Campylobacter-Associated Myocarditis in a 17-Year-Old Male.

Chest pain is a common presenting complaint in adolescent patients. Myocarditis is an important and potentially serious etiology of chest pain for clinicians who care for these patients to recognize. Myocarditis is commonly virally mediated, while extra-intestinal cardiac manifestations of bacterial enteritis, such as Campylobacter infections,are rare. Awareness of this uncommon, but potentially life-threatening pathophysiology is important for clinicians to understand.  In our case, a 17-year-old male presented with chest discomfort, chest pain on inspiration, headache, myalgias, vomiting, and diarrhea. He denied recent viral illnesses or immunizations. He lived in rural Ohio, swam recently in a freshwater lake, and had eaten home-prepared deer meat. His father had diarrhea as well. Presenting vital signs were within normal limits for age. The patient was obese (BMI 48.5), with an otherwise normal physical exam, including a thorough cardiopulmonary assessment. Laboratory workup revealed leukocytosis (16.1 x 109/L) and elevated high-sensitivity troponin (15,857 ng/L, >22,000 ng/L three hours later, ref range <20). Gastrointestinal polymerase chain reaction (PCR) panel detected Campylobacter spp., and stool culture was positive for Campylobacter jejuni. ECG, echocardiography, chest X-ray, and CT angiography were normal. Cardiac MRI revealed an increased T2 signal consistent with myocarditis. The patient was treated with non-steroidal anti-inflammatory drugs (NSAIDs) and azithromycin and had complete resolution in symptoms. He was exercise-restricted for six months.  Myocarditis is a potentially fatal pathology, representing a significant cause of sudden death in young adults. Myocarditis can present with a broad spectrum of signs and symptoms as well as variable clinical severity. Bacterial causes of myocarditis are uncommon, with Campylobacter among the least common. Campylobacter gastroenteritis, however, is quite common worldwide. Extra-intestinal and cardiac manifestations are rare; thus, it is important to maintain a high index of suspicion. Due in part to its rarity, treatment for Campylobacter-associated myocarditis is not well established. Treatment for myocarditis, regardless of etiology, is largely supportive in nature. Campylobacter-directed antibiotics, such as azithromycin, have been used successfully in adolescents with Campylobacter-associated myocarditis. Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for symptom control, though their use remains controversial. Activity restriction is recommended for six months to reduce the risk of sudden cardiac death.  Myocarditis is an important cause of sudden death in young adults and is a rare extra-intestinal manifestation of Campylobacter bacterial gastroenteritis. Pediatric and adult providers should be aware of this presentation and its pathophysiology. They should also utilize a multi-modal workup, aggressive supportive care, appropriate subspecialty consultation, and appropriate antibiotics for patients with diarrheal illness and a high clinical suspicion for extra-intestinal involvement, such as myocarditis.

Sintilimab-induced myocarditis suspected in a patient with esophageal cancer and followed septic shock: case report and literature review.

Background: Immune checkpoint inhibitors (ICIs) have become a prevalent tool in anti-tumor therapy in recent years. They may cause immune-related adverse events (irAEs) including potentially life-threatening cardiovascular toxicities such as myocarditis. Case presentation: In this report, we describe a 69-year-old man with recurrent esophageal cancer who developed myocarditis after receiving three cycles of sintilimab combined with nab-paclitaxel. Despite a rising cardiac troponin I (cTnI), he initially reported no discomfort. He was later suspected of having with sintilimab-induced myocarditis. Although treatment with methylprednisolone reduced his cTnI levels, he still experienced significant discomfort. Moreover, he developed pneumonia and septic shock. Conclusion: In our literature search to identify all reported cases of sintilimab-associated adverse events involving myocarditis, we found 14 patients, including those with esophageal cancer, thymoma, lung cancer, gastric cancer, hepatobiliary carcinoma, and chordoma. The primary treatment for ICI-induced cardiotoxicity is methylprednisolone. However, the long-term or high-dose use of steroids can also induce side effects, which have not been the focus of these case reports. This is the first reported case of asymptomatic immune-mediated myocarditis occurring during the treatment of esophageal cancer with sintilimab. It is also the first to address the side effects of methylprednisolone used in the treatment of sintilimab-related myocarditis. To facilitate an early diagnosis, regular monitoring is required during sintilimab treatment. We should also focus on the prevention and management of adverse effects related to steroid use.

