Treatment Of Myocarditis Research Articles

Presentations, Diagnosis, and Treatment of Post-COVID Viral Myocarditis in the Inpatient Setting: A Narrative Review.

While coronavirus disease 2019 (COVID-19) infection rates have declined, and mortality outcomes have improved with vaccines, targeted antiviral therapies, and improved care practices over the course of the pandemic, post-acute sequelae of SARS CoV-2 infection (PASC, also referred to as "long COVID") has emerged as a significant concern, even among individuals who appear to have fully recovered from their initial infection. Acute COVID-19 infection is associated with myocarditis and cardiomyopathies, but the prevalence and presentation of post-infectious myocarditis are unclear. We provide a narrative review of post-COVID myocarditis, including symptoms and signs, physical exam findings, diagnosis, and treatment strategies. Post-COVID myocarditis has a wide range of presentations, from very mild symptoms to severe ones that can include sudden cardiac death. Several studies have noted what appears to be a bimodal distribution of affected patients, with individuals under age 16 (particularly males) most affected, followed by those over age 50. The gold standard of diagnosis for myocarditis is endomyocardial biopsy and cardiac magnetic resonance imaging with a confirmed diagnosis of COVID-19. However, if these are not available, other studies such as electrocardiogram, echocardiography, and inflammatory markers can guide clinicians to diagnose post-COVID myocarditis when appropriate. Treatment is largely supportive and may include oxygen therapy, intravenous hydration, diuretics, steroids, and antivirals. Post-COVID myocarditis is rare but important to recognize as more patients present with this condition in the inpatient setting.

Experience of successful treatment of fulminant myocarditis

The incidence of myocarditis in children ranges from 0.026 to 2 cases per 100,000 children. It is known that approximately 0.05 % of all hospitalizations of children are associated with myocarditis. The total mortality of children from myocarditis in the acute period reaches 7–17 %, and in the fulminant course — up to 30 %. Currently, there is a tendency to decrease mortality, which is associated with the acquisition of new knowledge and the introduction of new methods of treatment of myocarditis, according to modern clinical recommendations. This report presents a case of a favorable outcome of fulminant myocarditis in a 13-year-old 4-month-old girl who became acutely ill. Clinical manifestations of the onset of the disease, issues of differential diagnosis, treatment tactics at the stages of routing are described.

Revitalizing myocarditis treatment through gut microbiota modulation: unveiling a promising therapeutic avenue.

Numerous studies have demonstrated that gut microbiota plays an important role in the development and treatment of different cardiovascular diseases, including hypertension, heart failure, myocardial infarction, arrhythmia, and atherosclerosis. Furthermore, evidence from recent studies has shown that gut microbiota contributes to the development of myocarditis. Myocarditis is an inflammatory disease that often results in myocardial damage. Myocarditis is a common cause of sudden cardiac death in young adults. The incidence of myocarditis and its associated dilated cardiomyopathy has been increasing yearly. Myocarditis has gained significant attention on social media due to its association with both COVID-19 and COVID-19 vaccinations. However, the current therapeutic options for myocarditis are limited. In addition, little is known about the potential therapeutic targets of myocarditis. In this study, we review (1) the evidence on the gut-heart axis, (2) the crosslink between gut microbiota and the immune system, (3) the association between myocarditis and the immune system, (4) the impact of gut microbiota and its metabolites on myocarditis, (5) current strategies for modulating gut microbiota, (6) challenges and future directions for targeted gut microbiota in the treatment of myocarditis. The approach of targeting the gut microbiota in myocarditis is still in its infancy, and this is the study to explore the gut microbiota-immune system-myocarditis axis. Our findings are expected to pave the way for the use of gut microbiota as a potential therapeutic target in the treatment of myocarditis.

A combination of Sophoraflavescens alkaloids and Panaxquinquefolium saponins attenuates coxsackievirus B3‑induced acute myocarditis in mice via NF‑κB signaling.

