
Immune-related cardiotoxicities are uncommon but potentially fatal. The study aims to evaluate the value of pacemakers and methylprednisolone pulse therapy (MPPT) to patients with immune-related myocarditis concomitant with complete heart block (CHB). We first reviewed medical records of three patients with immune-related myocarditis concomitant with CHB. For the pooled analysis, we searched related cases with immune-related myocarditis in the PubMed database and screened the patients. Clinical characteristics, management, and outcomes were summarized. Our three patients developed immune-related myocarditis concomitant with CHB about 2 weeks after receiving pembrolizumab, and were successfully treated with pacemaker implantation and high-dose steroids (two received MPPT). In the pooled analysis, 21 cases were eligible with an overall fatality rate of 52%. Patients with pacemakers had a fatality rate of 38%, significantly lower than patients without them (38% vs 100%; = 0.035), particularly the MPPT subgroup (25% vs 100%; = 0.019). All five patients without pacemakers expired. Among patients with pacemakers, MPPT patients tended to have an inferior rate compared with non-MPPT patients. Timely pacemaker implantation played a crucial role in improving the outcomes of patients with immune-related myocarditis concomitant with CHB. Patients receiving MPPT appeared to have a better prognosis. Additionally, multidisciplinary consultation should be recommended for better management.
10.1515/med-2022-0611
Elevated Troponin in the First 72 h of Hospitalization for Pediatric Viral Myocarditis is Associated with ECMO: An Analysis of the PHIS+ Database.
Butto Arene,Rossano Joseph W,Nandi Deipanjan,Ravishankar Chitra,Lin Kimberly Y,O'Connor Matthew J,Shaddy Robert E,Shamszad Pirouz
Pediatric cardiology
Serum troponin (Tn) is often elevated in viral myocarditis; however, its prognostic significance is unknown. We tested the hypothesis that abnormal serum Tn is associated with mortality in children hospitalized with myocarditis. We retrospectively studied data from six large children's hospitals participating in the Pediatric Health Information System Plus (PHIS+) database. Analysis was performed on patients hospitalized with viral myocarditis between 2007 and 2013, in whom at least one Tn was recorded within 72 h of admission. Abnormal baseline Tn was defined as any value outside the upper limit of normal within the first 72 h. Primary outcome was mortality. Secondary outcomes included mechanical support, defined as use of extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD), cardiac transplantation, intravenous immunoglobulin (IVIg), mechanical ventilation, and inotrope use. A total of 149 patients with myocarditis (61% male, 48% adolescents) across all PHIS+ centers had TnI (n = 113) or TnT (n = 36) recorded. At least one abnormal Tn was present in 81% of cases. Overall mortality was 7.3% and was not associated with abnormal baseline Tn. Abnormal baseline Tn was associated with ECMO (7.1 vs. 25.6%, p = 0.03) and IVIg (46.4 vs. 83.5%, p < 0.001). Abnormal baseline Tn was not associated with transplantation, mechanical ventilation or inotrope use. Abnormal Tn in the first 72 h of hospitalization for myocarditis was associated with the use of ECMO and IVIg, but was not associated with mortality. This finding may help risk stratify this population if it can be prospectively validated.
10.1007/s00246-018-1871-2
Inflammatory Arthritis and Heart Disease.
Castaneda Santos,Gonzalez-Juanatey Carlos,Gonzalez-Gay Miguel A
Current pharmaceutical design
BACKGROUND:The term inflammatory joint disease (IJD) includes a group of chronic conditions, particularly rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), with predominant joint involvement and increased risk of cardiovascular (CV) complications and premature mortality. OBJECTIVE:The study aims to review of the most relevant CV manifestations from clinical point of view associated with IJD. METHODS:To update the current knowledge on CV manifestations in patients with IJD, we review the most relevant literature studies published in English (PubMed database) from January 2007 to February 2017. RESULTS:Ischemic heart disease and congestive heart failure are the most relevant complications and those causing higher mortality. Pericarditis and myocarditis may be seen in patients with RA, especially in flares of disease, although they are often asymptomatic. Left ventricular diastolic ventricular dysfunction is an increasing recognized problem. Arrhythmias and cardiac conduction disturbances may be observed in patients with IJD. Chronic inflammation and fibrosis of the cardiac conduction system may be responsible for these complications. Noninvasive diagnostic tools including cardiac magnetic resonance imaging and echocardiography have improved considerably our understanding of the cardiovascular disease in IJD. CONCLUSION:Cardiac manifestations in IJD are frequent and they are the leading cause of an increased morbimortality in IJD. Clinicians would be aware of that, given that early diagnosis of these complications may reduce the frequency of CV events and improve survival of patients with IJD.
10.2174/1381612824666180123102632
Myocarditis or "true" infarction by cardiac magnetic resonance in patients with a clinical diagnosis of myocardial infarction without obstructive coronary disease: A meta-analysis of individual patient data.
Tornvall P,Gerbaud E,Behaghel A,Chopard R,Collste O,Laraudogoitia E,Leurent G,Meneveau N,Montaudon M,Perez-David E,Sörensson P,Agewall S
Atherosclerosis
OBJECTIVE:Myocardial Infarction with Non-Obstructed Coronary Arteries (MINOCA) is common, but the causes are to a large extent unknown. Thus, we aimed to study the prevalence of myocarditis and "true" myocardial infarction determined by cardiac magnetic resonance (CMR) imaging in MINOCA patients, and risk markers for these two conditions in this population. METHODS:A search was made in the PubMed and Cochrane databases using the search terms "Myocardial infarction", "Coronary angiography", "Normal coronary arteries" and "MRI". All relevant abstracts were read and seven of the studies fulfilled the inclusion criteria; studies describing case series of patients fulfilling the diagnosis of acute myocardial infarction with normal or non-obstructive coronary arteries on coronary angiography that were investigated with CMR imaging. Data from five of these studies are presented. RESULTS:A total of 556 patients from 5 different sites were included. Fifty-one percent were men with a mean age of 52 ± 16 years. Thirty-three per cent of the patients had myocarditis (n = 183), whereas 21% of the patients had infarction on CMR (n = 115). Young age and a high CRP were associated with myocarditis whereas male sex, treated hyperlipidemia, high troponin ratio and low CRP were associated with "true" myocardial infarction. CONCLUSION AND RELEVANCE:The results of this meta-analysis of individual data showed that myocarditis and "true" myocardial infarction are common in MINOCA when determined by CMR imaging. This information emphasizes the importance of performing CMR imaging in MINOCA patients and can be used clinically to guide diagnostics and treatment of MINOCA patients.
10.1016/j.atherosclerosis.2015.04.816
Identification of prognostic factors for pediatric myocarditis with a random forests algorithm-assisted approach.