LncRNA MALAT1 to Enhance Pyroptosis in Viral Myocarditis Through UPF1-Mediated SIRT6 mRNA Decay and Wnt-ß-Catenin Signal Pathway.

Viral myocarditis (VMC) is an inflammatory disease of the myocardium caused by cardioviral infection, especially coxsackievirus B3 (CVB3), and is a major contributor to acute heart failure and sudden cardiac death in children and adolescents. LncRNA MALAT1 knockdown reportedly inhibits the differentiation of Th17 cells to attenuate CVB3-induced VMC in mice. Moreover, long non-coding RNAs (lncRNAs) interact with RNA-binding proteins (RBPs) to regulate UPF1-mediated mRNA decay. However, it remains unclear whether MALAT1 can bind to UPF1 to mediate the mRNA decay of its target genes in VMC. Herein, we aimed to explore the effect of lncRNA MALAT1 on UPF1-mediated SIRT6 mRNA decay in VMC using in vivo and in vitro experiments. CVB3-infected BABL/C mice were used as VMC models, and MALAT1 interfering adenovirus was injected to achieve MALAT1 knockdown. The heart function of the VMC mice was assessed using echocardiography. Pathological changes in myocardial tissues were assessed after hematoxylin-eosin staining. Myocardial injury and inflammation were evaluated by measuring creatine kinase isoenzyme B, cardiac troponin T, interleukin (IL)-1ß, and IL-18. TUNEL staining was performed to assess apoptosis in myocardial tissues. In vitro experiments were performed using H9c2 cells after transfection and CVB3 infection. The lactic dehydrogenase release, caspase-1 activity, and IL-1ß and IL-18 levels in the cellular supernatant were detected. Western blotting was performed to determine the expression of pyroptosis-related proteins (GSDMD-N, NLRP3, ASC, and Cleaved-Caspase-1) and Wnt/ß-catenin signal pathway-related proteins (Wnt1, ß-catenin, and p-GSK-3ß). RNA immunoprecipitation and RNA stability assays assessed the relationship between MALAT1, UPF1, and SIRT6. CVB3-infected mice and H9c2 cells exhibited elevated MALAT1 and reduced SIRT6 expression. MALAT1 knockdown or SIRT6 overexpression suppressed inflammation and pyroptosis and inhibited the activation of the Wnt/ß-catenin signal pathway in myocardial tissues and cells. MALAT1 enhanced the enrichment of SIRT6 mRNA by UPF1 and disturbed the stability of SIRT6 mRNA to promote the development of VMC. MALAT1 can bind UPF1 to mediate SIRT6 mRNA decay and activate the Wnt/ß-catenin signal pathway in VMC.

The Ambivalence of Post COVID-19 Vaccination Responses in Humans.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has prompted a massive global vaccination campaign, leading to the rapid development and deployment of several vaccines. Various COVID-19 vaccines are under different phases of clinical trials and include the whole virus or its parts like DNA, mRNA, or protein subunits administered directly or through vectors. Beginning in 2020, a few mRNA (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273) and adenovirus-based (AstraZeneca ChAdOx1-S and the Janssen Ad26.COV2.S) vaccines were recommended by WHO for emergency use before the completion of the phase 3 and 4 trials. These vaccines were mostly administered in two or three doses at a defined frequency between the two doses. While these vaccines, mainly based on viral nucleic acids or protein conferred protection against the progression of SARS-CoV-2 infection into severe COVID-19, and prevented death due to the disease, their use has also been accompanied by a plethora of side effects. Common side effects include localized reactions such as pain at the injection site, as well as systemic reactions like fever, fatigue, and headache. These symptoms are generally mild to moderate and resolve within a few days. However, rare but more serious side effects have been reported, including allergic reactions such as anaphylaxis and, in some cases, myocarditis or pericarditis, particularly in younger males. Ongoing surveillance and research efforts continue to refine the understanding of these adverse effects, providing critical insights into the risk-benefit profile of COVID-19 vaccines. Nonetheless, the overall safety profile supports the continued use of these vaccines in combating the pandemic, with regulatory agencies and health organizations emphasizing the importance of vaccination in preventing COVID-19's severe outcomes. In this review, we describe different types of COVID-19 vaccines and summarize various adverse effects due to autoimmune and inflammatory response(s) manifesting predominantly as cardiac, hematological, neurological, and psychological dysfunctions. The incidence, clinical presentation, risk factors, diagnosis, and management of different adverse effects and possible mechanisms contributing to these effects are discussed. The review highlights the potential ambivalence of human response post-COVID-19 vaccination and necessitates the need to mitigate the adverse side effects.

