Heart failure with preserved ejection fraction (HFpEF) represents a complex clinical syndrome characterized by limited therapeutic options, which are largely due to its intricate pathophysiology. The role of mechanical stress is pivotal in maintaining cardiovascular homeostasis; conversely, its dysregulation may precipitate the progression of cardiovascular diseases. In HFpEF, both macroscopic structural alterations and intricate molecular processes might be influenced by mechanical stress. This review examines the potential associations between mechanical stress and HFpEF, exploring the pathophysiological underpinnings to the effects of mechanotransduction effectors on cardiac remodeling and the progression of heart failure, providing novel insights into the pathological mechanisms of HFpEF. Therapeutic strategies targeting these mechanotransduction effectors have shown promise in mitigating pathological cardiac remodeling in models of metabolic-associated heart failure, underscoring their potential as innovative treatments for HFpEF. Considering the clinical heterogeneity of HFpEF, it is imperative to pursue phenotype-specific personalized treatments to optimize therapeutic efficacy.

BACKGROUND:Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS:We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS:Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS:In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.

BACKGROUND:Patients with coronary heart disease (CHD) complicated by diabetes mellitus (DM) remain at substantial residual cardiovascular risk despite contemporary guideline-directed medical therapy. However, the long-term trajectory of this excess risk and its temporal pattern have not been fully clarified. METHODS:This is a retrospective cohort study based on a large-scale public database and real-world clinical data. The primary cohort was derived from the UK Biobank (UKB), including 7491 CHD patients and 2322 CHD with DM patients; the validation cohort included 362 CHD patients from Tongji Hospital. Both cohorts were followed for up to 10 years, with major adverse cardiovascular events (MACE) as the primary endpoint. Propensity score matching (PSM) was employed to balance baseline confounders. Kaplan-Meier analysis combined with piecewise log-rank tests were used to assess cumulative risk differences at various follow-up time points. Multivariable Cox proportional hazards models were constructed to evaluate the independent impact of diabetes. RESULTS:In the UKB cohort, CHD with DM patients exhibited significantly higher risks of MACE and cardiovascular death before matching. After 1:1 PSM, no significant difference in MACE risk was observed during the early follow-up period (1 year, p > 0.05). However, survival curves showed progressive divergence over time, with the risk difference reaching statistical significance at 10 years (p = 0.0004), demonstrating a pronounced time-cumulative effect. The Tongji validation cohort similarly confirmed that event-free survival was significantly lower in the CHD with DM group (p = 0.0028). Independent risk factor analysis using multivariable Cox regression showed that after adjusting for age, sex, smoking, and lipid parameters, diabetes remained an independent risk factor for long-term MACE (UKB cohort HR > 1; Tongji cohort HR = 1.86, 95% CI: 1.20-2.86, p = 0.005). CONCLUSIONS:Diabetes significantly increases the long-term residual cardiovascular risk in CHD patients. This excess risk is characterized by a clear time-cumulative effect: under modern guideline-directed medical therapy, early risk may be effectively buffered, but long-term adverse events remain markedly elevated. More proactive and intensified long-term intervention strategies are urgently needed for CHD patients with comorbid diabetes.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) continues to be a major global health burden, with substantial residual cardiovascular risk remaining. Growing evidence highlights the liver’s pivotal role in the onset and development of ASCVD through multiple interconnected pathways. MAIN BODY: As the metabolic center of the body, the liver regulates the synthesis, secretion, and clearance of several atherogenic lipoproteins while simultaneously serving as a systemic inflammation amplifier, producing cytokines, acute-phase proteins, and coagulation factors. Traditional liver-targeted therapies, such as statins, have demonstrated that regulating liver metabolism can confer significant cardiovascular benefits. Subsequently, advances in nucleic acid-based drugs and in vivo gene-editing tools have broadened this strategy, enabling accurate and durable modulation of hepatic gene expression. However, recent clinical trials suggest that improvements in laboratory biomarkers do not always translate into proportional reductions in major adverse cardiovascular events. Moreover, the long-term safety and durability of lipid nanoparticles and gene-editing platforms remain ongoing concerns. Future research should focus on the classification of patients based on multiple omics data, and distinguish those whose main problem is metabolic disorder from those who are mainly at high risk of inflammation, thereby facilitating personalized therapeutic targeting. CONCLUSION: Overall, current evidence indicates that the liver represents a convergent therapeutic target for modulating both lipid metabolism and inflammation, offering a promising opportunity for deeper and more durable cardiovascular risk reduction.