Chou Fu-Sheng,Ghimire Laxmi V
Pediatric research
BACKGROUND:Pediatric myocarditis is a rare disease with substantial mortality. Little is known regarding its prognostic factors. We hypothesize that certain comorbidities and procedural needs may increase risks of poor outcomes. This study aims to identify prognostic factors for pediatric myocarditis. METHODS:The national Kids' Inpatient Database was used in the study. A random forests algorithm was implemented for mortality prediction based on comorbidities and procedures. Linear regression analysis was then performed to quantify their associations with mortality and length of stay. RESULTS:The prevalence of pediatric myocarditis among all pediatric hospitalizations doubled from 2003 to 2016. The mortality rate peaked in 2006 (6.7%) and declined steadily thereafter, with a rate of 3.2% in 2016. Brain injury (including encephalopathy, cerebral edema, and intracranial hemorrhage), acute kidney injury, dysrhythmias, coagulopathy, sepsis, and ECMO use were all independent prognostic factors associated with increased mortality and prolonged hospital stay. CONCLUSION:Prognostic factor identification may not be straightforward in rare diseases such as pediatric myocarditis due to small cohort size in each treating facility. Findings from this report provide insights into the prognostic factors for pediatric myocarditis, and may allow clinicians to be better prepared when informing patients and their families regarding disease outcomes. IMPACT:The rate of hospitalization due to pediatric myocarditis was increasing but the mortality rate was declining over the past decade. End organ damage, including the brain and the kidney, was associated with mortality and prolonged hospital stay in pediatric myocarditis. Tachyarrhythmias and cardiac function compromise requiring ECMO were also associated with mortality and prolonged hospital stay. A data science approach combining machine learning algorithms and conventional regression modeling using a large dataset may facilitate risk factor identification and outcome correlation in rare diseases, as illustrated in this study.
10.1038/s41390-020-01268-7
Increased risk of ventricular tachycardia and cardiovascular death in patients with myocarditis during the long-term follow-up: A national representative cohort from the National Health Insurance Research Database.
Medicine
The incidence of acute myocarditis complicated with ventricular tachycardia (VT) is unknown. This study aimed to investigate the association between myocarditis and the incidence of VT and mortality. We also aimed to determine the independent predictors that increased the VT risk in those patients. From 2000 to 2004, 13,250 patients with a history of myocarditis were identified from the Taiwan National Health Insurance Research Database. The same number of individuals without heart disease with a matched sex and underlying diseases were selected as the control group. The long-term risks of life-threatening ventricular arrhythmias and mortality in patients with a history of myocarditis were investigated by an adjusted Cox proportional hazards regression. After a mean follow-up of 10.4 ± 2.94 years (interquartile range: 12, 10.19-12), the myocarditis patients showed a higher incidence of new onset VT events compared with healthy controls (5.4% [519 per 100,000 person-year] in the myocarditis group vs, 0.47% [43 per 100,000 person-year] in the healthy controls; adjusted hazard ratio [HR]: 16.1, 95% confidence interval [CI]: 12.4-20.9; P < .001). A higher incidence of cardiovascular death was noted in the myocarditis group than healthy controls (6.52% vs 3.18%; HR: 2.42, 95% CI: 2.14-2.73; P < .001) after adjusting for the multivariate confounders including sex, age, underlying comorbidities, and medications. The results of this study suggested that there was higher incidence of life-threatening VT and mortality during the very long-term follow-up in patients with a history of myocarditis. Future work should focus on an in-depth risk stratification of VT in myocarditis patients.
10.1097/MD.0000000000006633
Acute Myocarditis in Children: a 10-year Nationwide Study (2007-2016) based on the Health Insurance Review and Assessment Service Database in Korea.
Kim Jinmi,Cho Min Jung
Korean circulation journal
BACKGROUND AND OBJECTIVES:We performed a nationwide study to assess the incidence, treatment patterns, and outcomes of acute myocarditis in Korean children. METHODS:The nationwide incidence, treatment patterns, and outcomes of acute myocarditis in Korean children were assessed using data between 2007 and 2016 from the Health Insurance Review and Assessment database. RESULTS:We investigated 1,627 children during the study period. The overall incidence of acute myocarditis was 1.4 per 100,000 children in 2007 and 2.1 per 100,000 children in 2016, which indicates a significant increase in the trend over time. A bimodal age distribution was observed with a larger peak in infancy and a smaller peak in the mid-teenage years. No sex difference was observed in the incidence rate of acute myocarditis in children aged ≤5 years (373 boys vs. 366 girls); however, the incidence rate of acute myocarditis in adolescents aged ≥13 years showed significant male preponderance (482 boys vs. 152 girls). Acute fulminant myocarditis occurred in 371 children (22.8%) who needed extracorporeal membrane oxygenation and/or mechanical ventilator support. Of the 371 children with acute fulminant myocarditis, 258 (69.5%) survived. The survival rate of children with acute fulminant myocarditis remained nearly identical over the 10-year study period. CONCLUSIONS:This was the first nationwide epidemiological study to investigate acute myocarditis in Korean children. In our view, this study would help clinicians in decision-making and planning for optimal management of acute myocarditis in children.
10.4070/kcj.2020.0108
Establishment of a novel myocarditis mouse model based on cyclosporine A.
Genes & genomics
BACKGROUND:Myocarditis is a myocardial injury that can easily cause adolescent death. Traditional research models of animal invasion with viral components, lipopolysaccharide (LPS) or porcine myocardial myosin, among others, have the shortcomings of potential biological safety hazards and high animal mortality. OBJECTIVE:To explore the construction of a novel myocarditis model with cyclosporine A and the potential genes and pathways associated with it. METHODS:BALB/c mice were used in this study, and cyclosporin A and LPS were injected into the peritoneal cavity of mice. The successful establishment of the model was assessed by detecting serum myocardial injury markers and inflammatory factors levels, HE, IHC staining, and RT-qPCR methods. Key genes were obtained using the GSE35182 dataset from the GEO database and validated with the RT-qPCR method. RESULTS:We found that a large number of inflammatory cells infiltrated the myocardium of mice in each group of Cyclosporin A constructed model, while the expression of inflammatory factor indicators was increased, and this model has the characteristics of high degree of local inflammation in myocardial tissue, low mortality, and safe and non-toxic treatment. Using GSE35182 data, we selected 18 Hub genes and validated Hub genes in myocardial tissue with RT-qPCR and found that multiple signaling pathways such as Toll-likereceptor signaling pathway(TLRs), Rap1 signal pathway(Rap1), and Chemokine signaling pathway may be involved in the development of myocarditis. CONCLUSION:Cyclosporin A can construct a new myocarditis model, and TLRs, Chemokines and Rap1 signaling pathways may be the core pathways of myocarditis.
10.1007/s13258-022-01267-4
Global, regional, and national burdens of myocarditis, 1990-2019: systematic analysis from GBD 2019 : GBD for myocarditis.
BMC public health
OBJECTIVES:Myocarditis, a health-threatening heart disease, is attracting increasing attention. This systematic study was conducted to study the prevalence of disease through the trends of incidence, mortality, disability-adjusted life years (DALYs) over the last 30 years, which would be helpful for the policymakers to better the choices for reasonable decisions. METHODS:The global, regional, and national burdens of myocarditis from 1990-2019 were analyzed by using the 2019 Global Burden of Disease (GBD) database. This study on myocarditis produced new findings according to age, sex, and Social-Demographic Index (SDI) by investigating DALYs, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and corresponding estimated annual percentage change (EAPC). RESULTS:The number of myocarditis incidence increased by 62.19%, from 780,410 cases in 1990 to 1,265,770 cases in 2019. The ASIR decreased by 4.42% (95%CI, from -0.26% to -0.21%) over the past 30 years. The number of deaths from myocarditis increased by 65.40% from 19,618 in 1990 to 324,490 in 2019, but the ASDR was relatively stable over the investigated period. ASDR increased in low-middle SDI regions (EAPC=0.48; 95%CI, 0.24 to 0.72) and decreased in low SDI regions (EAPC=-0.97; 95%CI, from -1.05 to -0.89). The age-standardized DALY rate decreased by 1.19% (95%CI, from -1.33% to -1.04%) per year. CONCLUSIONS:Globally, the ASIR and DALY for myocarditis decreased and the ASDR was stable over the past 30 years. The risk of incidences and death cases increased with age. Measures should be taken to control the risk of myocarditis in high-burden regions. Medical supplies should be improved in the high-middle SDI regions and middle SDI regions to reduce the deaths from myocarditis in these regions.