The Role of MicroRNA in the Pathophysiology and Diagnosis of Viral Myocarditis.

Myocarditis is a non-ischemic condition with a heterogeneous etiology, clinical course and prognosis. The most common etiology of myocarditis are viral infections, whereas the most severe complications are acute and chronic heart failure and sudden cardiac death. The heterogeneous clinical course of the disease, as well as the availability and costs of diagnostic tools such as cardiac magnetic resonance and endomyocardial biopsy, hinder the diagnosis of myocarditis and its underlying cause. Non-coding RNAs such as micro-RNAs (miRNAs; miR) have been shown to be involved in the disease's pathophysiology; however, their potential in disease diagnosis and treatment should also be considered. Non-coding RNAs are RNAs that are not translated into proteins, and they have the ability to regulate several intracellular pathways. MiRNAs regulate gene expression by binding with their targets and inhibiting protein synthesis by interfering with the translation of coding genes or causing the degradation of messenger RNA. Several miRNAs, such as miR-1, -133, -21, -15, -98, -126, -155, -148, -203, -208, -221, -222, -203 and -590, have been shown to be involved in the pathophysiology of viral myocarditis (VMC), and some of them have been shown to have diagnostic abilities. This article summarizes the available data on miRNAs and their associations with VMC.

What are the early warning signs of myocarditis during the pathway of care?

INTRODUCTION: Myocarditis is an inflammatory disease of the myocardial layer of the heart that can be prone to dilation of chambers with presentation as heart failure secondary to dilated cardiomyopathy. Myocarditis can lead to remodeling and fibrosis that can affect the heart's relaxation-lusitropy and chronotropic function. The current techniques for identifying myocarditis, such as endomyocardial biopsy and imaging, are costly, and intrusive. The current literature aims to identify reliable, accurate, and prognostically educative biomarkers of myocarditis. AREAS COVERED: This review covers the definition, clinical features, diagnostic markers, cardiac imaging, prognosis, and complications of myocarditis. PubMed, Embase, and the Cochrane data bank were searched from inception to 1 January 2024 for relevant articles. EXPERT OPINION: By adopting these diagnostic and prognostic biomarkers, clinicians can have a better comprehension of the progression of the disease and provide early diagnosis and treatment for myocarditis.

Clinical Presentation and Outcomes of Myocarditis Among the COVID-19 Pediatric Population: A Review of 100 Cases.

