Treatment Of Viral Myocarditis Research Articles

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

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

Effect of Yangxin Huoxue Jiedu recipe on inflammatory factors and oxidative stress on viral myocarditis in children.

This observation purposed to investigate the effect of the Yangxin Huoxue Jiedu formula on children with viral myocarditis and its effect on inflammatory factors and oxidative response. A total of 121 children with viral myocarditis were randomly divided into two groups, namely the control group (N = 60) and the traditional Chinese medicine group (N = 61). The control group was mainly treated with routine therapy, while the traditional Chinese medicine group was treated with Yangxin Huoxue Jiedu recipes based on the control group. The creatine kinase, creatine kinase myocardial isoenzyme, aspartate aminotransferase, lactic dehydrogenase, hydroxybutyrate dehydrogenase, cardiac troponin I, brain natriuretic peptide, interleukin-6, interleukin-8, and tumour necrosis factor-alpha, superoxide dismutase and malondialdehyde in viral myocarditis patients were tested to estimate the myocardial function, inflammation, and oxidative situation. After Yangxin Huoxue Jiedu treatment, 15 cases were recovered, 20 were excellent, and 21 were effective, which had a significant difference from the control group. The concentration of creatine kinase, creatine kinase myocardial isoenzyme, aspartate aminotransferase, lactic dehydrogenase, hydroxybutyrate dehydrogenase, cardiac troponin I and brain natriuretic peptide was decreased in the traditional Chinese medicine group. The levels of interleukin-6, interleukin-8, and tumour necrosis factor-alpha in the traditional Chinese medicine group were significantly lower than those in the control group. Superoxide dismutase was higher and malondialdehyde was lower than those in the control group. The use of Yangxin Huoxue Jiedu in the treatment of viral myocarditis has a definite clinical effect, which could improve myocardial function, reduce body inflammation, and promote oxidative recovery.

Identification of the communal pathogenesis and immune landscape between viral myocarditis and dilated cardiomyopathy.

Studies have confirmed that viral myocarditis (VMC) is one of the risk factors for dilated cardiomyopathy (DCM). The molecular mechanisms underlying the progression from VMC to DCM remain unclear and require further investigation. The mRNA microarray datasets GSE57338 (DCM) and GSE1145 (VMC) were obtained from the Gene Expression Omnibus database. The candidate key genes were further screened using weighted correlation network analysis (WGCNA), protein-protein interaction and external dataset validation, and the correlation between the candidate key genes and immune cells and the signalling pathways of the candidate key genes were observed by enrichment analysis and immune infiltration analysis. The expression of key genes was validated in the external dataset GSE35182. The crosstalk genes between DCM and VMC were mainly enriched in 'transcriptional misregulation in cancer', 'FoxO signalling pathway', 'AGE-RAGE signalling pathway in diabetic complications', 'thyroid hormone signalling pathway', 'AMPK signalling pathway', and other signalling pathways. The immune infiltration analysis indicated that VMC was mainly associated with resting dendritic cells and M0 macrophages, while DCM was mainly associated with monocytes, M0 macrophages, CD8+ T cells, resting CD4 memory T cells, naive CD4+ T cells, and resting mast cells. In DCM-related dataset GSE57338 and VMC-related dataset GSE1145, a total of 18 candidate key genes were differentially expressed. BLC6, FOXO1, and UBE2M were identified as the key genes that lead to the progression from VMC to DCM by GSE35182. Three key genes (BLC6, FOXO1, and UBE2M) were identified and provided new insights into the diagnosis and treatment of VMC with DCM.

Jingfang Granule mitigates Coxsackievirus B3-induced myocardial damage by modulating mucolipin 1 expression

