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Background The exact mechanisms underlying the pathogenesis of myocarditis are not always understood, but there is emerging evidence to suggest that genetic factors may play a significant role. Case summary Herein, we present six cases in which clinical, biochemical, and cardiovascular magnetic resonance data were consistent with myocarditis, and genetic testing subsequently revealed pathogenic filamin C (FLNC) mutations. Three patients presented with ventricular arrhythmias, two with severe biventricular dysfunction, and two suffered sudden cardiac arrest. Three received an implantable cardioverter defibrillator, and one underwent heart transplantation. Cascade testing was useful in identifying other relatives with FLNC mutation. We also present relevant histology results of myocardial specimens showing the presence of lymphocytic infiltration and inflammation, further supporting the potential association between FLNC mutations and a myocarditis phenotype. Discussion Genetic testing of affected individuals for FLNC mutations and cascade screening in the setting of acute myocarditis may be considered in selected clinical context, such as in acute myocarditis accompanied by severe left ventricular systolic dysfunction, biventricular failure, significant ventricular arrhythmias, or right ventricular involvement. [ABSTRACT FROM AUTHOR]

Background Congenital disorders of glycosylation (CDG) are rare genetically inherited defects leading to enzyme deficiency or malfunction in the glycosylation pathway. Normal glycosylation is essential to the development of normal cardiac anatomy and function. Congenital disorders of glycosylation–related cardiomyopathy are often the first manifestation detected in early life and may lead to sudden cardiac death. Approximately one-fifth of CDG types are related to cardiac diseases that include cardiomyopathy, rhythm disturbances, pericardial effusions, and structural heart disease. Case summary We report a rare case of a 26-year-old lady with CDG-1 who presented with acute-onset dyspnoea. She had respiratory tract symptoms for the past 2 weeks. With the relevant clinical and biochemical findings, including supportive findings on echocardiogram and cardiac magnetic resonance imaging, we have managed to arrive at a diagnosis of severe pneumonia leading to acute decompensated heart failure, as well as the discovery of an underlying CDG-associated dilated cardiomyopathy (DCM) and acute myocarditis. Anti-failure medications and i.v. methylprednisolone were commenced, and she showed gradual clinical improvement with an increase of her left ventricular function. She was discharged home well with anti-failure therapy, prednisolone, and a follow-up echocardiogram with further review in the heart failure clinic. Discussion In conclusion, this case report highlights the need for accurate diagnosis and prompt management of CDG-associated DCM, leading to a successful recovery and discharge from hospital care. With this, we hope to add to the increasing number of reported cases of CDG-related cardiac disease in the medical literature to emphasize the importance of screening and follow-up for any underlying cardiac diseases in patients with CDG. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aims: 'Hot phases', characterized by chest pain and troponin release, may represent the first clinical presentation of arrhythmogenic cardiomyopathies. Differential diagnosis with acute myocarditis is an unmet challenge for the clinicians. We sought to investigate histological and genetic features in patients with cardiomyopathy presenting with hot phases. Methods and results: We evaluated a case series of consecutive patients hospitalized for suspected 'hot‐phase cardiomyopathy' in two Italian centres from June 2017 to March 2022 (median follow‐up 18 months) that underwent both endomyocardial biopsy (EMB) and genetic testing. Apoptosis was confirmed with TUNEL assay. Among the 17 enrolled patients (mean age 34 ± 15 years, 76% male), only six patients (35%) presented standard histological and immunohistochemical markers for significant cardiac inflammation at EMB. Conversely, apoptosis was found in 13 patients (77%). Genetic testing was positive for a pathogenic/likely pathogenic (P/LP) variant in genes involved in cardiomyopathies (most frequently in DSP) in eight patients (48%), rising to 62% among patients with apoptosis on EMB. Notably, all patients without apoptosis tested negative for P/LP disease‐related variants. Left ventricular ejection fraction was lower in patients showing apoptosis at EMB compared to those without (p = 0.003). Conclusions: Apoptosis, rather than significant inflammation, was mostly prevalent in this case series of patients with 'hot‐phase' presentation, especially in carriers of variants in cardiomyopathy‐related genes. Detecting apoptosis on EMB might guide clinicians in performing genetic testing and in more tailored therapeutic choices in 'hot‐phase cardiomyopathy'. [ABSTRACT FROM AUTHOR]

Objective: The aims of our study were to investigate the effect of the extent and location of late gadolinium enhancement (LGE) on the left atrium (LA) function in patients with acute myocarditis (AM) using cardiovascular magnetic resonance (CMR). Method: This retrospective study performed CMR scans in 113 consecutive patients (89 males, 24 females; mean age 45.8 ± 17.3 years) with AM that met the updated Lake Louise criteria. Reservoir, conduit, and booster LA functions were analyzed by CMR feature tracking using dedicated software. Besides LA strain measurements, myocardial scar location and extent were assigned and quantified by LGE imaging. Results: AM patients with septal LGE had impaired reservoir, conduit, and conduit strain rate function in comparison with AM patients with non-septal LGE (p = 0.001, for all). In fully adjusted multivariable linear regression, reservoir and conduit were significantly associated with left ventricle (LV) LGE location (β coefficient = 8.205, p = 0.007; β coefficient = 5.185, p = 0.026; respectively). In addition, LA parameters decreased according to the increase in the extent of LV fibrosis (LGE ≤ 10%; LGE 11–19%; LGE ≥ 20%). After adjustment in multivariable linear regression, the association with LV LGE extent was no longer statistically significant. Conclusion: In patients with acute myocarditis, LA function abnormalities are significantly associated with LV LGE location, but not with LGE extent. Septal LGE is paralleled by a deterioration of LA reservoir and conduit function. Clinical relevance statement: Left atrium dysfunction is associated with the presence of late gadolinium enhancement in the left ventricle septum and can be useful in the clinical prognostication of patients with acute myocarditis, allowing individually tailored treatment. Key Points: • Myocardial fibrosis is related to atrial impairment. • The location of myocardial fibrosis is the main determinant of atrial dysfunction in myocarditis patients. • The quantification of atrial mechanisms may provide more in-depth insight into myocarditis pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular magnetic resonance (CMR) has emerged as the most accurate, non-invasive method to support the diagnosis of clinically suspected myocarditis and as a risk-stratification tool in patients with cardiomyopathies. We aim to assess the diagnostic and prognostic role of CMR at diagnosis in patients with myocarditis. Methods: We enrolled consecutive single-center patients with 2013 ESC consensus-based endomyocardial biopsy (EMB)-proven or clinically suspected myocarditis undergoing CMR at diagnosis. The pre-specified outcome was defined as NYHA class > I and echocardiographic left ventricular ejection fraction (LVEF) < 50% at follow-up. Results: We included 207 patients (74% male, median age 36 years; 25% EMB-proven). CMR showed the highest sensitivity in myocarditis with infarct-like presentation. Patients with EMB-proven myocarditis were more likely to have diffuse LGE and right ventricular LGE (p < 0.001), which was also more common among patients with arrhythmic presentation (p = 0.001). The outcome was met in 17 patients at any follow-up time point, more commonly in those with larger biventricular volumes (p < 0.001), CMR-based diagnosis of dilated cardiomyopathy (p < 0.001), and ischemic LGE (p = 0.005). Higher biventricular systolic function (p < 0.001) and greater LGE extent (p = 0.033) at diagnosis had a protective effect. Conclusions: In our single-center cohort of rigorously defined myocarditis patients, higher biventricular systolic function and greater LGE extent on CMR at diagnosis identified patients with better functional class and higher left ventricular ejection fraction at follow-up. Conversely, larger biventricular volumes, CMR-based DCM features, and the presence of an ischemic LGE pattern at diagnosis were predictors of worse functional class and LV systolic dysfunction at follow-up. Larger prospective studies are warranted to extend our findings to multi-center cohorts. [ABSTRACT FROM AUTHOR]

