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Background: Analysis of left atrial (LA) strain and left atrioventricular coupling index (LACI) have prognostic value in cardiovascular diseases. However, the prognostic value of LA strain and LACI in patients with suspected myocarditis and preserved left ventricular ejection fraction (LVEF) is unclear., Purpose: To investigate the prognostic value of LA strain and LACI in patients with suspected myocarditis and preserved LVEF in comparison with conventional MRI outcome predictors., Study Type: Retrospective., Population: One hundred sixty-five patients with clinically suspected myocarditis and preserved LVEF with available follow-up data., Field Strength/sequence: Steady-state free precession cine and phase-sensitive inversion recovery segmented gradient echo late gadolinium enhancement sequences at 3.0 T., Assessment: Left ventricular (LV) and LA strain were evaluated using feature tracking. LACI was calculated as the ratio of LA and LV volumes at LV end-diastole. Patients were followed-up with the primary endpoint being major adverse cardiovascular events (MACE)., Statistical Tests: Independent-samples t-test and Mann-Whitney U test to compare patients with and without MACE, receiver operating characteristic (ROC) curve analysis to define high/low risk groups, Kaplan-Meier survival analysis and Cox proportional hazards regression to assess prognosis. A P value of <0.05 was considered statistically significant., Results: The associations of LV strain parameters (including global radial, circumferential, and longitudinal strain) and LACI with MACE were not significant (P = 0.511, 0.108, 0.148, and 0.847, respectively). An optimal LA conduit strain (Ԑe) cutoff value of 10.4% was identified to best classify patients into low- and high-risk groups. Only Ԑe was significantly associated with MACE in both univariable (hazards ratio [HR] 0.936, 95% confidence interval [CI] 0.884-0.991) and multivariable Cox survival analyses (HR 0.937, 95% CI 0.884-0.994)., Data Conclusion: LA conduit strain has prognostic value in patients with suspected myocarditis and preserved LVEF, incremental to conventional MRI outcome predictors, whereas LACI was not associated with MACE occurrence., Evidence Level: 3 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Previous studies have shown that epicardial edipose tissue(EAT) appears to be associated with myocardial inflammation and fibrosis, but this is not clear in patients with new-onset atrial arrhythmias after STEMI. The present study focused on using CMR to assess the association of epicardial fat with myocardial inflammation and fibrosis and its predictive value in patients with new-onset atrial arrhythmias after STEMI., Methods: This was a single-centre, retrospective study. We consecutively selected patients who completed CMR during their hospitalisation for PCI after STEMI from May 2019-January 2023, and then underwent regular follow-up, grouped by the presence or absence of new atrial arrhythmias, and enrolled patients were divided into atrial arrhythmia and non-atrial arrhythmia groups., Results: In the atrial arrhythmia group, age, heart rate, Peak hs-TnT, PeakNT-proBNP, EATV, LAES, LAED, T1 native, T1*, ECV, and T2 were higher than those in the non-atrial arrhythmia group, and LVEF was lower than those in the non-atrial arrhythmia group. EATV showed a positive and significant correlation with T1native, T1*, ECV, and T2. (T1 native: r = 0.476,p < 0.001; ECV: r = 0.529,p < 0.001; T1*: r = 0.467,p < 0.001; T2: r = 0.538,p < 0.001). Multifactorial logistic regression analysis showed age, LVEF, EATV, T1*,ECV, T2 as independent risk factors for atrial arrhythmia. (p < 0.05) ROC analysis showed that the AUC for age was 0.568; AUC for LVEF was 0.656; AUC for EATV was 0.768; AUC for ECV was 0.705; AUC for T1* was 0.612; and AUC for T2 was 0.772., Conclusion: In patients with STEMI, EAT is associated with myocardial inflammation, fibrosis. Age, LVEF, EATV, T1*,ECV, T2 are independent risk factors for new onset atrial arrhythmias and have good predictive value., Competing Interests: Declarations. Ethics approval and consent to participate: The requirement for signed written consent was waived owing to no risk to the patient in accordance with the relevant IRB regulatory guidelines. This study was approved by the Ethics Committee of Xuzhou Medical University Affiliated Hospital, and complied with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cardiogenic shock (CS) is a complex, multisystem disorder precipitated by hypoperfusion from cardiac dysfunction. Our current approach to defining and treating CS encompasses all patients under 1 umbrella regardless of phenotype. This has created challenges for clinical trials and patient care owing to the heterogeneity of the patient population with CS. The Society of Coronary Angiography and Interventions shock classification has created a universal language for CS that has been rapidly adopted by researchers and clinicians. Its latest iteration established the 3-axis model incorporating shock severity, risk modifiers, and phenotypes. Phenotypes of CS have unique hemodynamic profiles that require nuanced adjustment approaches. In this study, we discuss representative cases including acute myocardial infarction, acute-on-chronic heart failure, fulminant myocarditis, and right ventricular failure. For each phenotype, specific hemodynamic parameters may help confirm appropriate diagnosis and direct to therapeutic targets signaling stability and recovery. The underlying pathophysiology of each phenotype can also help predict the extent of stabilization with pharmacologic interventions or the need to escalate to mechanical circulatory support. In conclusion, this tailored approach to CS, rather than a 1-size-fits-all approach, could help improve outcomes., Competing Interests: Declaration of competing interest Dr. Alam is a speaker for Abbott. Dr. Katz is a consultant/advisor for Abiomed and receives research funding from Abbott. Dr. Hall is a consultant/advisor for Abiomed, Abbott. Dr. Patlolla has no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: Hot phases are a challenging clinical presentation in arrhythmogenic cardiomyopathy (ACM), marked by acute chest pain and elevated cardiac troponins in the absence of obstructive coronary disease. These episodes manifest as myocarditis and primarily affect young patients, contributing to a heightened risk of life-threatening arrhythmias and potential disease progression. This review aims to synthesize recent research on the pathophysiology, diagnostic challenges, and therapeutic management of hot phases in ACM., Recent Findings: Hot phases have been linked to genetic mutations, particularly in desmosomal proteins such as Desmoplakin (DSP). Diagnostic challenges include differentiating hot phases from isolated acute myocarditis, through identification of red flags and a multimodal approach, including CMR, FDG-PET, endomyocardial biopsy and genetic testing. Emerging therapies, such as immunosuppressive and anti-inflammatory treatments, show promise in managing hot-phase episodes. Hot phases in ACM present a significant risk for arrhythmias and disease progression, necessitating a comprehensive diagnostic and therapeutic management. A multimodal diagnostic approach is essential for accurate diagnosis, but further research is needed to refine these strategies and improve prognosis for affected patients., Competing Interests: Declarations. Human and Animal Rights and Informed Consent: No animal or human subjects by the authors were used in this study. Conflict of Interest: The authors declare no competing interests., (© 2025. The Author(s).)