Ethnopharmacological relevanceJingfang Granules (JFG) originate from the traditional herbal formula Jingfang Baidu powder. It has the effects of inducing sweating and dispelling wind. It is a classic medication used for treating external pathogenic factors and viral diseases. However, the therapeutic mechanism of JFG for viral myocarditis needs further clarification. Aim of the studyThis study aimed to explore the therapeutic efficacy of JFG on coxsackievirus B3-induced viral myocarditis (VMC), along with the elucidation of its underlying mechanisms. Materials and methodsC57 BL/6JNifdc mice were divided randomly into several groups: control, model, Jingfang Granule groups (0.23, 0.46, and 0.69 g/20g, respectively), and a positive group (oseltamivir, 19.33 mg/kg). Following the establishment of the VMC model, the mice underwent an 8 -week treatment regimen. Pathological alterations in cardiac tissues and inflammatory protein expression were monitored. Differential gene analysis was conducted utilizing transcriptomic techniques. The differential gene mucolipin 1 (Mcoln1) was knocked down by transfection with siRNA in H9C2 cell, and investigative techniques such as immunoblotting, qRT-PCR, immunofluorescence, JC-1 staining, reactive oxygen species (ROS) detection, and mitochondrial stress testing were employed to examine its mechanism of action. ResultsJFG significantly mitigates the pathological damage observed in the cardiac tissues of CVB3-induced VMC mice and attenuates the expression of inflammatory genes. Subsequently, differentially expressed genes are identified through transcriptomic analysis and validated via PCR. Among these, the upregulation of Mcoln1 promotes autophagy, facilitating the clearance of damaged mitochondria and excessive ROS. This has been substantiated through in vitro experiments. Excessive ROS precipitates a reduction in mitochondrial membrane potential, instigating cell apoptosis. In accordance with TUNEL staining results, JFG acts to inhibit cell apoptosis. To ascertain whether Mcoln1 is a crucial target for JFG in treating VMC, Mcoln1 was suppressed in H9C2 cells. The suppression of Mcoln1 hinders the elevation in autophagy levels post-JFG treatment, obstructs the enhancement of mitochondrial function, and impedes the clearance of ROS. Furthermore, the inhibitory effect of JFG on cell apoptosis is attenuated. ConclusionThe research findings indicate that JFG has a protective effect on CVB3-induced H9C2 cell injury. JFG may exert its effects in VMC treatment by enhancing autophagy to suppress cell apoptosis through the mitochondrial pathway, thereby counteracting cell damage.

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.

Trehalose induces B cell autophagy to alleviate myocardial injury via the AMPK/ULK1 signalling pathway in acute viral myocarditis induced by Coxsackie virus B3.

Viral myocarditis (VMC) is the main cause of sudden acute heart failure and cardiac death in adolescents; however, treatment for VMC is limited. Trehalose is a natural non-reductive disaccharide that protects against cardiovascular diseases by inducing autophagy. The protective effect of trehalose on VMC and the specific mechanism remains unclear. In this study, we established a VMC mouse model, treated with trehalose in vivo, and cultured B cells from VMC mice with trehalose in vitro to elucidate the effect of trehalose on B cells in acute VMC. Trehalose alleviated myocardial injury in VMC mice and increased the number of autophagosomes, LC3II/LC3I ratio, and expression level of LAMP2, whereas it decreased the expression of p62 in VMC-B cells. Bafilomycin A1 suppressed VMC-B cell autophagy induced by trehalose. At the mechanistic level, trehalose treatment significantly upregulated the phosphorylation of AMPK and ULK1 in VMC-B cells. Dorsomorphin and SBI-0206965 abolished the increased phosphorylation level and altered the expression levels of autophagy-related proteins. In conclusion, trehalose alleviates myocardial inflammatory damage of VMC by inducing B cell autophagy, mediated by the AMPK/ULK1 signalling pathway. Thus, trehalose may be a potentially useful molecule for alleviating myocardial injury in VMC.

