Predicting Acute Cardiovascular Complications in COVID-19: Insights from a Specialized Cardiac Referral Department.

BACKGROUND COVID-19 increases the risk of acute cardiovascular diseases (CVDs), including acute coronary syndrome (ACS), acute pulmonary embolism (APE), and acute myocarditis (AMyo). The actual impact of CVDs on mortality of patients with COVID-19 remains unknown. This study aimed to determine whether CVDs influence the course of COVID-19 pneumonia and if they can be easily detected by using common tests and examinations. MATERIAL AND METHODS Data of 249 consecutive patients with COVID-19 hospitalized in a dedicated cardiology department were analyzed. On admission, clinical status, biomarkers, computed tomography, and bedside echocardiography were performed. RESULTS D-dimer level predicted APE (AUC=0.850 95% CI [0.765; 0.935], P<0.001) with sensitivity of 69.4% and specificity of 96.2% for a level of 4968.0 ng/mL, and NT-proBNP predicted AMyo (AUC=0.692 95% CI [0.502; 0.883], P=0.004) and showed sensitivity of 54.5%, with specificity of 86.5% for the cut-off point of 8970 pg/mL. Troponin T levels were not useful for diagnostic differentiation between CVDs. An extent of lung involvement predicted mortality (OR=1.03 95% CI [1.01;1.04] for 1% increase, P<0.001). After adjusting for lung involvement, ACS increased mortality, compared with COVID-19 pneumonia only (OR=5.27 95% CI [1.76; 16.38] P=0.003), while APE and AMyo did not affect risk for death. CONCLUSIONS D-dimer and NT-proBNP, but not troponin T, are useful in differentiating CVDs in patients with COVID-19. ACS with COVID-19 increased in-hospital mortality independently from extent of lung involvement, while coexisting APE or AMyo did not.

Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination.

Loss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice.

Viral myocarditis, an inflammatory disease of the myocardium, is a significant cause of sudden death in children and young adults. The current coronavirus disease 19 pandemic emphasizes the need to understand the pathogenesis mechanisms and potential treatment strategies for viral myocarditis. Here, we found that TRIM29 was highly induced by cardiotropic viruses and promoted protein kinase RNA-like endoplasmic reticulum kinase (PERK)-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses that promote viral replication in cardiomyocytes in vitro. TRIM29 deficiency protected mice from viral myocarditis by promoting cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive monocytic myeloid-derived suppressor cells (mMDSC) in vivo. Mechanistically, TRIM29 interacted with PERK to promote SUMOylation of PERK to maintain its stability, thereby promoting PERK-mediated signaling pathways. Finally, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK connection, thereby bolstering cardiac function, enhancing cardiac antiviral responses, and curbing inflammation and immunosuppressive mMDSC in vivo. Our findings offer insight into how cardiotropic viruses exploit TRIM29-regulated PERK signaling pathways to instigate viral myocarditis, suggesting that targeting the TRIM29-PERK axis could mitigate disease severity.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Pfizer COVID19 vaccine is not associated with acute cardiovascular events excluding myocarditis- a national self-controlled case series study.

BACKGROUND: Despite publications assuring no increased risk for acute cardiovascular events (excluding myocarditis) and sudden death following administration of COVID19 vaccines, these issues still stir much public ado. We assessed the risk for acute cardiovascular events that require hospitalization (excluding myocarditis) and for mortality in the short-term following administration of the second dose of the Pfizer COVID19 vaccine in Israel. METHODS: Using a self-controlled case series (SCCS) study design and national databases, all second-dose vaccinees, who had not been diagnosed with COVID19 and who had an acute cardiovascular event (acute myocardial infarction/acute stroke/acute thromboembolic event) that required hospitalization in the 60 days following vaccine administration between Jan 11th, 2021 and Oct 31st 2021, were included. A similar analysis was carried out for mortality. The first 30 days following vaccination were defined as risk period while the next 30 days were defined as control period. The probability for an event between these periods was compared using a conditional logistic regression model, accounting for sex, age group, background morbidity and seasonal risk. RESULTS: Out of 5,700,112  second dose vaccinees, 4,163 had an acute cardiovascular event in the 60 days following vaccine administration. Following exclusion of 106 due to technical considerations, 1,979 events occurred during the risk period and 2,078 during the control period: Odds ratio, OR = 0.95, 95% confidence interval, CI 0.90-1.01, p = 0.12. Adjusted OR was similar (OR = 0.88, 95%CI 0.72-1.08). Stratifying by age showed no increased risk in any age group. Mortality assessment indicated low number of events in both periods. These results were consistent in sensitivity analyses. CONCLUSIONS: There was no increased risk for acute cardiovascular events (excluding myocarditis) in the risk period compared to the control period following administration of the second dose of Pfizer COVID19 vaccine. Mortality data raised no concerns either, but may have been biased.