10.1186/s12889-023-15539-5
Intravenous immunoglobulin for presumed viral myocarditis in children and adults.
Robinson Joan,Hartling Lisa,Vandermeer Ben,Klassen Terry P
The Cochrane database of systematic reviews
BACKGROUND:This is an update of a previous review. Case reports and case series have described dramatic responses to intravenous immunoglobulin (IVIG) in people with presumed viral myocarditis, and its administration has become commonplace. OBJECTIVES:The primary objective of this review was to compare transplant-free survival of adults and children with presumed viral myocarditis treated with IVIG versus those who did not receive IVIG. A secondary objective was to determine if a group of patients with presumed viral myocarditis could be identified (on the basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function at presentation, virological results or the presence or absence of histological evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was performed) who would be the most likely to benefit from IVIG. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 12 of 12), the Database of Abstracts of Reviews of Effects (DARE) (2013, Issue 4 of 4), MEDLINE (Ovid, 1946 to January Week 3 2014), EMBASE (Ovid, 1980 to Week 4 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Web of Science (Thomson Reuters, 1970 to 24 January 2014), the Latin American and Caribbean Health Science Information Database (LILACS) (1982 to 30 January 2014), trials registries and conference proceedings. We contacted authors of trials and checked reference lists of relevant papers. We applied no language restrictions. SELECTION CRITERIA:We included studies if (1) participants had a clinical diagnosis of acute myocarditis with a left ventricular ejection fraction (LVEF) ≤ 0.45, left ventricular end-diastolic diameter (LVEDD) > 2 standard deviations (SDs) above the norm or a shortening fraction (SF) > 2 SDs below the mean with duration of cardiac symptoms < 6 months; (2) participants had no evidence of non-infectious or bacterial cardiac disease; and (3) participants were randomly assigned to receive at least 1 g/kg of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had received immunosuppression before outcome assessment; or (2) onset of myocarditis was reported to occur < 6 months post partum. DATA COLLECTION AND ANALYSIS:Two review authors screened searches and extracted data independently. We assessed quality using the 'Risk of bias' tool. Meta-analysis was not possible because only two relevant studies were found, and researchers analysed markedly different populations. MAIN RESULTS:In this update, review authors added one study to the study from the original review. The first relevant study involved 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The overall risk of bias was unclear. The incidence of death or the requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (odds ratio (OR) for event-free survival 0.52, 95% confidence interval (CI) 0.12 to 2.30). Follow-up at six months and at 12 months showed equivalent improvement in LVEF (mean difference (MD) 0.00, 95% CI -0.07 to 0.07 at six months; MD 0.01, 95% CI -0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen consumption was equivalent in the two groups at 12 months (MD -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all were reported to be mild (OR 30.16, 95% CI 1.69 to 539.42).The second study added at this update included 83 children in India with suspected viral encephalitis and myocarditis. The overall risk of bias was high. The odds ratio for event-free survival was 7.39 (95% CI 0.91 to 59.86). Follow-up occurred only until hospital discharge, and LVEF was 49.5% in the treated group versus 35.9% in the placebo group (risk difference 13.6%, 95% CI 5.1 to 22.1%; P value = 0.001). AUTHORS' CONCLUSIONS:Evidence from one trial does not support the use of IVIG for the treatment of adults with presumed viral myocarditis. The only paediatric trial had high risk of bias but suggested that benefit may be seen in the select group of children beyond the neonatal period who have viral encephalitis with myocarditis. Until higher-quality studies have demonstrated benefit in a particular group of patients, IVIG for presumed viral myocarditis should not be provided as routine practice in any situation. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research.
10.1002/14651858.CD004370.pub3
Evaluating the relationship between myocarditis and mRNA vaccination.
Switzer Charlotte,Loeb Mark
Expert review of vaccines
INTRODUCTION:Inflammatory conditions affecting the heart and surrounding tissues have been recently reported following mRNA vaccination. Evaluating trends in the epidemiology of these events and possible mechanisms related to vaccination will enhance vaccine safety surveillance and inform best practices for future vaccine campaigns. AREAS COVERED:Epidemiology of the burden of vaccine-associated myocarditis are reviewed. Key summaries of available data from public health advisory bodies and vaccine safety surveillance databases are critically reviewed. The possible biological pathways for vaccine-associated heart inflammations are introduced. A critical synthesis of available information to inform vaccine recommendations and best practices is provided. The citations were selected by the authors based on PubMed searches of the literature, national vaccine safety surveillance databases and summaries from national public health bodies. EXPERT OPINION:Myocarditis may be associated with vaccination, through several biological mechanisms. Studies have shown that live viral vaccinations can act as a trigger for hypersensitivity inflammatory reactions, but further work is required to examine how the mRNA formulation may induce these autoimmune responses. Given that the risk of these adverse events is low, and the benefit of protection against disease is so great, the receipt of mRNA vaccines is recommended.
10.1080/14760584.2022.2002690
Herbal medicines for viral myocarditis.
Liu Zhao Lan,Liu Zhi Jun,Liu Jian Ping,Kwong Joey S W
The Cochrane database of systematic reviews
BACKGROUND:Herbal medicines are being used as a treatment for viral diseases such as viral myocarditis and numerous clinical trials have been conducted to investigate their efficacy. Despite this wealth of evidence, the role of herbal medicines in the treatment of viral myocarditis is yet to be established. This is an update of the review published in 2010. OBJECTIVES:To assess the effects of herbal medicines on clinical (for example mortality, incidence of complications) and indirect outcomes (for example cardiac function, biochemical response) in patients with viral myocarditis. SEARCH METHODS:We searched CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE (January 1966 to June 2011), EMBASE (January 1998 to June 2011), Chinese Biomedical Database (1979 to 2011), China National Knowledge Infrastructure (1979 to 2011), Chinese VIP Information (1989 to 2011), Chinese Academic Conference Papers Database and Chinese Dissertation Database (1980 to 2011), AMED (June 2011), LILACS (June 2011), and the Cochrane Complementary Medicine Field Trials Register. We handsearched Chinese journals and conference proceedings. No language restrictions were applied. SELECTION CRITERIA:Randomised controlled trials of herbal medicines (with a minimum of seven days treatment duration) compared with placebo, no intervention, or conventional interventions were included. Trials of herbal medicine plus conventional drug versus drug alone were also included. Only trials that reported an adequate description of allocation sequence generation were included. DATA COLLECTION AND ANALYSIS:Two review authors independently extracted data and evaluated trial quality. Adverse effects information was collected from the trials. MAIN RESULTS:Twenty randomised controlled trials involving 2177 people were included. All trials were conducted and published in China. The controls included anti-arrhythmic drugs, corticosteroids, and antiviral therapies such as ribavirin or interferon. Combining the risk of bias on random sequence generation, allocation concealment, selective reporting, and incomplete outcome data, the included trials were assessed to be at high risk of bias. Thirteen different herbal medicines were tested in the included trials. None of the trials reported outcomes on mortality. The trials reported electrocardiogram results, level of myocardial enzymes, cardiac function, and adverse effects.A meta-analysis showed a significant effect of Astragalus membranaceus injection plus supportive therapy on the number of patients with an abnormal electrocardiogram (RR 0.28, 95% CI 0.13 to 0.61), ST-T changes (RR 0.72, 95% CI 0.54 to 0.95), creatine phosphate kinase (CPK) levels (MD -21.54, 95% CI -33.80 to -9.28), and lactate dehydrogenase (LDH) levels (MD -30.33, 95% CI -46.78 to -13.88).Shengmai injection plus supportive therapy showed a significant effect on the number of patients with an abnormal electrocardiogram (RR 0.11, 95% CI 0.01 to 0.86), CPK levels (MD -103.90, 95% CI -114.97 to -92.83), LDH levels (MD -34.60, 95% CI -51.25 to -17.95), and on myocardial enzyme CK-MB levels (MD -10.87, 95% CI -14.50 to -7.24). Shengmai decoction plus supportive therapy showed a significant effect on improving quality of life measured by the SF-36 (MD 40.20, 95% CI 18.13 to 62.27) compared to supportive therapy. Data on adverse events were only available from six of the included trials and no serious adverse effects were reported. AUTHORS' CONCLUSIONS:Some herbal medicines may lead to improvement of ventricular premature beat, electrocardiogram, level of myocardial enzymes, and cardiac function in viral myocarditis. However, these findings should be interpreted with care due to the high risk of bias of the included studies, small sample size, and limited number of trials on individual herbs. Further robust trials are needed to explore the use of herbal medicines in viral myocarditis.
