Diphtheria's Dual Threat: Amplifying Awareness of Cardiac Complications for Enhanced Intervention.

Even though immunization can prevent illness, diphtheria, which is caused by toxic strains of Corynebacterium diphtheriae, remains a serious public health risk. Although the worldwide incidence has declined, it still poses a serious hazard in developing countries, such as Pakistan, where new data suggest an increase in cases. A significant proportion of patients with respiratory diphtheria experience cardiac complications, specifically myocarditis, which carries a high death risk of 50% to 75%. The diphtheria toxin's affinity for cardiac tissues is the cause of these consequences, which include arrhythmias and myocardial dysfunction. Recent studies from Lady Reading Hospital in Peshawar show the seriousness of the situation, with 73 patients presenting with cardiac complications in just one year, resulting in a devastating fatality rate despite early management. This highlights the pressing need for increased awareness and all-encompassing immunization campaigns, particularly for children who have received insufficient vaccinations. Timely vaccination and booster doses are critical for reducing myocarditis-related mortality, mandating prioritizing immunization efforts to defend susceptible populations globally.

Enteric Fever Presenting With Complete Heart Block (CHB): A Rare Case of Reversible Arrhythmia.

Salmonella enterica serovar Typhi is the causative agent of enteric fever, commonly called "typhoid". This fever can be mistaken for a variety of other febrile disorders. It is an endemic sickness, especially in developing nations. Enteric fever typically manifests with fever, abdominal pain, and constitutional symptoms, making it a diagnostic challenge due to its broad clinical spectrum. Enteric fever also affects various other systems, causing complications, amongst which the cardiovascular system is no exception. Complications in the cardiovascular system may range from myocarditis to cardiomyopathy and various arrhythmias. This case report describes a case of a 28-year-old male who presented to us with fever and giddiness. Examination revealed profound bradycardia and electrocardiography (ECG) revealed features of a complete heart block (CHB). Investigations for fever confirmed enteric fever. This case report highlights one of the rarest complications of enteric fever.

Low rates of myocardial fibrosis and ventricular arrhythmias in recreational athletes after SARS-CoV-2 infection.

Introduction: High rates of cardiac involvement were reported in the beginning of the coronavirus disease 2019 (COVID-19) pandemic. This led to anxiety in the athletic population. The current study was set up to assess the prevalence of myocardial fibrosis and ventricular arrhythmias in recreational athletes with the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: Consecutive adult recreational athletes (≥18 years old, ≥4 h of mixed type or endurance sports/week) underwent systematic cardiac evaluation after a prior confirmed COVID-19 infection. Evaluation included clinical history, electrocardiogram (ECG), 5-day Holter monitoring, and cardiac magnetic resonance (CMR) imaging with simultaneous measurement of high-sensitive cardiac Troponin I. Data from asymptomatic or mildly symptomatic athletes (Group 1) were compared with those with moderate to severe symptoms (Groups 2-3). Furthermore, a comparison with a historical control group of athletes without COVID-19 (Master@Heart) was made. Results: In total, 35 athletes (18 Group 1, 10 female, 36.9 ± 2.2 years, mean 143 ± 20 days following diagnosis) were evaluated. The baseline characteristics for the Group 1 and Groups 2-3 athletes were similar. None of the athletes showed overt myocarditis on CMR based on the updated Lake Louise criteria for diagnosis of myocarditis. The prevalence of non-ischemic late gadolinium enhancement [1 (6%) Group 1 vs. 2 (12%) Groups 2-3; p = 0.603] or ventricular arrhythmias [1 Group 1 athlete showed non-sustained ventricular tachycardia (vs. 0 in Groups 2-3: p = 1.000)] were not statistically different between the groups. When the male athletes were compared with the Master@Heart athletes, again no differences regarding these criteria were found. Conclusion: In our series of recreational athletes with prior confirmed COVID-19, we found no evidence of ongoing myocarditis, and no more detection of fibrosis or ventricular arrhythmias than in a comparable athletic pre-COVID cohort. This points to a much lower cardiac involvement of COVID-19 in athletes than originally suggested.

Mast cells: a novel therapeutic avenue for cardiovascular diseases?

Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodeling and fibrosis. Mast cells release preformed mediators (e.g., histamine, tryptase, chymase) and de novo synthesized mediators [e.g., cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)], as well as cytokines and chemokines, which can activate different resident immune cells (e.g., macrophages) and structural cells (e.g., fibroblasts, endothelial cells) in the human heart and aorta. The transcriptional profiles of various mast cell populations highlight their potential heterogeneity and distinct gene and proteome expression. Mast cell plasticity and/or heterogeneity enable these cells the potential for performing different, even opposite, functions in response to changing tissue contexts. Human cardiac mast cells display significant differences compared to mast cells isolated from other organs. These characteristics make cardiac mast cells intriguing, given their dichotomous potential roles of inducing or protecting against cardiovascular diseases. Identification of cardiac mast cell subpopulations represents a prerequisite for understanding their potential multifaceted roles in health and disease. Several new drugs specifically targeting human mast cell activation are under development or in clinical trials. Mast cells and/or their subpopulations can potentially represent novel therapeutic targets for cardiovascular disorders.

Management of Select Adverse Events Following Delandistrogene Moxeparvovec Gene Therapy for Patients With Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare, degenerative, recessive X-linked neuromuscular disease. Mutations in the gene encoding dystrophin lead to the absence of functional dystrophin protein. Individuals living with DMD exhibit progressive muscle weakness resulting in loss of ambulation and limb function, respiratory insufficiency, and cardiomyopathy, with multiorgan involvement. Adeno-associated virus vector-mediated gene therapy designed to enable production of functional dystrophin protein is a new therapeutic strategy. Delandistrogene moxeparvovec (Sarepta Therapeutics, Cambridge, MA) is indicated for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD who have an indicated mutation in the DMD gene. OBJECTIVE: Evidence-based considerations for management of potential adverse events following gene therapy treatment for DMD are lacking in clinical literature. Our goal was to provide interdisciplinary consensus considerations for selected treatment-related adverse events (TRAEs) (vomiting, acute liver injury, myocarditis, and immune-mediated myositis) that may arise following gene therapy dosing with delandistrogene moxeparvovec. METHODS: An interdisciplinary panel of 12 specialists utilized a modified Delphi process to develop consensus considerations for the evaluation and management of TRAEs reported in delandistrogene moxeparvovec clinical studies. Panelists completed 2 Questionnaires prior to gathering for an in-person discussion. Consensus was defined as a majority (≥58% ; 7/12) of panelists either agreeing or disagreeing. RESULTS: Panelists agreed that the choice of baseline assessments should be informed by individual clinical indications, the treating provider's judgment, and prescribing information. Corticosteroid dosing for treatment of TRAEs should be optimized by considering individual risk versus benefit for each indication. In all cases involving patients with a confirmed TRAE, consultations with appropriate specialists were suggested. CONCLUSIONS: The Delphi Panel established consensus considerations for the evaluation and management of potential TRAEs for patients receiving delandistrogene moxeparvovec, including vomiting, acute liver injury, myocarditis, and immune-mediated myositis.

Comparative safety profile of bivalent and original COVID-19 mRNA vaccines regarding myocarditis/pericarditis: A pharmacovigilance study.

OBJECTIVES: Bivalent COVID-19 mRNA vaccines, which contain two different components, were authorized to provide protection against both the original strain of SARS-CoV-2 and the Omicron variant as a measure to address the COVID-19 pandemic. Concerns regarding the risk of myocarditis/pericarditis associated with bivalent vaccination have been raised due to the observed superior neutralizing antibody responses. This study aimed to investigate the risk of myocarditis/pericarditis following bivalent COVID-19 mRNA vaccination compared to monovalent vaccination. METHODS: The CDC COVID Data Tracker and the Vaccines Adverse Event Reporting System (VAERS) were analyzed between December 13, 2020 to March 8, 2023. Reporting rates were determined by dividing the number of myocarditis/pericarditis cases by the total number of vaccine doses administered. Disproportionality patterns regarding myocarditis/pericarditis were evaluated for various COVID-19 mRNA vaccinations using reporting odds ratios (RORs). RESULTS: The reporting rate for myocarditis/pericarditis following original monovalent COVID-19 mRNA vaccination was 6.91 (95 % confidence interval [95 %CI] 6.71-7.12) per million doses, while the reporting rate for bivalent vaccination was significantly lower (1.24, 95%CI 0.96-1.58). Disproportionality analysis revealed a higher reporting of myocarditis/pericarditis following original vaccination with a ROR of 2.21 (95 %CI 2.00-2.43), while bivalent COVID-19 mRNA vaccination was associated with fewer reports of myocarditis/pericarditis (ROR 0.57, 95 %CI 0.45-0.72). Sub-analyses based on symptoms, sex, age and manufacturer further supported these findings. CONCLUSION: This population-based study provides evidence that bivalent COVID-19 mRNA vaccination is not associated with risk of myocarditis/pericarditis. These findings provide important insights into the safety profile of bivalent COVID-19 mRNA vaccines and support their continued use as updated boosters.