Chronic inflammatory cardiomyopathy (infl-CMP) is a long-term sequela caused by the chronicity of acute myocarditis, especially fulminant myocarditis (FM). Hydroxychloroquine (HCQ) may benefit these patients by inhibiting the excessive inflammatory response. In this multicenter, randomized trial, we evaluated the efficacy and safety of HCQ in patients with chronic infl-CMP after FM. The primary outcome of the trial was a composite of the cardiovascular outcomes of time to cardiovascular death or heart transplant, hospitalization for heart failure or recurrence of myocarditis, permanent pacemaker, or implantable cardioverter defibrillator implantation. Secondary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular internal diastolic diameter (LVIDd), plasma levels of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) from baseline to 12 months. Fifty patients were randomized to receive HCQ combined with prednisolone (PDN) or PDN monotherapy for 12 months. Compared to PDN monotherapy, HCQ combined with PDN therapy reduced the primary composite outcome [hazard ratio (HR) = 0.28, 95

Introduction: To assess the short-term and long-term outcomes of percutaneous endomyocardial biopsy (EMB) in patients with myocarditis and to identify the risk factors for EMB-related complications in this patient population. Methods: A retrospective analysis was conducted on 294 hospitalized patients with clinically suspected myocarditis at Tongji Hospital from October 2019 to October 2023, with a median follow-up duration of 18 months. Patients were divided into an EMB group (n = 151) and a non-EMB group (n = 143) based on whether they underwent EMB procedure. The incidence of endpoints was compared between the two groups, and the Kaplan-Meier survival curve was used to assess the survival rate without endpoints. Endpoints included major adverse cardiovascular events (MACE), ventricular enlargement, and decline in cardiac function. Multivariate logistic regression analysis was employed to evaluate the risk factors for EMB-related complications. Results: The incidence of major short-term complications following EMB was 2.0% (3/151), while the incidence of minor complications was 9.3% (14/151). Multivariate risk regression analysis revealed that operative duration (OR: 1.101, 95% CI: 1.02-1.079, p < 0.05) and BNP levels (OR: 1.083, 95% CI: 0.931-1.26, p < 0.05) were associated with short-term complications following EMB. Compared to the non-EMB group, the EMB group had no significant increase in hospital stay (10 [8, 15] vs. 9 [7, 16], p = 0.27) and no significant decline in cardiac function. Long-term follow-up results showed that 8 patients (5.3%) in the EMB group experienced MACE, 14 patients (9.3%) had left ventricular enlargement, and 18 patients (11.9%) had a decline in left ventricular ejection fraction (LVEF) after discharge; in the non-EMB group, 12 patients (8.4%) experienced MACE, 30 patients (19.9%) had left ventricular enlargement, and 18 patients (11.9%) had a decline in LVEF after discharge. The Kaplan-Meier curve revealed a lower incidence of endpoint events in the EMB group (p < 0.05). Conclusions: In patients with myocarditis, EMB is associated with a risk of short-term complications, with higher levels of BNP and operative duration being independent risk factors for EMB-related complications. However, EMB does not adversely affect cardiac function or hospital stay during the inpatient period and may contribute to the improvement of long-term outcomes in patients with myocarditis.