Timely treatment of viral myocarditis (VMC), a form of cardiac inflammation caused by viral infections, can reduce the occurrence of dilated cardiomyopathy and sudden death. Our previous study demonstrated the anti-inflammatory and anti-fibrotic effects of KX, a combination of Sophora flavescens alkaloids and Panax quinquefolium saponins, on an autoimmune myocarditis model in vivo. The present study explored the effects of KX on coxsackievirus B3 (CVB3)-induced acute VMC in mice. Mice were randomly divided into four groups: Control, VMC, KX-high (275 mg/kg) and KX-low (138 mg/kg). Mice in the VMC, KX-high and KX-low groups received injections of CVB3 to establish the VMC model, and those in the KX-high and KX-low groups also received KX by gavage (10 ml/kg) 2 h after virus injection until euthanasia was performed on day 7 or 21. Mice in the control group received an equal KX volume of purified water. The levels of lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTn-I), IL-1β, IL-6, TNF-α and high-sensitive C-reactive protein (hs-CRP) in mouse serum was measured using ELISA. Myocardial tissue structure and degree of injury were observed using hematoxylin and eosin staining. Western blotting and reverse transcription-quantitative PCR were performed to detect the expression levels of NF-κB pathway-related mRNA and protein in myocardial tissue. The results showed that the inflammation and myocardial damage levels of the mice in the VMC group were higher at 7 days than those at 21 days. At both 7 and 21 days, KX decreased the serum CK-MB, LDH, cTn-I, IL-6, TNF-α and hs-CRP levels, and inhibited NF-κB pathway-related mRNA and protein expression in the myocardium of mice. These findings indicated that KX may reduce the inflammatory response and attenuate the pathological damage in the acute and subacute phases of CVB3-induced VMC through the NF-κB pathway.

B-arrestin deletion abrogates the innate immune response in murine CVB3 myocarditis

β-arrestins (βarrs), initially discovered as desensitizers of GPCR signaling, are now known to function as intracellular scaffolds and signaling transducers mediating a wide array of signaling cascades including immune responses to inflammatory stimuli. An important cause of immune cell infiltration and cardiac inflammation are viral pathogens such as enterovirus coxsackievirus B3 (CVB3) induced myocarditis. While viral myocarditis is a leading cause of dilated cardiomyopathy, the precise molecular mechanisms for the acute immune response to CVB3 infection are not well understood. Given the important role for βarrs in the acute immune response, we tested the hypothesis that βarrs are necessary for the activation of the acute immune response and mediate the progression and severity of cardiotropic CVB3-induced myocarditis in mice. Five to 7-week-old mice devoid of βarr1 (βarr1 KO) or βarr2 (βarr2 KO) were infected intraperitoneally with 1x103-1x104 plaque forming units (PFU) of CVB3 per animal. Wild type (WT) C57BL/6 mice infected with CVB3 were used as controls. The survival rate 7 days post infection (dpi) was significantly improved in male βarr1 KOs (80%) and βarr2 KOs (75%) compared to male WT control mice (35%, p=0.013). Female WT, βarr1 KO, and βarr2 KO mice showed similar survival rates 7 dpi., ranging from 70% to 80%. Early mortality among all groups before 5 dpi was associated with high viral titers (~6.0 ± 0.5 log10PFU/mg) in the liver compared to mortality after 5 dpi (~2.4 ± 1.7 log10PFU/mg) as determined by plaque assay. Viral titers in the heart (WT=3.7 ± 0.9 log10PFU/mg, βarr1KO=3.6 ± 1.3 log10PFU/mg, βarr2KO=3.5 ± 1.2log10PFU/mg) were similar among all groups suggesting that βarrs are not involved in viral replication. Morphometric analysis showed similar weight loss (~18%) across all groups at 7 dpi corroborated by viral cardiac PFU. Immunofluorescent staining of the heart with the pan-inflammatory marker, CD45, revealed high immune cell infiltration in infected WT mice (34.2% ± 4.5%), whereas immune cell infiltration was significantly blunted in infected βarr1 KO (6.0% ± 1.1%; p<0.0001) and βarr2 KO (8.5% ± 0.9%; p<0.0001) mice. The degree of immune cell infiltration in hearts of infected WT mice was directly correlated with an increase in heart viral titer, whereas immune cell infiltration remained blunted across a broad range of heart viral titers in both βarr1 and 2 KO mice. The blunted immune response in both βarr KOs compared to WT infected controls was consistent across multiple immune cell markers including CD4 for helper T cells and CD11b for innate immune cells. In conclusion, we demonstrate that βarrs are necessary for immune cell recruitment to the heart in CVB3 myocarditis and deletion of βarrs in male mice may be cardioprotective as indicated by an increase in survival rate. These data suggest that βarrs may serve as potential therapeutic targets in the treatment of acute viral myocarditis. This work was supported by the National Institutes of Health Grants HL056687 (to H.A.R.). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis

JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis

Clinical and Economic Evaluation of Impella Treatment for Fulminant Myocarditis - A Preliminary Retrospective Cohort Study in Japan.

