Transplantation of Fibroblast Sheets with Blood Mononuclear Cell Culture Exerts Cardioprotective Effects by Enhancing Anti-Inflammation and Vasculogenic Potential in Rat Experimental Autoimmune Myocarditis Model

Fulminant myocarditis causes impaired cardiac function, leading to poor prognosis and heart failure. Cell sheet engineering is an effective therapeutic option for improving cardiac function. Naïve blood mononuclear cells (MNCs) have been previously shown to enhance the quality and quantity of cellular fractions (QQMNCs) with anti-inflammatory and vasculogenic potential using the one culture system. Herein, we investigated whether autologous cell sheet transplant with QQMNCs improves cardiac function in a rat model with experimental autoimmune myocarditis (EAM). Fibroblast sheets (F-sheet), prepared from EAM rats, were co-cultured with or without QQMNCs (QQ+F sheet) on temperature-responsive dishes. QQ+F sheet induced higher expression of anti-inflammatory and vasculogenic genes (Vegf-b, Hgf, Il-10, and Mrc1/Cd206) than the F sheet. EAM rats were transplanted with either QQ+F sheet or F-sheet, and the left ventricular (LV) hemodynamic analysis was performed using cardiac catheterization. Among the three groups (QQ+F sheet, F-sheet, operation control), the QQ+F sheet transplant group showed alleviation of end-diastolic pressure–volume relationship on a volume load to the same level as that in the healthy group. Histological analysis revealed that QQ+F sheet transplantation promoted revascularization and mitigated fibrosis by limiting LV remodeling. Therefore, autologous QQMNC-modified F-sheets may be a beneficial therapeutic option for EAM.

Fulminant Myocarditis Following COVID-19 Vaccination: A Case Report

Background The BNT162b2 vaccine received emergency use authorization from the U.S. Food and Drug Administration for the prevention of severe COVID-19 infection. We report a case of biopsy and MRI-proven severe myocarditis that developed in a previously healthy individual within days of receiving the first dose of the BNT162b2 COVID-19 vaccine. Case Summary An 80-year-old female with no significant cardiac history presented with cardiogenic shock and biopsy-proven fulminant myocarditis within 12 days of receiving the BNT162b2 COVID-19 vaccine. She required temporary mechanical circulatory support, inotropic agents and high-dose steroids for stabilization and management. Ultimately her cardiac function recovered, and she was discharged in stable condition after 2 weeks of hospitalization. A repeat cardiac MRI 3 months after her initial presentation demonstrated stable biventricular function and continued improvement in myocardial inflammation. Discussion Fulminant myocarditis is a rare complication of vaccination. Clinicians should stay vigilant to recognize this rare, but potentially deadly complication. Due to the high morbidity and mortality associated with COVID-19 infection, the clinical benefits of the BNT162b2 vaccine greatly outweighs the risks of complications.

Prognostic factors in children with acute fulminant myocarditis receiving venoarterial extracorporeal membrane oxygenation

BackgroundPediatric acute fulminant myocarditis (AFM) is a very dangerous disease that may lead to acute heart failure or even sudden death. Previous reports have identified some prognostic factors in adult AFM; however, there is no such research on children with AFM on venoarterial extracorporeal membrane oxygenation (VA-ECMO). This study aimed to find relevant prognostic factors for predicting adverse clinical outcomes.MethodsA retrospective analysis was performed in an affiliated university children’s hospital with consecutive patients receiving VA-ECMO for AFM from July 2010 to November 2020. These children were classified into a survivor group (n=33) and a non-survivor group (n=8). Patient demographics, clinical events, laboratory findings, and electrocardiographic and echocardiographic parameters were analyzed.ResultsPeak serum creatinine (SCr) and peak creatine kinase isoenzyme MB during ECMO had joint predictive value for in-hospital mortality (p=0.011, AUC=0.962). Based on multivariable logistic regression analysis, peak SCr level during ECMO support was an independent predictor of in-hospital mortality (OR=1.035, 95% CI 1.006 to 1.064, p=0.017, AUC=0.936, with optimal cut-off value of 78 μmol/L).ConclusionTissue hypoperfusion and consequent end-organ damage ultimately hampered the outcomes. The need for left atrial decompression indicated a sicker patient on ECMO and introduced additional risk for complications. Earlier and more cautious deployment would likely be associated with decreased risk of complications and mortality.

Case Report: Fulminant Myocarditis Successfully Treated With Extracorporeal Membrane Oxygenation in Ikeda Strain Orientia tsutsugamushi Infection

Scrub typhus is an acute zoonotic febrile illness caused by Orientia tsutsugamushi having a specific geographic endemic area. This infection could be complicated with multi-organ involvement including myocarditis with variable severity. Here, we report a rare case of scrub typhus with biopsy-proven acute fulminant myocarditis which progressed very rapidly to cardiac arrest and was treated successfully with extracorporeal cardiopulmonary resuscitation. Clinicians should be alert to possible rapid progression of scrub typhus myocarditis to fulminant form and be prepared for close monitoring and temporary mechanical support if indicated.

Influenza myocarditis in paediatric patients

Acute myocarditis is a rare but potentially fatal disease. Endomyocardial biopsy and histologic examination are key to an accurate diagnosis. Despite being an uncommon cause, Influenza A and B viruses are a well-documented aetiology. Myocarditis may complicate about 0 to 10% of influenza virus infections (0.4 to 5% in paediatric cases). The clinical presentation varies widely, from ischemic-like chest pain to fulminant myocarditis with acute hemodynamic compromise, requiring mechanical circulatory support, with high mortality in the acute phase. We report a series of paediatric patients with myocarditis due to Influenza virus, to emphasize the importance of considering this uncommon aetiology.

Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.

Case Report: Cardiac Toxicity Associated With Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1–2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0–10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.