Background: Fulminant myocarditis (FM) constitutes a severe and life-threatening form of acute cardiac injury associated with cardiogenic shock. The condition is characterised by rapidly progressing myocardial inflammation, leading to significant impairment of cardiac function. Due to the acute and severe nature of the disease, affected patients require urgent medical attention to mitigate adverse outcomes. Besides symptom-oriented treatment in specialised intensive care units (ICUs), the necessity for temporary mechanical cardiac support (MCS) may arise. Numerous patients depend on these treatment methods as a bridge to recovery or heart transplantation, while, in certain situations, permanent MCS systems can also be utilised as a long-term treatment option. Methods: This review consolidates the existing evidence concerning the currently available MCS options. Notably, data on venoarterial extracorporeal membrane oxygenation (VA-ECMO), microaxial flow pump, and ventricular assist device (VAD) implantation are highlighted within the landscape of FM. Results: Indications for the use of MCS, strategies for ventricular unloading, and suggested weaning approaches are assessed and systematically reviewed. Conclusions: Besides general recommendations, emphasis is put on the differences in underlying pathomechanisms in FM. Focusing on specific aetiologies, such as lymphocytic-, giant cell-, eosinophilic-, and COVID-19-associated myocarditis, this review delineates the indications and efficacy of MCS strategies in this context. [ABSTRACT FROM AUTHOR]

Purpose of Review: Coronavirus disease-2019 (COVID-19) vaccines have been related to rare cases of acute myocarditis, occurring between 1 in 10,000 and 1 in 100,000 individuals, approximately. Incidence of COVID-19 vaccine-associated myocarditis varies with age, sex, and type of vaccine. Although most patients with acute myocarditis temporally associated with COVID-19 vaccines have an uneventful course, a small subpopulation presents with cardiogenic shock (termed fulminant myocarditis [FM]). This review explored the prevalence, clinical presentation, management, and prognosis of COVID-19 vaccine-associated acute myocarditis, specifically focusing on FM and comparing patients with fulminant versus non-fulminant myocarditis. Recent Findings: Cases of FM represent about 2–4% (0 to 7.5%) of COVID-19 vaccine-associated acute myocarditis cases, and mortality is around 1%, ranging between 0 and 4.4%. First, we identified 40 cases of FM up to February 2023 with sufficient granular data from case reports and case series of COVID-19 vaccine-associated acute myocarditis that occurred within 30 days from the last vaccine injection. This population was compared with 294 cases of non-fulminant acute myocarditis identified in the literature during a similar time. Patients with FM were older (48 vs. 27 years), had a larger proportion of women (58% vs. 9%), and mainly occurred after the first shot compared with non-fulminant cases (58% vs. 16%). The reported mortality was 27% (11 out of 40), in line with non-vaccine-associated fulminant myocarditis. These data were in agreement with 36 cases of FM from a large Korean registry. Herein, we reviewed the clinical features, imaging results, and histological findings of COVID-19 vaccine-associated fulminant myocarditis. Summary: In conclusion, COVID-19 vaccine-associated FM differs from non-fulminant forms, suggesting potential specific mechanisms in these rare and severe forms. Mortality in vaccine-associated FM remains high, in line with other forms of FM. [ABSTRACT FROM AUTHOR]

Objective Since vaccination for coronavirus disease 2019 (COVID-19) has been initiated, rare cases of COVID-19 mRNA vaccination-associated myocarditis (VAM) have been reported worldwide. This study aimed to report the short-term outcomes and the clinical presentation of VAM in South Korean adolescents. Methods In this prospective multicenter study across five tertiary hospitals in South Korea, patients aged 12 to 17 years with symptoms of VAM were included from October 18, 2021, to April 30, 2022. We performed laboratory tests, electrocardiography, chest radiography, echocardiography, and cardiac magnetic resonance imaging studies on these patients. Results A total of 14 patients were diagnosed with VAM during the study period. The median age of the patients was 15.2 years (interquartile range [IQR], 14.6–15.9) and 11 patients (78.6%) were male. All patients had received a messenger RNA Pfizer-BioNTech COVID-19 vaccine. The median latent period from vaccination to symptom onset was 1 (range, 0–8; IQR, 0.8–3.5) day. Chest pain was the most common symptom (11/14, 78.6%), and the median duration of symptoms was 1 week. Except for one patient (7.1%) who was admitted to intensive care unit, most patients (13/14, 93.8%) had a minor and short clinical course without an intensive treatment including an immune modulator. Conclusion VAM in South Korean adolescents had self-limiting clinical courses as reported by previous studies. Despite the small number of cases, our findings, consistent with previous studies, revealed that East Asian adolescents might have a similar or even milder clinical course than adolescents of other ethnicities. [ABSTRACT FROM AUTHOR]