Long-term efficacy and safety of tailored immunosuppressive therapy in immune-mediated biopsy-proven myocarditis: A propensity-weighted study.

AIMS: Standardized immunosuppressive therapy (IS) had been previously investigated in biopsy-proven (BP) lymphocytic myocarditis with heart failure (HF). This study evaluated efficacy and safety of tailored IS in BP immune-mediated myocarditis, irrespective of histology and clinical presentation. METHODS AND RESULTS: Consecutive BP myocarditis patients treated with long-term tailored IS on top of optimal medical therapy (OMT), were compared with OMT non-IS controls using propensity-score weighting. The primary outcome was a composite of death or heart transplant, the secondary outcome was a composite of biventricular function, New York Heart Association (NYHA) class variation, and relapse. IS was managed by a multidisciplinary Cardioimmunology Team, involved a safety checklist and active patients' education. Ninety-one IS patients were compared with 267 non-IS patients. IS patients more frequently had systemic immune-mediated diseases (35% vs. 9.7%), lower baseline echocardiographic left ventricular ejection fraction (35% vs. 43%), lower right ventricular fractional area change (34% vs. 41%) and higher frequency of active lymphocytic, eosinophilic and giant cell myocarditis (71% vs. 58%, 12% vs. 1.1%, and 6.6% vs. 1.5%, respectively). At 5-year follow up, no difference was observed in the primary outcome (survival rate 93% in IS vs. 87% in non-IS), but IS patients had a higher relapse rate. Thus, IS patients, with a lower biventricular function and a higher risk profile at baseline, presented similar biventricular function and NYHA class to non-IS patients at follow-up. Minor adverse drug reactions occurred in 13% of patients, all resolved with therapy switch. CONCLUSIONS: Prolonged tailored IS is effective and safe in BP immune-mediated myocarditis irrespective of histology and clinical presentation.

Changes in Cardiac Function Following Fulminant Myocarditis.

BACKGROUND: The natural history of myocardial dysfunction in patients with fulminant myocarditis is poorly understood. This study aims to evaluate changes in cardiac function in patients with fulminant myocarditis using a nationwide registry in Japan. METHODS: This retrospective cohort study included patients with biopsy-proven fulminant myocarditis and available for left ventricular ejection fraction (LVEF). We described the LVEF on admission, at discharge, and 1 year after discharge. We divided patients into 2 groups based on LVEF at discharge (reduced ejection fraction of <50% or preserved ejection fraction of ≥50%) and analyzed changes in LVEF and prognosis according to groups. RESULTS: We included 214 patients (the median [first-third quartiles] age of the cohort was 48 [35-62] years, and 63 [38%] were female). Of 153 patients available for LVEF at 1 year, the median (first-third quartiles) LVEF increased from 33% (21-45%) on admission to 59% (49-64%) at discharge and further to 61% (55-66%) at 1 year. Of 153 patients, 45 (29%) and 22 (14%) had LVEF <50% at discharge and at 1 year, respectively. Comparisons between patients with LVEF <50% and those with LVEF ≥50% demonstrated that the former group had a higher adjusted probability of death or heart transplantation (hazard ratio, 8.19 [95% CI, 2.13-31.5]; P=0.002). CONCLUSIONS: Some patients with fulminant myocarditis had left ventricular dysfunction in the chronic phase. Patients with reduced left ventricular function at discharge had a worse prognosis than those with preserved left ventricular function. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045352; Unique identifier: UMIN000039763.

