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.

CXCL4/CXCR3 axis regulates cardiac fibrosis by activating TGF-ß1/Smad2/3 signaling in mouse viral myocarditis.

BACKGROUND: Severe myocarditis is often accompanied by cardiac fibrosis, but the underlying mechanism has not been fully elucidated. CXCL4 is a chemokine that has been reported to have pro-inflammatory and profibrotic functions. The exact role of CXCL4 in cardiac fibrosis remains unclear. METHODS: Viral myocarditis (VMC) models were induced by intraperitoneal injection of Coxsackie B Type 3 (CVB3). In vivo, CVB3 (100 TCID50) and CVB3-AMG487 (CVB3: 100 TCID50; AMG487: 5 mg/kg) combination were administered in the VMC and VMC+AMG487 groups, respectively. Hematoxylin and eosin staining, severity score, Masson staining, and immunofluorescence staining were performed to measure myocardial morphology in VMC. Enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to quantify inflammatory factors (IL-1ß, IL-6, TNF-α, and CXCL4). Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB) levels were analyzed by commercial kits. CXCL4, CXCR3B, α-SMA, TGF-ß1, Collagen I, and Collagen III were determined by Western blot and immunofluorescence staining. RESULTS: In vivo, CVB3-AMG487 reduced cardiac injury, α-SMA, Collagen I and Collagen III levels, and collagen deposition in VMC+AMG487 group. Additionally, compared with VMC group, VMC+AMG group decreased the levels of inflammatory factors (IL-1ß, IL-6, and TNF-α). In vitro, CXCL4/CXCR3B axis activation TGF-ß1/Smad2/3 pathway promote mice cardiac fibroblasts differentiation. CONCLUSION: CXCL4 acts as a profibrotic factor in TGF-ß1/Smad2/3 pathway-induced cardiac fibroblast activation and ECM synthesis, and eventually progresses to cardiac fibrosis. Therefore, our findings revealed the role of CXCL4 in VMC and unveiled its underlying mechanism. CXCL4 appears to be a potential target for the treatment of VMC.

[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.

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.

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.

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.

Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism by regulating microRNA-145-5P/insulin receptor substrate 1 axis.

The treatment of patients with acute pulmonary embolism (APE) is extremely challenging due to the complex clinical presentation and prognosis of APE related to the patient's hemodynamic status and insufficient arterial blood flow and right ventricular overload. Protective efficacy against cardiovascular diseases of curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. However, the direct effect of curcumin on APE has rarely been studied. Therefore, the present study aimed to investigate the therapeutic potential of curcumin in APE and associated myocardial injury to provide new insights into curcumin as a promising competitive new target for the treatment of APE. A suspension of 12 mg/kg microspheres was injected intravenously into rats. An APE rat model was built. Before modeling, intragastric 100 mg/kg curcumin was given, and/or lentiviral plasmid vector targeting microRNA-145-5p or insulin receptor substrate 1 (IRS1) was injected. Pulmonary artery pressure was measured to assess right ventricular systolic pressure (RVSP). Hematoxylin and eosin (H&E) staining was performed on liver tissues and myocardial tissues of APE rats. TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) staining and immunohistochemical (IHC) staining were conducted to measure apoptosis and CyPA-CD147 expression in the myocardium, respectively. Inflammatory indices interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA in cardiac tissues. RT-qPCR and Western blot were performed to determine the expression levels of related genes. In addition, by dual luciferase reporter assay and RIP assay, the relationship between microRNA-145-5p and insulin receptor substrate 1 (IRS1) was confirmed. In results: curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. MicroRNA-145-5p overexpression protected against APE-induced myocardial injury, and microRNA-145-5p silencing abolished the beneficial effects of curcumin in APE-induced myocardial injury. IRS1 was targeted by microRNA-145-5p. IRS1 silencing attenuated APE-induced myocardial injury, and enhanced therapeutic effect of curcumin on myocardial injury in APE rats. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.

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.

Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall.

In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.

Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma: A case report and review of literature.