10.1002/14651858.CD003711.pub4
A Systematic Review of Myocarditis Induced by Immune Checkpoint Inhibitors: How Concerning Is the Most Common Cardiotoxicity of Immune Checkpoint Inhibitors?
Cureus
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.
10.7759/cureus.42071
5-Aminosalicylic Acid-Associated Myocarditis and Pericarditis: A Narrative Review.
Brown Glen
The Canadian journal of hospital pharmacy
BACKGROUND:Use of medications containing the 5-aminosalicylic acid (5-ASA) moiety may cause a rare but potentially lethal side effect involving inflammation of the heart (myocarditis) or pericardium (pericarditis) or both (myopericarditis). Early recognition of 5-ASA as the cause is important to prevent progression of the inflammation. OBJECTIVE:To provide clinicians with information to assist in recognizing the signs and symptoms of 5-ASA-induced cardiac inflammation and the characteristics of the suspected therapy, and in determining the appropriate approach to treatment. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION:The Embase database was searched, for the period 1974 to July 17, 2015, for published descriptions of cases of cardiac inflammation caused by 5-ASA-containing medications. The search terms included the names of specific agents, as well as terms for different types of cardiac inflammation. Articles in any language were retained for inclusion in this narrative review. FINDINGS:There is no symptom, sign, laboratory test, or constellation of symptoms and signs that is pathognomonic for 5-ASA-induced myocardial-pericardial toxicity. Similarly, there is no single laboratory, electrocardiographic, or echocardiographic finding or combination of findings that implicates 5-ASA as the cause of nonspecific symptoms. However, most patients present with chest pain, shortness of breath, and fever within the first 28 days after initiating 5-ASA. Physical examination, electrocardiography, and diagnostic imaging will yield findings consistent with myocarditis, with or without accompanying pericarditis. Prompt discontinuation of the 5-ASA will result in resolution of symptoms within days, without the need for any adjunctive therapies. Rechallenge with any 5-ASA-containing compound carries a high risk for recurrence of the inflammation. CONCLUSIONS:Any patient presenting with chest pain, shortness of breath, or fever within 28 days after initiating a 5-ASA-containing drug should be considered as exhibiting drug-induced inflammation. The 5-ASA-containing drug should be stopped immediately until other causes can be proven (or excluded); if no other cause is discovered, the 5-ASA should not be restarted.
Clinical Characteristics and Outcomes in Immune Checkpoint Inhibitor Therapy-Associated Myocarditis.
Thakker Ravi A,Lee Marissa A,Albaeni Aiham,Elbadawi Ayman,Suthar Krishna H,Perez Christopher,Sonstein Lindsay K,Farr Norman M,Venkatesan Rohit,Khalife Wissam,Berbarie Rafic F,Chatila Khaled F
Cardiology research
Immune checkpoint inhibitor (ICI) therapy has played an important role in the treatment of several groups of cancers. Although a life prolonging treatment, many side effects have been shown with ICI therapy. This study looked at individual level clinical characteristics and outcomes with ICI therapy in patients who developed ICI-related myocarditis. A comprehensive review of the National Library of Medicine PubMed database was performed. Inclusion criteria were all studies that were composed of case reports and case series of individual patients undergoing ICI therapy that developed myocarditis. To appreciate individual patient level data, observational studies, clinical trials, systematic reviews, and meta-analyses were excluded. Our search yielded 333 results with 71 cases reviewed of ICI therapy-related myocarditis. The findings included an average age of 68 years, higher incidence in men, and pretreatment cardiac history of hypertension. Melanoma was the most prevalent malignancy with nivolumab being the most used ICI therapy. Heart failure was the most prevalent adverse event that was co-prevalent with myocarditis. Corticosteroid therapy alone was the most utilized therapy to treat ICI-related myocarditis. Mortality was seen in nearly half of the patient population. Our study reviewed the preexisting literature of prior reported myocarditis secondary to ICI therapy. Periodic surveillance should be performed by the cardio-oncologist and internist. Due to the expanding role of ICI therapy in treating a variety of cancer patients, appreciation of its impact on the development of myocarditis is needed.
10.14740/cr1319
Immune Checkpoint Inhibitor-Associated Myocarditis: A Literature Review.
Cureus
Recently in the field of oncology, immune checkpoint inhibitors (ICI) are being increasingly utilized both in clinical trials and in clinical practice. It is a form of biological therapy that targets tumors by activating the immune system, which in turn eliminates proliferating cancer cells. These have numerous immune-related adverse events (irAEs), one of which is myocarditis, which has high rates of mortality. This article was a narrative review of myocarditis related to ICI use. Studies from the PubMed, Cochrane, and American Society of Clinical Oncology (ASCO) databases were used in writing this review. The databases were searched for original publications for adverse effects related to ICI use and myocarditis specifically. There are numerous published instances of cancer immunotherapy causing myocarditis. ICI therapy has numerous benefits, as it upregulates the immune system to target cancer cells, utilizing the body's own defense mechanisms to target proliferating cells. Myocarditis is a serious side effect, however. Therefore, on balance, these monotherapies are worth using. While this literature review primarily identifies cross-reaction as the main mechanism of myocarditis, there are other possible mechanisms. One proposed mechanism involves a shared antigen between the myocardial tissue and the tumor. This mechanism is called molecular mimicry, where the monoclonal antibody attacks both the myocardial tissue and the tumor cell. Management of ICI-induced myocarditis has not been studied by randomized controlled trials or prospective studies, but based on previous case reports and case series it is mostly treated with steroids initially. An ICI rechallenge after temporary discontinuation appears conceivable in many cases, especially given its therapeutic effects, but only limited data are available on the safety of a rechallenge after an irAE. The lack of RCTs regarding rechallenge with an ICI after irAE, more so specifically about myocarditis, along with the overall results and the complexity involved in such cases once again emphasize the need to make decisions on an individual basis by a multidisciplinary expert working group. At the same time, the focus should also be on publishing more data as the need will grow along with the indications for ICI therapies.
10.7759/cureus.52952
Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination.