BACKGROUND: COVID-19 has been associated with myocarditis in the pediatric population, leading to severe cardiac complications. OBJECTIVE: To determine the clinical presentations and outcomes of myocarditis among the COVID-19-positive pediatric population. MATERIALS AND METHODS: This retrospective cross-sectional study included 100 cases from the Saidu Group of Teaching Hospitals, Swat. Inclusion criteria involved children of both genders, confirmed COVID-19 by PCR, and a myocarditis diagnosis. Exclusion criteria were other comorbid conditions, incomplete records, and age over five years. Data included age, gender, weight, clinical features, cardiac enzyme levels, ejection fraction, PCR results, immunoglobulin treatment, outcomes, and hospital stay duration. Statistical analysis was performed in SPSS employing descriptive statistics, chi-square tests, and Fisher's exact tests. RESULTS: The mean age was 24.72±18.67 months, with 67 males and 33 females. Irritability was noted in 18 children, cyanosis in 27, and cough in 74. Tachycardia was observed in 91 children. Elevated cardiac enzymes and positive Troponin-I levels were found in 91 and 84 children, respectively. The mean ejection fraction was 36.29±9.12%. The average hospital stay was 7.11±2.49 days. Among 100 children, 26 died while 74 recovered. Immunoglobulin administration showed no significant difference between the expired and improved groups (p=0.6). Longer hospital stays were associated with mortality (p=0.002). Troponin-I levels were significantly higher in the expired group (p=0.01). CONCLUSION: Key factors associated with poor outcomes include low ejection fraction, elevated cardiac enzymes, positive Troponin-I levels, and shorter hospital stays.

Acute myocarditis and haemoptysis in an adult with human bocavirus monoinfection: a case report.

Background: Bocavirus monoinfection-related acute myocarditis is an aetiology that has rarely been described in the literature. Case summary: A 36-year-old male, with no significant medical history, presented to the emergency department with a 4-day history of dyspnoea, haemoptysis, left-sided chest pain, and high-grade pyrexia. The initial investigations revealed a raised troponin T, raised C-reactive protein, and a normal electrocardiogram. A comprehensive microbiological and virological work-up (testing for 14 viruses and bacteria) detected human bocavirus (HBoV) DNA monoinfection. Cardiac magnetic resonance imaging showed left ventricular ejection fraction of 48%, with subepicardial late gadolinium enhancement. Other imaging modalities (chest X-ray, echocardiography, computed tomography pulmonary angiography, and bronchoscopy) revealed no other causative pathology. The patient was treated with anti-inflammatory medications and left ventricle remodelling therapy. He had a good clinical outcome. Moreover, a collateral history revealed that the patient's infant had presented with a severe respiratory illness, which was felt to be of viral aetiology, several days prior to the patient's own onset of symptoms. Discussion: To our knowledge, this is the fourth case of HBoV-related acute myocarditis in an immunocompetent adult. This case also displays new clinical features for HBoV infection-haemoptysis, high-grade pyrexia, and a potential for vertical transmission from infants.

No Muscle Left Behind: Cardiac Arrest and Myocarditis in a Patient With Idiopathic Inflammatory Myopathy.

Idiopathic inflammatory myopathies (IIM) are known to have extramuscular involvement, the most concerning of which is the involvement of the myocardium. Constituting a large burden of morbidity and mortality, there remains a paucity of literature describing cardiac manifestations in inflammatory myopathies, and definitive treatment and screening guidelines have yet to be published. Here, we present a rare case of cardiac arrest and fulminant myocarditis in a patient with newly diagnosed myositis. A 71-year-old non-Hispanic White male with type 1 diabetes mellitus and hyperlipidemia presented to the rheumatology clinic with five months of progressive proximal muscle weakness and myalgias accompanied by a persistently elevated creatine kinase level and elevated liver-associated enzymes despite cessation of atorvastatin therapy three months prior. The initial examination was notable for reduced quadriceps strength bilaterally and the absence of visible skin rashes. He was found to have positive anti-Mi-2 antibody, elevated aldolase, and positive antinuclear antibody in a speckled pattern. After magnetic resonance imaging (MRI) of the left thigh demonstrated a pattern consistent with inflammatory myositis, steroid therapy was initiated, and he was referred for muscle biopsy to confirm the presumptive diagnosis of dermatomyositis. Two weeks later, before a muscle biopsy could be performed, the patient experienced a witnessed pulseless electrical activity (PEA) cardiac arrest from which he was successfully resuscitated by emergency medical services prior to hospital arrival. Subsequent cardiac evaluation showed a nonischemic cardiomyopathy with evidence of myocarditis on cardiac magnetic resonance (CMR) imaging with inferior wall hypokinesis and a left ventricular ejection fraction (LVEF) of 27%. He underwent placement of a subcutaneous implantable cardioverter defibrillator (ICD), and he responded well to intravenous immunoglobulin (IVIG), diuresis, and initiation of guideline-directed medical therapy with post-treatment transthoracic echocardiogram (TTE) demonstrating an LVEF of 40%. This case highlights one of the rather protean and severe cardiac manifestations of IIM. Typically, the cardiac manifestations observed in IIM include subclinical electrocardiogram (ECG) and echocardiographic changes but can present, as detailed here, with fulminant myocarditis and heart failure (HF). Our purpose herein is to heighten clinician awareness of and advocate for the establishment of definitive screening and management guidelines for cardiac disease in idiopathic inflammatory myopathies.