424 Considerations Mid-Translation of a Novel Extracellular Vesicle Product in Myocarditis

OBJECTIVES/GOALS: Myocarditis is an inflammatory cardiomyopathy commonly caused by viral infections. The residual burden of this disease after guideline-based therapies is substantial, as there are no pathway-specific therapies. Our long-term goal is to find and translate treatments that reduce acute myocarditis severity and prevent progression of disease. METHODS/STUDY POPULATION: Of available therapies, extracellular vesicles (EVs) are ideally suited to the task of simultaneous, specific reprogramming of multiple pathogenesis mechanisms necessary in diseases like myocarditis, without similar immunosuppressive risks as their pharmacologic counterparts. We obtained plasma from healthy men and women and isolated nanoparticles, which were analyzed for physiochemical markers of human EVs. After confirming presence of EVs, we injected these plasma-derived extracellular vesicles (PEV) into male BALB/c mice vs. PBS control intraperitoneally on days -1, 0, 1 of viral infection (day 0) in a highly translational, mouse model of myocarditis. Hearts were examined at day 10 at the peak of acute myocarditis, using standard histological and cell composition analyses. RESULTS/ANTICIPATED RESULTS: Mice treated with PEV had significantly less myocardial inflammation both histologically and by gene expression of immune markers in the heart. The immunoregulation by PEV treatment decreased many key components of innate immune response networks that are known to be upregulated during acute myocarditis: TLR4+ mast cells and macrophages and complement. These pathways drive the profibrotic gene and protein changes that lead to remodeling, fibrosis, and disease progression observed in patients. We anticipate that when we analyze later timepoints in this model (day 35 post infection) which are normally associated with development of chronic myocarditis, dilated cardiomyopathy, we will see reduction of this fibrosis and of damage-associated changes. DISCUSSION/SIGNIFICANCE: These data suggest that EVs from plasma may be a novel treatment for viral myocarditis, but translation of EVs is hindered by their heterogeneity. We demonstrate characterization both physiochemically and functionally in a well-defined model. Such practices are necessary as these contemporary products challenge current regulation standards.

Pharmacoeconomic evaluation of Qidong Yixin Oral Liquid in treatment of viral myocarditis (Qi-Yin deficiency syndrome) with TreeAge Pro

To evaluate the pharmacoeconomic value of Qidong Yixin Oral Liquid in the treatment of viral myocarditis(Qi-Yin deficiency syndrome) by supplementing Qi, nourishing the heart, calming the mind, and relieving palpitation, the present study performed the Meta-analysis based on the published papers on Qidong Yixin Oral Liquid by AMSTAR and carried out pharmacoeconomic evaluation using TreeAge Pro by the cost-effectiveness analysis. The results showed that the quality of the included papers was good. After four weeks of treatment, Qidong Yixin Oral Liquid combined with the conventional treatment regimen was superior to the conventional treatment in improving creatine kinase isoenzyme, and the difference was statistically significant. Furthermore, the treatment cost was also higher than that of conventional treatment, with an incremental cost-effectiveness ratio of CNY 95.89, accounting for 0.30% of per capita disposable income. The results of sensitivity analysis showed that the research results were robust. Therefore, based on the assumption that the per capita disposable income in 2020 was the threshold of patients' willingness to pay, it is more economical for patients with viral myocarditis to use Qidong Yixin Oral Liquid combined with conventional secondary prevention regimen than conventio-nal secondary prevention regimen alone. The economic evaluation of Qidong Yixin Oral Liquid in the treatment of viral myocarditis will help physicians and patients choose optimal treatment options, improve rational clinical medication, and provide references for the efficient allocation and utilization of medical resources in China.

Symptomatology, prognosis, and clinical findings of COVID 19 induced myocarditis: a systematic review

Abstract Background With the advent of the novel coronavirus (COVID-19) in December 2019, numerous case studies have been reported on its impact on cardiac cells, and we purpose to perform a systematic review that explains the symptomatology, prognosis, and clinical findings of COVID-19-related myocarditis patients. Methods PRISMA guidelines were employed and peer–reviewed journals in English related to COVID – 19 were included. Exclusion criteria included <50 y, known heart problems. Age criteria was guided by prior systematic report by Kariyanna et al (2020). Search engines included Pubmed, Google scholar, Cochrane Central and Web of Science database using “SARS-CoV-2” or “COVID 19” and “myocarditis”. The data were analyzed and synthesized qualitatively using MS Excel PIVOT and quality was rated using the “Research and Quality Scoring Method” by Sackett and Haynes, the Jadad scale, and the items published by Cho and Bero (Han et al., 2011). Results A total of 22 studies on 37 patients were included; 6 were confirmed myocarditis while the rest have possible myocarditis. Among all these 62% were male and showing dominance. The most common presenting symptoms appear to be fever, chest pain, shortness of breath, and cough. Most of the patients have shown elevation in cardiac biomarkers (troponin levels, CRP, CK level, CK-MB, NT-pro BNP). Electrocardiogram changes include sinus rhythm, tachycardia, and non specific ST - segment elevation and T wave changes. Echocardiography results commonly found were left ventricular dysfunction and increased wall thickness. CMR was performed in 8 patients, with features of reduced ejection fraction, myocardial edema, and hypokinesia, whereas biopsy has been performed among 3 patients due to the invasive nature of the procedure and common findings include inflammatory biomarkers were raised. Overall Prognosis appears to be bad in which 25% of patients were not able to survive and 75% of them were recovered. Conclusions Myocarditis-related COVID-19 mortality continues to be high and under-estimated. The patient manifestations are identical and difficult to distinguish from COVID-19-related symptoms. Just a limited number of patients undergo confirmatory tests, such as an MRI or an endomyocardial biopsy, which may not be available. Further studies are needed to confirm and quantify the actual prognosis and outcomes of patients with COVID-19 myocarditis. Moreover, available data on the usage of glucocorticoids in the coronavirus infection is controversial to our knowledge. Corticosteroid therapy is unsuccessful in the treatment of viral myocarditis, according to a Cochrane systematic review conducted in 2013. It also allows viral clearance to be overdue. Corticosteroids, on the other hand, reduce the chance of mortality for ICU patients in Wuhan. To concede, more studies, clinical trials, and duration is needed for a thorough understanding of COVID – 19, and its impact on cardiac health Funding Acknowledgement Type of funding sources: Other.