JAMA cardiology
Importance:Vaccine-associated myocarditis is an unusual entity that has been described for the smallpox vaccine, but only anecdotal case reports have been described for other vaccines. Whether COVID-19 vaccination may be linked to the occurrence of myocarditis is unknown. Objective:To describe a group of 7 patients with acute myocarditis over 3 months, 4 of whom had recent messenger RNA (mRNA) COVID-19 vaccination. Design, Setting, and Participants:All patients referred for cardiovascular magnetic resonance imaging at Duke University Medical Center were asked to participate in a prospective outcomes registry. Two searches of the registry database were performed: first, to identify patients with acute myocarditis for the 3-month period between February 1 and April 30 for 2017 through 2021, and second, to identify all patients with possible vaccine-associated myocarditis for the past 20 years. Once patients with possible vaccine-associated myocarditis were identified, data available in the registry were supplemented by additional data collection from the electronic health record and a telephone interview. Exposures:mRNA COVID-19 vaccine. Main Outcomes and Measures:Occurrence of acute myocarditis by cardiovascular magnetic resonance imaging. Results:In the 3-month period between February 1 and April 30, 2021, 7 patients with acute myocarditis were identified, of which 4 occurred within 5 days of COVID-19 vaccination. Three were younger male individuals (age, 23-36 years) and 1 was a 70-year-old female individual. All 4 had received the second dose of an mRNA vaccine (2 received mRNA-1273 [Moderna], and 2 received BNT162b2 [Pfizer]). All presented with severe chest pain, had biomarker evidence of myocardial injury, and were hospitalized. Coincident testing for COVID-19 and respiratory viruses provided no alternative explanation. Cardiac magnetic resonance imaging findings were typical for myocarditis, including regional dysfunction, late gadolinium enhancement, and elevated native T1 and T2. Conclusions and Relevance:In this study, magnetic resonance imaging findings were found to be consistent with acute myocarditis in 7 patients; 4 of whom had preceding COVID-19 vaccination. Further investigation is needed to determine associations of COVID-19 vaccination and myocarditis.
10.1001/jamacardio.2021.2828
Giant cell myocarditis: diagnosis and treatment.
Cooper L T
Herz
Giant cell myocarditis is a rare but devastating disease that usually affects young otherwise healthy individuals. Associations with thymoma, inflammatory bowel disease, and a variety of autoimmune disorders have been reported. The rate of death or heart transplantation is approximately 70% at 1 year. Data from a Lewis rat model and from observational human studies suggest that giant cell myocarditis is mediated by T lymphocytes and may respond to treatment aimed at attenuating T cell function. Recent findings from the Giant Cell Myocarditis Registry, a clinical and pathologic database from 63 cases of giant cell myocarditis gathered from 36 medical centers, include the following: The sensitivity of endomyocardial biopsy for giant cell myocarditis for patients who undergo transplantation or autopsy is 82 to 85%. Registry subjects who received cyclosporine in combination with steroid, azathioprine, or muromonab-CD3 have prolonged transplant-free survival (12.6 months vs. 3.0 months for no immunosuppression). Post-transplantation survival is approximately 71% at 5 years despite a 25% rate of giant cell infiltration in the donor heart. To confirm and extend these findings, a randomized trial of immunosuppression including muromonab-CD3, cyclosporine, and steroids is underway.
10.1007/s000590050023
Biomarkers in Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Updated Review of the Literature.
Journal of clinical medicine
Myocarditis is a disease caused by cardiac inflammation that can progress to dilated cardiomyopathy, heart failure, and eventually death. Several etiologies, including autoimmune, drug-induced, and infectious, lead to inflammation, which causes damage to the myocardium, followed by remodeling and fibrosis. Although there has been an increasing understanding of pathophysiology, early and accurate diagnosis, and effective treatment remain challenging due to the high heterogeneity. As a result, many patients have poor prognosis, with those surviving at risk of long-term sequelae. Current diagnostic methods, including imaging and endomyocardial biopsy, are, at times, expensive, invasive, and not always performed early enough to affect disease progression. Therefore, the identification of accurate, cost-effective, and prognostically informative biomarkers is critical for screening and treatment. The review then focuses on the biomarkers currently associated with these conditions, which have been extensively studied via blood tests and imaging techniques. The information within this review was retrieved through extensive literature research conducted on major publicly accessible databases and has been collated and revised by an international panel of experts. The biomarkers discussed in the article have shown great promise in clinical research studies and provide clinicians with essential tools for early diagnosis and improved outcomes.
10.3390/jcm12237214
Myocarditis in the forensic setting.
Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
Diagnosis of myocarditis as the cause of death in the forensic setting at post-mortem is currently determined by a forensic pathologist. There is no systematic method for diagnosis and thus the determination is subject to inter-observer variability and is often non-reproducible. The primary aim of this study was to investigate the differences in the amount of inflammation between cases where myocarditis was deemed the cause of death, compared to cases where myocardial inflammation was incidentally present at autopsy, but not determined to be the cause of death. Participants were sourced from the Victorian Institute of Forensic Medicine (VIFM) database, from full autopsies conducted on reportable death in Victoria, Australia between the years 2011 and 2021. Cases of fatal myocarditis were significantly more likely to experience infection-like symptoms prior to death, and to be in hospital at the time of death. Histopathological examination revealed fatal cases had a significantly higher inflammatory index compared to the incidental group. Lethal cases were also significantly more likely to have myocyte necrosis, and a diffuse pattern of inflammation. There are significant differences between cases where myocardial inflammation has been determined to be the cause of death and cases where inflammation in the myocardium was an incidental finding. These results could be used in the forensic autopsy to help pathologists determine if inflammation should be considered fatal or incidental.
10.1016/j.carpath.2022.107476
Toxoplasmosis and the Heart.
Zhou Zier,Ortiz Lopez Hector Isaac Alejandro,Pérez Gonzalo Emanuel,Burgos Lucrecia Maria,Farina Juan María,Saldarriaga Clara,Lopez-Santi Ricardo,Cotella Juan Ignacio,Pérez Ana Laura Sauce,Baranchuk Adrian
Current problems in cardiology
Toxoplasmosis is a common disease caused by Toxoplasma gondii, a parasite with high prevalence in tropical regions. Most infections show minimal symptoms, but immunocompromised patients tend to have a poor prognosis. Cardiovascular manifestations in toxoplasmosis are rare and reported in a limited number of patients. As part of the "Neglected Tropical Diseases and Other Infectious Diseases Affecting the Heart" (NET-Heart) project, this paper aims to systematically review all available information regarding the cardiovascular implications of toxoplasmosis. Relevant studies were identified in the MEDLINE and/or PubMed database, and 48 articles were ultimately included. This was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Cardiac compromise in toxoplasmosis mainly involves myocarditis, and complications vary widely in severity. Toxoplasmic myocarditis is challenging to diagnose, as endomyocardial biopsy is usually required. This article provides a summary of cardiac toxoplasmosis, including an original algorithm facilitating diagnosis and treatment.
10.1016/j.cpcardiol.2020.100741
Parvovirus B19-Associated Myocarditis: A Literature Review of Pediatric Cases.