Successful high-dose glucocorticoid therapy for anti-mitochondrial antibody-positive myocarditis arising during tocilizumab and low-dose glucocorticoid therapy for rheumatoid arthritis.

Anti-mitochondrial antibody (AMA)-positive myopathy, a recently identified condition with significant cardiac involvement, poses a serious challenge in treatment consensus due to its extreme rarity. While several studies demonstrate the efficacy of high-dose prednisolone in managing this disease, the current literature lacks substantial evidence regarding the effectiveness of biologic therapy or low-dose prednisolone for remission induction. Here, we present a case of AMA-positive myocarditis that emerged during rheumatoid arthritis treatment with tocilizumab (TCZ) and low-dose prednisolone (PSL). Successfully, intensive immunosuppressive therapy with high-dose PSL proved effective in stabilizing this condition. Our case highlights the necessity of a robust immunosuppressive approach, favoring high-dose PSL over the combination of low-dose PSL and TCZ in this disease.

Use of point-of-care ultrasound to assess the severity of scorpion stings in hospitalized patients.

INTRODUCTION: Scorpionism is a public health problem, especially in tropical regions. In Brazil, the prevalence of envenomation by scorpions is high, and the average national lethality is around 0.16 percent. The Tityus serrulatus scorpion is the primary species of medical importance. However, objective tools to predict and define the severity of these envenomations are lacking. MATERIALS AND METHODS: This was an observational study conducted among patients aged 0-19 years with scorpionism. Patients were admitted to a reference hospital between December 2020 and May 2022. Point-of-care ultrasound was performed within 24 hours of the scorpion sting. RESULTS: Forty-nine patients were included, with a median age of 3.6 (interquartile range 2.3-5.3) years and a predominance of females (51 percent). Fifteen patients (30.6 percent) presented major life-threatening signs, 32 (65.3 percent) minor systemic manifestations, and two (4.1 percent) only local manifestations. Left ventricular dysfunction was identified in 13 patients (26.5 percent). Ten patients (20.4 percent) presented pattern B (visualization of three or more B lines in the evaluated quadrant) in at least one lung window. The sensitivity and specificity of cardiac and pulmonary ultrasound to identify the most severely ill patients were 86 percent and 94 percent, respectively. DISCUSSION: The changes found on point-of-care ultrasound were associated with life-threatening signs. All patients with class III envenomation were referred to the intensive care unit, showing the importance of early identification of this subgroup. The main limitations were the small sample size and the fact that admission to intensive care was not based on systematic criteria. CONCLUSIONS: Point-of-care ultrasound is able to identify early signs of pulmonary congestion and heart failure in scorpionism. It can be useful for the objective selection of patients who are at a higher risk of complications and death and who require intensive support; it may also be valuable for periodic reassessments. Point-of-care ultrasound is a valuable tool for identifying and monitoring severe cases of scorpionism.

Two case reports of fulminant giant cell myocarditis treated with rabbit anti-thymocyte globulin.

Background: Giant cell myocarditis (GCM) is an inflammatory form of acute heart failure with high rates of cardiac transplantation or death. Standard acute treatment includes multi-drug immunosuppressive regimens. There is a small but growing number of case reports utilizing rabbit anti-thymocyte globulin in severe cases. Case summary: Two cases are presented with similar presentations and clinical courses. Both are middle-aged patients with no significant past medical history, who presented with new acute decompensated heart failure that quickly progressed to cardiogenic shock requiring inotropic and mechanical circulatory support. Both underwent endomyocardial biopsies that diagnosed GCM. Both were treated with a multi-agent immunosuppressive regimen, notably including rabbit anti-thymocyte globulin, with subsequent resolution of shock and recovery of left ventricular ejection fraction. Both remain transplant-free and without ventricular arrhythmias at 7 months and 26 months, respectively. Discussion: In aggregate, these cases are typical of GCM. They add to growing observational data that upfront rabbit anti-thymocyte globulin may reduce morbidity and mortality in GCM, including potentially preventing the need for complex interventions like orthotopic heart transplantation.

