Icariin ameliorates viral myocarditis by inhibiting TLR4-mediated ferroptosis

Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability,inflammation,and apoptosis.Moreover,the effects of icariin on ferroptosis and TLR4 signaling were assessed.After AC16 cells were transfected with TLR4 overexpression plasmids,the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated.Results:Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α,IL-1β,IL-6,and IL-18.Flow cytometry revealed that icariin decreased apoptosis rate,and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes.Additionally,it suppressed ferroptosis including lipid peroxidation and ferrous ion,as well as the TLR4 signaling.However,TLR4 overexpression abrogated the modulatory effects of icariin.Conclusions:Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis.Further animal study is needed to verify its efficacy.

Handheld bedside ultrasound in the diagnosis of myocarditis

Myocarditis is a disease process that every emergency physician fears missing.Its severity can be mild to life-threatening,and many cases are likely undetected because they are subclinical with nonspecifi c signs.[1]Subtle cardiac signs may be overshadowed by systemic symptoms of the underlying infectious process.Fever,myalgias,lethargy,symptoms commonly associated with viral syndrome,can mask the life-threatening myocarditis that may be present.In fact,in the United States Myocarditis Treatment Trial,almost 90%of patients reported symptoms consistent with a viral prodrome.[2]Ammirati et al[3]reported that 27%of patients with myocarditis had either reduced left ventricular ejection fraction,ventricular arrhythmias,or low cardiac output.Here,we present a case report,in which handheld point-of-care ultrasound was utilized at the bedside to aid in the critical diagnosis of myocarditis.With the additional information provided through this imaging modality,this patient was able to be transferred to the appropriate tertiary care facility in an expeditious manner and receive possible defi nitive treatment.

COVID-19 and cardiac complications:Myocarditis and multisystem inflammatory syndrome in children

Coronavirus is an important pathogen causing disease in humans and animals.At the end of 2019,an investigation into an increase in pneumonia cases in Wuhan,Hubei Province,China,found that the cause was a new coronavirus.This disease,which spread rapidly across China and caused an outbreak worldwide,resulted in a pandemic.Although this virus has previously been referred to as 2019-nCoV,which causes coronavirus disease 2019(COVID-19),later it was named severe acute respiratory syndrome coronavirus 2.Children were usually asymptomatic and rarely severely affected.In April 2020,reports from the United Kingdom indicated that children may have Kawasaki disease or a clinical condition similar to toxic shock syndrome.This clinical picture was later defined as multisystem inflammatory syndrome in children.Since then,similarly affected children as well as cases with other cardiac complications have been reported in other parts of the world.In this review,we aimed to evaluate COVID-19 in terms of cardiac involvement by reviewing the literature.

Development and Validation of a Prediction Model on Adult Emergency Department Patients for Early Identification of Fulminant Myocarditis

Objective It is difficult to predict fulminant myocarditis at an early stage in the emergency department.The objective of this study was to construct and validate a simple prediction model for the early identification of fulminant myocarditis.Methods A total of 61 patients with fulminant myocarditis and 160 patients with acute myocarditis were enrolled in the training and internal validation cohorts.LASSO regression and multivariate logistic regression were selected to develop the prediction model.The selection of the model was based on overall performance and simplicity.A nomogram based on the optimal model was built,and its clinical usefulness was evaluated by decision curve analysis.The predictive model was further validated in an external validation group.Results The resulting prediction model was based on 4 factors:systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality.The Brier scores of the final model were 0.078 in the training data set and 0.061 in the internal testing data set,respectively.The C-indexes of the training data set and the testing data set were 0.952 and 0.968,respectively.Decision curve analysis showed that the nomogram model developed based on the 4 predictors above had a positive net benefit for predicting probability thresholds.In the external validation cohort,the model also showed good performance(Brier score=0.007,and C-index=0.989).Conclusion We developed and validated an early prediction model consisting of 4 clinical factors(systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality)to identify potential fulminant myocarditis patients in the emergency department.