Immunoglobin attenuates fulminant myocarditis by inhibiting overactivated innate immune response.

BACKGROUND AND PURPOSE: Fulminant myocarditis (FM) is a myocardial inflammatory disease that can result from either viral diseases or autoimmune diseases. In this study, we have determined the treatment effects of immunomodulatory drugs on FM. EXPERIMENTAL APPROACH: FM was induced in A/JGpt mice by intraperitoneal administration of coxsackievirus B3, after which immunoglobins were administered daily by intraperitoneal injection. On the seventh day, the cardiac structure and function were determined using echocardiography and cardiac catheterisation. Single-cell RNA sequencing (scRNA-seq) was performed to evaluate CD45+ cells in the heart. KEY RESULTS: Immunoglobin, a typical immunomodulatory drug, dramatically reduced mortality and significantly improved cardiac function in mice with FM. ScRNA-seq revealed that immunoglobin treatment effectively modulated cardiac immune homeostasis, particularly by attenuating overactivated innate immune responses. At the cellular level, immunoglobin predominantly targeted Plac8+ monocytes and S100a8+ neutrophils, suppressing their proinflammatory activities, and enhancing antigen processing and presentation capabilities, thereby amplifying the efficiency and potency of the immune response against the virus. Immunoglobin benefits are mediated by the modulation of multiple signalling pathways, including relevant receptors on immune cells, direction of inflammatory cell chemotaxis, antigen presentation and anti-viral effects. Subsequently, Bst2-ILT7 ligand-receptor-mediated cellular interactions manipulated by immunoglobin were further confirmed in vivo. CONCLUSIONS AND IMPLICATIONS: Immunoglobin treatment significantly attenuated FM-induced cardiac inflammation and improved cardiac function by inhibiting overactivated innate immune responses.

A systematic review of cardiovascular toxicities induced by cancer immune therapies: underlying mechanisms, clinical manifestations and therapeutic approaches.

Immunotherapy has revolutionized the management of various types of cancers, even those previously deemed untreatable. Nonetheless, these medications have been associated with inflammation and damage across various organs. These challenges are exemplified by the adverse cardiovascular impacts of cancer immunotherapy, which need comprehensive understanding, clarification, and management integrated into the overall care of cancer patients. Numerous anticancer immunotherapies have been linked to the prevalence and severity of cardiovascular toxicity. These challenges emphasize the importance of conducting fundamental and applied research to elucidate disease causes, discover prognostic indicators, enhance diagnostic methods, and create successful therapies. Despite the acknowledged importance of T cells, there remains a knowledge gap regarding the inciting antigens, the reasons for their recognition, and the mechanisms of how they contribute to cardiac cell injury. In this review, we summarize the molecular mechanism, epidemiology, diagnosis, pathophysiology and corresponding treatment of cardiovascular toxicity induced by immunotherapy, including immune checkpoint inhibitors (ICIs), adoptive cell therapies (ACT), and bi-specific T-cell engagers (BiTEs) among others. By elucidating these aspects, we aim to provide a better understanding of immunotherapies in cancer treatment and offer guidance for their clinical application.

Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis.

Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (TRM) cells, we characterized cardiac TRM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia-reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC TRM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC TRM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human TRM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69+ TRM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial TRM cells.