Purposeof the Review: In this review article, we aim to provide an overview of the pathophysiology, the clinical features, the therapeutic management and prognosis of patients affected by Multisystemic inflammatory syndrome (MIS) with cardiac involvement, focusing on myocarditis and pericarditis., Recent Findings: MIS is a multiorgan hyperinflammatory condition due to a cytokine storm following (within 4-12 weeks) SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection. First described in children, it also affects young adults without comorbidities, predominantly males with highly heterogeneous clinical manifestations, including cardiac involvement. Pericardial and myocardial involvement are prevalent among patients affected by MIS leading to different clinical manifestations including myocarditis with arrhythmias, acute heart failure and cardiogenic shock that significantly affect the patient's prognosis. The heterogeneity of its clinical features and the significant overlap with other hyperinflammatory diseases make the diagnosis particularly challenging. Moreover, the evidence on the efficacy of pharmacological treatments targeting the hyperinflammatory response is scarce, as well as data on long-term prognosis., Competing Interests: Declarations. Conflict of Interests: Dr. Bonaventura serves on the scientific advisory board for Monte Rosa Therapeutics. Dr. Abbate has served as a consultant to Novo Nordisk, Monterosa Tx, and Kiniksa; and he also served on the Data Safety Monitoring Board/Advisory Board for Applied Therapeutic Inc. Dr. Sanna serves as a consultant to Medtronic. The other authors declare that they have no conflict of interest. The authors declare no competing interests. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors., (© 2025. The Author(s).)

Purpose of Review: This review aims to assess the current landscape of animal models used in myocarditis research, with a focus on understanding their utility in uncovering the pathophysiology of the disease. The goal is to evaluate these models' strengths and weaknesses and propose optimizations to make them more relevant and reliable for both mechanistic studies and therapeutic interventions in myocarditis., Recent Findings: Recent studies have primarily utilized animal models, particularly viral and autoimmune myocarditis models, to study disease mechanisms. Coxsackievirus remains the most common virus used in viral myocarditis models, offering high success rates but limited applicability to human cases due to differences in infection patterns. Autoimmune myocarditis models, often involving humanized mice, have made strides in mimicking human immune responses but still face challenges in accuracy and clinical relevance. COVID-19 has introduced new avenues for research, especially concerning vaccine-induced myocarditis, although findings remain preliminary. Animal models remain crucial for myocarditis research, but each comes with distinct challenges. Viral models excel in success rate but suffer from partial relevance to human conditions. Autoimmune models are useful in immunological studies, though costly and less replicable. Vaccine-associated models are closely related to modern clinical conditions, but lack theoretical support and therefore lack reliability. Optimizing these models could improve our understanding of myocarditis and lead to more effective treatments. Future research should aim to refine these models to better simulate human conditions and enhance their clinical applicability, ultimately advancing the diagnosis and treatment of myocarditis., Competing Interests: Declarations. Ethical Approval: This article does not contain any studies with human participants or animals performed by any of the authors. Competing Interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To assess the clinical course and long-term outcomes of complicated and uncomplicated AM in Saudi Arabia. Acute myocarditis (AM) can have different presentations and outcomes based on different factors, one of which is left ventricular ejection fraction (LVEF)., Methods: Data from 382 patients with suspected AM, admitted between January 2016 and October 2023, were reviewed. Clinical course, in-hospital complications, and all-cause mortality were evaluated in both the acute and follow-up phases. Outcomes were compared between 2 groups: LVEF <50% (n=43); and normal LVEF (≥50% [n=41]) at presentation., Results: Data from 84 patients (mean [±SD] age, 33.5±10.2 years; 26.2% female) who fulfilled the inclusion criteria were analyzed. The most common symptom was chest pain (83.3%) and 11 (13.1%) patients had fulminant presentation. ST-T changes were found on electrocardiography in 45.2% of patients. The mean LVEF was 46±12.4% at presentation. Patients in the LVEF <50% group were significantly more likely to experience a first-time cardiac-related adverse event (CRAE) (hazard ratio 2.6 [95% confidence interval 1.1-6.2]; p =0.031) with a mean time of 38.8±3.8. The all-cause in-hospital and follow-up mortality rates in the LVEF <50% group were 4.7% (one-half cardiac-related) ( p =0.494) and 4.7% (all cardiac-related) ( p =0.494), respectively., Conclusion: Of 84 patients diagnosed with AM, those with LVEF <50% were more likely to experience first-time CRAEs and exhibited low short- and long-term mortality rates., (Copyright: © Saudi Medical Journal.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a pandemic and affected public health greatly. While COVID-19 primarily damages the lungs, leading to cough, sore throat, pneumonia, or acute respiratory distress syndrome, it also infects other organs and tissues, including the cardiovascular system. In particular, myocarditis is a well-recognized severe complication of COVID-19 infection and could result in adverse outcomes. Angiotensin-Converting Enzyme2 is thought to play a pivotal role in SARS-CoV-2 infection, and immune overresponse causes overwhelming damage to the host's myocardium. Direct viral infection and injury do take a part as well, but more evidence is needed to strengthen this proposal. The clinical abnormalities include elevated cardiac biomarkers and electrocardiogram changes and impaired cardiac function that might be presented in echocardiography and cardiovascular magnetic resonance imaging. If necessary, the endomyocardial biopsy would give more forceful information to diagnosis and aid in treatment. Comparisons between COVID-19 myocarditis and other viral myocarditis are also discussed briefly., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Viral myocarditis is associated with the development of dilated cardiomyopathy (DCM), left ventricular dysfunction, and heart failure. This review addresses the mechanisms of viral myocarditis and its treatment., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Objective: Cardiovascular magnetic resonance (CMR) is increasingly used in the diagnosis of myocarditis, with myocardial injury and systolic dysfunction playing key roles in the prognosis of this clinical setting. The clinical determinants of myocardial injury and systolic impairment in acute myocarditis are poorly defined. The aim of the current study is to assess the association of laboratory markers, late gadolinium enhancement (LGE) and left ventricular ejection fraction (LVEF) in patients with acute myocarditis., Methods: We completed a retrospective cohort study from a tertiary referral centre in London with CMR and acute myocarditis. Cases with cardiomyopathy were excluded. Missing data was imputed for selected clinical variables. We evaluated the association between peak troponin and LGE extent and LVEF. We adjusted the models for age, sex and time to CMR with a sensitivity analysis adjusting for body mass index and cardiovascular risk factors including hypertension, dyslipidaemia, diabetes mellitus and smoking., Results: 127 patients had abnormal T2-weighted imaging/mapping results with 118 (93%) presenting with chest pain and/or shortness of breath. Left ventricular LGE was identified in 118 (93%) patients and LVEF was 58±11%. The median time from the peak troponin to CMR was 1 day (IQR 0-6 days). The highest tertile of peak troponin was associated with more LGE (incident rate ratio 1.33, 95% CI: 1.07 to 1.64) and a lower LVEF (coefficient -5.3%, 95% CI: -9.5% to -1.1%). Diabetes was also associated with more LGE (incident rate ratio 1.90, 95% CI: 1.37 to 2.61) and lower LVEF (coefficient -8.9%, 95% CI: -14.7% to -1.8%)., Conclusions: Peak troponin is associated with more LGE and a lower LVEF even after accounting for demographics and comorbidities. Myocardial injury and systolic dysfunction play key roles in prognosis and future work incorporating clinical features into a risk prediction model may enable better risk stratification in acute myocarditis., Competing Interests: Competing interests: SEP reports a consultancy for Circle Cardiovascular Imaging, Inc., Calgary, Alberta, Canada., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Usual clinical testing rarely reveals cardiac abnormalities persisting after hospitalization for COVID. Such testing may overlook residual changes causing increased adverse cardiac events post-discharge. To clarify status post-hospitalization, we related exercise stress echocardiography (ESE) in 15 recovering patients (RP) age 30-63 without myocarditis to matching published data from healthy subjects (HS). RP exercise, average duration 8.2 ± 2.2 SD, was halted by dyspnea or fatigue. RP baselines matched HS except for higher heart rate. At peak stress, RP had significantly lower mean left ventricular (LV) ejection fraction (67% ± 7 vs. 73% ± 5, p < 0.0017) and higher peak early mitral inflow velocity/early mitral annular velocity (E/e', 9.1 ± 2.5 vs. 6.6 ± 2.5, p < 0.006) compared with HS performing equal exercise (8.5 ± 2.6 min). Thus, when stressed, patients without known cardiac impairment showed diminished systolic contractile function and diastolic LV compliance vs. HS. RP peak heart rate was significantly higher (172 ± 18 vs. 153 ± 20); peak systolic blood pressure trended higher (192 ± 31 vs. 178 ± 19). Pulmonary artery systolic pressures among RP remained normal. ESE uniquely identified residual abnormality in cardiac contractile function not evident unstressed, exposing previously unrecognized residual influence of COVID-19. This may reflect autonomic dysfunction, microvascular disease, or diffuse interstitial changes; these results may have implications for clinical management and later prognosis., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Objective: To determine the short- and medium-term cardiac outcomes in children admitted with multisystem inflammatory syndrome in children at a tertiary care centre in Pakistan., Methods: Children fulfilling the criteria for multisystem inflammatory syndrome and admitted to the hospital between April 2020 and March 2022 were enrolled in this prospective longitudinal cohort study. From admission to discharge, laboratory and cardiac parameters were recorded for all patients, who were subsequently followed up in clinics at various intervals. Data analysis was conducted using STATA version 15.0., Results: A total of 51 children were included, with viral myocarditis (41.2%) and toxic shock syndrome (33.3%) being the most common phenotypes. The cardiovascular system was most commonly affected in 27 children (53%) with laboratory evidence of inflammation and myocardial injury with median and interquartile levels of ferritin 1169 (534-1704), C-reactive protein 83 (24-175), lactate dehydrogenase 468 (365-1270), N-terminal pro-B-type natriuretic peptide 8,656 (2,538-31,166), and troponin 0.16 (0.02-2.0).On admission, decreased left ventricular ejection fraction was observed in 58.8% of patients and impaired global longitudinal strain in 33.3%. At discharge, left ventricular ejection fraction had normalised in 83% of patients. Pericardial effusion resolved in all patients, and valvulitis resolved in 86% by 12 months. Paediatric ICU admission was required in 42 (82%) of patients with an overall mortality of 12% ( n = 6)., Conclusion: Our study finds high hospital mortality for multisystem inflammatory syndrome in children compared to 1-2% from previous studies. Yet, in Pakistan, surviving children with multisystem inflammatory syndrome show favourable short- to medium-term cardiac outcomes.