From post-COVID-19-associated myocarditis to hemopericardium: a dangerous domino effect

The majority of patients infected with Severe Acute Respiratory Syndrome-COrona-Virus-2(SARS-CoV-2)either completely recover from symptoms in a few days or stay asymptomatic.[1−3]Nevertheless,a consistent proportion of subjects with a history of probable or confirmed SARS-CoV-2 infection refers persistency,new occurrence,relapse,or fluctuation of symptoms,and these manifestations are defined as post-COVID-19 condition.[4]Of note,the post-acute sequelae of COVID-19 include several cardiac manifestations,including direct myocardial and pericardial injury/inflammation,as well as cardiomyopathies and arrythmias,sustained by viral infiltration and/or dysregulation of adaptive immune response.[5]Even though rare,acute myocarditis may be an important post-COVID-19 condition and may be associated with the occurrence of new-onset atrial fibrillation.

Myocarditis after COVID-19 Vaccination

Aim: The ongoing COVID-19 pandemic is an acute medical, social, political and economic problem. Acute myocarditis is a rare complication of the widely used mRNA-based vaccines. Case Presentation: 20-year old male with no preexisting disease or cardiovascular risk factor presented in October 2021 with chest pain after receiving the second dose of the Moderna COVID-19 vaccine 2 days previously. He discharged from ward care only a few days after his initial presentation. Conclusion: Despite the meta-analysis results suggesting a higher risk of myocarditis with COVID-19 vaccination, vaccination should still be recommended because benefits of the vaccine likely outweigh its harms.

Contribution of Cardiac MRI in the Diagnosis of Acute Myocarditis

Objective: To describe the MRI abnormalities observed in acute myocarditis. Materials and Methods: Retrospective cross-sectional study with a descriptive aim, carried out at the North Franche-Comte Hospital, over a period of 12 months, from January 2021 to December 2021. It covered all patients who received an MRI of heart disease and were diagnosed with myocarditis. The diagnosis of myocarditis was retained in all patients on the basis of two arguments: a T2 PSIR hyper signal and a late enhancement at 15 min in T1 PSIR with gadolinium. Results: Myocarditis was diagnosed in 20 patients out of a total of 214 who performed cardiac MRI, i.e. 10.30% of cases. The average age was 33.7 ± 14.3 with extremes of 17 and 69 years. We observed a male predominance with 11 men (55%) for 9 women (45%) or a sex ratio of 1.2. Clinical suspicion of myocarditis and acute coronary syndrome were the main indications for MRI. The lesion sites were subepicardial (95%) and/or intramural (30%), respecting the subendocardium, interesting for the majority, segments 12 (anterolateral) in 50% and/or 11 (inferolateral) in 43% of cases. Global hypokinesia was observed in 30% of patients associated with a decrease in LVEF. There was no cardiac volume abnormality or valvular abnormality. Conclusion: Cardiac MRI is nowadays the most efficient non-invasive imaging in the diagnosis of acute myocarditis. The diagnosis of myocarditis was made on 2 pathognomonic signs, namely a T2 STIR hyper signal and late enhancement at 15 min in T1 PSIR after injection of gadolinium. The morphology and lesion locations were in agreement with those described in previous studies. Global hypokinesia and pericardial effusion were observed in some patients. On the other hand, there was neither valvular anomaly, nor cardiac volume anomaly.