A comparison of four self-controlled study designs in an analysis of COVID-19 vaccines and myocarditis using five European databases.

INTRODUCTION: The aim of this study was to assess the possible extent of bias due to violation of a core assumption (event-dependent exposures) when using self-controlled designs to analyse the association between COVID-19 vaccines and myocarditis. METHODS: We used data from five European databases (Spain: BIFAP, FISABIO VID, and SIDIAP; Italy: ARS-Tuscany; England: CPRD Aurum) converted to the ConcePTION Common Data Model. Individuals who experienced both myocarditis and were vaccinated against COVID-19 between 1 September 2020 and the end of data availability in each country were included. We compared a self-controlled risk interval study (SCRI) using a pre-vaccination control window, an SCRI using a post-vaccination control window, a standard SCCS and an extension of the SCCS designed to handle violations of the assumption of event-dependent exposures. RESULTS: We included 1,757 cases of myocarditis. For analyses of the first dose of the Pfizer vaccine, to which all databases contributed information, we found results consistent with a null effect in both of the SCRI and extended SCCS, but some indication of a harmful effect in a standard SCCS. For the second dose, we found evidence of a harmful association for all study designs, with relatively similar effect sizes (SCRI pre = 1.99, 1.40 - 2.82; SCRI post 2.13, 95 %CI - 1.43, 3.18; standard SCCS 1.79, 95 %CI 1.31 - 2.44, extended SCCS 1.52, 95 %CI = 1.08 - 2.15). Adjustment for calendar time did not change these conclusions. Findings using all designs were also consistent with a harmful effect following a second dose of the Moderna vaccine. CONCLUSIONS: In the context of the known association between COVID-19 vaccines and myocarditis, we have demonstrated that two forms of SCRI and two forms of SCCS led to largely comparable results, possibly because of limited violation of the assumption of event-dependent exposures.

Prevalence and impact of viral myocarditis in patients with severe fever with thrombocytopenia syndrome.

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease.

Granulomatous Myocarditis Caused by Candida Spp Infection in a Spontaneously Diabetic Torii Rat.

Background: Myocarditis refers to myocardial inflammation with necrosis caused by non-infectious of infectious agents such as bacteria, fungi, or drugs. Candida is known to cause myocarditis in healthy and immunocompromised individuals. Diabetes mellitus causes chronic hyperglycemia due to impaired secretion or hypofunction of insulin, induces a compromised state, and increases the risk of contracting various infections. Objective: We report a case of granulomatous myocarditis caused by Candida in a Spontaneously Diabetic Torii rat, a non-obese diabetic model. Case report: A male SDT rat, 61 weeks of age, was housed in conventional environment. The rat was provided a commercial diet and tap water ad libitum. The heart was sampled and prepared the specimen of hematoxylin-and-eosin-, Sirius-red-, Giemsa-, Grocott-stain. Histologically, formation of large granulation tissue was observed in the left ventricular wall. A center of the foci showed necrosis. Moreover, inflammatory cells infiltration and fibrous component were increased surrounding the foci and between myocardial cells. A Grocott and Giemsa staining-positive cell masses occasionally appearing in the foci were considered to be Candida because of their characteristic form. Conclusion: The development and progression of myocarditis were potentially related to a diabetes-induced compromised state.

[Cardiac sarcoidosis: a diagnostic and therapeutic challenge]. / Sarcoïdose cardiaque : un défi diagnostique et thérapeutique.

The diagnosis of cardiac sarcoidosis, particularly in its isolated cardiac form, represents a major challenge due to non-specific symptoms and the limited sensitivity and specificity of basic cardiac investigations. MRI and metabolic PET-CT are important elements in the diagnostic process. Corticosteroids remain the cornerstone for the treatment of the inflammatory phase, in association with biological agents and steroid-sparing therapies. The goal is to limit the progression of fibrosis, which is a source of malignant arrhythmias and heart failure. The indication for implantation of a cardiac defibrillator must be carefully evaluated to reduce the risk of sudden death. Multidisciplinary collaboration is essential for optimal care.