European Association of Cardiovascular Imaging (EACVI) survey on Cardiovascular Multimodality Imaging in Acute Myocarditis.

AIMS: To assess the current role of cardiac imaging in the diagnosis, management, and follow-up of patients with acute myocarditis (AM) through an European Association of Cardiovascular Imaging survey. METHODS AND RESULTS: A total of 412 volunteers from 74 countries responded to the survey. Most participants worked in tertiary centres(56%). All participants had access to echocardiography, while 79% and 75% had access to cardiac computed tomography (CCTA) and cardiac magnetic resonance (CMR), respectively. Less than half(47%) had access to myocardial biopsy and only 5% used this test routinely. CMR was performed within 7 days of presentation in 73% of cases. Non-ischemic late gadolinium enhancement (LGE,88%) and high-signal intensity in T2-weighted images(74%) were the most used diagnostic criteria for AM. CCTA was preferred to coronary angiography by 47% of participants to exclude coronary artery disease. Systematic prescription of beta-blockers and ACEi was reported by 38% and 32% of participants. Around a quarter of participants declared considering LGE burden as a reason to treat. Most participants (90%) reported performing a follow-up echocardiogram, while 63% scheduled a follow-up CMR. The main reason for treatment discontinuation was improvement of left ventricular ejection fraction(89%), followed by LGE regression(60%). In two-thirds of participants the decision to resume high-intensity sport was influenced by residual LGE. CONCLUSION: This survey confirms the high utilization of cardiac imaging in AM, but reveals major differences in how cardiac imaging is used and how the condition is managed between centres, underlining the need for recommendation statements in this topic.

Prevalence of Pathogenic Variants in Cardiomyopathy-Associated Genes in Acute Myocarditis: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute myocarditis is an inflammatory condition that may precede the development of dilated or arrhythmogenic cardiomyopathy. OBJECTIVES: The aim of this study was to investigate the reported prevalence of pathogenic or likely pathogenic (P/LP) variants in cardiomyopathy-associated genes in patients with acute myocarditis. METHODS: For this systematic review and meta-analysis, the PubMed and Embase databases were searched on March 4, 2023. Observational studies evaluating the prevalence of P/LP variants in cardiomyopathy-associated genes in patients with acute myocarditis were included. Studies were stratified into adult and pediatric age groups and for the following scenarios: 1) complicated myocarditis (ie, presenting with acute heart failure, reduced left ventricular ejection fraction, or life-threatening ventricular arrhythmias); and 2) uncomplicated myocarditis. The study was registered with the International Prospective Register of Systematic Reviews (CRD42023408668) and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of 732 studies identified, 8 met the inclusion criteria, providing data for 586 patients with acute myocarditis. A total of 89 P/LP variants in cardiomyopathy-associated genes were reported in 85 patients. For uncomplicated myocarditis, the pooled prevalence was 4.2% (95% CI: 1.8%-7.4%; I2 = 1.4%), whereas for complicated myocarditis, the pooled prevalence was 21.9% (95% CI: 14.3%-30.5%; I2 = 38.8%) and 44.5% (95% CI: 22.7%-67.4%; I2 = 52.8%) in adults and children, respectively. P/LP variants in desmosomal genes were predominant in uncomplicated myocarditis (64%), whereas sarcomeric gene variants were more prevalent in complicated myocarditis (58% in adults and 71% in children). CONCLUSIONS: Genetic variants are present in a large proportion of patients with acute myocarditis. The prevalence of genetic variants and the genes involved vary according to age and clinical presentation.

Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Feasibility of cardiac magnetic resonance imaging in temporary permanent pacemaker implants in pediatric myocarditis and complete atrioventricular block.

Background: Diagnosing myocarditis in children presenting with complete AV block (CAVB) is challenging. Temporary permanent pacing support using standard transvenous active fixation lead can be inserted percutaneously until recovery. However, access to cardiac magnetic resonance (CMR) imaging may be limited due to safety concerns. Cases: We report three cases where CMR was performed using temporary permanent pacemaker in situ. We evaluated the effect of device artefacts on image quality and examined any instances of device malfunction. Conclusion: In children with CAVB and myocarditis, a temporary permanent pacemaker can provide reliable pacing until recovery, and CMR can be safely performed with the implanted pacemaker without compromising image quality.