ACUTE REVERSAL OF SYSTOLIC HEART FAILURE IN A CASE OF COXSACKIEVIRUS MYOCARDITIS

TOPIC: Cardiovascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Viral Myocarditis is generally a self-limiting condition. Patients usually recover from viral myocarditis within a few weeks to months. Some patients can develop hemodynamic instability and may require critical care management. We present a unique case of acute systolic heart failure secondary to Coxsackievirus myocarditis which recovered within a few days. CASE PRESENTATION: A 19-year-old male came to ER for vomiting and abdominal pain for five days. Initial vitals were Temperature of 98 F, BP of 80/47 mm Hg HR of 124/min, and oxygen saturation of 93% on room air. EKG showed sinus tachycardia without ischemic changes. Initial labs were creatinine-2.6 mg/dl, troponin-2.15 ng/ml. CT of abdomen was unremarkable. CT of chest showed bilateral pulmonary edema and pleural effusion. Lung perfusion scan showed no perfusion defect. He did not respond to intravenous(IV) fluid. Initially it required IV vasopressor support- norepinephrine, phenylephrine, and dobutamine. Echocardiogram showed ejection fraction(EF) of 20-24% with severe global hypokinesis. COVID-19 PCR was negative. The pleural fluid study revealed transudative in nature. On day 3, he was weaned off from vasopressors. Acute kidney injury also resolved. Cytomegalovirus, HIV, autoimmune panel, and respiratory virus panel were negative. Coxsackievirus antibody came back positive. It was consistent with viral myocarditis. Patient showed clinical improvement, and we decided to repeat echocardiogram before discharge. On day 6, repeat echocardiogram showed significant improvement of EF to 54%. The patient was discharged on low dose carvedilol and lisinopril. Clinic follow up showed the patient's significant clinical recovery within a few weeks. DISCUSSION: In case of severe cardiomyopathy secondary to viral myocarditis, patient generally recovers within a few weeks to months. However, in our case, the patient developed acute systolic heart failure from Coxsackievirus myocarditis recovered within a few days after aggressive hemodynamic support. Repeat echocardiogram on the same admission also showed significant improvement in ejection fraction from 24% to 54%. It is a rapid recovery as per our knowledge and published data. CONCLUSIONS: Our case highlights that viral myocarditis has the potency to recover quickly, even from severe systolic dysfunction. This case also emphasizes the importance of repeating an echocardiogram on the same admission rather than waiting for a couple of months to ensure cardiac function recovery, particularly with very low ejection fraction on presentation. REFERENCE #1: Tschöpe, C., Cooper, L., Torre-Amione, G., & Van Linthout, S. (2019). Management of Myocarditis-Related Cardiomyopathy in Adults. Circulation Research, 124(11), 1568-1583. https://doi.org/10.1161/circresaha.118.313578 REFERENCE #2: 3. Schultz J, Hilliard A, Cooper L, Rihal C. Diagnosis and Treatment of Viral Myocarditis. Mayo Clin Proc. 2009;84(11):1001-1009. doi:10.4065/84.11.1001 DISCLOSURES: No relevant relationships by Gnananandh Jayaraman, source=Web Response No relevant relationships by Ramesh Babu Kesavan, source=Web Response No relevant relationships by Tusharkumar Pansuriya, source=Web Response No relevant relationships by Hytham Rashid, source=Web Response No relevant relationships by Sivatej Sarva, source=Web Response No relevant relationships by Aswin Srinivasan, source=Web Response No relevant relationships by BRANDEN WILSON, source=Web Response

Overview of systematic reviews on Shenmai Injection in prevention and treatment of diseases

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.