Keramari Stergiani,Poutoglidis Alexandros,Chatzis Stefanos,Keramaris Michael,Savopoulos Christos,Kaiafa Georgia
Cureus
Parvovirus B19 (B19V) infection may lead to myocarditis, a life-threatening condition in pediatric patients. In this review, we aim to present published pediatric cases of B19V-associated myocarditis in order to understand the deep complex connections and draw useful conclusions. We performed a comprehensive search of MEDLINE, Science Direct, and Google Scholar electronic databases. A total of 32 cases were included in our study. The most common presenting symptom was tachycardia in 22/32 patients (68.7%), followed by tachypnoea (21/32, 65.6%), fever, and rash (12/32, 37.5% for both of them). Cardiac arrest, loss of consciousness, and systemic infection were associated with the worst prognosis, with statistically significant differences (p-value 0.001, 0.02, 0.001. respectively). A percentage as high as 90.4% of patients with left ventricular (LV) dysfunction and reduced ejection fraction (EF) were discharged. Twelve patients required ventilatory support, five required extracorporeal membrane oxygenation (ECMO), and three underwent heart surgery. Treatment with immunosuppressive agents and immunoglobulin was found to be beneficial for patients (p-value 0.006 and 0.004, respectively). In conclusion, B19V myocarditis has high mortality rates in children. There is no specific antiviral treatment for B19V infection and therapeutic strategies for myocarditis aim to delay the worsening of heart failure and to preserve the LV function. Inotropic drugs, diuresis, ventilatory support, Intravenous immunoglobulin (IVIG), and immunosuppressive therapy seem to help the recovery of the myocardium in children with LV dilation, dysfunction, and reduced EF. Children with cardiac arrest, arrhythmias, and loss of consciousness have the worst prognosis.
10.7759/cureus.21726
Varicella-Zoster Virus Myocarditis: Early Clinical Diagnosis and Outcome.
Cureus
Varicella-zoster virus (VZV) is a viral infection that causes chickenpox and shingles. Although it is usually self-limiting, it can lead to severe complications, especially in pediatric and immunocompromised patients. VZV was first discovered as a cause of myocarditis in 1953. In this review article, we aim to investigate the early clinical diagnosis of myocarditis in VZV infections and the efficacy of the VZV vaccine in preventing myocarditis. The literature search was done using PubMed, Google Scholar, and Sci-Hub databases. A high VZV mortality rate was noted among adults, infants, and immunocompromised patients. The early diagnosis and treatment of VZV myocarditis can reduce mortality.
10.7759/cureus.38015
Corticosteroids for viral myocarditis.
Chen Huai Sheng,Wang Wei,Wu Sheng Nan,Liu Jian Ping
The Cochrane database of systematic reviews
BACKGROUND:Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Experimental evidence suggests that autoimmune mechanisms follow viral infection, resulting in inflammation and necrosis in the myocardium. However, the use of corticosteroids as immunosuppressives for this condition remains controversial. OBJECTIVES:The existing review was updated. The primary objective of this review is to assess the beneficial and harmful effects of treating acute or chronic viral myocarditis with corticosteroids. The secondary objective is to determine the best dose regimen. SEARCH METHODS:We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7 of 12, 2012) on The Cochrane Library, MEDLINE OVID (1946 to July Week 2, 2012), EMBASE OVID (1980 to Week 29, 2012), BIOSIS Previews (1969 to 20 July 2012), ISI Web of Science (1970 to 20th July, 2012), and LILACS (from its inception to 25 July, 2012) , Chinese Biomed Database, CNKI and WANFANG Databases (from their inception to 31 December 2012). We applied no language restrictions. SELECTION CRITERIA:Randomised controlled trials (RCTs) of corticosteroids for viral myocarditis compared with no intervention, placebo, supportive therapy, antiviral agents therapy or conventional therapy, including trials of corticosteroids plus other treatment versus other treatment alone, irrespective of blinding, publication status, or language. DATA COLLECTION AND ANALYSIS:Two review authors extracted data independently. Results were presented as risk ratios (RRs) and mean differences (MDs), both with 95% confidence intervals (CIs). MAIN RESULTS:Eight RCTs (with 719 participants) were included in this update. The trials were small in size and methodological quality was poor. Viral detection was performed in 38% of participants, among whom 56% had positive results. Mortality between corticosteroids and control groups was non-significant (RR, 0.93, 95% CI 0.70 to 1.24). At 1 to 3 months follow-up, left ventricular ejection fraction (LVEF) was higher in the corticosteroids group compared to the control group (MD 7.36%, 95% CI 4.94 to 9.79), but there was substantial heterogeneity. Benefits were observed in LVEF in two trials with 200 children given corticosteroids (MD 9.00%, 95% CI 7.48 to 10.52). New York Heart Association (NYHA) class and left ventricular end-stage systole diameter (LVESD) were not affected. Creatine phosphokinase (CPK) (MD -104.00 U/L, 95% CI -115.18 to -92.82), Isoenzyme of creatine phosphate MB (CKMB) (MD 10.35 U/L, 95% CI 8.92 to 11.78), were reduced in the corticosteroids group compared to the control group, although the evidence is limited to small participant numbers. There were insufficient data on adverse events. AUTHORS' CONCLUSIONS:For people diagnosed with viral myocarditis and low LVEF, corticosteroids do not reduce mortality. They may improve cardiac function but the trials were of low quality and small size so this finding must be regarded as uncertain. High-quality, large-scale RCTs should be careful designed to determine the role of corticosteroid treatment for viral myocarditis. Adverse events should also be carefully evaluated.
10.1002/14651858.CD004471.pub3
Association between immune checkpoint inhibitor-induced myocarditis and concomitant use of thiazide diuretics.
International journal of cancer
Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)-induced myocarditis is affected by concomitant diuretics. Thus, the aim of this work was to evaluate the impact of concomitant diuretics on ICI-induced myocarditis. This cross-sectional study used disproportionality analysis and a pharmacovigilance database to assess the risk of myocarditis with various diuretics in patients receiving ICIs via the analysis of data entered into the VigiBase database through December 2022. Multiple logistic regression analysis was performed to identify risk factors for myocarditis in patients who received ICIs. A total of 90 611 patients who received ICIs, including 975 cases of myocarditis, were included as the eligible dataset. A disproportionality in myocarditis was observed for loop diuretic use (reporting odds ratio 1.47, 95% confidence interval [CI] 1.02-2.04, P = .03) and thiazide use (reporting odds ratio 1.76, 95% CI 1.20-2.50, P < .01) in patients who received ICIs. The results of the multiple logistic regression analysis showed that the use of thiazides (odds ratio 1.67, 95% CI 1.15-2.34, P < .01) was associated with an increased risk of myocarditis in patients who received ICIs. Our findings may help to predict the risk of myocarditis in patients receiving ICIs.
10.1002/ijc.34616
From Streptococcal Pharyngitis/Tonsillitis to Myocarditis: A Systematic Review.
Journal of cardiovascular development and disease
(1) Background: Myocarditis following group A streptococcal pharyngitis and tonsillitis is a relatively rare medical condition. The aim of this systematic review was to identify specific ECG changes, laboratory parameters and signs, and symptoms associated with this disease. (2) Methods: A systematic literature review was performed in concordance with the current PRISMA guidelines, including the databases PubMed/MEDLINE, Web of Science, CDSR, CENTRAL, CCAs, EBM Reviews, and LILACS. Articles were included if they covered myocarditis after streptococcal pharyngitis/tonsillitis in humans. Exclusion criteria were rheumatic, autoimmune, or toxic myocarditis. (3) Results: Patients that developed myocarditis after group A streptococcal throat infection frequently presented with chest pain, elevated cardiac markers, and ST-segment elevations, making it a condition that shows more similarities to acute coronary syndrome than viral myocarditis. (4) Conclusions: Myocarditis after streptococcal pharyngitis and/or tonsillitis is a rather infrequently described disease; however, it is necessary to consider this condition when investigating streptococcal sore throat because it can be associated with severe adverse events for the individual patient.
10.3390/jcdd9060170
Hospital Outcomes Among COVID-19 Hospitalizations With Myocarditis from the California State Inpatient Database.