Myocarditis, characterized by inflammation of the myocardial tissue, presents substantial risks to cardiovascular functionality, potentially precipitating critical outcomes including heart failure and arrhythmias. This investigation primarily aims to identify the optimal cardiovascular magnetic resonance imaging (CMRI) views for distinguishing between normal and myocarditis cases, using deep learning (DL) methodologies. Analyzing CMRI data from a cohort of 269 individuals, with 231 confirmed myocarditis cases and 38 as control participants, we implemented an innovative DL framework to facilitate the automated detection of myocarditis. Our approach was divided into single-frame and multi-frame analyses to evaluate different views and types of acquisitions for optimal diagnostic accuracy. The results demonstrated a weighted accuracy of 96.9%, with the highest accuracy achieved using the late gadolinium enhancement (LGE) 2-chamber view, underscoring the potential of DL in distinguishing myocarditis from normal cases on CMRI data., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent to publish: All authors have read and agreed to the published version of the manuscript., (© 2024. The Author(s).)

Background: Ventricular arrhythmias (VAs) frequently occur in the acute phase of myocarditis. Possible arrhythmic recurrences and the risk of sudden cardiac death (SCD) in this setting are reasons for concern, and limited data have been published to guide clinical management of these patients. The aim of the present paper is to report the incidence of major arrhythmic events, defined as sustained VA, SCD and appropriate implantable cardiac-defibrillator (ICD) treatment, in patients with acute myocarditis and ventricular arrhythmic phenotype., Methods: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to evaluate studies reporting long-term outcomes in patients with acute myocarditis and arrhythmic presentation. We systematically searched PubMed, EMBASE and Scopus databases for relevant studies up to 2 August 2024. Study quality was assessed by the Newcastle-Ottawa Scale. The primary outcome was a composite of SCD, VA recurrence and appropriate ICD therapy. Random-effect models were used to calculate pooled ORs and CIs., Results: Five observational studies enrolling 322 patients were identified. The pooled proportion of patients who experienced VA recurrence was 0.41 (95% CI 0.30 to 0.53, p=0.13). An increased risk of adverse outcomes during follow-up was observed in patients presenting with monomorphic ventricular tachycardia (OR 3.77, 95% CI 1.23 to 11.53) and left ventricular ejection fraction (LVEF) <50% (OR 2.74, 95% CI 0.78 to 9.63). Gender and anteroseptal late gadolinium enhancement were not found as potential risk factors in this analysis., Conclusions: Patients with myocarditis with arrhythmic ventricular presentation have a high recurrence rate of VA, underscoring the importance of careful monitoring and management in this patient population. Risk stratification for SCD during follow-up should be individualised, and monomorphic VA at presentation or a reduced LVEF may be markers of poor prognosis. In these cases, an ICD implantation may be cautious pending further dedicated studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ Group.)