Le diagnostic de sarcoïdose cardiaque, en particulier dans sa forme cardiaque isolée, représente un défi majeur en raison de symptômes aspécifiques et d'une sensibilité et spécificité limitées des explorations cardiologiques de base. L'IRM et le PET-CT métabolique sont devenus des éléments essentiels dans le processus diagnostique. Les corticostéroïdes restent la pierre angulaire du traitement dans la phase inflammatoire, parallèlement aux agents biologiques et aux thérapies d'épargne cortisonique. L'objectif est d'éviter la progression vers la fibrose, source d'arythmies malignes et d'insuffisance cardiaque. L'indication à l'implantation d'un défibrillateur cardiaque doit être soigneusement évaluée afin de réduire le risque de mort subite. Une collaboration multidisciplinaire est essentielle afin d'assurer une prise en charge optimale.

Utility of new FDG-PET/CT guidelines for diagnosing cardiac sarcoidosis in patients with implanted cardiac pacemakers for atrioventricular block.

Diagnosing cardiac sarcoidosis (CS), especially in isolated cases, is challenging, particularly due to the limitations of endomyocardial biopsy, leading to potential undiagnosed cases in pacemaker-implanted patients. This study aims to provide real world findings to support new guideline for CS using 18F-fluoro-deoxyglucose positron-emission tomography computed tomography (FDG-PET/CT) which give a definite diagnosis of isolated CS (iCS) without histological findings. We examined consecutive patients with cardiac pacemakers for atrioventricular block (AV-b) attending our outpatient pacemaker clinic. The patients underwent periodical follow-up echocardiography and were divided into two groups according to echocardiographic findings: those with suspected CS and those without suspected CS. Patients suspected of having nonischemic cardiomyopathy underwent FDG-PET/CT for CS diagnosis. We investigated the utility of the new guideline for CS using FDG-PET/CT. Among the 272 patients enrolled, 97 patients were implanted with cardiac pacemakers for AV-b. Twenty-two patients were suspected of having CS during a median observation period of 5.4 years after pacemaker implantation. Of these, one did not consent, and nine of 21 cases (43%) were diagnosed with definite CS according to the new guidelines. Five of these nine patients were diagnosed with iCS using FDG-PET/CT. The number of patients diagnosed with definite CS using the new guidelines tended to be approximately 2.3 times that of the conventional criteria (p = 0.074). Three of the nine patients underwent steroid treatment. The composite outcome, comprising all-cause death, heart failure hospitalization, and a substantial reduction in left ventricular ejection fraction, were significantly lower in patients receiving steroid treatment compared to those without steroid treatment (p = 0.048). The utilization of FDG-PET/CT in accordance with the new guidelines facilitates the diagnosis of CS, including iCS, resulting in approximately 2.3 times as many diagnoses of CS compared to the conventional criteria. This guideline has the potential to support the early identification of iCS and may contribute to enhancing patient clinical outcomes.

Changes in Cardiac Function Following Fulminant Myocarditis.

BACKGROUND: The natural history of myocardial dysfunction in patients with fulminant myocarditis is poorly understood. This study aims to evaluate changes in cardiac function in patients with fulminant myocarditis using a nationwide registry in Japan. METHODS: This retrospective cohort study included patients with biopsy-proven fulminant myocarditis and available for left ventricular ejection fraction (LVEF). We described the LVEF on admission, at discharge, and 1 year after discharge. We divided patients into 2 groups based on LVEF at discharge (reduced ejection fraction of <50% or preserved ejection fraction of ≥50%) and analyzed changes in LVEF and prognosis according to groups. RESULTS: We included 214 patients (the median [first-third quartiles] age of the cohort was 48 [35-62] years, and 63 [38%] were female). Of 153 patients available for LVEF at 1 year, the median (first-third quartiles) LVEF increased from 33% (21-45%) on admission to 59% (49-64%) at discharge and further to 61% (55-66%) at 1 year. Of 153 patients, 45 (29%) and 22 (14%) had LVEF <50% at discharge and at 1 year, respectively. Comparisons between patients with LVEF <50% and those with LVEF ≥50% demonstrated that the former group had a higher adjusted probability of death or heart transplantation (hazard ratio, 8.19 [95% CI, 2.13-31.5]; P=0.002). CONCLUSIONS: Some patients with fulminant myocarditis had left ventricular dysfunction in the chronic phase. Patients with reduced left ventricular function at discharge had a worse prognosis than those with preserved left ventricular function. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045352; Unique identifier: UMIN000039763.

Letter to the Editor: A comparison of post-COVID vaccine myocarditis classification using the Brighton Collaboration criteria versus (United States) Centers for Disease Control criteria: an update.

Abstract: (No abstract provided).