We present the case of a 23-month-old child who died less than 24 h after the onset of cardiac symptoms, despite being admitted to the hospital 72 h earlier. Autopsy revealed no significant macroscopic changes, and histologic examination revealed focal lymphocytic myocarditis with myocyte disruption, diffuse alveolar damage in the exudative phase, and generalized lymphocytic immune activation in other organs. Ante-mortem and post-mortem microbiological exams did not clearly prove a causative role of infectious agents. The peculiarity of this case was characterized by the contrast between the severe clinical features and the mild cardiac histological findings. This discrepancy, coupled with the suspicion of a viral causative role based on both ante-mortem and post-mortem microbiological examinations, presented significant challenges in reaching an etiological diagnosis. This case also confirms that the diagnosis of myocarditis in children cannot be made solely on the basis of histological cut-offs or microbiological results. Using abductive reasoning, various diagnostic hypotheses were formulated and evaluated to arrive at the final diagnosis of fatal myocarditis of viral or post-viral origin. Data from post-mortem examination are often the only source of information that is available to the experts, especially in cases of sudden infant death syndrome. In such cases, the forensic pathologists should accurately evaluate findings that may appear to indicate a different etiology, and, in the absence of clinical or radiological data, interpret post-mortem data in a logically correct manner. The autopsy is the first essential step to evaluate the cause of death and must be integrated with the results of ante- and post-mortem diagnostic tests in a holistic approach, which is crucial to allow forensic pathologists to provide an appropriate and relevant opinion. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following COVID-19 infection. Cardiac involvement is common and includes left ventricular systolic dysfunction, cardiac marker elevation, electrocardiogram (ECG) changes, and coronary artery dilation. This single-center retrospective cohort study compares cardiovascular disease between three major SARS-CoV-2 variants and describes the evolution of findings in medium-term follow-up. Of 69 total children (mean age 9.2 years, 58% male), 60 (87%) had cardiovascular involvement with the most common features being troponin elevation in 33 (47%) and left ventricular dysfunction in 22 (32%). Based on presumed infection timing, 61 patients were sorted into variant cohorts of Alpha, Delta, and Omicron. Hospitalization was longer for the Delta group (7.7 days) vs Alpha (5.1 days, p = 0.0065) and Omicron (4.9 days, p = 0.012). Troponin elevation was more common in Delta compared to Alpha (13/20 vs 7/25, p = 0.18), and cumulative evidence of cardiac injury (echocardiographic abnormality and/or troponin elevation) was more common in Delta (17/20) compared with Alpha (12/25, p = 0.013) or Omicron (8/16, p = 0.034). Forty-nine (77%) of the original cohort (n = 69) had no cardiac symptoms or findings beyond 3 months post-hospitalization. Cardiac MRI was performed in 28 patients (between 3 and 6 months post-hospitalization) and was normal in 25 patients (89%). The differences in the variant cohorts may be due to alteration of the immune landscape with higher severity of COVID-19 infection. Despite overall reassuring cardiac outcomes, it is important to note the variability of presentation and remain vigilant with future variants. [ABSTRACT FROM AUTHOR]

Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis. [ABSTRACT FROM AUTHOR]

Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis. [ABSTRACT FROM AUTHOR]

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. Conclusion: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. What is Known: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. What is New: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis. [ABSTRACT FROM AUTHOR]

Introduction: Covid-19 patients can have both regional and global ventricular dysfunction. We aim to study the spectrum of myocardial involvement in Covid-19 patients on echocardiography. Methods: This is a single center, observational study where wall motion abnormality patterns were studied in Covid-19 patients along with global and regional longitudinal strain analysis (GLS). Results: 30 Covid-19 patients were included in the study, with a mean age of 35.3±6.4 years. Echocardiography revealed characteristic wall motion abnormality involving hypokinesia of anterolateral and apical segments, which produced an operculum like appearance in all patients. Strain derived ejection fraction(EF) was lower in 4 chamber as compared to 2 chamber indicating regional myocardial dysfunction. Reduced GLS values in presence of normal EF indicates global systolic function impairment. Endocardial effacement was also noted in these segments along with stretching of interventricular septum. Conclusion: Specific myocardial involvement pattern can be detected on echocardiography, thus helping in diagnosis of Covid myocarditis. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01–1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06–1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01–1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04–1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09–1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01–1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01–1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00–1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75–0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76–0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62–0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61–0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to analyze trends in the burden of myocarditis in the Chinese population during 1990-2019. Methods: The Global Burden of Disease (GBD) database aims to assess the burden of various diseases and injuries on a global scale, and the contribution of relevant risk factors to the burden of disease was also included. In this study, we collected age-standardized incidence and mortality rates for myocarditis in China from 1990 to 2019 using GBD 2019. The age-period-cohort model was utilized to calculate local drift, longitudinal age patterns, as well as the ratios of period and cohort. Results: The age-standardized incidence and mortality rates of myocarditis in both men and women presented a decreasing trend during 1990-2019 [average annual percentage change (AAPC) of men = -0.202 (95% CI: -0.213 to -0.191); AAPC of women = -0.263 (95% CI: -0.27 to -0.256) for incidence; AAPC of men = -0.233 (95% CI: -0.371 to -0.094); AAPC of women = -0.872 (95% CI: -1.112 to -0.631) for mortality]. Longitudinal age curves showed that myocarditis incidence and mortality rates elevated with age among individuals aged 15-95+ years, with a higher growth rate in men than in women. The period and cohort ratios for both men and women showed similar decreasing trends. Local drift values for the incidence and mortality rates of myocarditis showed an increasing trend among individuals aged 70-75 years and above. Conclusion: Although the overall burden of myocarditis in China presented a decreasing trend during 1990-2019, the male and elderly populations still have a higher risk of incidence and mortality. Therefore, it is essential for the health-care system to introduce effective prevention and treatment measures for myocarditis. [ABSTRACT FROM AUTHOR]

The clinical spectrum of Coronavirus disease 2019 (COVID-19) varies from asymptomatic infection to severe disease with multiorgan dysfunction. Cardiovascular involvement is common and in rare cases can lead to serious complications, such as fulminant myocarditis. The clinical course of COVID-19 myocarditis varies from complete recovery to death in rare cases. The pathophysiology of COVID-19-related myocarditis is still unclear but is believed to involve direct viral injury and cardiac damage due to the host's immune response. Guidelines on the management of COVID-19-related myocarditis are yet to be established. We present here the case of a male patient in his early fifties admitted with life-threatening myocarditis in the course of COVID-19 infection who was successfully treated and recovered without any sequelae. [ABSTRACT FROM AUTHOR]

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction where patients present with fever, morbilliform rash and multiorgan manifestations, which may include acute renal failure, acute respiratory distress syndrome and eosinophilic myocarditis. We present a case of a 60‐year‐old woman with acute heart failure, DRESS syndrome features and human herpesvirus 6 reactivation in the absence of a drug trigger. She was diagnosed with eosinophilic myocarditis and successfully treated with corticosteroid therapy. [ABSTRACT FROM AUTHOR]