Evaluation of the Efficacy and Safety of Chinese Herbal Injection Combined With Trimetazidine for Viral Myocarditis: A Network Meta-Analysis.

Background: Viral myocarditis (VMC) is a common emergency of cardiovascular disease. Current treatment for VMC includes the prohibition of exercise plus supportive and symptomatic treatment, given the lack of specific antiviral therapeutic options and insufficient evidence for the use of novel immunosuppressive therapies. Trimetazidine, a drug used to improve myocardial energy metabolism, is frequently used for the treatment of viral myocarditis. In China, Chinese herbal injections (CHIs) are often used in combination with trimetazidine. Therefore, we evaluate the efficacy and safety of CHI combined with trimetazidine in the treatment of VMC through the method of network meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Scientific Journals Full-text Database (VIP), and China Biology Medicine Database (CBM) databases from inception to September 1, 2020, to identify eligible randomized controlled trials. The Cochrane risk of bias tool was used to assess the risk of bias among selected studies and the Stata 16.0 software was used to perform the network meta-analysis. Results: A total of 29 studies were included, representing data from 2,687 patients. The effectiveness rate, level of myocardial injury marker, and the adverse reaction rate were evaluated. Compared with conventional treatment or conventional treatment combined with trimetazidine, CHIs combined with trimetazidine appeared to have a better therapeutic effect, with higher effectiveness rate and better reduction of the levels of creatine kinase, creatine kinase-MB, and lactate dehydrogenase. Based on surface under the cumulative ranking, Shenmai injection combined with trimetazidine appeared to be superior in terms of effective rate, while Astragalus injection or Salviae miltiorrhizae and ligustrazine hydrochloride injection combined with trimetazidine appeared most effective in reducing myocardial injury markers. There was no significant difference in safety between the interventions. However, a lack of safety monitoring in some selected studies meant that the safety of some interventions could not be fully evaluated. Conclusion: CHIs combined with trimetazidine may have therapeutic value in the treatment of viral myocarditis, and Shenmai injection, Astragalus injection, and Salviae miltiorrhizae and ligustrazine hydrochloride injection may represent the most effective CHIs. Further clinical investigation is required to confirm these results.

The Effects of Sodium Phosphocreatine on ECG Abnormalities and Cardiac Markers of Neonatal Asphyxia Based on Big Data Statistics

Myocardial damage after neonatal asphyxia is one of the common diseases of newborn, its harm is great, can affect the prognosis of newborn asphyxia. Serum creatine kinase isoenzyme (ck-mb), troponin (cTnI), creating kinase (CK), lactate dehydrogenase (LDH), poly hydroxybutyrate dehydrogenase (HBDH) and myoglobin (MB) are commonly used markers of serum myocardial injury. The determination of these indicators is of certain value for the diagnosis, treatment and efficacy evaluation of myocardial injury after suffocation. CP has been widely used in adult angina pectoris, myocardial infarction, various causes of cardiac dysfunction and other diseases, used to protect the myocardial function, has achieved good efficacy. In pediatric clinical work, CP has been used in the treatment of viral myocarditis, pediatric pneumonia or viral infection with heart damage, but few studies have been conducted on the myocardial damage in neonatal asphyxia.

Acute Myocarditis in Children: An Overview of Treatment and Recent Patents.