Multi-lineage differentiating stress-enduring (Muse) cells, identified as pluripotent surface marker SSEA-3(+) cells, are stress tolerant endogenous pluripotent-like stem cells, and are involved in tissue repair. However, the significance of Muse cells in acute myocarditis has not been evaluated. In the present study, we counted Muse cells/area in biopsied myocardial tissue samples from 17 patients with fulminant myocarditis, and 6 with non-inflammatory myocardial disease as controls. Compared with controls, patients with fulminant myocarditis had significantly more Muse cells (p = 0.00042). Patients with mechanical circulatory support (p = 0.006) and myocardial degeneration (p = 0.023) had significantly more Muse cells than those without them. The Muse cell number was correlated with acute phase CK-MB level (ρ = 0.547, p = 0.029), indicating the severity of myocardial injury, and was also correlated with acute/recovery phase ratio of CK-MB (ρ = 0.585, p = 0.023) and cardiac troponin I (ρ = 0.498, p = 0.047) levels, indicating resilience of myocardial injury. In fulminant myocarditis, the Muse cell number was associated with the severity of clinical features in the acute phase, and also with the recovery from myocardial damage in the chronic phase. Endogenous Muse cells might be mobilized and accumulate to the myocardial tissues in fulminant myocarditis, and might participate in the repair of injured myocardium., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aim: To study the concentration of immunoglobulin free light chains (FLCs) in patients with myocarditis in comparison with non-inflammatory heart diseases, their relationship with inflammatory markers and the severity of chronic heart failure (CHF)., Material and Methods: This study included 77 patients (31 women, mean age 54.1±13.3 years): 41 patients with myocarditis verified by myocardial biopsy (n=18) or using a noninvasive diagnostic algorithm, 31 patients with noninflammatory CHF (comparison group), and 5 patients with monoclonal gammopathy identified during the study (4 of them were diagnosed with AL amyloidosis with heart damage). In the myocarditis group, CHF was diagnosed in 29 patients, mean stage IIA, functional class (FC) 2-3, with a mean left ventricular ejection fraction 43%. In the comparison group, patients had predominantly IIA stage, FC 2-3 CHF without systolic dysfunction. The blood concentration of kappa and lambda FLC types was measured with Cloneus S-FLC-K TIA Kit and Cloneus S-FLC-L TIA Kit. Concentrations were considered normal at FLC-kappa 4.84-14.20 mg/l, FLC-lambda 7.03-22.50 mg/l, and the FLC-kappa/lambda ratio 0.426-1.050., Results: Increased FLC concentrations were found in 58% of patients with myocarditis and in 77% of patients in the comparison group. The FLC-lambda concentration was significantly higher in the comparison group; there were no significant differences between the groups in FLC-kappa and their ratio. The closest significant correlations in both groups and the entire cohort were noted between FLCs of either type and CHF, as well as the requirement for loop diuretics (correlation coefficients, 0.60-0.90), independent on the severity of systolic dysfunction. Myocarditis patients also showed correlations of FLCs with the titer of antibodies to cardiomyocyte nuclear antigens, levels of C-reactive protein, leukocytes, neutrophils, erythrocyte sedimentation rate, and the concentration of N-terminal fragment of brain natriuretic peptide. In a subgroup of 10 myocarditis patients who were treated with immunosuppressants, FLCs of both types were significantly lower than in the comparison group; only with the persistence of severe CHF was an increase in FLCs noted., Conclusion: An increased FLC concentration can be considered as an important pathogenesis component that reflects both the specific mechanisms of myocarditis and the severity of CHF. In the absence of a statistically significant increase in general inflammatory markers in the blood of myocarditis patients, the measurement of FLCs can be used as an additional diagnostic marker and predictor of the decompensated variant of the course of myocarditis. However, the diagnostic and prognostic significance of FLC concentration in patients without CHF requires a further study.

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.

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.

Myocarditis is a potentially life-threatening inflammatory disease of the myocardium, often resulting from infectious and immune-mediated responses. Clinical presentation in severe cases often results in a devastating illness requiring extracorporeal membrane oxygenation support as a result of cardiogenic shock. Although endomyocardial biopsy is still considered the gold standard for diagnosis, it often reveals nonspecific lymphocytic infiltration. Because the precise cause is usually unknown, the initial treatment typically involves immunosuppression and frequent assessment of myocardial contractility. This report presents 3 rare cases of autoimmune diseases (polymyositis, immunoglobulin G4-related disease, and systemic lupus erythematosus) that require extracorporeal membrane oxygenation support as a result of fulminant myocarditis, including their follow-up periods., (© 2024 The Authors. Published by The Texas Heart Institute®.)

Background: Chronic Chagas cardiomyopathy (CCC) is caused by an inflammatory process induced by Trypanosoma cruzi, which leads to myocarditis with reactive and reparative fibrosis. CCC progresses with myocardial perfusion abnormalities and histopathological events that affect cardiorespiratory fitness (CRF)., Objectives: We evaluated the effects of aerobic physical training (APT) on myocardial perfusion and on morphological and functional impairments related with inflammation and fibrosis in Syrian hamsters with CCC. As a secondary objective, we analyzed the cross-sectional areas of the skeletal muscle., Methods: Hamsters with CCC and their respective controls were divided into four groups: CCC sedentary, CCC-APT, sedentary control and APT control. Seven months after infection, the animals underwent echocardiography, myocardial perfusion scintigraphy and cardiopulmonary exercise testing. Moderate-intensity APT was performed for fifty minutes, five times a week, for eight weeks. Subsequently, the animals were reassessed. Histopathological analysis was conducted after the above-mentioned procedures. The level of significance was set at 5% in all analyses (p<0.05)., Results: CCC sedentary animals presented worse myocardial perfusion defects (MPD) over time, reduced left ventricle ejection fraction (LVEF) and showed more inflammation and fibrosis when compared to other groups (mixed ANOVA analysis). Conversely, APT was able to mitigate the progression of MPD, ameliorate inflammation and fibrosis and improve CRF efficiency in CCC-APT animals., Conclusions: Our study demonstrated that APT ameliorated cardiac dysfunction, MPD, and reduced inflammation and fibrosis in CCC hamster models. Additionally, CCC-SED animals presented skeletal muscle atrophy while CCC-APT animals showed preserved skeletal muscle CSA. Understanding APT's effects on CCC's pathophysiological dimensions is crucial for future research and therapeutic interventions.