Oxidative Stress in Patients With Acute Coxsackie Virus Myocarditis

Objective To study the state of oxidative stress in patients with acute coxsackie virusmyocarditis (ACM), and to investigate the pathological chain reactions of a series of freeradicals and oxidative and lipoperoxidative damages in their bodies. Methods Eighty ACMpatients and 80 healthy adult volunteers (HAV) were enrolled in a case-control study, inwhich concentrations of nitric oxide (NO) in plasma, lipoperoxides (LPO) in plasma andLPO in erythrocytes (RBC), vitamin C (VC), vitamin E (VE) and b-carotene (b-CAR) inplasma as well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathioneperoxidase (GSH-Px) in RBC were determined by using spectrophotometric assays. ResultsCompared with the average values (AV) of the above biochemical parameters (BP) in theHAV group, the AV of NO in plasma, and LPO in plasma and RBC in the ACM group weresignificantly increased (P=0.0001), while the AV of VC, VE, b-CAR, SOD, CAT and GSH-Px in the ACM group were significantly decreased (P=0.0001). The values of the above BPwere used to estimate the relative risk ratio (RR) between the ACM group and the HAVgroup; the RR and its 95 % confidence interval were 12.467 (5.745~27.051), 4.333(2.126~8.834), 6.517 (3.225~13.618), 3.310 (1.598~6.858), 31.000 (12.611~76.201),4.663 (2.228~9.759), 11.769 (5.440~25.462), 3.043 (1.486~6.229) and 6.594 (3.045~14.281)respectively, and their P levels ranged from 0.002 to 0.0001. The results were asfollows: D = 22.143 - 0.017SOD + 0.008NO + 0.244LPO in RBC, Eigenvalue = 13.659,Canonical correlation = 0.965, Wilks’λ= 0.068, c2 = 420.212, P = 0.0001. The correct rateof discrimination to the ACM group and to the HAV group was 87.5% and 95.0 %, respectively,and 91.3 % of originally grouped cases was correctly classified. Conclusion The findingsin this study suggested that the oxidative stress in bodies of ACM patients was severelyaggravated, and marked high oxidative constituents and low antioxidants and antioxidasesin the human body might increase the relative risk of inducing acute coxsackie virusmyocarditis, and measuring the values of NO in plasma, SOD and LPO in RBC mightincrease the correct rates of discriminatory analysis of the ACM.

Clinical presentation and early predictors for poor outcomes in pediatric myocarditis:A retrospective study

BACKGROUND Myocarditis is an important cause of morbidity and mortality in children, leading to long-term sequelae including chronic congestive heart failure, dilated cardiomyopathy, heart transplantation, and death. The initial diagnosis of myocarditis is usually based on clinical presentation, but this widely ranges from the severe sudden onset of a cardiogenic shock to asymptomatic patients. Early recognition is essential in order to monitor and start supportive treatment prior to the development of severe adverse events. Of note, many cases of fulminant myocarditis are usually misdiagnosed as otherwise minor conditions during the weeks before the unexpected deterioration.AIM To provide diagnostic clues to make an early recognition of pediatric myocarditis.To investigate early predictors for poor outcomes.METHODS We conducted a retrospective cross-sectional single-center study from January 2008 to November 2017 at the Pediatric Department of our institution, including children < 18-years-old diagnosed with myocarditis. Poor outcome was defined as the occurrence of any of the following facts: death, heart transplant, persistent left ventricular systolic dysfunction or dilation at hospital discharge(early poor outcome), or after 1 year of follow-up(late poor outcome). We analyzed different clinical features and diagnostic test findings in order to provide diagnostic clues for myocarditis in children. Multivariable stepwise logistic regression analysis was performed using all variables that had been selected by univariate analysis to determine independent factors that predicted a poor early or late outcome in our study population.RESULTS A total of 42 patients [69% male; median age of 8(1.5-12) years] met study inclusion criteria. Chest pain(40%) was the most common specific cardiac symptom. Respiratory tract symptoms(cough, apnea, rhinorrhea)(38%),shortness of breath(35%), gastrointestinal tract symptoms(vomiting, abdominal pain, diarrhea)(33%), and fever(31%) were the most common non-cardiac initial complaints. Tachycardia(57%) and tachypnea(52%) were the most common signs on the initial physical exam followed by nonspecific signs of respiratory tract infection(44%) and respiratory distress(35%). Specific abnormal signs of heart failure such as heart murmur(26%), systolic hypotension(24%), gallop rhythm(20%), or hepatomegaly(20%) were less prevalent. Up to 43% of patients presented an early poor outcome, and 16% presented a late poor outcome. In multivariate analysis, an initial left ventricular ejection fraction(LVEF) < 30%remained the only significant predictor for early [odds ratio(OR)(95%CI) = 21(2-456), P = 0.027) and late [OR(95%CI) = 8(0.56-135), P = 0.047) poor outcome in children with myocarditis. LVEF correlated well with age(r = 0.51, P = 0.005),days from the initiation of symptoms(r =-0.31, P = 0.045), and N-terminal probrain natriuretic peptide levels(r = 0.66, P < 0.001), but not with troponin T(r =-0.05, P = 0.730) or C-reactive protein levels(r =-0.13, P = 0.391). N-terminal probrain natriuretic peptide presented a high diagnostic accuracy for LVEF < 30% on echocardiography with an area under curve of 0.931(95%CI: 0.858-0.995, P <0.001). The best cut-off point was 2000 pg/mL with a sensitivity of 90%,specificity of 81%, positive predictive value of 60%, and negative predictive value of 96%.CONCLUSION The diagnosis of myocarditis in children is challenging due to the heterogeneous and unspecific clinical presentation. The presence of LVEF < 30% on echocardiography on admission was the major predictor for poor outcomes.Younger ages, a prolonged course of the disease, and N-terminal pro-brain natriuretic peptide levels could help to identify these high-risk patients.