Pediatric myocarditis is rare but challenging. This overview summarized the current knowledge and recent patents on childhood myocarditis. Clinical queries and keywords of "myocarditis" and "childhood" were used as search engine. Viral infections are the most common causes of acute myocarditis. Affected children often have a prodrome of fever, malaise, and myalgia. Clinical manifestations of acute myocarditis in children can be nonspecific. Some children may present with easy fatigability, poor appetite, vomiting, abdominal pain, exercise intolerance, respiratory distress/tachypnea, dyspnea at rest, orthopnea, chronic cough with wheezing, chest pain, unexplained tachycardia, hypotension, syncope, and hepatomegaly. Supraventricular arrhythmias, ventricular arrhythmias, and heart block may be present. A subset of patients have fulminant myocarditis and present with cardiovascular collapse, which may progress to severe cardiogenic shock, and even death. A high index of suspicion is crucial to its diagnosis and timely management. Cardiac magnetic resonance imaging is important in aiding clinical diagnosis while, endomyocardial biopsy remains the gold standard. The treatment consists of supportive therapy, ranging from supplemental oxygen and fluid restriction to mechanical circulatory support. Angiotensinconverting enzyme inhibitors, angio-tensin II receptor blockers, β-blockers, and aldosterone antagonists might be used for the treatment of heart failure while, immunosuppression treatments remain controversial. There are a few recent patents targeting prevention or treatment of viral myocarditis, including an immunogenic composition comprising a PCV-2 antigen, glutathione-S-transferase P1, neuregulins, NF-[kappa] B inhibitor, a pharmaceutical composition which contains 2-amino-2- (2- (4-octyl phenyl) - ethyl) propane 1,3-diol, a composition containing pycnojenol, Chinese herbal concoctions, and a Korean oral rapamycin. Evidence of their efficacy is still lacking. This article reviews the current literature regarding etiology, clinical manifestations, diagnosis, and management of acute myocarditis in children.

Qidong Yixin Oral Liquid for Viral Myocarditis: A Systematic Review and Meta-Analysis.

Objective This study aimed to evaluate the efficacy and safety of Qidong Yixin (QY) oral liquid in the treatment of viral myocarditis (VMC). Methods We searched seven databases for randomized clinical trials on QY for treating VMC. The retrieval period was from database establishment to December 31, 2019. Cochrane risk of bias tool in the Cochrane Handbook was used to assess the methodological quality. Review Manager (RevMan) 5.3 was used to analyze the results. Results We included 19 studies comprising 2,608 patients, albeit with low methodological quality. Our meta-analysis revealed that combination therapy with QY and western medicine was more effective than western medicine alone (QY vs other Chinese patent medicines: RR = 1.37, 95% Cl: 1.23∼1.52, P < 0.00001; QY + coenzyme Q10 + routine treatment vs coenzyme Q10 + routine treatment: RR = 1.20, 95% Cl: 1.14∼1.27, P < 0.00001; QY + trimetazidine + acyclovir vs trimetazidine + acyclovir: RR = 1.59, 95% Cl: 1.38∼1.83, P < 0.00001; QY + routine treatment vs routine treatment: RR = 1.09, 95% Cl: 1.03∼1.15, P < 0.003). A study on posttreatment myocardial enzyme levels revealed that QY with western medicine downregulated creatine kinase isoenzyme (CK-MB) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment group: MD = −11.28, 95% CI: −13.33∼−9.22, P < 0.00001; QY + routine treatment vs routine treatment: MD = −4.96, 95% CI: −5.56∼−4.32, P < 0.00001), creatine kinase (CK) (MD = −32.10, 95% CI: −35.63∼−28.57, P < 0.00001), and lactate dehydrogenase (LDH) (QY + antiviral treatment + routine treatment vs antiviral treatment + routine treatment: MD = −48.76 95% CI: −58.18∼−39.33, P < 0.00001; QY + routine treatment vs routine treatment: MD = −23.52, 95% CI: −30.10–16.94, P < 0.00001) rather than western medicine alone, with no evidence of aspartate aminotransferase (AST) downregulation on treatment with QY with western medicine (MD = 2.88, 95% CI: −0.95∼6.71, P < 0.00001) in patients. Two studies reported adverse events, indicating that QY is relatively safe. Conclusion Although QY may have potential advantages in treating VMC, they remain unclear owing to the poor methodological quality of most studies. Larger, multicenter, high-quality randomized controlled trials are required to verify the effectiveness of QY.

IL-17 stimulates the expression of CCL2 in cardiac myocytes via Act1/TRAF6/p38MAPK-dependent AP-1 activation.