Background:Coronary Heart Disease (CHD) with renal insufficiency is a significant global health issue. This study aimed to develop and validate a predictive model for in-hospital mortality to enable early risk identification in these patients. Methods:We analyzed data from 11,830 CHD patients with renal insufficiency treated at Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China (1994-2023). Among 113 clinical variables, five key features-age, high-sensitivity C-reactive protein (hs-CRP), estimated glomerular filtration rate (eGFR), creatine kinase (CK), and blood urea-were selected using Recursive Feature Elimination. Six machine learning models (Random Forest, XGBoost, Decision Tree, Neural Network, Logistic Regression, and Support Vector Machine) were developed and assessed for discrimination, calibration, and clinical utility. Temporal validation was performed using data from May 16, 2023 to October 31, 2024. SHapley Additive exPlanations (SHAP) were used for model interpretation. Results:Of the 11,830 patients, 694 (5.9 %) died during hospitalization. Among the six models, XGBoost showed the best overall performance in the test set, achieving the highest AUC (0.926), lowest Brier score (0.034), highest accuracy (0.957), and balanced sensitivity (0.381) and F1 score (0.512). Decision curve analysis confirmed its superior clinical utility. In a temporally independent validation cohort of 5983 patients, XGBoost maintained strong predictive performance (AUC = 0.901), demonstrating excellent robustness and generalizability. Conclusions:The XGBoost-based model accurately predicts in-hospital mortality in CHD patients with renal insufficiency, supporting early risk stratification and clinical decision-making.

Viral myocarditis, an inflammatory heart disorder caused by viral infections, often leads to poor outcomes due to the lack of effective prevention and treatment strategies. Despite the characteristic feature of cardiomyocyte death in this condition, the underlying mechanisms and potential therapeutic approaches remain poorly understood. Traditional Chinese medicine (TCM), despite its extensive history in treating various diseases, has not yet been approved for the treatment of viral myocarditis. Here, we screened six TCM patent injections recommended by clinical practice guidelines for treating cardiovascular diseases and discovered that Danhong Injection (DHI) markedly reduced cardiomyocyte death induced by Coxsackievirus B3 (CVB3). Additionally, in a CVB3-infected mouse model of viral myocarditis, DHI treatment notably alleviated cardiomyocyte death (including apoptosis, necroptosis and pyroptosis), as well as inflammation, cardiac dysfunction, and mortality. Mechanistically, DHI exerted its protective effects by inhibiting CaMKII through its active monomer Dihydrotanshinone I (Dih-I), identified as a CaMKII inhibitor. In viral myocarditis patients, CaMKII phosphorylation was upregulated in the hearts. The anti-inflammatory properties and CaMKII inhibition effects of DHI were further validated in primary human peripheral blood mononuclear cells. Our findings not only demonstrate the central role of CaMKII-mediated cardiomyocyte death in the progression of viral myocarditis, but also highlight DHI as a promising therapeutic intervention for managing viral myocarditis-induced cardiac injury and related pathological response.

Background:Although temporary mechanical circulatory supports (tMCS) combined with immunoregulatory therapy (IT) can reduce the mortality of patients with fulminant myocarditis (FM), a considerable proportion still progress to chronic persistent cardiac dysfunction. It is unclear if angiotensin-converting enzyme (ACE) inhibitors can further prevent such dysfunction under tMCS combined with IT. Methods:This multicenter, retrospective, observational study included 124 FM patients with a left ventricular ejection fraction (LVEF) ≤ 40%. Among them, 90 (72.58%) received ACE inhibitors and 34 (27.42%) did not. Patients had echocardiography during follow-up. Logistic regression analysis, subgroup analysis, and restricted cubic spline modeling were used to identify clinical variables associated with the primary outcome. Results:The primary outcome was defined as an LVEF < 55% at the last follow-up. The median follow-up was 12 (6, 18) months. 46 patients (37.1%) had an LVEF < 55% at the last follow-up. Among them, 25 (27.78%) received ACE inhibitors and 21 (61.76%) did not. In the non-ACE inhibitors group, LVEF declined from baseline over 24 months. Among the 49 patients (39.52%) with a left ventricular end-diastolic dimension (LVEDD) ≥ 5cm at admission, 29 (59.18%) had an LVEF < 55% at the last follow-up. 15 patients (51.72%) took ACE inhibitors and 14 (48.28%) did not. Multivariate logistic regression analysis revealed that ACE inhibitors (HR = 0.19, 95% CI: 0.04-0.96, P = 0.045) and LVEDD (HR = 9.18, 95% CI: 2.73-30.83, P < 0.001) were independently associated with an LVEF < 55% at the last follow-up, and the risk increased linearly with LVEDD (P for nonlinear > 0.05). Conclusion:ACE inhibitors may improve left ventricular (LV) function and prevent chronic persistent cardiac dysfunction in FM patients. Although they can partially reverse LV remodeling, increased LVEDD during long-term follow-up may reduce their therapeutic benefits.