Global study of viral myocarditis: A systematic review and meta-analysis

Objective:To investigate the prevalence of viral myocarditis worldwide.Methods:We conducted a systematic search for the prevalence of the most common viruses in myocarditis and 75 studies were included for statistical analysis of the prevalence of adenovirus,hepatitis C virus,cytomegalovirus,Ebola virus,human herpesvirus 6,influenza virus,parvovirus,and non-polio enteroviruses.Results:The highest prevalence was related to B19(25.0%)and non-polio enteroviruses(18%).The prevalence of human herpesvirus 6,cytomegalovirus,and Ebola virus was12.8%,5.5%,and 3.1%,respectively.Hepatitis C virus accounted for 6.1%of the disease,the adenoviruses contributed to 5.2%of viral myocarditis.The lowest incidence was related to the influenza virus with 2.0%.Conclusions:Treatment of myocarditis is still problematic and may depend on the etiologic diagnosis.So it is important to know the commonly occurring viral factors in myocarditis and timely diagnosis and treatment are also imperative.

Fulminant myocarditis in adults: a narrative review

Fulminant myocarditis(FM)is an uncommon syndrome characterized by sudden and severe hemodynamic compromise secondary to acute myocardial inflammation,often presenting as profound cardiogenic shock,life-threatening ventricular arrhythmias and/or electrical storm.FM may be refractory to conventional therapies and require mechanical circulatory support(MCS).The immune system has been recognized as playing a pivotal role in the pathophysiology of myocarditis,leading to an increased focus on immunosuppressive treatment strategies.Recent data have highlighted not only the fact that FM has significantly worse outcomes than non-FM,but that prognosis and management strategies of FM are heavily dependent on histological subtype,placing greater emphasis on the role of endomyocardial biopsy in diagnosis.The impact of subtype on severity and prognosis will likewise influence how aggressively the myocarditis is managed,including whether MCS is warranted.Many patients with refractory cardiogenic shock secondary to FM end up requiring MCS,with venoarterial extracorporeal membrane oxygenation demonstrating favorable survival rates,particularly when initiated prior to the development of multiorgan failure.Among the challenges facing the field are the need to more precisely identify immunopathophysiological pathways in order to develop targeted therapies,and the need to better optimize the timing and management of MCS to minimize complications and maximize outcomes.