INTRODUCTION: In rare occasions, coxsackievirus infections can cause serious illness, such as encephalitis and myocarditis. The immunotherapies of cancer could increase the risk of myocarditis, especially when applying immune checkpoint inhibitors. Herein, we report a rare case of Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma. CASE PRESENTATION: A 32-year-old woman was admitted to the hospital with recurrent fever for more than 20 days, and she had a history of lymphoma. Before admission, the positron emission tomography/computed tomography result indicated that the patient had no tumor progression, and she was not considered the cancer-related fever upon arriving at our hospital. Patient's red blood cell, platelet count, and blood pressure were decreased. In addition, she had sinus bradycardia and 3 branch blocks, which was consistent with acute high lateral and anterior wall myocardial infarction. During hospitalization, the patient had recurrent arrhythmia, repeated sweating, poor mentation, dyspnea, and Coxsackie B virus were detected in patient's blood samples by pathogen-targeted next-generation sequencing. The creatine kinase, creatine kinase MB, and N-terminal pro-brain natriuretic peptide were persistently elevated. Consequently, the patient was diagnosed with viral myocarditis induced by Coxsackie B virus, and treated with acyclovir, gamma globulin combined with methylprednisolone shock therapy, trimetazidine, levosimendan, sildenan, continuous pump pressors with m-hydroxylamine, entecavir, adefovir, glutathione, pantoprazole, and low-molecular-weight heparin. Her symptoms worsened and died. CONCLUSION: We reported a case with a history of lymphoma presented with fever, myocardial injury, who was ultimately diagnosed with Coxsackie B virus-induced myocarditis. Moreover, pathogen-targeted next-generation sequencing indeed exhibited higher sensitivity compared to mNGS in detecting Coxsackie B virus.

An Autopsy Case of Fulminant Myocarditis with Massive Left Ventricular Calcification.

Myocardial calcification in myocarditis is rare and may be linked to poor outcomes. We herein report a case of fulminant myocarditis with massive myocardial calcification and its pathological outcomes at autopsy. A 49-year-old man experienced chest pain and was diagnosed with acute myocarditis. His cardiac function did not recover despite mechanical circulatory support in combination with V-A extracorporeal membrane oxygenation and IMPELLA CP®. He eventually developed sepsis and gastrointestinal bleeding and died on day 27. Diffuse myocardial calcification was observed on computed tomography at autopsy. The pathological autopsy depicted that calcification filled every myocardial cell in the left ventricle.

Relationship of Mild to Moderate Impairment of Left Ventricular Ejection Fraction With Fatal Ventricular Arrhythmic Events in Cardiac Sarcoidosis.

BACKGROUND: Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). METHODS AND RESULTS: We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex-specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49-7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04-4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates. CONCLUSIONS: Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.

CD73/adenosine axis exerts cardioprotection against hypobaric hypoxia-induced metabolic shift and myocarditis in a sex-dependent manner.

BACKGROUND: Clinical and experimental studies have shown that the myocardial inflammatory response during pathological events varies between males and females. However, the cellular and molecular mechanisms of these sex differences remain elusive. CD73/adenosine axis has been linked to anti-inflammatory responses, but its sex-specific cardioprotective role is unclear. The present study aimed to investigate whether the CD73/adenosine axis elicits sex-dependent cardioprotection during metabolic changes and myocarditis induced by hypobaric hypoxia. METHODS: For 7 days, male and female mice received daily injections of the CD73 inhibitor adenosine 5'- (α, ß-methylene) diphosphate (APCP) 10 mg/kg/day while they were kept under normobaric normoxic and hypobaric hypoxic conditions. We evaluated the effects of hypobaric hypoxia on the CD73/adenosine axis, myocardial hypertrophy, and cardiac electrical activity and function. In addition, metabolic homeostasis and immunoregulation were investigated to clarify the sex-dependent cardioprotection of the CD73/adenosine axis. RESULTS: Hypobaric hypoxia-induced cardiac dysfunction and adverse remodeling were more pronounced in male mice. Also, male mice had hyperactivity of the CD73/adenosine axis, which aggravated myocarditis and metabolic shift compared to female mice. In addition, CD73 inhibition triggered prostatic acid phosphatase ectonucleotidase enzymatic activity to sustain adenosine overproduction in male mice but not in female mice. Moreover, dual inhibition prostatic acid phosphatase and CD73 enzymatic activities in male mice moderated adenosine content, alleviating glycolytic shift and proinflammatory response. CONCLUSION: The CD73/adenosine axis confers a sex-dependent cardioprotection. In addition, extracellular adenosine production in the hearts of male mice is influenced by prostatic acid phosphatase and tissue nonspecific alkaline phosphatase.