Background: Diphtheria is a contagious bacterial infection caused by Corynebacterium diphtheriae with a fatality rate of 5 - 10%. In 2020, there were about 1991 cases and 28 deaths due to diphtheria in India. Sore throats, fever, swollen glands, thick gray colored pseudo membrane over the throat are the common clinical features of Diphtheria. Environmental factors like overcrowded houses and poor socio-economic conditions lead to higher transmission of disease. Objective: To assess the clinical and laboratory profile of patients admitted in infectious disease hospital with symptoms of diphtheria. Materials and Methods: A Hospital record based cross sectional study, was carried out at an infectious disease hospital which is a tertiary care center in Hyderabad, Telangana from November 2014 to October 2015.A total of 1140 patients admitted with the symptoms and signs of Diphtheria during the period 2006 - 2010 were taken. Results: Female preponderance was noted (60.53%) and majority (24.44%) of cases were in the age group of 6 -10 years. The most common presentation was sore throat (62%), fever (60%), cough (46.3%) and dysphagia (40%). Around 2.11% patients reported myocarditis and 37.89% had positive throat swab for Klebsiella Loeffler's Bacilli. Anti-diphtheritic serum was administered to 12.8% of patients. Conclusion: Primary immunization with all 3 doses of DPT vaccine can reduce disease burden, morbidity and mortality. There is need for emphasis on effective surveillance of the disease and early detection of cases so as to promote timely initiation of treatment and prevent complications. [ABSTRACT FROM AUTHOR]

Myocarditis can be caused by viral infection, drug reaction or general inflammatory condition. To provide understanding on inflammatory myocarditis, we describe clinical, genetic, and immunological properties of a young male patient who suffered from recurrent myocarditis episodes since the age of four years. Electrocardiography, troponin I/T, echocardiography, myocardial magnetic resonance imaging and histological findings were consistent with recurrent myocarditis episodes. Homozygous c.245 A > G p.Tyr82Cys pathogenic variant in Hepatitis A Virus Cellular Receptor 2 (HAVCR2) gene encoding T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) receptor was found. Peripheral blood mononuclear cells were collected when the patient was asymptomatic; CD4+ and CD8+ T lymphoblasts, CD56+ natural killer cells and CD14+ monocytes were negative for surface TIM-3 expression. In vitro, TLR4 mediated interleukin-1β (IL-1β) response was high after LPS/ATP stimulation. Clinical symptoms responded to IL-1 receptor antagonist anakinra. TIM-3 p.Tyr82Cys CD4+ and CD8+ T cell proliferation in vitro was unrestrained. Findings on IL-2, interferon gamma, regulatory T cells, signal transducer and activator of transcription (STAT) 1, 3 and 4 phosphorylation, and PD-1 and LAG-3 checkpoint inhibitor receptor analyses were comparable to controls. We conclude that TIM-3 deficiency due to homozygous HAVCR2 c.245 A > G p.Tyr82Cys pathogenic variant in the patient described here is associated with autoinflammatory symptoms limited to early onset recurrent febrile myocarditis. Excessive IL-1β production and defective regulation of T cell proliferation may contribute to this clinical condition responsive to anakinra treatment. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism by which icariin alleviates viral myocarditis. Methods: CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability, inflammation, and apoptosis. Moreover, the effects of icariin on ferroptosis and TLR4 signaling were assessed. After AC16 cells were transfected with TLR4 overexpression plasmids, the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated. Results: Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α, IL-1β, IL-6, and IL-18. Flow cytometry revealed that icariin decreased apoptosis rate, and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes. Additionally, it suppressed ferroptosis including lipid peroxidation and ferrous ion, as well as the TLR4 signaling. However, TLR4 overexpression abrogated the modulatory effects of icariin. Conclusions: Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis. Further animal study is needed to verify its efficacy. [ABSTRACT FROM AUTHOR]

Although most cases of myocarditis are self-limiting with a gradual improvement in cardiac function, the involvement of myocarditis in sudden cardiac death among children and young adults remains substantial, with rates of 3–17 % and 8.6–12 %, respectively. Moreover, the risk of developing chronic dilated cardiomyopathy ranges from 21 % to 30 % in all cases confirmed by biopsy. Current therapeutic strategies for myocarditis and its complications range from standard supportive care for heart failure and arrhythmias to etiologically oriented, case-based therapeutic options. For example, immunosuppression is indicated only in certain forms of acute myocarditis with clinical or endomyocardial biopsy evidence of immune checkpoint inhibitor-induced myocarditis and autoimmune diseases, including giant cell myocarditis, eosinophilic myocarditis, vasculitis, or cardiac sarcoidosis. However, our views on myocarditis treatment have changed considerably over the past two decades, thanks to the emergence of regenerative cells/tissues as well as drug and gene delivery systems. Cell-based therapies are now growing in popularity in any field of medicine. Studies evaluating the therapeutic efficacy of different stem cells in the treatment of acute myocarditis and its chronic complications have shown that although the experimental characteristics varied from study to study, in general, these strategies reduced inflammation and myocardial fibrosis while preventing myocarditis-induced systolic dysfunction and adverse remodeling in animal models. [Display omitted] • Mesenchymal stem cells commonly employed for treating acute myocarditis. • All cell types demonstrated functional and histological improvement in studies. • M2 macrophages were effective in cardiac and non-cardiac disease models. • Stem cells can reduce reliance on mechanical circulatory support/transplantation. • M2 macrophages show great promise in acute myocarditis treatment. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory disease of the myocardium secondary to infectious and noninfectious insults. The most feared consequence of myocarditis is sudden cardiac death owing to electrical instability and arrhythmia. Typical presenting symptoms include chest pain, dyspnea, palpitations and/or heart failure. Diagnosis is usually made with history, electrocardiogram, biomarkers, echocardiogram, and cardiac MRI (CMR). Application of the Lake Louise criteria to CMR results can help identify cases of myocarditis. Treatment is usually supportive with medical therapy, and patients are recommended to abstain from exercise for 3 to 6 months. Exercise restrictions may be lifted after normalization on follow-up testing. [ABSTRACT FROM AUTHOR]

Dystrophic calcification is a rare but fatal complication associated with severe myocarditis. Detecting calcified lesions and evaluating ventricular function are essential for the management of myocarditis. We report a case of neonatal acute myocarditis with dystrophic calcification successfully assessed by two-dimensional speckle-tracking echocardiography. The calcification spontaneously resolved, and the recovery of myocardial function was evaluated by speckle-tracking echocardiography. Speckle-tracking echocardiography could be a useful method to evaluate regional ventricular dysfunction corresponding to dystrophic calcification as well as that caused by myocarditis and the follow-up because of its repeatability. 1) Dystrophic calcification can occur as a rare complication associated with severe myocarditis. 2) Dystrophic calcification can spontaneously resolve with the recovery of myocardial function. 3) Speckle-tracking echocardiography is a useful tool for the evaluation of the extent of and myocardial function in dystrophic calcification and the follow-up. [ABSTRACT FROM AUTHOR]