Murine model of acute myocarditis and cerebral cortical neuron edema induced by coxsackievirus B4

Globally, coxsackievirus B4 （CV-B4） has been continuously isolated and evidence suggests an association with the development of pancreatitis and type I diabetes. In addition, CV-B4 is also associated with myocarditis and severe central nervous system （CNS） complications, which remain poorly studied and understood. In the present study, we established an institute for Cancer Research （ICR） mouse model of CV-B4 infection and examined whether CV-B4 infection resulted in a predisposition to myocarditis and CNS infection. We found high survival in both the treatment and control group, with no significant differences in clinical outcomes observed. However, pathological lesions were evident in both brain and heart tissue of the CV-B4-infected mice. in addition, high viral loads were found in the neural and cardiac tissues as early as 2 days post infection. Expressions of IFN-y and IL-6 in sera were significantly higher in CV-B4-infected mice compared to uninfected negative controls, suggesting the involvement of these cytokines in the development of histopathological lesions. Our murine model successfully reproduced the acute myocarditis and cerebral cortical neuron edema induced by CV-B4, and may be useful for the evaluation of vaccine candidates and potential antivirals against CV-B4 infection.

Myocarditis in athlete and myocardial bridge:An innocent bystander?

Myocarditis is a bacterial or viral inflammatory disease,often unnoticed or misdiagnosed.Athletes with myocarditis must stop practicing their activity since International medical Literature described some cases of sudden death.In the present report,we describe a case of an asymptomatic,apparently healthy,competitive athletes,who was diagnosed a myocarditis and as incidental finding a myocardial bridging.We focused the attention on the importance of anamnesis,electrocardiogram and athletes' entourage for the diagnosis of such insidious pathologies and we evaluated the follow up,focusing the attention on electrocardiogram changes as well as on restitution ad integrum and prognosis,especially for the athletes.

Role of hepatitis C virus in myocarditis and cardiomyopathies

Recent nationwide clinico-epidemiological surveys in Japan showed that the occurrence of cardiomyopathies was most frequently seen in the age of sixties, and that cardiomyopathies are important causes of heart failure in the elderly. Viral infection was conventionally considered to cause myocarditis, which resulted in the development of dilated cardiomyopathy. Recent studies suggest that hepatitis C virus (HCV) is involved in the development of dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy in addition to myocarditis. Furthermore, left ventricular aneurysm represents the same morbid state not only after myocardial infarction but also after myocarditis. There were wide variations in the frequency of detection of HCV genomes in cardiomyopathy in different regions and in different populations. Major histocompatibility complex class Ⅱ genes may play a role in the susceptibility to HCV infection, and may influence the development of different phenotypes of cardiomyopathy. If in fact the myocardial damage is caused by HCV, it might be expected that interferon (IFN) administration would be useful for its treatment. Hepatitis patients receiving IFN treatment for hepatitis were screened by thallium myocardial scintigraphy, and an abnormality was discovered in half of the patients. Treatment with IFN resulted in a disappearance of the image abnormality. It has thus been suggested that mild myocarditis and myocardial damage may be cured with IFN. We have recently found that high concentrations of circulating cardiac troponin T are a specific marker of cardiac involvement in HCV infection. By measuring cardiac troponin T in patients with HCV infection, the prevalence of cardiac involvement in HCV infection will be clarified. We are proposing a collaborative work on a global network on myocarditis/cardiomyopathies due to HCV infection. (J Geriatr Cardiol 2004;1(2):83-89. )

Molecular phenotypes of human parvovirus B19 in patients with myocarditis

AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients with myocarditis and DCMwere analyzed using molecular methods and functional experiments.EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers.Control tissues were obtained at autopsy from 34 victims of accidents,crime or suicide.Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining.Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay(ELISA).B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction(PCR).For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism(RFLP)-PCR was established.B19V-genotyping was verified by direct DNAsequencing and sequences were aligned using BLAST and BioEdit software.B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments.Transfection experiments were conducted using human endothelial cells 1.Luciferase reporter assays were performed to determine B19Vreplication activity.Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS:The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy(iCMP) compared to uninflamed DCM(59.6% vs 35.3%)(P < 0.0001).The detection of B19V-mRNA replication intermediates proved that replication of B19V was present.RFLP-PCR assays showed that B19V-genotype 1(57.4%) and B19V-genotype 2(36.7%) were the most prevalent viral genotypes.B19V-genotype 2 was observed more frequently in EMBs with iCMP(65.0%) compared to DCM(35%)(P = 0.049).Although there was no significant difference in gender-specific B19V-loads,women were more frequently infected with B19V-genotype 2(44.6%) than men(36.0%)(P = 0.0448).Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissuesamples and was associated with higher B19V viral load compared to B19V-monoinfected tissue(P = 0.0012).The most frequent coinfecting virus was human herpes virus 6(HHV6,16.5%).B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs(P = 0.0033),suggesting that HHV6 had transactivated B19V.In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION:The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP.Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.