Novel Insights into the Kallikrein-Kinin System in Fulminant Myocarditis: Physiological Basis and Potential Therapeutic Advances.

Fulminant myocarditis (FM) is characterized by rapid cardiac deterioration often instigated by an inflammatory cytokine storm. The kallikrein-kinin system (KKS) is a metabolic cascade known for releasing vasoactive kinins, such as bradykinin-related peptides, possessing diverse pharmacological activities that include inflammation, regulation of vascular permeability, endothelial barrier dysfunction, and blood pressure modulation. The type 1 and type 2 bradykinin receptors (B1R and B2R), integral components of the KKS system, mediate the primary biological effects of kinin peptides. This review aims to offer a comprehensive overview of the primary mechanisms of the KKS in FM, including an examination of the structural components, regulatory activation, and downstream signaling pathways of the KKS. Furthermore, it explores the involvement of the tissue kallikrein/B1R/inducible nitric oxide synthase (TK/B1R/iNOS) pathway in myocyte dysfunction, modulation of the immune response, and preservation of endothelial barrier integrity. The potential therapeutic advances targeting the inhibition of the KKS in managing FM will be discussed, providing valuable insights for the development of clinical treatment strategies.

Clinical Manifestations and Adverse Cardiovascular Events in Patients with Cardiovascular Symptoms after mRNA Coronavirus Disease 2019 Vaccines.

PURPOSE: The number of patients presenting with vaccination-related cardiovascular symptoms after receiving mRNA vaccines (mRNA-VRCS) is increasing. We investigated the incidence of vaccine-related adverse events (VAEs), including myocarditis and pericarditis, in patients with mRNA-VRCS after receiving BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna vaccines. MATERIALS AND METHODS: We retrospectively collected data on patients presenting with mRNA-VRCS who visited the outpatient clinic of two tertiary medical centers. Clinical characteristics, laboratory findings, echocardiographic findings, and electrocardiographic findings were evaluated. VAE was defined as myocarditis or pericarditis in patients after mRNA vaccination. Clinical outcomes during short-term follow-up, including emergency room (ER) visit, hospitalization, or death, were also assessed among the patients. RESULTS: A total of 952 patients presenting with mRNA-VRCS were included in this study, with 89.7% receiving Pfizer-BioNTech and 10.3% receiving Moderna vaccines. The mean duration from vaccination to symptom was 5.6±7.5 days. VAEs, including acute myocarditis and acute pericarditis, were confirmed in 11 (1.2%) and 10 (1.1%) patients, respectively. The VAE group showed higher rates of dyspnea, echocardiography changes, and ST-T segment changes. During the short-term follow-up period of 3 months, the VAE group showed a higher hospitalization rate compared to the control group; there was no significant difference in ER visit (p=0.320) or mortality rates (p>0.999). CONCLUSION: Amongst the patients who experienced mRNA-VRCS, the total incidence of VAEs, including acute myocarditis and pericarditis, was 2.2%. Patients with VAEs showed higher rates of dyspnea, echocardiographic changes, and ST-T segment changes compared to those without VAEs. With or without the cardiovascular events, the prognosis in patients with mRNA-VRCS was favorable.

The global, regional, and national burden of myocarditis in 204 countries and territories, 1990-2021: Results from the Global Burden of Disease Study 2021.