Influenza B is one of the infective agents that can cause rapid and fatal myocarditis in children. Here, we describe a fatal case of myocarditis in a previously healthy child, after infection with an influenza B/Victoria-lineage virus during the 2022–23 epidemic season in Italy. Influenza B virus was isolated also in a second case, a younger family member showing only a mild influenza-like illness. Genotypic and phenotypic analyses have been performed on both virus samples and results showed that HA1 sequences were identical and genetically and antigenically related to other B viruses circulating in 2022–23 season in Italy. However, a D129N substitution was found in the receptor binding domain of the HA of the two viruses, not detected in other circulating viruses in Italy but only in a proportion of those circulating in other European countries. Phenotypic analyses assessed the susceptibility towards either neuraminidase inhibitors and baloxavir. Annual influenza vaccination remains one of the best interventions to prevent complications such as myocarditis, particularly in children. [ABSTRACT FROM AUTHOR]

Background: The cardiovascular system is among the least systems affected by immune-related adverse events. We report a rare life-threatening case of pembrolizumab-induced myocarditis with complete atrioventricular block and concomitant myositis in a metastatic bladder cancer patient. Case presentation: An 82-year-old Caucasian female with invasive urothelial carcinoma, started on first-line pembrolizumab, was admitted four days after receiving her second dose for severe asthenia, diffuse muscle aches, neck pain, and lethargy. In the emergency department, she had several episodes of bradycardia reaching 40 beats per minute associated with general discomfort and fatigue. Electrocardiography showed a third-degree atrioventricular heart block, while the patient remained normotensive. Cardiac damage parameters were altered with elevated levels of creatine phosphokinase of 8930 U/L, suggestive of immune checkpoint inhibitor-induced myositis, and troponin T of 1.060 ng/mL. Transthoracic echocardiography showed a preserved ejection fraction. Pembrolizumab-induced myocarditis was suspected. Therefore, treatment was initiated with high-dose glucocorticoids for 5 days, followed by a long oral steroid taper. A pacemaker was also implanted. Treatment resulted in the resolution of heart block and a decrease in creatine phosphokinase to the normal range. Conclusion: Life-threatening cardiac adverse events in the form of myocarditis may occur with pembrolizumab use, warranting vigilant cardiac monitoring. Troponin monitoring in high-risk patients, along with baseline echocardiography may help identify this complication promptly to prevent life-threatening consequences. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. Methods: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. Results: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001–1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. Conclusion: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, and lymphocyte activation gene-3 (LAG-3) have improved cancer patient outcomes by enhancing anti-tumor responses. However, some patients are unresponsive, and others experience immune-related adverse events (irAEs), affecting organs like the lung, liver, intestine, skin and now the cardiovascular system. These cardiac irAEs include conditions like myocarditis, atherosclerosis, pericarditis, arrhythmias, and cardiomyopathy. Ongoing clinical trials investigate promising alternative co-inhibitory receptor targets, including T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT). This review delves into the mechanisms of approved ICIs (CTLA-4, PD-1, PD-L1, and LAG-3) and upcoming options like Tim-3 and TIGIT. It explores the use of ICIs in cancer treatment, supported by both preclinical and clinical data. Additionally, it examines the mechanisms behind cardiac toxic irAEs, focusing on ICI-associated myocarditis and atherosclerosis. These insights are vital as ICIs continue to revolutionize cancer therapy, offering hope to patients, while also necessitating careful monitoring and management of potential side effects, including emerging cardiac complications. [ABSTRACT FROM AUTHOR]

Background: Myocarditis is commonly diagnosed in the intensive care cardiology unit (ICCU). No current recommendation nor guideline aids exist for aetiological assessments. Methods: From September 2021 to October 2023, 84 patients with acute myocarditis underwent thorough and systematic serum and blood cell panel evaluations to determine the most common causes of myocarditis. Results: Of the 84 patients (median age 34 years, range 22–41 years, 79% male), 16 presented with complicated myocarditis. The systematic aetiological assessment revealed that 36% of patients were positive for lupus anticoagulant, 12% for antinuclear antibodies, 8% for anti-heart antibodies, and 12% for anti-striated muscle antibodies. Viral serology did not yield any significant results. After the aetiological assessment, one patient was diagnosed with an autoimmune inflammatory disorder (Still's disease). T-cell subset analyses indicated that myocarditis severity tended to increase with the T-cell lymphopenia status. Conclusions: A comprehensive, systematic aetiological assessment was of limited value in terms of predicting the clinical or therapeutic outcomes in myocarditis patients presenting to the ICCU. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Thyroid storm represents a critical and life‐threatening complication from hyperthyroidism, with a notable mortality risk. Limited literature reports have explored the correlation between thyroid storm and peri‐myocarditis, although the precise pathophysiological underpinnings remain unclear. The pathophysiology of how thyroid storm and peri‐myocarditis are associated is not clearly understood; however, unfavorable prognostic factors include atrial fibrillation and recurrent thyrotoxicosis. Here, we present a case concerning recurrent peri‐myocarditis concomitant with a thyroid storm. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of a short non-contrast CMR (ShtCMR) protocol relative to a matched standard comprehensive CMR (StdCMR) protocol in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). Methods: This multicenter retrospective study included patients with a working diagnosis of MINOCA who underwent a StdCMR between January 2019 and December 2020. An expert and a non-expert reader performed a blinded reading with the ShtCMR (long-axis cine images, T2w-STIR, T1- and T2-mapping). A consensus reading of the StdCMR (reference standard) was performed at least 3 months after the ShtCMR reading session. Readers were asked to report the following: (1) diagnosis; (2) level of confidence in their diagnosis with the ShtCMR; (3) number of myocardial segments involved, and (4) functional parameters. Results: A total of 179 patients were enrolled. The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). ShtCMR allowed reaching the same diagnosis as StdCMR in 85% of patients when interpreted by expert readers (rising from 66% for poor confidence to 99% for good, p = 0.0001) and in 73% (p = 0.01) by non-expert ones (60% for poor vs 89% for good confidence, p = 0.0001). Overall, the ShtCMR overestimated the ejection fraction, underestimated cardiac volumes (p < 0.01), and underestimated the number of segments involved by pathology (p = 0.0008) when compared with the StdCMR. Conclusion: The ShtCMR was found to be a debatable alternative to the StdCMR in patients with MINOCA. Nevertheless, when an experienced reader reaches a good or very good diagnostic confidence using the ShtCMR, the reader may choose to stop the examination, reducing the length of the CMR without affecting the patient's diagnosis. Clinical relevance statement: A short non-contrast CMR protocol may be a viable alternative to standard protocols in selected CMR studies of patients with MINOCA, allowing for faster diagnosis while reducing time and resources and increasing the number of patients who can be scanned. Key Points: • The ShtCMR lasted 21 ± 9 min and the StdCMR 45 ± 11 min (p < 0.0001). • In 57% of patients with MINOCA, the experienced reader considers that contrast medium is probably not necessary for diagnosis without affecting the patient's diagnosis (99% of agreement rate between ShtCMR and StdCMR). [ABSTRACT FROM AUTHOR]