Fulminant myocarditis (FM) is rare but has an extremely poor prognosis. Impella, a catheter-based heart pump, is a new therapeutic strategy, but reports regarding its health economics are lacking. This retrospective cohort study compared Impella treatment (Group I) with existing treatments (Group E) using medical data collected from October 2017 to September 2021, with a 1-year analysis period. Cost-effectiveness indices were life-years (LY; effect index) and medical fee amount (cost index). Results were validated using probabilistic sensitivity analysis. The incremental cost-effectiveness ratio (ICER) was calculated using quality-adjusted LY (QALY) and medical costs. Each group included 7 patients, and more than half (57.1%) received combined Impella plus extracorporeal membrane oxygenation. There was no significant difference between Groups I and E in 1-year mortality rates (28.6% vs. 57.1%, respectively) or LY (mean [±SD] 163.1±128.3 vs. 107.8±127.3 days, respectively), but mortality risk was significantly lower in Group I than Group E (95% confidence interval 0.02-0.96; P<0.05). Compared with Group E, Group I had higher total costs (9,270,597±4,121,875 vs. 6,397,466±3,801,364 JPY/year; P=0.20) and higher cost-effectiveness (32,443,987±14,742,966 vs. 92,637,756±98,225,604 JPY/LY; P=0.74), which was confirmed in the sensitivity analysis. ICER probability distribution showed 23.2% and 51.5% reductions below 5 million and 10 million JPY/QALY, respectively. Impella treatment is more cost-effective than conventional FM treatments. Large-scale studies are needed to validate the added effects and increasing costs.

Trends and characteristics of COVID-19 and cardiovascular disease related studies.

Introduction: The new coronavirus has caused a pandemic that has infected hundreds of millions of people around the world since its outbreak. But the cardiovascular damage caused by the new coronavirus is unknown. We have analyzed the current global scenario and the general pattern of growth. After summarizing the known relationship between cardiovascular diseases and new coronary pneumonia, relevant articles are analyzed through bibliometrics and visualization. Methods: Following our pre-designed search strategy, we selected publications on COVID-19 and cardiovascular disease in the Web of Science database. In our relevant bibliometric visualization analysis, a total of 7,028 related articles in the WOS core database up to 20th October 2022 were summarized, and the most prolific authors, the most prolific countries, and the journals and institutions that published the most articles were summarized and quantitatively analyzed. Results: SARS-CoV-2 is more infectious than SARS-CoV-1 and has significant involvement in the cardiovascular system in addition to pulmonary manifestations, with a difference of 10.16% (20.26%/10.10%) in the incidence of cardiovascular diseases. The number of cases increases in winter and decreases slightly in summer with temperature changes, but the increase in cases tends to break out of seasonality across the region as mutant strains emerge. The co-occurrence analysis found that with the progress of the epidemic, the research keywords gradually shifted from ACE2 and inflammation to the treatment of myocarditis and complications, indicating that the research on the new crown epidemic has entered the stage of prevention and treatment of complications. Conclusion: When combined with the current global pandemic trend, how to improve prognosis and reduce human body damage could become a research focus. At the same time, timely detection, prevention, and discovery of new mutant strains have also become key tasks in the fight against the epidemic, and full preparations have been made to prevent the spread of the next wave of mutant strains, and still need to continue to pay attention to the differential performance of the variant "omicron."

Leitlinie Myokarditis der Deutschen Gesellschaft für Pädiatrische Kardiologie

This consensus statement presents updated recommendations on diagnosis and treatment of myocarditis in childhood.

Varicella-Zoster Virus Myocarditis: Early Clinical Diagnosis and Outcome.

Varicella-zoster virus (VZV) is a viral infection that causes chickenpox and shingles. Although it is usually self-limiting, it can lead to severe complications, especially in pediatric and immunocompromised patients. VZV was first discovered as a cause of myocarditis in 1953. In this review article, we aim to investigate the early clinical diagnosis of myocarditis in VZV infections and the efficacy of the VZV vaccine in preventing myocarditis. The literature search was done using PubMed, Google Scholar, and Sci-Hub databases. A high VZV mortality rate was noted among adults, infants, and immunocompromised patients. The early diagnosis and treatment of VZV myocarditis can reduce mortality.