AIMS: To estimate the global burden of myocarditis in the general population from 1990 to 2021. METHODS AND RESULTS: Data on myocarditis were retrieved from the Global Burden of Disease Study 2021. Incidence, deaths, and disability-adjusted life years (DALYs), along with their age-standardized rates (ASRs) per 100 000 population, were used to measure the burden of myocarditis. Global, regional, and national analyses were performed for the period between 1990 and 2021. Further sub-analyses were conducted based on age group, sex, and sociodemographic index (SDI). In 2021, there were 1.3 million (95% uncertainty interval [UI]: 1.1 to 1.6) incident cases, 31.7 thousand (95% UI: 25.5 to 37.1) deaths, and 96.3 thousand (95% UI: 79.6 to 114.8) DALY cases globally. The ASRs of incidence, death, and DALYs significantly decreased from 1990 to 2021, with percentage changes of -3.9% (95% UI: -4.7% to -2.9%), -28.2% (95% UI: -42.2% to -12.5%), and -37.8% (95% UI: -50.5% to -24.3%), respectively. The global burden of myocarditis was higher in males, children, and the elderly. Additionally, the burden of myocarditis varied widely across different SDI regions, with high SDI regions having the highest ASR of incidence, and high-middle SDI regions having the highest ASRs of deaths and DALYs. CONCLUSION: Although the ASRs of incidence, deaths, and DALYs significantly decreased from 1990 to 2021, the global number of incidences, deaths, and DALYs increased substantially. Certain populations, including males, children, the elderly, and regions with advanced sociodemographic levels, experienced a heavier burden of myocarditis.

Prognostic Value of Speckle Tracking Echocardiography-Derived Strain in Unmasking Risk for Arrhythmias in Children with Myocarditis.

Background/Objectives: Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Methods: Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis "MYKKE". Age- and sex-adjusted logistic regression and ROC analysis identified predictors of cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, atrioventricular blockage III°) and major adverse cardiac events (MACE: need for mechanical circulatory support (MCS), cardiac transplantation, and/or cardiac death). Results: Echocardiograms from 175 patients (median age 15 years, IQR 7.9-16.5 years; 70% male) across 13 centers were included. Cardiac arrhythmias occurred in 36 patients (21%), and MACE in 28 patients (16%). Impaired LV LS strongly correlated with reduced LVEF (r > 0.8). Impaired layer-specific LV LS, reduced LVEF, LV dilatation, and increased BSA-indexed LV mass, were associated with the occurrence of MACE and cardiac arrhythmias. In patients with preserved LVEF, LV LS alone predicted cardiac arrhythmias (p < 0.001), with optimal cutoff values of -18.0% for endocardial LV LS (sensitivity 0.69, specificity 0.94) and -17.0% for midmyocardial LV LS (sensitivity 0.81, specificity 0.75). Conclusions: In pediatric myocarditis, STE-derived LV LS is not only a valuable tool for assessing systolic myocardial dysfunction and predicting MACE but also identifies patients at risk for cardiac arrhythmias, even in the context of preserved LVEF.

Not Just Myocarditis: Mixed Connective Tissue Disease (MCTD) and Overlap Myositis With Anti-Ku Positivity in a Young Male With Shortness of Breath.

Mixed connective tissue disease (MCTD) is an autoimmune disorder characterized by high levels of anti-U1 ribonucleoprotein (RNP) antibodies and overlapping clinical features of autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis (PM). Anti-Ku antibodies have been associated with overlap syndromes, which can present with symptoms such as Raynaud's phenomenon, arthritis, and myositis.  A 19-year-old male athlete presented with myositis, notable for cardiac involvement. Diagnostic testing revealed elevated anti-RNP and anti-Ku antibodies, and a muscle biopsy indicated scleromyositis/overlap myositis. The patient was treated with high-dose corticosteroids, intravenous immunoglobulin (IVIG), rituximab, and mycophenolate mofetil, which led to significant improvement in muscle strength and cardiac function. This case highlights the diagnostic complexity of MCTD when associated with positive anti-Ku antibodies, overlap syndromes, and cardiac involvement. Successful management emphasizes the importance of a tailored, multi-modal therapeutic approach.

Acute Heart Failure in a Young Patient Treated in ICU-Diagnostic Pitfalls.