This article describes the case of a 40-year-old individual who presented with fulminant myocarditis. Initial ECG displayed sinus tachycardia with a heart rate of 117 bpm, QS complexes in leads V1-V3, ST-segment depression in leads II, III, aVF, V5-V6, and ST-segment elevation >0.2 mV in leads V1 through V3. The initial clinical assessment suggested an acute anteroseptal myocardial infarction. However, subsequent diagnostic evaluation through coronary angiography disclosed that the coronary arteries were normal. Therefore, clinicians should carefully consider the differential diagnosis between these conditions, as their management strategies differ markedly. Two hours after admission, the patient unexpectedly developed syncope. The ECG findings were consistent with the typical characteristics of bidirectional ventricular tachycardia. Our report described the appearance and morphology as well as mechanism of bidirectional ventricular tachycardia in detail. Additionally, we delineate differential diagnoses for disease that can cause bidirectional ventricular tachycardia, such as aconite poisoning, digoxin overdose, immune checkpoint inhibitor (ICI), myocardial ischemia, and hereditary channelopathies, such as catecholaminergic polymorphic ventricular tachycardia (CPVT) and Andersen-Tawil syndrome. Therefore, clinicians should recognize this ECG finding immediately and initiate appropriate treatment promptly as these measures may be vital in saving the patient's life., (© 2024 The Author(s). Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Advances in the etiological classification of myocarditis and inflammatory cardiomyopathy (ICM) have reached a consensus. However, the mechanism of myocarditis/ICM remains unclear, which affects the development of treatment and the improvement of outcome. Cellular transcription and metabolic reprogramming, and the interactions between cardiomyocytes and non-cardiomyocytes, such as the immune cells, contribute to the process of myocarditis/ICM. Recent efforts have been made by multi-omics techniques, particularly in single-cell RNA sequencing, to gain a better understanding of the cellular landscape alteration occurring in disease during the progression. This article aims to provide a comprehensive overview of the latest studies in myocarditis/ICM, particularly as revealed by single-cell sequencing., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Patients with viral myocarditis can present with challenging life-threatening arrhythmias. Catheter ablation can be a life-saving procedure in some patients with recurrent drug-refractory ventricular arrhythmias., Methods and Results: A patient with three prior ablations targeting two different monomorphic ventricular tachycardias (MMVTs) presented with recurrent ventricular tachycardia (VT). Consequently, he underwent epicardial mapping with adjuvant AI-enabled CT images with the creation of a three-dimensional model, which demonstrated a midmyocardial scar. Fractionated potentials were noted during mapping in this region, and entrainment suggested an inner loop. Interestingly, pacing showed two different QRS morphologies identical to his previously ablated VTs with a long stim-QRS at this region. Epicardial ablation carried on during the VT successfully terminated it, but the VT remained inducible and required endocardial ablation to make it noninducible., Conclusion: This case emphasizes the importance of recognizing possible three-dimensional VT circuits in some patients and the need to understand and target mid-myocardial substrate from both the endocardium and epicardium to achieve the elimination of the VT circuits., (© 2024 Wiley Periodicals LLC.)

Objective: To investugate the unique electrocardiogram (ECG) characteristics of fulminant myocarditis (FM) patients and provide important clues for the diagnosis of FM. Methods: This was a retrospective study. Patients diagnosed with acute myocarditis at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 2017 to April 2022 were enrolled and divided into fulminant myocarditis group (FM) and non-fulminant myocarditis group (NFM) according to clinical diagnosis. A total of 246 healthy people who underwent physical examination in the Health examination Center of Tongji Hospital at the same period were selected as the control group. The clinical data and ECG characteristics of the above 3 groups were analyzed and compared. Logistic regression model was used to analyze the influence of ECG parameters on left ventricular ejection fraction in FM patients. Receiver operating curves were constructed to evaluate the predictive value of different ECG parameters for FM. Results: A total of 180 patients were included in this study (FM group: n =123; NFM group: n =57), with an age of (35.0±16.2) years and 106 males (58.89%). Compared with NFM group, ECG was significantly abnormal in FM group, with a higher incidence of sinus tachycardia, ventricular tachycardia or ventricular fibrillation, escape rhythm, right bundle branch block, third degree atrioventricular block, ST-segment elevation, low voltage, prolonged QTc interval, and widened QRS wave in the FM group (all P <0.05). The ECG parameters showed that the amplitude of the full lead QRS wave in FM group was lower than that in NFM group ( P <0.01). The average heart rate and QTc interval of FM group were significantly higher than those of NFM and control groups (all P <0.05). Although ST-segment elevation had a higher incidence in the FM group, ECG parameters showed that except for leads Ⅲ and aVF, the ST segment levels in all leads in the FM group were lower than those in the control group (all P <0.05). There was a statistically significant difference in some ST segment changes between FM and NFM groups, while there was no statistical difference between the NFM and control groups. Multivariate regression analysis showed that widened QRS wave and increased heart rate were the influencing factors for left ventricular systolic dysfunction in FM patients ( OR =16.914, 95% CI : 1.367-209.224, P =0.028; OR =1.026, 95% CI : 1.010-1.042, P =0.001). Receiver operating curve analysis showed that heart rate>86.90 beat/min, QTc>431.50 ms, and RV5+SV1<1.72 mV had certain predictive value for FM diagnosis. Conclusions: FM patients displayed marked and severe ECG abnormalities, and characteristic changes in ECG can provide important first clues for the diagnosis of FM.