IL-17 participates in the development of many autoimmune diseases by promoting the expression of some chemokines. Chemokine C-C motif ligand 2 (CCL2) is an important factor at the infiltration of mononuclear cells in the myocardial tissue of viral myocarditis (VMC). It was found that IL-17 could aggravate myocardial injury by upregulating CCL2. But the underlying mechanism involved in CCL2 secretion induced by IL-17 in cardiac myocytes remains unclear. This study investigated the role of transcription factor AP-1 in IL-17 induced CCL2 expression. The results showed that IL-17 mediated the activation of Act1, TRAF6, p38MAPK and c-Jun/AP-1 not Wnt or PI3K signalling pathway to upregulate CCL2 expression in cardiac myocytes. After blocking Act1/TRAF6/p38MAPK cascade and interfering AP-1 with Curcumin or c-Jun siRNA, CCL2 expression induced by IL-17 was significantly attenuated at both mRNA and protein levels. Furthermore, the phosphorylation of c-Jun was suppressed when cardiac myocytes were treated with Act1 siRNA, TRAF6 siRNA, SB203580 (p38MAPK inhibitor) or SP600125 (JNK inhibitor) in cardiac myocytes. In conclusion, IL-17 could stimulate the expression of CCL2 in cardiac myocytes via Act1/TRAF6/p38MAPK-dependent AP-1 activation, which may provide a new target for the diagnosis and treatment of VMC.

Exosomes derived from cardiac progenitor cells attenuate CVB3-induced apoptosis via abrogating the proliferation of CVB3 and modulating the mTOR signaling pathways

Viral myocarditis is potentially fatal and lacking a specific treatment. Exosomes secreted by cardiac progenitor cells (CPCs) have emerged as a promising tool for cardioprotection and repair. In this study, we investigated whether CPCs-derived exosomes (CPCs-Ex) could utilize the mTOR signal pathway to reduce the apoptosis in viral myocarditis. In vitro, exosomes were, respectively, added to H9C2 cells after CVB3 infection to detect the anti-apoptosis effect of CPCs-Ex. Compared with the controls, the apoptosis rate was reduced, accompanied with the depressed expression of viral capsid protein 1 (VP1) and pro-apoptosis factors of Bim/caspase families. Meanwhile, the phosphorylation of Akt, mTOR, and p70S6K were promoted, but that of 4EBP1 was suppressed. In vivo, the results of apoptosis, expression of CVB3 and pro-apoptosis factors, and phosphorylation of Akt/mTOR factors of CVB3-infected cardiomyocytes were consistent with that of vitro. Following that, we use Rapamycin and MK-2206 to inhibit the Akt/mTOR signaling pathway, meanwhile, Rattus 4EBP1, p70S6K, Akt1 and Akt2 were transfected to H9C2 cells to establish the stably transfected cell lines. In the group with Rapamycin or MK-2206 pretreatment, CPCs-Ex also could decrease the apoptosis of H9C2 cells and expression of CVB3 mRNA, followed by decreased expression of apoptosis factors. In Akt2, p70S6K and 4EBP1 overexpression groups, CPCs-Ex promoted CVB3-induced apoptosis, VP1 expression and cleavage of caspase-3. Our results therefore identify CPCs-Ex exerts an anti-apoptosis effect in CVB3-infected cells by abrogating the proliferation of CVB3 and modulating the mTOR signaling pathways as well as the expression of Bcl-2 and caspase families. Viral myocarditis, mainly caused by CVB3 infection, is lacking a specific treatment. Our study identified an anti-apoptosis role of CPCs-Ex in CVB3-infected cells and rats, which shown that CPCs-Ex may be an effective tool to treat viral myocarditis. We believe that with more in-depth research on the functionality of CPCs-Ex, there will be a breakthrough in the treatment of viral myocarditis.

Clinical observation of Huangqi injection combined with ribavirin in children with viral myocarditis