Background:Chlamydia pneumoniae and human herpesvirus 6 (HHV-6) are uncommon aetiological agents in respiratory tract infections and are rarely associated with cardiogenic shock. This case report presents a rare instance of severe cardiomyopathy linked to these infections in a 19-year-old Asian female. The case highlights the importance of considering a broad differential diagnosis in acute heart failure, especially in young adults. Case report: The patient was admitted with chest pain and diagnosed with ST-elevation myocardial infarction (STEMI) based on electrocardiography. She subsequently developed heart failure, with a marked reduction in myocardial contractility and a left ventricular ejection fraction (LVEF) of 20%. Treatment included broad-spectrum antibiotics and inotropic support guided by hemodynamic monitoring, leading to clinical improvement. The patient was discharged in a significantly improved condition following a stay in the intensive care unit (ICU). Conclusions: This case emphasizes the importance of considering Takotsubo syndrome in differential diagnoses, especially in ICU patients presenting with cardiogenic shock, to improve outcomes and reduce mortality through timely and appropriate management. Inotropic support, often used in the ICU to treat hypoperfusion, may worsen outcomes in patients with Takotsubo syndrome by exacerbating basal hypercontractility and prolonging the acute phase through catecholamine receptor activation.

Myocarditis: Differences in Clinical Expression between Patients with ST-Segment Elevation in Electrocardiogram vs. Patients without ST-Segment Elevation.

BACKGROUND/OBJECTIVES: In cases of myocarditis, electrocardiograms (ECGs) may suggest a pattern of ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI). NSTEMI patterns are less frequent in myocarditis cases, but it remains unclear if the presence of ST-segment elevation in myocarditis cases is related to a more severe condition and more damage in the myocardium. METHODS: This is a retrospective study involving 38 patients admitted to hospital with myocarditis. Patients were divided into two groups: patients with ST-segment elevation (STE) patterns in the ECG (25), and patients without ST-segment elevation (non-STE) patterns (13). The data compared included results from epidemiological, laboratory, and instrumental tests. Data were analysed using IBM SPSS Statistics v26.0. A p value of <0.05 was established as the threshold for statistical significance. RESULTS: C-reactive protein (CRP) levels were higher in the STE group (103.40 ± 82.04 mg/L vs. 43.54 ± 61.93 mg/L, p = 0.017). The left ventricle ejection fraction (LVEF) was significantly higher in the non-STE pattern group (49.71 ± 4.14 vs. 56.58 ± 3.99, p < 0.001). A lower LVEF correlates with higher TnI levels (r= -0.353, p = 0.032) and higher CRP levels (r = -0.554, p < 0.001). Lower left ventricle (LV) strain correlates with higher levels of Troponin I (TnI) (r = -0.641, p = 0.013). CONCLUSIONS: LVEFs in the STE group were lower compared to those in the non-STE pattern group. STE pattern was associated with higher CRP levels. Higher TnI levels in cases of myocarditis were associated with lower LV strain and lower LVEF; higher CRP levels also correlated with lower LVEF. Based on a 6-month echocardiographic follow-up, the prognosis of myocarditis was favourable.

Cardiac Magnetic Resonance Speckle Tracking Analysis of Right Ventricle Function in Myocarditis with Preserved Right Ventricular Ejection Fraction.

Background and Objectives: Diagnosis of myocarditis remains a challenge in clinical practice; however, magnetic resonance imaging (CMRI) can ease the diagnostic approach by providing various parameters. The prevalence of right ventricular involvement in acute myocarditis is suggested to be more frequent than previously hypothesized. In this study, we sought to investigate subclinical RV involvement in patients with acute myocarditis and preserved RV ejection fraction (EF), using CMRI RV speckle-tracking imaging. Materials and Methods: CMRI of 27 patients with acute myocarditis (nine females, age 35.1 ± 12.2 y) was retrospectively analyzed. A control group consisting of CMRI images of 27 healthy individuals was included. Results: No significant differences were found regarding left ventricle (LV) and atrium dimensions. LV ejection fraction was significantly different between groups (56.6 ± 10.6 vs. 62.1 ± 2.6, p < 0.05). No significant differences were present between parameters used for conventional assessment of RV. However, RV strain absolute values were significantly lower in the acute myocarditis group in comparison with that of the control group (18.4 ± 5.4 vs. 21.8 ± 2.8, p = 0.018). Conclusions: Subclinical RV dysfunction detected by CMR-derived strain may be present in patients with acute myocarditis even with preserved RVEF.