Background: This study assesses the diagnostic utility of strain parameters from cardiovascular magnetic resonance feature tracking across all cardiac chambers in patients with acute myocarditis, stratified by ejection fraction., Methods and Results: Our cohort included 65 patients with acute myocarditis and 25 healthy controls; all underwent cardiac magnetic resonance imaging. Patients were divided into 2 groups based on left ventricular ejection fraction (EF)with a 55% cutoff: acute myocarditis with preserved EF, EF ≥55%, n=48; and acute myocarditis with reduced EF, EF <55%, n=17. The control group matched for age and sex. Cardiovascular magnetic resonance feature tracking evaluated strain parameters across all cardiac chambers. Both acute myocarditis with preserved EF and acute myocarditis with reduced EF groups showed significant decreases in left atrial peak early negative strain rate compared with controls. The acute myocarditis with reduced EF group had significantly reduced left ventricular circumferential strain relative to acute myocarditis with preserved EF and controls. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy in distinguishing patients with acute myocarditis with preserved EF from controls, with left atrial peak early negative strain rate achieving 92.9% specificity, left ventricular circumferential strain demonstrating an area under the curve of 0.832, and similarly effective results for left ventricular longitudinal strain and right ventricular longitudinal strain. Additionally, left atrial peak early negative strain rate and left ventricular circumferential strain showed significant correlations with troponin I levels, indicating myocardial injury., Conclusions: Cardiovascular magnetic resonance feature-tracking-derived strain parameters, particularly left atrial peak early negative strain rate and left ventricular circumferential strain, effectively diagnose acute myocarditis across different EFs, enhancing diagnostic accuracy and facilitating early detection, notably in patients with preserved EF.

Purpose of the Review: Cardiac involvement in systemic sarcoidosis or isolated cardiac sarcoidosis plays a pivotal role in the clinical manifestation and prognostication. Active-inflammatory cardiac sarcoidosis is associated with a regional impairment of coronary microvascular function that may confer further detrimental effects on myocardial function needing further characterization., Recent Findings: Clinical investigations with cardiac positron emission tomography/computed tomography in conjunction with 18 F-fluorodeoxyglucose to determine myocardial inflammation and 13 N-ammonia to quantify myocardial blood flow (MBF) in patients with known or suspected cardiac sarcoidosis outlined that sarcoidosis-induced myocardial inflammation was associated with adverse effects on corresponding regional coronary microvascular function. Notably, immune-suppressive treatment caused reductions in myocardial inflammation were paralleled by improvements of coronary microvascular dysfunction outlining direct adverse effect of inflammation on coronary arteriolar function. This review summarizes contributions of cardiac PET imaging in the identification and characterization of active-inflammatory cardiac sarcoidosis, its effect on coronary microvascular function, treatment responses, and prognostic implications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Arrhythmogenic cardiomyopathy (ACM) is a familial heart disease characterized by cardiac dysfunction, arrhythmias, and myocardial inflammation. Exercise and stress can influence the disease's progression. Thus, an investigation of whether a high-fat diet (HFD) contributes to ACM pathogenesis is warranted. In a robust ACM mouse model, 8-week-old Desmoglein-2 mutant ( Dsg2 mut/mut ) mice were fed either an HFD or rodent chow for 8 weeks. Chow-fed wildtype (WT) mice served as controls. Echo- and electrocardiography images pre- and post-dietary intervention were obtained, and the lipid burden, inflammatory markers, and myocardial fibrosis were assessed at the study endpoint. HFD-fed Dsg2 mut/mut mice showed numerous P-wave perturbations, reduced R-amplitude, left ventricle (LV) remodeling, and reduced ejection fraction (%LVEF). Notable elevations in plasma high-density lipoprotein (HDL) were observed, which correlated with the %LVEF. The myocardial inflammatory adipokines, adiponectin (AdipoQ) and fibroblast growth factor-1, were substantially elevated in HFD-fed Dsg2 mut/mut mice, albeit no compounding effect was observed in cardiac fibrosis. The HFD not only potentiated cardiac dysfunction but additionally promoted adverse cardiac remodeling. Further investigation is warranted, particularly given elevated AdipoQ levels and the positive correlation of HDL with the %LVEF, which may suggest a protective effect. Altogether, the HFD worsened some, but not all, disease phenotypes in Dsg2 mut/mut mice. Notwithstanding, diet may be a modifiable environmental factor in ACM disease progression.

Heart failure (HF) is characterized by a progressive decline in cardiac function and represents one of the largest health burdens worldwide. Clinically, 2 major types of HF are distinguished based on the left ventricular ejection fraction (EF): HF with reduced EF and HF with preserved EF. While both types share several risk factors and features of adverse cardiac remodeling, unique hallmarks beyond ejection fraction that distinguish these etiologies also exist. These differences may explain the fact that approved therapies for HF with reduced EF are largely ineffective in patients suffering from HF with preserved EF. Improving our understanding of the distinct cellular and molecular mechanisms is crucial for the development of better treatment strategies. This article reviews the knowledge of the immunologic mechanisms underlying HF with reduced and preserved EF and discusses how the different immune profiles elicited may identify attractive therapeutic targets for these conditions. We review the literature on the reported mechanisms of adverse cardiac remodeling in HF with reduced and preserved EF, as well as the immune mechanisms involved. We discuss how the knowledge gained from preclinical models of the complex syndrome of HF as well as from clinical data obtained from patients may translate to a better understanding of HF and result in specific treatments for these conditions in humans., Competing Interests: Disclosures M. Kallikourdis is listed as inventor in patents covering therapeutic manipulation of immune responses in HF. The other authors report no conflicts.

Background: There is little literature on the use of temporary pacemakers in children with fulminant myocarditis. Therefore, we summarized the use of temporary cardiac pacemakers in children with fulminant myocarditis in our hospital., Methods: The clinical data of children with fulminant myocarditis treated with temporary pacemakers in Wuhan Children's Hospital from January 2017 to May 2022 were retrospectively analyzed., Results: A total of 6 children were enrolled in the study, including 4 boys and 2 girls, with a median age of 50 months and a median weight of 15 kg. The average time from admission to pacemaker placement was 2.75 ± 0.4 h. The electrocardiogram showed that all 6 children had third-degree atrioventricular block (III°AVB). The initial pacing voltage, the sensory sensitivity of the ventricle and the pacing frequency were set to 5-10 mV, 5 V and 100-120 bpm respectively. The sinus rhythm was recovered in 5 patients within 61 h (17-134) h, and the median time of using temporary pacemaker was 132 h (63-445) h. One of the children had persistent III°AVB after the temporary pacemaker. With parental consent, the child was fitted with a permanent pacemaker on the 12th day of his illness., Conclusions: When fulminant myocarditis leads to severe bradycardia or atrioventricular block in children, temporary pacemakers have the characteristics of high safety to improve the heart function., (© 2024. The Author(s).)