Background Fulminant myocarditis (FM) is the most severe form of myocarditis, characterized by rapid clinical progression and circulatory instability. However, its pathological features and their relationship to clinical presentation are not well understood. Objectives This study aims to provide an overview of the clinicopathologic features of FM. Methods A total of 80 patients with FM were enrolled between January 2021 and September 2022 in Wuhan, China. Endomyocardial biopsies and subsequent histochemical staining were performed on all patients who were followed up for 3 months. The pathological features of the myocardium were described. The relationship between myocardial inflammatory cell infiltration and clinical presentation was analyzed. Results According to hematoxylin and eosin staining, 76 out of 80 patients with FM were diagnosed with lymphocytic myocarditis, while 4 were diagnosed with eosinophilic myocarditis. Microscopically, various forms of cell degeneration were observed, especially myocardial edema and cardiomyocyte necrosis. Histochemical analysis indicated that innate immune cells (primarily macrophages and neutrophils) predominated in the acute stage of FM. Proper treatment with immunomodulatory agents, such as glucocorticoids and immunoglobulin, promoted macrophage polarization into the M2 subtype. A high density of total inflammatory cell infiltration was associated with elevated levels of inflammatory biomarkers (hs-CRP and ESR) and more severe circulatory deterioration, which necessitated more frequent use of IABP, ECMO, and pacemakers. Conclusions To date, this largest cohort of histochemical analyses of FM, based on endomyocardial biopsy samples, has revealed dominant infiltration of innate immune cells in the early stage, followed by lymphocytes. This finding suggests that the activation of innate immunity is the initial mechanism triggering the cytokine storm in FM. The results also support the beneficial effects of immunomodulatory therapy using glucocorticoids and immunoglobulins rather than immunosuppression by promoting M2 macrophage polarization. This study was registered at https://clinicaltrials.gov/study/NCT03268642.

Background Traditionally, amiodarone or electrical cardioversion was used if radiofrequency catheter ablation (RFCA) could not terminate atrial fibrillation during the procedure in patients with persistent atrial fibrillation (PeAF). Objective To investigate whether the nifekalant instead of amiodarone during RFCA improve procedure outcomes in patients with PeAF. Methods This study enrolled patients with PeAF who failed to achieve cardioversion after initial ablation at our center between January 2020 and December 2022. These patients were classified into the nifekalant (N) group and the amiodarone (A) group. And patients were followed for 1 year to evaluate long-term success rates. Subgroup analyses and the logistic regression analyses were performed. Results The study comprised 300 participants and included N (n = 121) and A (n = 179) groups. Following propensity score matching (PSM), 101 participants were in each group. Within the N and A groups, 57(56.44 %) and 19(18.81 %) cases successfully terminated AF, 45 (44.56 %) and 15(14.85 %) cases achieved conversion to atrial tachycardia (P < 0.001), respectively. The ventricular tachycardia was observed in only one case in the N group (P > 0.05). The follow-up results demonstrated that one-year success rates were 63.37 % and 49.50 % for the N and A groups (P < 0.05). Conclusion For patients with PeAF that persists after initial catheter ablation, compared to amiodarone, administration of nifekalant could convert atrial fibrillation into atrial tachycardia, following by target ablation, has the potential to improve the procedure outcomes.