(1) Objective: Myocarditis can be associated with ventricular arrhythmia (VA), individual non-invasive risk stratification through cardiovascular magnetic resonance (CMR) is of great clinical significance. Our study aimed to explore whether left atrial (LA) and left ventricle (LV) myocardial strain serve as independent predictors of VA in patients with myocarditis. (2) Methods: This retrospective study evaluated CMR scans in 141 consecutive patients diagnosed with myocarditis based on the updated Lake Louise criteria (29 females, mean age 41 ± 20). The primary endpoint was VA; this encompassed ventricular fibrillation, sustained ventricular tachycardia, nonsustained ventricular tachycardia, and frequent premature ventricular complexes. LA and LV strain function were performed on conventional cine SSFP sequences. (3) Results: After a median follow-up time of 23 months (interquartile range (18–30)), 17 patients with acute myocarditis reached the primary endpoint. In the multivariable Cox regression analysis, LA reservoir (hazard ratio [HR] and 95% confidence interval [CI]: 0.93 [0.87–0.99], p = 0.02), LA booster (0.87 95% CI [0.76–0.99], p = 0.04), LV global longitudinal (1.26 95% CI [1.02–1.55], p = 0.03), circumferential (1.37 95% CI [1.08–1.73], p = 0.008), and radial strain (0.89 95% CI [0.80–0.98], p = 0.01) were all independent determinants of VA. Patients with LV global circumferential strain > −13.3% exhibited worse event-free survival compared to those with values ≤ −13.3% (p < 0.0001). (4) Conclusions: LA and LV strain mechanism on CMR are independently associated with VA events in patients with myocarditis, independent to LV ejection fraction, and late gadolinium enhancement location. Incorporating myocardial strain parameters into the management of myocarditis may improve risk stratification. [ABSTRACT FROM AUTHOR]

Carditis in childhood is a rare disease with several etiologies. We report a case of infant death due to pericarditis and myocarditis after the mRNA vaccine against COVID-19 (COVIDmRNAV). A 7-year-old male child received the first dose of the COVIDmRNAV and presented with monoarthritis and a fever non-responsive to oral antibiotics. The laboratory investigation showed signs of infection (leukocytosis, high levels of c-reactive protein). His condition rapidly deteriorated, and the patient died. The autopsy identified pericardial fibrin deposits, hemorrhagic areas in the myocardium, and normal valves. A diffuse intermyocardial inflammatory infiltrate composed of T CD8+ lymphocytes and histiocytes was identified. An antistreptolysin O (ASO) dosage showed high titers. The presence of arthritis, elevated ASO, and carditis fulfills the criteria for rheumatic fever. However, valve disease and Aschoff's nodules, present in 90% of rheumatic carditis cases, were absent in this case. The temporal correlation with mRNA vaccination prompted its inclusion as one of the etiologies. In cases of myocardial damage related to COVID-19mRNAV, it appears to be related to the expression of exosomes and lipid nanoparticles, leading to a cytokine storm. The potential effects of the COVID-19mRNAV must be considered in the pathogenesis of this disease, whether as an etiology or a contributing factor to a previously initiated myocardial injury. [ABSTRACT FROM AUTHOR]

Background: An exuberant and dysregulated inflammatory response contributes to the development and progression of cardiovascular diseases (CVDs). Methods: This narrative review includes original articles and reviews published over the past 20 years and found through PubMed. The following search terms (or combination of terms) were considered: "acute pericarditis," "recurrent pericarditis," "myocarditis," "cardiac sarcoidosis," "atherosclerosis," "acute myocardial infarction," "inflammation," "NLRP3 inflammasome," "Interleukin‐1" and "treatment." Results: Recent evidence supports the role of inflammation across a wide spectrum of CVDs including myocarditis, pericarditis, inflammatory cardiomyopathies (i.e. cardiac sarcoidosis) as well as atherosclerotic CVD and heart failure. Interleukins (ILs) are the signalling mediators of the inflammatory response. The NACHT, leucine‐rich repeat and pyrin‐domain containing protein 3 (NLRP3) inflammasome play a key role in producing IL‐1β, the prototypical pro‐inflammatory cytokine involved in CVDs. Other pro‐inflammatory cytokines (e.g. tumour necrosis factor) have been implicated in cardiac sarcoidosis. As a proof of this, IL‐1 blockade has been proven efficacious in pericarditis and chronic coronary syndrome. Conclusion: Tailored strategies aiming at quenching the inflammatory response have emerged as promising to treat CVDs. In this review article, we summarize recent evidence regarding the role of inflammation across a broad spectrum of CVDs. We also review novel evidence regarding targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Summary: Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment. [ABSTRACT FROM AUTHOR]

Patient prognoses have been significantly enhanced by immune checkpoint inhibitors (ICIs), altering the standard of care in cancer treatment. These novel antibodies have become a mainstay of care for metastatic non-small-cell lung cancer (mNSCLC) patients. Several types of adverse events related to ICIs have been identified and documented as a result of the launch of these innovative medicines. We present here a 74-year-old female patient with a stage IV lung adenocarcinoma, treated with nivolumab plus ipilimumab, who developed perimyocarditis two weeks after receiving the third cycle of immune checkpoint inhibitor therapy. The patient was diagnosed using troponin levels, computed tomography (CT) angiography, and echocardiography. After hospitalization, her cardiac condition was successfully resolved with corticosteroids, colchicine, and symptomatic treatment. To the best of our knowledge, this is one of the rarest cases to be reported of perimyocarditis as a toxicity of immunotherapy in a patient treated for adenocarcinoma of the lung. [ABSTRACT FROM AUTHOR]

Background: Cryptococcus neoformans is the third most common cause of invasive fungal infection in solid organ transplant (SOT) recipients. While cryptococcal infection can involve any organ, cases of myocarditis are exceedingly rare. Methods: A retrospective chart review was completed for this case report. Results: We present the case of a 21‐year‐old heart transplant recipient who developed disseminated cryptococcal infection with biopsy‐proven cryptococcal myocarditis. Conclusions: Cryptococcal disease in SOT recipients poses diagnostic and therapeutic challenges. There are no current guidelines for the duration of cryptococcal myocarditis treatment. Repeat myocardial biopsy may play a role in guiding length of therapy. [ABSTRACT FROM AUTHOR]