Background: Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear., Methods: Rats with myosin peptide-induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat's RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca 2+ transients, and Ca 2+ -modulated protein expression in individual myocytes isolated from the RVOTs., Results: The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca 2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca 2+ transients, lower L-type Ca 2+ currents, larger late Na + currents , larger Na + -Ca 2+ exchanger currents, higher reactive oxygen species levels, and higher Ca 2+ /calmodulin-dependent protein kinase II levels than did those of the control and treatment groups., Conclusion: Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling., (© 2024. The Author(s).)

According to updated Lake-Louise Criteria, impaired regional myocardial function serves as a supportive criterion in diagnosing myocarditis. This study aimed to assess visual regional wall motional abnormalities (RWMA) and novel quantitative regional longitudinal peak strain (RLS) for risk stratification in the clinical setting of myocarditis. In patients undergoing CMR and meeting clinical criteria for suspected myocarditis global longitudinal strain (GLS), late gadolinium enhancement (LGE), RWMA and RLS were assessed in the anterior, septal, inferior, and lateral regions and correlated to the occurrence of major adverse cardiac events (MACE), including heart failure hospitalization, sustained ventricular tachycardia, recurrent myocarditis, and all-cause death. In 690 consecutive patients (age: 48.0 ± 16.0 years; 37.7% female) with suspected myocarditis impaired RLS was correlated with RWMA and LV-GLS but not with the presence of LGE. At median follow up of 3.8 years, MACE occurred in 116 (16.8%) patients. Both, RWMA and RLS in anterior-, septal-, inferior-, and lateral- locations were univariately associated with outcomes (all p < 0.001), but not after adjusting for clinical characteristics and LV-GLS. In the subgroup of patients with normal LV function, RWMA were not predictive of outcomes, whereas septal RLS had incremental and independent prognostic value over clinical characteristics (HR adjusted  = 1.132, 95% CI 1.020-1.256; p = 0.020). RWMA and RLS can be used to assess regional impairment of myocardial function in myocarditis but are of limited prognostic value in the overall population. However, in the subgroup of patients with normal LV function, septal RLS represents a distinctive marker of regional LV dysfunction, offering potential for risk-stratification., (© 2024. The Author(s).)

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., (© 2024 Wiley Periodicals LLC.)

Background: The diagnosis of myocarditis by cardiovascular magnetic resonance (CMR) requires the use of T2 and T1 weighted imaging, ideally incorporating parametric mapping. Current two-dimensional (2D) mapping sequences are acquired sequentially and involve multiple breath-holds resulting in prolonged scan times and anisotropic image resolution. We developed an isotropic free-breathing three-dimensional (3D) whole-heart sequence that allows simultaneous T1 and T2 mapping and validated it in patients with suspected myocarditis., Methods: Eighteen healthy volunteers and 28 patients with suspected myocarditis underwent conventional 2D T1 and T2 mapping with whole-heart coverage and 3D joint T1/T2 mapping on a 1.5T scanner. Acquisition time, image quality, and diagnostic performance were compared. Qualitative analysis was performed using a 4-point Likert scale. Bland-Altman plots were used to assess the quantitative agreement between 2D and 3D sequences., Results: The 3D T1/T2 sequence was acquired in 8 min 26 s under free breathing, whereas 2D T1 and T2 sequences were acquired with breath-holds in 11 min 44 s (p = 0.0001). All 2D images were diagnostic. For 3D images, 89% (25/28) of T1 and 96% (27/28) of T2 images were diagnostic with no significant difference in the proportion of diagnostic images for the 3D and 2D T1 (p = 0.2482) and T2 maps (p = 1.0000). Systematic bias in T1 was noted with biases of 102, 115, and 152 ms for basal-apical segments, with a larger bias for higher T1 values. Good agreement between T2 values for 3D and 2D techniques was found (bias of 1.8, 3.9, and 3.6 ms for basal-apical segments). The sensitivity and specificity of the 3D sequence for diagnosing acute myocarditis were 74% (95% confidence interval [CI] 49%-91%) and 83% (36%-100%), respectively, with a c-statistic (95% CI) of 0.85 (0.79-0.91) and no statistically significant difference between the 2D and 3D sequences for the detection of acute myocarditis for T1 (p = 0.2207) or T2 (p = 1.0000)., Conclusion: Free-breathing whole-heart 3D joint T1/T2 mapping was comparable to 2D mapping sequences with respect to diagnostic performance, but with the added advantages of free breathing and shorter scan times. Further work is required to address the bias noted at high T1 values, but this did not significantly impact diagnostic accuracy., Competing Interests: Declaration of competing interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Alina Hua reports financial support was provided by the British Heart Foundation. The Institution reports infrastructure financial support was provided by the National Institute for Health and Care Research (UK). Dr. Karl P. Kunze is an employee of Siemens Healthcare Limited. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Myocarditis is one of the presentations of multisystemic inflammatory syndrome in children (MIS-C) following coronavirus disease 2019 (COVID-19). Although the reported short-term prognosis is good, data regarding medium-term functional capacity and limitations are scarce. This study aimed to evaluate exercise capacity as well as possible cardiac and respiratory limitations in children recovered from MIS-C related myocarditis., Methods: Fourteen patients who recovered from MIS-C related myocarditis underwent spirometry and cardiopulmonary exercise testing (CPET), and their results were compared with an age-, sex-, weight- and activity level-matched healthy control group (n = 14)., Results: All participants completed the CPET with peak oxygen uptake (peak [Formula: see text]), and the results were within the normal range (MIS-C 89.3% ± 8.9% and Control 87.9% ± 13.7% predicted [Formula: see text]). Five post-MIS-C patients (35%) had exercise-related cardio-respiratory abnormalities, including oxygen desaturation and oxygen-pulse flattening, compared to none in the control group. The MIS-C group also had lower peak exercise saturation (95.6 ± 3.5 vs. 97.6 ± 1.1) and lower breathing reserve (17.4% ± 7.5% vs. 27.4% ± 14.0% of MVV)., Conclusions: Patients who recovered from MIS-C related myocarditis may present exercise limitations. Functional assessment (e.g., CPET) should be included in routine examinations before allowing a return to physical activity in post-MIS-C myocarditis. Larger, longer term studies assessing functional capacity and focusing on physiological mechanisms are needed., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

Background: The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin., Objective: Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case., Methods: We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar., Results: Only two cases of KFD after COVID infection have been described so far., Conclusion: SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD., (© 2022. The Author(s).)