Mechanical Circulatory Support Systems in Fulminant Myocarditis: Recent Advances and Outlook.

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.

CMR Predictors of Favorable Outcome in Myocarditis: A Single-Center Experience.

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.

Case report: acute myocarditis complicated with persistent complete heart block: a clinical dilemma when myocardial inflammation remains.

Background: Atrioventricular conduction abnormalities due to acute myocarditis are typically transient and do not require ventricular pacing beyond the acute phase of myocardial inflammation. Notwithstanding, selective injury and necrosis of the heart's conduction system may lead to persistent complete heart block (CHB) requiring device implantation. Case summary: We report the case of a 23-year-old man with acute lymphocytic myocarditis complicated by cardiogenic shock, cardiac arrest due to ventricular fibrillation, and persistent CHB. Endomyocardial biopsy (EMB) showed signs of subacute myocarditis, with no evidence of granulomas or giant cells, nor criteria for eosinophilic myocarditis. Aetiological work-up found serological evidence of previous Epstein-Barr virus (EBV) infection; Borrelia burgdorferi serology for Lyme disease was negative. The real time-polymerase chain reaction (RT-PCR) of the EMB was positive for the presence of EBV DNA, but in situ hybridization for viral ribosomal RNA (rRNA) was negative. The patient progressed favourably, and left ventricle ejection fraction recovered 2 weeks after initial presentation. However, CHB persisted for more than 3 weeks, and the patient underwent definitive pacemaker implantation with left bundle branch pacing. Discussion: Persistent CHB after acute myocarditis is generally considered unlikely, but in rare circumstances the damage portended by inflammation may be irreversible. Besides the play of chance, possible mechanisms behind the apparent predilection for the conduction system of the myocardium warrant further research.

Drug-induced myocarditis precipitated by amlodipine overdose: a case report.

Background: Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis. Case summary: A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable. Discussion: Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear.

miR-29b-3p regulates cardiomyocytes pyroptosis in CVB3-induced myocarditis through targeting DNMT3A.

BACKGROUND: Viral myocarditis (VMC) is a disease resulting from viral infection, which manifests as inflammation of myocardial cells. Until now, the treatment of VMC is still a great challenge for clinicians. Increasing studies indicate the participation of miR-29b-3p in various diseases. According to the transcriptome sequencing analysis, miR-29b-3p was markedly upregulated in the viral myocarditis model. The purpose of this study was to investigate the role of miR-29b-3p in the progression of VMC. METHODS: We used CVB3 to induce primary cardiomyocytes and mice to establish a model of viral myocarditis. The purity of primary cardiomyocytes was identified by immunofluorescence. The cardiac function of mice was detected by Vevo770 imaging system. The area of inflammatory infiltration in heart tissue was shown by hematoxylin and eosin (H&E) staining. The expression of miR-29b-3p and DNMT3A was detected by quantitative real time polymerase chain reaction (qRT-PCR). The expression of a series of pyroptosis-related proteins was detected by western blot. The role of miR-29b-3p/DNMT3A in CVB3-induced pyroptosis of cardiomyocytes was studied in this research. RESULTS: Our data showed that the expression of miR-29b-3p was upregulated in CVB3-induced cardiomyocytes and heart tissues in mice. To explore the function of miR-29b-3p in CVB3-induced VMC, we conducted in vivo experiments by knocking down the expression of miR-29b-3p using antagomir. We then assessed the effects on mice body weight, histopathology changes, myocardial function, and cell pyroptosis in heart tissues. Additionally, we performed gain/loss-of-function experiments in vitro to measure the levels of pyroptosis in primary cardiomyocytes. Through bioinformatic analysis, we identified DNA methyltransferases 3A (DNMT3A) as a potential target gene of miR-29b-3p. Furthermore, we found that the expression of DNMT3A can be modulated by miR-29b-3p during CVB3 infection. CONCLUSIONS: Our results demonstrate a correlation between the expression of DNMT3A and CVB3-induced pyroptosis in cardiomyocytes. These findings unveil a previously unidentified mechanism by which CVB3 induces cardiac injury through the regulation of miR-29b-3p/DNMT3A-mediated pyroptosis.