Creatine phosphate improves myocardial function and myocardial enzyme profile in children with myocarditis

ABSTRACT Myocarditis in children is more common in clinical practice, which can cause different degrees of cardiac function damage. We investigated the effects of creatine phosphate in the treatment of myocarditis in children. Children in the control group were treated with sodium fructose diphosphate, and children in the observation group were treated with creatine phosphate on the basis of the control group. After treatment, the myocardial enzyme profile and cardiac function of children in the observation group were better than the control group. The total effective rate of treatment for children in the observation group was higher than that in the control group. In conclusion, creatine phosphate could significantly improve myocardial function, improve myocardial enzyme profile and reduce myocardial damage in children with pediatric myocarditis and had a high safety of use, which was worthy of clinical promotion.

2023 TERMIS – AMERICAS Conference &amp; Exhibition Boston Marriott Copley Place April 11–14, 2023

2023 TERMIS – AMERICAS Conference &amp; Exhibition Boston Marriott Copley Place April 11–14, 2023

Use of mechanical circulatory support guided by imaging modalities in treatment of influenza myocarditis: a case report

Use of mechanical circulatory support guided by imaging modalities in treatment of influenza myocarditis: a case report

Integrating network pharmacology and experimental validation to decipher the mechanism of action of Jingfang Granule in the treatment of viral myocarditis.

This study investigated the mechanisms of Jingfang Granule (JFG) in viral myocarditis (VMC) treatment via network pharmacology-based approach combined with molecular docking and validated the results through in vitro and in vivo experiments. The chemical composition of JFG and its therapeutic targets was queried in Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The targets related to VMC were retrieved from the disease database, and the overlapping targets were screened. Based on the STRING database, a protein-protein interaction network was constructed. Cytoscape software was used to construct the "component-target-disease" interaction network for visualization. GO and KEGG pathway enrichment analyses were performed using Metascape data. Molecular docking was performed using PyMoL2.3.0 and AutoDock Vina software programs. The target genes were further verified in vitro and in vivo. JFG contains 88 active components. The main biological targets of JFG in VMC include quercetin, luteolin, and kaempferol. The molecular docking results showed that the three key targets showed strong binding properties with both the height components of the molecular docking interaction energies. The results of experimental verification results showed that JFG may be used to treat VMC mainly by down-regulating inflammatory factors TNF-α and NF-κB and inhibiting myocardial apoptosis. The results support the network pharmacological data. JFG reduces myocardial inflammation and myocardial cell apoptosis in VMC and protects myocardial tissue.

Successful treatment of two cases of acute myocarditis with colchicine.

Colchicine is an FDA-approved medicine that has been used for many years to prevent and treat gout flares as well as familial mediterranean fever. It is also used off-label to treat pericarditis, calcium pyrophosphate illness, and Behçet's syndrome. There are additional studies on the use of colchicine, which is accepted as the standard treatment for pericarditis in adults, post-pericardiotomy syndrome, post-operative and post-ablation atrial fibrillation, coronary artery disorders, prior to percutaneous coronary procedures, and myocarditis. Colchicine appears to be a promising oral cardiovascular treatment targeting the inflammatory axis, owing to its low cost and moderate side-effect profile. Our aim is to emphasise that colchicine treatment, which has a strong and effective anti-inflammatory effect profile, should be kept in mind in addition to conventional treatment in childhood myocarditis.

Corticosteroid in anti-inflammatory treatment of pediatric acute myocarditis: a systematic review and meta-analysis

BackgroundTo evaluate the efficacy of corticosteroids in anti-inflammatory treatment of pediatric acute myocarditis.MethodsWe searched PubMed, Embase and Cochrane library and included studies before October 2022 for clinical trials, observational studies and retrospective studies which reported on children with acute myocarditis treated with corticosteroid anti-inflammatory therapy. The quality of the clinical trials was assessed by Jadad score as an exclusion criterion.ResultsThis systematic review included 6 studies involving 604 pediatric patients with acute myocarditis. Corticosteroid therapy was not associated with reduced risk of mortality due to acute myocarditis (P = 0.53; RR = 0.87; 95% CI = 0.58 to 1.33) compared to anti-failure treatment. There was a significant improvement in pediatric patients’ left ventricular function measured by left ventricular ejection fraction in the group on corticosteroid anti-inflammatory treatment (P = 0.0009; MD = 11.93%; 95% CI = 4.87% to 18.99%). No conclusion can be drawn due to the high heterogeneity in meta-analyses of risk of getting to a clinical endpoint (death or heart transplantation) and changes in left ventricular end-diastolic diameter (LVEDD).ConclusionsCorticosteroid anti-inflammatory therapy in pediatric acute myocarditis patients showed no significant improvement in reducing the risk of mortality, but showed significant improvement in LVEF.