The American journal of cardiology
Many case reports have indicated that myocarditis could be a prognostic factor for predicting morbidity and mortality among patients with COVID-19. In this study, using a large database we examined the association between myocarditis among COVID-19 hospitalizations and in-hospital mortality and other adverse hospital outcomes. The present study was a retrospective analysis of data collected in the California State Inpatient Database during 2020. All hospitalizations for COVID-19 were included in the analysis and grouped into those with and without myocarditis. The outcomes were in-hospital mortality, cardiac arrest, cardiogenic shock, mechanical ventilation, and acute respiratory distress syndrome. Propensity score matching, followed by conditional logistic regression, was performed to find the association between myocarditis and outcomes. Among 164,417 COVID-19 hospitalizations, 578 (0.4%) were with myocarditis. After propensity score matching, the rate of in-hospital mortality was significantly higher among COVID-19 hospitalizations with myocarditis (30.0% vs 17.5%, p <0.001). Survival analysis with log-rank test showed that 30-day survival rates were significantly lower among those with myocarditis (39.5% vs 46.3%, p <0.001). Conditional logistic regression analysis showed that the odds of cardiac arrest (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.16 to 3.14), cardiogenic shock (OR 4.13, 95% CI 2.14 to 7.99), mechanical ventilation (OR 3.30, 95% CI 2.47 to 4.41), and acute respiratory distress syndrome (OR 2.49, 95% CI 1.70 to 3.66) were significantly higher among those with myocarditis. Myocarditis was associated with greater rates of in-hospital mortality and adverse hospital outcomes among patients with COVID-19, and early suspicion is important for prompt diagnosis and management.
10.1016/j.amjcard.2022.08.009
Determinants of COVID-19 vaccine-induced myocarditis.
Therapeutic advances in drug safety
Background:Following the roll-out of the Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, and Janssen Ad26.COV2.S coronavirus disease 2019 (COVID-19) injections in the United States, millions of individuals have reported adverse events (AEs) using the vaccine adverse events reports system (VAERS). The objective of this analysis is to describe the myocarditis data in VAERS and the COVID-19 vaccines as potential determinants of myocarditis. Methods:We used VAERS data to examine the frequency of reporting myocarditis since the beginning of the mass vaccination campaign and compared this with historical values in VAERS and COVID-19 vaccine administration data from the Our World in Data database. We examined myocarditis reports in VAERS in the context of sex, age, and dose. Statistical analysis was done using the Student's test to determine statistically significant differences between ages among myocarditis adverse events (AEs) and the chi-square test to determine relationships between categorical variables with statistical significance. Results:We found the number of myocarditis reports in VAERS after COVID-19 vaccination in 2021 was 223 times higher than the average of all vaccines combined for the past 30 years. This represented a 2500% increase in the absolute number of reports in the first year of the campaign when comparing historical values prior to 2021. Demographic data revealed that myocarditis occurred most in youths (50%) and males (69%). A total of 76% of cases resulted in emergency care and hospitalization. Of the total myocarditis reports, 92 individuals died (3%). Myocarditis was more likely after dose 2 ( < 0.00001) and individuals less than 30 years of age were more likely than individuals older than 30 to acquire myocarditis ( < 0.00001). Conclusion:COVID-19 vaccination is strongly associated with a serious adverse safety signal of myocarditis, particularly in children and young adults resulting in hospitalization and death. Further investigation into the underlying mechanisms of COVID-19 vaccine-induced myocarditis is imperative to create effective mitigation strategies and ensure the safety of COVID-19 vaccination programs across populations.
10.1177/20420986241226566
Clozapine-associated myocarditis in the World Health Organization's pharmacovigilance database: Focus on reports from various countries.
Revista de psiquiatria y salud mental
INTRODUCTION:The incidence of clozapine-associated myocarditis varies by country. These variations were explored in VigiBase, the World Health Organization's global database which has >25 million spontaneously reported adverse drug reaction (ADR) reports from 145 national drug agencies. METHODS:On January 15, 2021, a search of VigiBase since inception focused on myocarditis in clozapine patients. The 3572 individual reports were studied using the standard VigiBase logarithmic measure of disproportionality called information component (IC). The IC measures the disproportionality between the expected and the reported rates. After duplicates were eliminated there were 3274 different patients with myocarditis studied in logistic regression models. RESULTS:The first case was published in 1980 but since 1993 the VigiBase clozapine-myocarditis IC has been significant; moreover, currently it is very strong (IC=6.0, IC-IC=5.9-6.1) and statistically significantly different from other antipsychotics. Of the 3274 different patients with myocarditis, 43.4% were non-serious cases, 51.8% were serious but non-fatal, and 4.8% were fatal. More than half (1621/3274) of the reports came from Australia, of which 69.2% were non-serious, 27.7% serious but non-fatal, and 3.1% fatal. Asian countries contributed only 41 cases. CONCLUSIONS:In pharmacovigilance studies, confounding factors may explain statistical associations, but the strength and robustness of these results are compatible with the hypothesis that myocarditis is definitively associated with early clozapine treatment (84% [1309/1560] and 5% [82/1560] in the first and second months). Myocarditis reports from Australia are over-represented to a major degree. Asian countries may be underreporting myocarditis to their drug agencies.
10.1016/j.rpsmen.2021.07.005
Contemporary National Trends of Mechanical Circulatory Support Among Myocarditis Hospitalizations Before the Pandemic: A National In-patient Database (2005-2019) Study.
Current problems in cardiology
According to the Global Burden of Disease Project, the morbidity and mortality of myocarditis continue to be a significant worldwide burden. On October 1, 2015, hospital administrative data started using the International Classification of Diseases (ICD)-10 codes instead of the ICD-9. To our knowledge, nationwide trends of myocarditis have not been studied after this update. The NIS database from 2005-2019 was analyzed using ICD-9 and 10 codes. Our search yielded 141,369 hospitalizations due to myocarditis, with 40.9% females. There were 6627 (4.68%) patients who required mechanical circulatory support (MCS) using left ventricular assisted devices (LVAD), intra-aortic balloon pump (IABP), or extracorporeal membrane oxygenation (ECMO). The use of LVAD and ECMO increased significantly during the study period (p-trend 0.003 and <0.001, respectively), whereas the use of IABP decreased during the same period (p-trend 0.025). Our study demonstrated an overall increase in the use of MCS overall in myocarditis, with increasing utilization of more advanced MCS in the forms of LVAD and ECMO.
10.1016/j.cpcardiol.2023.102020
Myocarditis in Clinical Practice.
Sinagra Gianfranco,Anzini Marco,Pereira Naveen L,Bussani Rossana,Finocchiaro Gherardo,Bartunek Jozef,Merlo Marco
Mayo Clinic proceedings
Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class.
10.1016/j.mayocp.2016.05.013
Sex differences in myocarditis hospitalizations: Rates, outcomes, and hospital characteristics in the National Readmission Database.