[High-degree atrioventricular (AV) block]. / Borreliakardit ­ ovanlig orsak till atrioventrikulärt block.

In elderly patients high-degree atrioventricular (AV) block is often due to irreversible degeneration of the cardiac conduction system. Reversible causes must however be excluded prior to pacemaker implantation. In younger patients reversible causes are more likely, as well as more unusual etiologies. Lyme carditis is a rare, but reversible cause of AV block. It is a manifestation of Lyme borreliosis - an infectious disease caused by the bacteria Borrelia burgdorferi. Lyme carditis should particularly be considered in young and middle-aged patients with a high-degree AV block. When pretest probability is intermediate to high, a positive serological test makes the diagnosis of Lyme carditis highly likely. In these cases antibiotic treatment may revert the conduction disturbance, thus preventing unnecessary implantation of a permanent pacemaker.

Severe DRESS with myocarditis secondary to naproxen/esomeprazole.

A man in his 60s presented with a widespread erythematous rash and associated chills, paraesthesia and haematuria. He had recently commenced naproxen/esomeprazole. Blood tests showed hypereosinophilia (0.73×109/L) and moderate acute kidney injury. Histology revealed parakeratosis, mild spongiosis with eosinophils. He developed acute coronary syndrome with rapid atrial fibrillation. Coronary angiogram was non-obstructive. Cardiac MRI (CMR) revealed acute myocarditis secondary to Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Naproxen/esomeprazole was discontinued, and he was supported with oral corticosteroids. A repeat CMR 3 months later showed resolution of myocarditis. Naproxen/esomeprazole is not a common offending drug. DRESS is a rare drug-induced hypersensitivity reaction with a mortality rate of 10%. The objective of this case report is to highlight the significant but rare cardiac complications that can ensue from DRESS, which warrant prompt recognition and withdrawal of the causative drug.

Assessment of Risk for Sudden Cardiac Death Among Adolescents and Young Adults After Receipt of COVID-19 Vaccine - Oregon, June 2021-December 2022.

COVID-19 vaccination has been associated with myocarditis in adolescents and young adults, and concerns have been raised about possible vaccine-related cardiac fatalities in this age group. In April 2021, cases of myocarditis after COVID-19 vaccination, particularly among young male vaccine recipients, were reported to the Vaccine Adverse Event Reporting System. To assess this possibility, investigators searched death certificates for Oregon residents aged 16-30 years who died during June 2021-December 2022 for cardiac or undetermined causes of death. For identified decedents, records in Oregon's immunization information system were reviewed for documentation of mRNA COVID-19 vaccination received ≤100 days before death. Among 1,292 identified deaths, COVID-19 was cited as the cause for 30. For 101 others, a cardiac cause of death could not be excluded; among these decedents, immunization information system records were available for 88, three of whom had received an mRNA COVID-19 vaccination within 100 days of death. Of 40 deaths that occurred among persons who had received an mRNA COVID-19 vaccine dose, three occurred ≤100 days after vaccination. Two of these deaths were attributed to chronic underlying conditions; the cause was undetermined for one. No death certificate attributed death to vaccination. These data do not support an association between receipt of mRNA COVID-19 vaccine and sudden cardiac death among previously healthy young persons. COVID-19 vaccination is recommended for all persons aged ≥6 months to prevent COVID-19 and complications, including death.

Hemophagocytic lymphohistiocytosis and myopericarditis induced by campylobacter: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe disorder characterized by excessive activation of the immune system, leading to hypercytokinemia and damage to multiple organs. We report a rare case of HLH with myopericarditis caused by Campylobacter infection. CASE PRESENTATION: A 28-year-old male patient with a history of hypertension without medicine control presented at the hospital after a four-day fever, decreasing urine amount, rashes on his trunk and limbs, and other symptoms. He was admitted with a provisional diagnosis of atypical infection and allergic skin rash related to diclofenac. However, his condition deteriorated, and he developed shock, tachycardia, chest distress, and bilateral pleural effusion after admission. Further investigations revealed cardiogenic shock related to myopericarditis, and he was transferred to the ICU. In addition, a stool PCR panel subsequently revealed a positive result for Campylobacter. On day 6, he was diagnosed with HLH. Under Clarithromycin and dexamethasone infusion, leukocytosis, anemia and thrombocytopenia with cardiogenic shock status improved. Then, he was later discharged in stable condition. CONCLUSIONS: HLH and myopericarditis caused by Campylobacter are very rare. Early detection of Campylobacter-induced HLH and multiple organ failure, as well as prompt use of antibiotics and immunosuppressants, can be helpful for prognosis.