Objective To evaluate the efficacy of Huangqi injection combined with ribavirin in the treatment of viral myocarditis in children. Methods A total of 89 children with viral myocarditis were randomly divided into treatment group (45 cases) and control group (44 cases) by random number table method. The control group received ribavirin intravenously on the basis of routine treatment, and the treatment group was given Huangqi injection intravenously on the basis of the control group. Both groups were treated continuously for 14 days. The Serum creatine kinase (CK), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH) and aspartate transaminase (AST) were detected by automatic biochemical analyzer. The Serum IL-6, IL-8 and TNF-α were detected by ELISA.The level of CD3+, CD4+, and the ratio of CD4+/CD8+ in peripheral blood was measured by flow cytometry, and the clinical efficacy was evaluated. Results After treatment, the level of serum CK (110.19 ± 12.17 U/L vs. 143.81 ± 17.53 U/L, t=10.530), CK-MB (18.43 ± 4.40 U/L vs. 30.28 ± 5.21 U/L, t=11.602), LDH (139.57 ± 10.36 U/L vs. 162.18 ± 13.22 U/L, t=8.992), AST (24.14 ± 2.19 U/L vs. 35.58 ± 3.34 U/L, t=19.150) in the treatment group were significantly lower than those in the control group (P<0.01). The Serum level of IL-6, IL-8 and TNF-α in the treatment group were significantly lower than those of the control group (t=14.884, 17.043 and 14.364, respectively, P<0.01). The level of CD3+, CD4+, and the ratio of CD4+/CD8+ in peripheral blood of the treatment group was significantly higher than that of the control group (t=6.256, 0.219 and 3.895, respectively, P<0.01). Conclusions The Huangqi injection combined with ribavirin can significantly reduce the degree of myocardial injury and inflammation in children with viral myocarditis, and improve the immune function of children with viral myocarditis. Key words: Myocarditis; Virus diseases; Child; Huangqi injection; Ribavirin; Immunity

Abstract P-570: MiR-19b INHIBITS CVB3-INDUCED APOPTOSIS VIA SUPPRESSION OF TOLL-LIKE RECEPTOR-2

Aims & Objectives: To investigate the effect and mechanism of miR-19b on apoptosis in viral myocarditis (VMC). Methods MiR-19b expression was detected in cardiomyocytes with Coxsackievirus B3(CVB3) infection by quantitative PCR (qRT-PCR). The relevant target gene of miR-19b was predicted by software and was validated by luciferase report assays. miR-19bmimics were transfected into cardiomyocytes. The expression of Toll-like receptor-2 (TLR2) in cardiomyocytes was detected by qRT-PCR and Western blotting, and the apoptosis rate of cardiomyocytes was detected by flow cytometry (FCM)-based analysis. Results MiR-19b levels were down-regulated in cardiomyocytes with CVB3 infection(P<0.05). Compared with the control, the miR-19b mimic group showed a substantially decreased apoptosis rate. TLR2 was confirmed as a target gene of miR-19b. qRT-PCR and Western blot analyses showed that the expression of TLR2 in the miR-19b mimic group was significantly lower than that in the control group, and the expression of TLR2 in the miR-19b inhibitor group was significantly higher than that in control group, indicating that miR-19b can inhibit the expression of TLR2. Conclusions Our findings demonstrated that miR-19b inhibits apoptosis by regulating TLR2 expression. Thus, miR-19b may have a potential application in VMC treatment.

Role of coxsackievirus and adenovirus receptor (CAR) expression and viral load of adenovirus and enterovirus in patients with dilated cardiomyopathy.

Enteroviruses (EVs) and adenoviruses (AdVs) are two important etiological agents of viral myocarditis and dilated cardiomyopathy (DCM). Both these viruses share a common receptor, the coxsackievirus and adenovirus receptor (CAR), for their infection. However, the role of viral load and CAR expression in disease severity has not yet been completely elucidated. The present study aimed to determine viral load of EV and AdV in DCM patients and correlate them with the level of CAR expression in these patients. Sixty-three DCM cases and 30 controls, each of whom died of heart disease other than DCM and non-cardiac disease respectively, were included. Viral load was determined by TaqMan real-time PCR using primers and probes specific for the AdV hexon gene and the 5'UTR region of EV. The CAR mRNA level was semi-quantitated by RT-PCR, and antigen expression was studied by immunohistochemistry. A significantly high AdV load (p<0.05) and CAR expression (p<0.05) were observed in DCM cases versus controls, whereas the EV load showed no significant difference. The data suggests a clinical threshold of 128 AdV copies/500 ng of DNA for DCM, with 66.7% sensitivity and 65% specificity. A positive correlation between AdV load and CAR expression (p<0.001) was also observed in DCM cases. The high adenoviral load and increased CAR expression in DCM and their association with adverse disease outcome indicates role of both virus and receptor in disease pathogenesis. Thus, the need for targeting both the virus and the receptor for treatment of viral myocarditis and early DCM requires further confirmation with larger studies.