Immunosuppressive Therapy of Biopsy-Proven, Virus-Negative, Autoimmune/Immune-Mediated Myocarditis-Focus on Azathioprine: A Review of Existing Evidence and Future Perspectives.

The use of immunosuppressive therapy (IT) in biopsy-proven, autoimmune/immune-mediated (AI), virus-negative myocarditis has become the standard of care. In particular, according to recent guidelines, azathioprine (AZA), in association with steroids, is a cornerstone of first-line therapy regimens. IT may have a crucial impact on the natural history of AI myocarditis, preventing its progression to end-stage heart failure, cardiovascular death, or heart transplantation, provided that strict appropriateness and safety criteria are observed. In particular, AZA treatment for AI virus-negative myocarditis requires the consideration of some crucial aspects regarding its pharmacokinetics and pharmacodynamics, as well as a high index of suspicion to detect its overt and/or subclinical side effects. Importantly, besides a tight teamwork with a clinical immunologist/immuno-rheumatologist, before starting IT, it is also necessary to carry out a careful "safety check-list" in order to rule out possible contraindications to IT and minimize patient's risk. The aim of this review is to describe the pharmacological properties of AZA, as well as to discuss practical aspects of its clinical use, in the light of existing evidence, with particular regard to the new field of cardioimmunology.

Early identification, diagnosis and treatment of COVID-19 related myocarditis, save more lives

新型冠状（新冠）病毒奥密克戎毒株正在人群中迅速传播，由于新冠病毒能结合心肌细胞表面的血管紧张素2受体而表现出嗜心肌性，临床上新冠病毒相关心肌炎并不少见，且多为普通型，少数可进展为暴发性心肌炎。“过度免疫”和“炎症风暴”仍然是其核心发病机制。新冠病毒相关心肌炎的早期识别和诊断对后期治疗非常关键，需根据病情轻重分层管理，普通型强调抗病毒、β受体阻断剂和改善心肌代谢药物的治疗，暴发性心肌炎仍然强调“以生命支持为依托的综合救治方案”，做到“极早识别、极早诊断、极早预判和极早救治”，尽最大努力挽救更多生命。.

Inhibition of phosphoglycerate kinase 1 attenuates autoimmune myocarditis by reprogramming CD4+ T cell metabolism.

CD4+ T cells are the major drivers of cardiac-specific autoimmunity in myocarditis, specifically Th1, Treg, and most significant Th17 cells. But the molecular mechanisms of their activation remain unclear. We aimed to elucidate the regulatory role of phosphoglycerate kinase 1 (PGK1) in CD4+ T cells and experimental autoimmune myocarditis (EAM). EAM was induced in BALB/c mice by subcutaneous injections with alpha myosin heavy chain peptide emulsified in complete Freund's adjuvant. Single-cell sequencing analysis found that glycolysis and PGK1 expression were elevated in cardiac CD4+ T and Th17 cells from myocarditis mice. Mice treated with PGK1 inhibitor NG52 showed less cardiac inflammation and fibrosis and better contractile function, as well as reduced cardiac infiltrating Th17 and Th1 cells and increased proportion of Treg. NG52 suppressed CD4+ T cell activation and differentiation of mice and myocarditis patients in vitro. Mechanistically, inhibition of PGK1 suppressed glycolytic activity and decreased pyruvate dehydrogenase kinase 1 (PDHK1) phosphorylation, thereby increasing reactive oxygen species (ROS) production in mitochondria and thus preventing Th17 cell differentiation. PGK1 may act as a key metabolic regulator of CD4+ T cell differentiation and regulates Th17 cell differentiation by regulating glycolysis and the PDHK1-ROS axis. Targeting PGK1 might be a promising strategy for the treatment of myocarditis.

423 - Successful treatment of parechovirus meningoencephalitis and myocarditis in two neonates

423 - Successful treatment of parechovirus meningoencephalitis and myocarditis in two neonates