Myocarditis presenting as typical acute myocardial infarction: A case report and review of the literature

BACKGROUND Myocarditis refers to a variety of myocardial inflammatory lesions. A variety of factors such as infection and physical and chemical factors can cause myocarditis.Depending on the severity of myocardial damage, myocarditis patients can manifest heart failure, cardiogenic shock, and even sudden death. Here we present a case of viral myocarditis that mimicked acute coronary syndrome.CASE SUMMARY A middle-aged male patient presented with chest pain and elevated troponin I after a flu-like infection. This patient had a history of hypertension and a habit of alcohol and tobacco use. Electrocardiography showed typical changes in acute myocardial infarction, with the T-wave increasing. Coronary angiogram revealed no stenosis. Cardiac magnetic resonance imaging revealed edema of the middle and apical septal and apical anterior walls on T2-weighted images and the T1 mapping. Late gadolinium enhancement of the middle and apical septal and apical anterior walls could be found. Rubella virus immunoglobulin G and immunoglobulin M antibodies were abnormally elevated. The patient was given antiviral and antibiotic treatments, and serum biomarkers and electrocardiograph returned to normal after 5 d of treatment. After one-year follow-up, the patient showed no symptoms, and cardiac magnetic resonance showed that myocardial thickness was significantly thinner than before, and fibrosis was less than before.CONCLUSIONThis case illustrates the utility of cardiac magnetic resonance for diagnosis of infarction-like myocarditis when the angiogram is normal.

A rare case of Staphylococcus lugdunensis septicemia associated with myocarditis and atrioventricular block

Myocarditis is a relatively rare,possibly life-threatening disease characterized by the inflammation of the myocardium.111 The disease pathogenesis is primarily initiated by acute injury and necrosis of cardiomyocytes,leading to an inflammatory response mediated by the immune system that can potentially cause further aggravation of myocardial damage and organ dysfunction.Prognosis in patients with myocarditis depends on the clinical presentation,which ranges from an asymptomatic disease course to the concomitant development of cardiac arrhythmias,heart failure,cardiogenic shock and even the occurrence of death in extreme cases[1].

Impairment of Myocardial and Skeletal Mitochondria in Mice with Viral Myocarditis and Their Correlation

In order to investigate the impairment of mitochondrial membrane phospholipid local- ization and DNA3867 (mtDNA3867) deletion and the correlation between cardiac and skeletal muscle cells in mice with viral myocarditis, 50 BALB/c mice were divided into two groups randomly. In ex- perimental group (n=40), the mice were intraperitoneally injected with 0.1 mL Eagle liquid with CVB3 (TCID50=108), while in the control group (n=10), the mice were subjected to equal volume of Eagle liquid. The impairment of mitochondrial membrane phospholipid localization and mtDNA3867 deletion rate of cardiac and skeletal muscle were detected separately at day 3, 11 and 24 after injec- tion. The correlation of mitochondrial membrane phospholipid localization and mtDNA3867 deletion rate between cardiac and skeletal muscle cells cells was analyzed using Spearman method. At the day 3 after injection, in both cardiac and skeletal muscle cells, mtDNA3867 deletion rate was significantly higher in experimental group than in control group (P<0.05), but the localization of mitochondrial membrane phospholipid showed no difference between two groups (P>0.05). At day 11 after injec- tion, the mtDNA3867 deletion rate of both cells in experimental group was increased to the peak level (P<0.05), and the impairment of mitochondrial membrane phospholipid localization of both cells also increased markedly in experimental group as compared with control group (P>0.05). At the day 24 after injection, the impairment of mitochondrial membrane phospholipid localization and mtDNA3867 deletion of both cells showed a recovery tendency, but still severer than those at the day 3 after injec- tion (P<0.05). The impairment of mitochondrial membrane phospholipid localization and mtDNA3867 deletion were consistent and synchronistic between cardiac and skeletal muscle cells, and showed good correlations (P<0.05). The impairment of mitochondria plays an important role in the patho- genesis of viral myocarditis, and the skeletal muscle cells might act as a peripheral 'window' to re- flect the mitochondrial damage of cardiac myocytes.