Recent research suggests that T-cell receptor (TCR) sequences expanded during human immunodeficiency virus and SARS-CoV-2 infections unexpectedly mimic these viruses. The hypothesis tested here is that TCR sequences expanded in patients with type 1 diabetes mellitus (T1DM) and autoimmune myocarditis (AM) mimic the infectious triggers of these diseases. Indeed, TCR sequences mimicking coxsackieviruses, which are implicated as triggers of both diseases, are statistically significantly increased in both T1DM and AM patients. However, TCRs mimicking Clostridia antigens are significantly expanded in T1DM, whereas TCRs mimicking Streptococcal antigens are expanded in AM. Notably, Clostridia antigens mimic T1DM autoantigens, such as insulin and glutamic acid decarboxylase, whereas Streptococcal antigens mimic cardiac autoantigens, such as myosin and laminins. Thus, T1DM may be triggered by combined infections of coxsackieviruses with Clostridia bacteria, while AM may be triggered by coxsackieviruses with Streptococci. These TCR results are consistent with both epidemiological and clinical data and recent experimental studies of cross-reactivities of coxsackievirus, Clostridial, and Streptococcal antibodies with T1DM and AM antigens. These data provide the basis for developing novel animal models of AM and T1DM and may provide a generalizable method for revealing the etiologies of other autoimmune diseases. Theories to explain these results are explored. [ABSTRACT FROM AUTHOR]

Objective: To investigate characteristics and management of children presenting with chest complaints to a tertiary paediatric ED post‐mRNA COVID‐19 vaccine. Methods: This was a retrospective medical record review with data linkage to the Australian Immunisation Register. The study setting was the Royal Children's Hospital, Melbourne, Australia. Children <18 years who had a troponin blood test performed in hospital within 14 days of receiving mRNA COVID‐19 vaccination were included. Elevated troponin and myocarditis or pericarditis as per Brighton criteria was the primary outcome. Vaccination status, length of stay, investigations and clinical management were secondary outcomes. Results: Six hundred and ten patients had a troponin test in 13 months. After exclusion of trauma‐related tests (n = 31), known cardiac patients (n = 75) and others (n = 145), 359 troponins were obtained due to chest complaints and related symptoms, with 283 troponins assessed to be mRNA vaccination‐related. There was a temporal peak in presentations with a 30‐fold monthly increase in troponin post‐commencement of mRNA COVID‐19 vaccines. In those with chest complaints following mRNA vaccination, mean age was 14 years and 50.4% were female. Fourteen out of 283 (5%) vaccine‐related troponins were abnormal with 14 patients assessed to have vaccine‐associated myocarditis. No patients had pericarditis. Conclusions: There was a large number of possible mRNA COVID‐19 vaccine‐related chest complaints presenting to the ED. Few patients had abnormal troponins or myocarditis. [ABSTRACT FROM AUTHOR]

Myocarditis is an inflammatory heart disease that mostly affects young people. Myocarditis involves a complex immune network; however, its detailed pathogenesis is currently unclear. The diversity and plasticity of immune cells, either in the peripheral blood or in the heart, have been partially revealed in a number of previous studies involving patients and several kinds of animal models with myocarditis. It is the complexity of immune cells, rather than one cell type that is the culprit. Thus, recognizing the individual intricacies within immune cells in the context of myocarditis pathogenesis and finding the key intersection of the immune network may help in the diagnosis and treatment of this condition. With the vast amount of cell data gained on myocarditis and the recent application of single-cell sequencing, we summarize the multiple functions of currently recognized key immune cells in the pathogenesis of myocarditis to provide an immune background for subsequent investigations. [ABSTRACT FROM AUTHOR]

Background: Myocarditis in context of a SARS-CoV-2 infection is vividly discussed in the literature. Real-world data however are sparse, and relevance of the myocarditis diagnosis to outcome in coronavirus disease (COVID-19) is unclear. Patients and methods: Retrospective analysis of 75,304 patients hospitalized in Germany with myocarditis between 2007 and 2020 is reported by DESTATIS. Patients hospitalized between 01/2016 and 12/2019 served as reference cohort for the COVID-19 patients hospitalized in 2020. Results: A total of 75,304 patients were hospitalized between 2007 and 2020 (age 42.5 years, 30.1% female, hospital mortality 2.4%). In the reference cohort, 24,474 patients (age 42.8 years, 29.5% female, hospital mortality 2.2%) were registered. In 2020, annual myocarditis hospitalizations dropped by 19.6% compared to reference (4921 vs. 6119 annual hospitalization), of which 443/4921 (9.0%) were connected to COVID-19. In 2020, hospital mortality of myocarditis in non-COVID-19 patients increased significantly compared to reference (2.9% vs. 2.2%, p = 0.008, OR 1.31, 95% CI 1.08–1.60). In COVID-19 myocarditis, hospital mortality was even higher compared to reference (13.5% vs. 2.2%, p < 0.001, OR 6.93, 95% CI 5.18–9.18). Conclusion: The burden of patients with myocarditis and COVID-19 in 2020 was low. Hospital mortality was more than sixfold higher in patients with myocarditis and COVID-19 compared to those with myocarditis but without COVID-19. [ABSTRACT FROM AUTHOR]

Arrhythmogenic cardiomyopathy is a primary genetic disease caused by mutations in the desmosome genes. Ever since the introduction of new imaging techniques, like cardiovascular magnetic resonance, the diagnosis of arrhythmogenic cardiomyopathy has become more challenging as left ventricular or biventricular variants may have resemblance to other cardiomyopathies or myocarditis. Not only this but they may also share an acute phase, which might cause even more confusion and misdiagnoses and influence the prognosis and outcome. In this case report, we present a 31-year-old patient with multiple clinical pictures: his symptoms were acute chest pain, new onset of heart failure and arrhythmia symptoms, which determined a dynamic change in clinical diagnosis and management, ultimately taking into consideration arrhythmogenic cardiomyopathy. Through the article, we try to uncover and explain common pathophysiological pathways shared by arrhythmogenic cardiomyopathy and other clinical entities with a special focus on inflammation. The final question remains: "If there is more than one heart disorder that eventually leads to the same clinical image, one may wonder, is arrhythmogenic cardiomyopathy a syndrome rather than a specific condition?". [ABSTRACT FROM AUTHOR]