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth., Methods: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions., Results: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25)., Conclusions: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

Introduction: This study investigated the spontaneous clinical course of patients with endomyocardial biopsy (EMB)-proven lymphocytic myocarditis and cardiac human herpesvirus 6 (HHV6) DNA presence, and the effectiveness of steroid-based intervention in HHV6-positive patients., Results: 756 heart failure (HF) patients underwent an EMB procedure to determine the underlying cause of unexplained HF. Low levels of HHV6 DNA, detectable by nested PCR only, were found in 10.4% of the cases ( n = 79) of which 62% ( n = 49) showed myocardial inflammation. The spontaneous course of patients with EMB-proven HHV6 DNA-associated lymphocytic myocarditis ( n = 26) showed significant improvements in the left ventricular ejection fraction (LVEF) and clinical symptoms, respectively, in 15/26 (60%) patients, 3-12 months after disease onset. EMB mRNA expression of components of the NLRP3 inflammasome pathway and protein analysis of cardiac remodeling markers, analyzed by real-time PCR and MALDI mass spectrometry, respectively, did not differ between HHV6-positive and -negative patients. In another cohort of patients with ongoing symptoms related to lymphocytic myocarditis associated with cardiac levels of HHV6-DNA copy numbers <500 copies/µg cardiac DNA, quantified by real-time PCR, the efficacy and safety of steroid-based immunosuppression for six months was investigated. Steroid-based immunosuppression improved the LVEF (≥5%) in 8/10 patients and reduced cardiac inflammation in 7/10 patients, without an increase in cardiac HHV6 DNA levels in follow-up EMBs., Conclusion: Low HHV6 DNA levels are frequently detected in the myocardium, independent of inflammation. In patients with lymphocytic myocarditis with low levels of HHV6 DNA, the spontaneous clinical improvement is nearby 60%. In selected symptomatic patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid-based therapy was found to be effective and safe. This finding needs to be further confirmed in large, randomized trials.

Previous mouse studies have shown the increased presence of platelets in the myocardium during early stages of myocarditis and their selective detection by MRI. Here, we aimed to depict early myocarditis using molecular contrast-enhanced ultrasound of activated platelets, and to evaluate the impact of a P2Y 12 receptor platelet inhibition. Experimental autoimmune myocarditis was induced in BALB/c mice by subcutaneous injection of porcine cardiac myosin and complete Freund adjuvant (CFA). Activated platelets were targeted with microbubbles (MB) coupled to a single-chain antibody that binds to the "ligand-induced binding sites" of the GPIIb/IIIa-receptor (=LIBS-MB). Alongside myocarditis induction, a group of mice received a daily dose of 100 g prasugrel for 1 month. Mice injected with myosin and CFA had a significantly deteriorated ejection fraction and histological inflammation on day 28 compared to mice only injected with myosin. Platelets infiltrated the myocardium before reduction in ejection fraction could be detected by echocardiography. No selective binding of the LIBS-MB contrast agent could be detected by either ultrasound or histology. Prasugrel therapy preserved ejection fraction and significantly reduced platelet aggregates in the myocardium compared to mice without prasugrel therapy. Therefore, P2Y 12 inhibition could be a promising early therapeutic target in myocarditis, requiring further investigation.

Background Myocardial injury and inflammation at cardiac MRI in patients with COVID-19 have been described in recent publications. Concurrently, a chronic COVID-19 syndrome (CCS) after SARS-CoV-2 infection has been observed and manifests with symptoms such as fatigue and exertional dyspnea. Purpose To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals. Materials and Methods In this prospective study from January 2021 to April 2021, study participants without known cardiac or pulmonary diseases prior to SARS-CoV-2 infection who had persistent CCS symptoms such as fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI. The cardiac MRI protocol included evaluating the T1 and T2 relaxation times, extracellular volume, T2 signal intensity ratio, and late gadolinium enhancement (LGE). Student t tests, Mann-Whitney U tests, and χ 2 tests were used for statistical analysis. Results Forty-one participants with CCS (mean age, 39 years ± 13 [standard deviation]; 18 men) and 42 control participants (mean age, 39 years ± 16; 26 men) were evaluated. The median time between the initial incidence of mild to moderate COVID-19 not requiring hospitalization and undergoing cardiac MRI was 103 days (interquartile range, 88-158 days). Troponin T levels were normal. Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants (T1 relaxation times: 978 msec ± 23 vs 971 msec ± 25 [ P = .17]; T2 relaxation times: 53 msec ± 2 vs 52 msec ± 2 [ P = .47]; T2 signal intensity ratios: 1.6 ± 0.2 vs 1.6 ± 0.3 [ P = .10]). Visible myocardial edema was present in none of the participants. Three of 41 (7%) participants with CCS demonstrated nonischemic LGE, whereas no participants in the control group demonstrated nonischemic LGE (0 of 42 [0%]; P = .07). None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis. Conclusion Individuals with chronic COVID-19 syndrome who did not undergo hospitalization for COVID-19 did not demonstrate signs of active myocardial injury or inflammation at cardiac MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lima and Bluemke in this issue.

Background: Conventional transthoracic echocardiography (TTE) does often not accurately reveal pathologies in patients with acute myocarditis and preserved left ventricular ejection fraction (LVEEF). Therefore, we investigated the diagnostic value of two-dimensional (2D) speckle tracking echocardiography compared to late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) imaging in patients with acute myocarditis and normal global LVEF., Methods and Results: 31 patients (group 1) with the diagnosis of acute myocarditis confirmed by CMR according to the Lake Louise criteria and 20 healthy controls (group 2) were analyzed including global longitudinal strain (GLS) and regional longitudinal strain (RLS) derived by the bull's eye plot. Although preserved LVEF was present in both groups, GLS was significantly lower in patients with acute myocarditis (group 1: GLS - 19.1 ± 1.8% vs. group 2: GLS - 22.1 ± 1.7%, p < 0.001). Compared to controls, lower RLS values were detected predominantly in the lateral, inferolateral, and inferior segments in patients with acute myocarditis. Additionally RLS values were significantly lower in segments without LGE., Conclusion: In patients with acute myocarditis and preserved LVEF, a significant reduction of GLS compared to healthy subjects was detected. Further RLS adds important information to the localization and extent of myocardial injury., (© 2021. The Author(s).)

Objective: To better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD)., Methods: We compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature., Results: KD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s.d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s.d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s.d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients., Conclusion: On clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)