Risk factors analysis of prognosis of adult acute severe myocarditis

BACKGROUND Adult severe myocarditis is primarily caused by infection with any number of a variety of viruses.It arises quickly,progresses rapidly,and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock with a high hospital mortality rate.AIM To analyze the risk factors affecting the short-term prognosis of adult acute severe myocarditis(ASM).METHODS Adult patients with ASM(ASM group,n=218)and acute nonsevere myocarditis(ANSM group,n=80)who came to our department from January 2014 to January 2020 were enrolled in this study.Patients with ASM were divided into the ASM survival group(n=185)and ASM nonsurvival group(n=33)according to the treatment results during hospitalization.The clinical symptoms,laboratory examinations,treatment methods,complications,and the relationship between the treatment results of the two groups were retrospectively compared and discussed.The risk factors for death in patients with severe myocarditis were analyzed by binary logistic regression.A follow-up to 5.5 years was conducted on patients in the ASM survival group and ANSM group after discharge,and the readmission rate and incidence rate of dilated cardiomyopathy were analyzed.RESULTS Compared with the ASM survival group,the ASM nonsurvival group had longer QRS complex,higher incidence of cardiogenic shock,higher serum creatinine(SCr,235μmol/L vs 89μmol/L,P<0.05),higher sensitive cardiac troponin I(cTnI,4.45μg/L vs 1.66μg/L,P<0.05)and brain natriuretic peptide(BNP,1756 pg/mL vs 401 pg/mL,P<0.05).The binary logistic regression revealed that there were statistical differences between the two groups in SCr,cTnI,and BNP values(all P<0.05).After discharging from the hospital,patients in the ASM group and ANSM group had no significant differences in the readmission rate and incidencerate of dilated cardiomyopathy.CONCLUSION Elevated SCr,cTnI,and BNP are independent predictors for poor prognosis in patients with ASM.The long-term prognosis of patients in the ASM survival group is good.

Effect of Astragalus Injection on Levels of Blood Selenium and Immunity Function in Children with Viral Myocarditis

Objective: To observe the effect of Astragalus Injection (AD on levels of blood selenium (Se) and cytokines, and T cellular immune function with viral myocarditis (VM) in children. Methods: Eighty children with VM were randomly divided into 2 groups. The control group consisted of 38 patients, to whom conventional therapy, including energy mixture, vitamin C and coenzyme Q10, etc. were given. The treated group (n = 42), to whom combination therapy of conventional therapy and Al were given. The levels of blood Se and cytokine, including interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and also evaluation of T lymphocyte subsets and cardiac function were observed. Results: The results showed that after treatment, the levels of blood Se were significantly higher (P<0.01), while IL-1,IL-6 and TNF-a were significantly lower (P<0.01) than those before treatment in the control group. The left ventricular end diameter (LVED) were significantly decreased (P<0.01), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly increased than those before treatment in the treated group(P<0.01, P<0.05). T lymphocyte subsets got normalized (P<0.01), and compared with the control group, the difference was significant (P<0.01). Conclusion: Astragalus membranaceus possesses anti-viral effect, adjusts the balance of cytokine and T cellular immunity, and improves the clinical manifestation and cardiac function. It is an effective approach in treating viral myocarditis.