Myocarditis is one of the major causes of heart failure in children and young adults and can lead to dilated cardiomyopathy. Lymphocytic myocarditis could result from autoreactive CD4+ and CD8+ T cells, but defining antigen specificity in disease pathogenesis is challenging. To address this issue, we generated T cell receptor (TCR) transgenic (Tg) C57BL/6J mice specific to cardiac myosin heavy chain (Myhc)-α 334–352 and found that Myhc-α-specific TCRs were expressed in both CD4+ and CD8+ T cells. To investigate if the phenotype is more pronounced in a myocarditis-susceptible genetic background, we backcrossed with A/J mice. At the fourth generation of backcrossing, we observed that Tg T cells from naïve mice responded to Myhc-α 334–352, as evaluated by proliferation assay and carboxyfluorescein succinimidyl ester staining. The T cell responses included significant production of mainly pro-inflammatory cytokines, namely interferon (IFN)-γ, interleukin-17, and granulocyte macrophage-colony stimulating factor. While the naïve Tg mice had isolated myocardial lesions, immunization with Myhc-α 334–352 led to mild myocarditis, suggesting that further backcrossing to increase the percentage of A/J genome close to 99.99% might show a more severe disease phenotype. Further investigations led us to note that CD4+ T cells displayed the phenotype of cytotoxic T cells (CTLs) akin to those of conventional CD8+ CTLs, as determined by the expression of CD107a, IFN-γ, granzyme B natural killer cell receptor (NKG)2A, NKG2D, cytotoxic and regulatory T cell molecules, and eomesodermin. Taken together, the transgenic system described in this report may be a helpful tool to distinguish the roles of cytotoxic cardiac antigen-specific CD4+ T cells vs. those of CD8+ T cells in the pathogenesis of myocarditis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background:Dengue infection is one of the common tropical infectious diseases. Clinicalmanifestations of cardiacinvolvement can vary widely, from an incidental finding to severe cardiac failure resulting in death. Aim:To assess the prevalence and clinical significance of major acute cardiovascular events after dengue infection. Methods:A comprehensive longitudinal investigation took place at a tertiaryhealthcare facilitylocated inRaigad (Maharashtra). The sampling techniqueinvolved the inclusion of 140 eligible dengue fever cases who were selected on a first come first serve basisafter the beginning of the study.A previous history of any cardiac disease, history of chronic kidney disease(CKD), pregnant women and children, as well as admission ECG suggestive of old ischemicchanges, and use of medications affecting heart rate were excluded from the study. Results: Prevalence of cardiac inflammation in dengue fever cases were 26.4%. The elevatedhs-Troponin-T (pg/ml) in 25.0% cases and elevated CK-MB (U/L) in 23.6% cases.1st-degree heart block in 10.8%,2nd-degree heart block in 2.7%, complete heart block in 2.7%, atrial fibrillation in 10.8%, ST elevation in 5.4%, ventricular tachycardia in 2.7% and sinus tachycardi a in 13.5%. 37.8% cases found EF <40.0% echocardiography, 24.3% cases EF 40-50% and regional wall motion abnormality (RWMA) in 51.4% cases. Conclusion: Our study revealed that patients withnormal echo, ECG and serum levels of markers of cardiac injury are atlow risk for mortality and hence may need less monitoring or therapeutic intervention. Our study elucidates various significantfindings that advocate for tailored interventions, heightened awareness of cardiac involvement, andstrategic use of diagnostic tools. [ABSTRACT FROM AUTHOR]

• In 847 children admitted to the cardiac intensive care unit with the diagnosis of myocarditis, survival to discharge was 93.7%; 19.1% of patients received ECMO, 4.1% received VAD, and 2.5% of patients underwent heart transplantation before discharge. • Body surface area ≤ 0.3m 2 , eGFR < 30mL/min/1.73m2 at presentation, mechanical ventilation, and ECMO were independently associated with in-hospital mortality. • Survival rates after ECMO and cardiac arrest in this population are better now than they were in the past. • Creating a uniform and implementable way to diagnose myocarditis in children should be a priority so as to allow further improved outcomes. To describe contemporary management and outcomes in children with myocarditis who are admitted to a cardiac intensive care unit (CICU) and to identify the characteristics associated with mortality. All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry between August 2014 and June 2021 who were diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated the factors associated with in-hospital mortality. There were 847 CICU admissions for myocarditis in 51 centers. The median age was 12 years (IQR 2.7–16). In-hospital mortality occurred in 53 patients (6.3%), and 60 (7.1%) had cardiac arrest during admission. Mechanical ventilation was required in 339 patients (40%), and mechanical circulatory support (MCS) in 177 (21%); extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation in 43 (5%), and VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (P < 0.001). Mortality rates were similar in ECMO-only, ECMO-to-VAD and VAD-only groups. The median time from CICU admission to ECMO was 2.0 hours (IQR 0–9.4) and to VAD, it was 9.9 days (IQR 6.3–16.8). Time to MCS was not associated with mortality. In multivariable modeling of patients' characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation and ECMO were independent predictors of mortality. This contemporary cohort of children admitted to CICUs with myocarditis commonly received high-resource therapies; however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury and receipt of mechanical ventilation or ECMO were independently associated with mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Recently, Buergin et al. (Eur J Heart Fail 25(10):1871–1881, 2023 doi:10.1002/ejhf.2978) thoroughly measured a frequency of 2.8% elevated high-sensitivity cardiac troponin T levels, a sign of myocardial damage, after mRNA-1273 (Moderna) booster vaccinations. In their discussion, they claim that before vaccinations were available, the incidence and extent of myocardial damage associated with COVID-19 infection would have been much higher. We here scrutinize this claim based on empirical data. Main body: Burgin et al. have only cited papers in support of their claim which considered hospitalized COVID-19 patients. After extracting COVID-19 infection data from Germany and Switzerland and the expected frequency of elevated troponin levels after COVID-19 infection in both hospitalized and non-hospitalized individuals, we find that the extent of myocardial damage after vaccinating a considerable proportion of the general population is expected to be much higher than after natural infections. Conclusions: The claim that the extent of myocardial injury after COVID-19 infection would be higher than after vaccination is not supported by empirical evidence and therefore wrong. We conclude that cross-national systematic observational studies should be conducted that allow a more precise estimation of the risk–benefit ratio of COVID-19 mRNA vaccinations. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) present clinicians with the challenge of managing immune-related adverse events (irAEs), which can range from mild to severe due to immune system activation 1. While guidelines recommend discontinuing ICIs for grade 3 partial and all grade 4 irAEs, there is growing interest in rechallenging patients based on oncological outcomes, particularly for cardiovascular and neurological irAEs where data remains scarce 1,2. We retrospectively evaluated the safety of ICI rechallenge following grade 3-4 irAEs, specifically focusing on cardiovascular and neurological events, in patients discussed at our multidisciplinary immunotoxicity assessment board between 2019 and 2021. Fifteen patients were included, with a median time to severe irAE onset of 49 days. Among them, five patients experienced neurological adverse events (NAEs): aseptic meningitis (3), inflammatory polyradiculoneuropathy (1), and ophthalmoplegia (1), while one patient presented with myocarditis. Of the 15 patients retreated with ICIs after initial severe irAEs, 11 (73%) remained free of subsequent irAEs, two (13%) experienced recurrence of the initial irAE, and two (13%) developed new irAEs distinct from the initial event. The median time to event recurrence was 69 days, occurring no earlier than the initial severe irAE. In the subset analysis focusing on severe cardiovascular and neurological irAEs, rechallenge with ICIs was generally well tolerated. However, one patient treated with anti-PD1 experienced a relapse of grade 2 aseptic meningitis. Overall, our findings suggest that rechallenging with ICIs after severe irAEs, including those affecting the cardiovascular and neurological systems, may be safe, particularly after irAE regression and corticosteroid withdrawal.