Current problems in cardiology
Inflammation of the myocardium, or myocarditis, presents with varied severity, from mild to life-threatening such as cardiogenic shock or ventricular tachycardia storm. Existing data on sex-related differences in its presentation and outcomes are scarce. Using the Nationwide Readmission Database (2016-2019), we identified myocarditis hospitalizations and stratified them according to sex to either males or females. Multivariable regression analyses were used to determine the association between sex and myocarditis outcomes. The primary outcome was in-hospital mortality, and the secondary outcomes included sudden cardiac death (SCD), cardiogenic shock (CS), use of mechanical circulatory support (MCS), and 90-day readmissions. We found a total of 12,997 myocarditis hospitalizations, among which 4,884 (37.6 %) were females. Compared to males, females were older (51 ± 15.6 years vs. 41.9 ± 14.8 in males) and more likely to have connective tissue disease, obesity, and a history of coronary artery disease. No differences were noted between the two groups with regards to in-hospital mortality (adjusted odds ratio [aOR] 1.20; confidence interval [CI] 0.93-1.53; P = 0.16), SCD (aOR:1.18; CI 0.84-1.64; P = 0.34), CS (aOR: 1.01; CI 0.85-1.20;P = 0.87), or use of MCS (aOR: 1.07; CI:0.86-1.34; P = 0.56). In terms of interventional procedures, females had lower rates of coronary angiography (aOR: 0.78; CI 0.70-0.88; P < 0.01), however, similar rates of right heart catheterization (aOR 0.93; CI:0.79-1.09; P = 0.36) and myocardial biopsy (aOR: 1.16; CI:0.83-1.62; P = 0.38) compared to males. Additionally, females had a higher risk of 90-day all-cause readmission (aOR: 1.25; CI: 1.16-1.56; P < 0.01) and myocarditis readmission (aOR:1.58; CI 1.02-2.44; P = 0.04). Specific predictors of readmission included essential hypertension, congestive heart failure, malignancy, and peripheral vascular disease. In conclusion, females admitted with myocarditis tend to have similar in-hospital outcomes with males; however, they are at higher risk of readmission within 90 days from hospitalization. Further studies are needed to identify those at higher risk of readmission.
10.1016/j.cpcardiol.2023.102233
Long-Term Prognostic Value of Myocardial Viability by Myocardial Contrast Echocardiography in Patients after Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.
Medicina (Kaunas, Lithuania)
According to recent guidelines, myocardial contrast echocardiography (MCE) is recommended for detecting residual myocardial viability (MV). However, the long-term prognostic value of MV as assessed by MCE in identifying major adverse cardiac events (MACE) after acute myocardial infarction (AMI) remains undefined. We searched multiple databases, including PubMed, EMBASE, and Web of Science for studies on the prognostic value of MCE for clinical outcomes in AMI patients. The primary endpoints were MACEs during follow-up. Six studies that evaluated a total of 536 patients with a mean follow-up of 36.8 months were reviewed. The pooled sensitivity and specificity of MCE for predicting MACEs were 0.80 and 0.78, respectively, and the summary operating receiver characteristics achieved an area under the curve of 0.84. The pooled relative risks demonstrated that the MV evaluated by MCE after AMI was correlated with a high risk for total cardiac events (pooled relative risk: 2.07; 95% confidence interval: 1.28-3.37) and cardiac death (pooled relative risk: 2.48; 95% confidence interval: 1.03-5.96). MV evaluated by MCE was a highly independent predictor of total cardiac events (pooled hazard ratio: 2.09, 95% confidence interval: 1.14-3.81) in patients after AMI. Residual MV evaluated by MCE may be an effective long-term prognostic tool for predicting MACE in patients after AMI that can provide moderate predictive accuracy. The assessment of MV by MCE may become an alternative technique with the potential to rapidly provide important information for improving long-term risk stratification in patients after AMI, at the bedside in clinical practice, especially for patients who cannot tolerate prolonged examinations. The PROSPERO registration number is CRD42020167565.
10.3390/medicina58101429
PIK3CG Regulates NLRP3/GSDMD-Mediated Pyroptosis in Septic Myocardial Injury.
Inflammation
Cardiac insufficiency is a common complication of sepsis with high mortality. Inflammatory programmed cell death (pyroptosis) executed by NLRP3/gasdermin D (GSDMD) is intrinsically correlated with septic myocardial injury. However, it remains unclear whether PIK3CG, a classical target of septic myocardial injury, can affect pyroptosis by regulating NLRP3/GSDMD signaling. In this study, a series of experimental methods were used to observe the effect of PIK3CG on NLRP3/GSDMD-mediated pyroptosis in Cecal ligation and puncture (CLP)-injured BALB/c mice and lipopolysaccharide (LPS)-injured HL-1 cardiomyocytes. Transcriptome analysis of CLP-injured myocardium revealed a regulatory relationship between PIK3CG and NLRP3/GSDMD signaling, which was further verified in clinical myocardium samples from GEO database. Both in vitro and in vivo experiments showed that the protein and mRNA levels of PIK3CG, GSDMD, NLRP3, IL-1β, Caspase-1, and IL-18 were significantly increased. Importantly, PIK3CG siRNA was found to improve these changes, while PIK3CG overexpression worsened them. Notably, pyroptosis induced by CLP in the myocardium was reversed by the PIK3CG inhibitor (AS-604850). In conclusion, PIK3CG activates NLRP3 inflammasomes, thus promoting pyroptosis in septic myocardial injury.
10.1007/s10753-023-01889-0
Practical Implications of Myocardial Viability Studies.
Ker Wilter Dos Santos,Nunes Thais Helena Peixoto,Nacif Marcelo Souto,Mesquita Claudio Tinoco
Arquivos brasileiros de cardiologia
Many non-invasive methods, such as imaging tests, have been developed aiming to add a contribution to existing studies in estimating patients' prognosis after myocardial injury. This prognosis is proportional to myocardial viability, which is evaluated in coronary artery disease and left ventricular dysfunction patients only. While myocardial viability represents the likelihood of a dysfunctional muscle (resulting from decreased oxygen supply for coronary artery obstruction), hibernation represents post-interventional functional recovery itself. This article proposes a review of pathophysiological basis of viability, diagnostic methods, prognosis and future perspectives of myocardial viability. An electronic bibliographic search for articles was performed in PubMed, Lilacs, Cochrane and Scielo databases, according to pre-established criteria. The studies showed the ability of many imaging techniques in detecting viable tissues in dysfunctional areas of left ventricle resulting from coronary artery injuries. These techniques can identify patients who may benefit from myocardial revascularization and indicate the most appropriate treatment.
10.5935/abc.20180051
Myocardial Fibrosis in Athletes.
van de Schoor Freek R,Aengevaeren Vincent L,Hopman Maria T E,Oxborough David L,George Keith P,Thompson Paul D,Eijsvogels Thijs M H
Mayo Clinic proceedings
Myocardial fibrosis (MF) is a common phenomenon in the late stages of diverse cardiac diseases and is a predictive factor for sudden cardiac death. Myocardial fibrosis detected by magnetic resonance imaging has also been reported in athletes. Regular exercise improves cardiovascular health, but there may be a limit of benefit in the exercise dose-response relationship. Intense exercise training could induce pathologic cardiac remodeling, ultimately leading to MF, but the clinical implications of MF in athletes are unknown. For this comprehensive review, we performed a systematic search of the PubMed and MEDLINE databases up to June 2016. Key Medical Subject Headings terms and keywords pertaining to MF and exercise (training) were included. Articles were included if they represented primary MF data in athletes. We identified 65 athletes with MF from 19 case studies/series and 14 athletic population studies. Myocardial fibrosis in athletes was predominantly identified in the intraventricular septum and where the right ventricle joins the septum. Although the underlying mechanisms are unknown, we summarize the evidence for genetic predisposition, silent myocarditis, pulmonary artery pressure overload, and prolonged exercise-induced repetitive micro-injury as contributors to the development of MF in athletes. We also discuss the clinical implications and potential treatment strategies of MF in athletes.
10.1016/j.mayocp.2016.07.012