Transfer RNA-derived small RNAs (tsRNAs) have emerged as potential biomarkers of various human diseases. However, the clinical utility and biological functions of tsRNA in acute coronary syndrome (ACS) remain poorly understood. To investigate this, we performed high-throughput small RNA sequencing on peripheral blood monocyte cells (PBMCs) from 24 ACS patients and 12 healthy controls. Our analysis revealed distinct and characteristic expression patterns of tsRNAs in response to ACS, highlighting their potential as disease signatures in human PBMCs. Differentially expressed tsRNAs were validated using RT-qPCR in two independent case-control sets. Among these, tRF-Gly-GCC-06 was significantly upregulated in volunteers with unstable angina (UA) and acute myocardial infarction (AMI) (p < 0.05) and showed a statistically significant positive correlation with the Gensini score (r = 0.353, p < 0.001). Moreover, this tsRNA was independently associated with an increased risk of ACS after adjusting for conventional cardiovascular risk factors (odds ratio (OR) = 1.58, 95% confidence interval (CI): 1.37-1.83, p < 0.001). A series of functional studies showed that tRF-Gly-GCC-06 significantly facilitated macrophage proliferation and migration and modulated inflammation-related gene expression in vitro. This study identified a novel functional gene associated with ACS, tRF-Gly-GCC-06, as a potential clinical biomarker and therapeutic target.

(1) Background: Malignant arrhythmia complicating fulminant myocarditis is associated with high in-hospital mortality, but evidence regarding its long-term prognosis and specific risk factors is limited. (2) Methods: This single-center retrospective cohort study (2016-2025) analyzed 241 consecutive fulminant myocarditis patients, stratified by malignant arrhythmia status (n = 58 vs. 183). The malignant arrhythmia group was further subclassified into malignant tachyarrhythmia (n = 22) and bradyarrhythmia (n = 36). Endpoints included major adverse cardiovascular events (MACE), cardiac dysfunction, and structural abnormalities. (3) Results: At 3-month follow-up, malignant arrhythmia patients had a significantly higher incidence of MACE compared to non-malignant arrhythmia patients (15.5% vs. 4.9%, p = 0.008), but no significant differences were found in cardiac dysfunction or structural abnormalities. Multivariate analysis identified low triglyceride level as an independent risk factor for in-hospital malignant tachyarrhythmia. For in-hospital malignant bradyarrhythmia, independent risk factors were delayed, such as intrinsicoid deflection, low diastolic blood pressure, bradycardia, and an elevated E/Em ratio, with the predictive model showing high discriminatory power. (4) Conclusions: Malignant arrhythmia is an independent predictor of adverse short-term, but not long-term, prognosis in fulminant myocarditis patients, with distinct risk factor profiles identified for malignant tachyarrhythmia and malignant bradyarrhythmia subtypes.

The APOA1/C3/A4/A5 cluster is an essential component in regulating lipoprotein metabolism and maintaining plasma lipid homeostasis. A genome-wide association analysis and Mendelian randomization have revealed potential associations between genetic variants within this cluster and lipid metabolism disorders, including hyperlipidemia and cardiovascular events. An enhanced understanding of the complexity of gene regulation has led to growing recognition regarding the role of epigenetic variation in modulating APOA1/C3/A4/A5 gene expression. Intensive research into the epigenetic regulatory patterns of the APOA1/C3/A4/A5 cluster will help increase our understanding of the pathogenesis of lipid metabolism disorders and facilitate the development of new therapeutic approaches. This review discusses the biology of how the APOA1/C3/A4/A5 cluster affects circulating lipoproteins and the current progress in the epigenetic regulation of the APOA1/C3/A4/A5 cluster.

Background: Long QT syndrome (LQTS) is an inherited malignant arrhythmia syndrome that poses a risk of sudden death. Variants in the Potassium Voltage-Gated Channel Subfamily H Member 2 (KCNH2) gene are known to cause Long QT syndrome through an autosomal dominant inheritance pattern. However, as of now, there have been no reports of any KCNH2 variant leading to Long QT syndrome exhibiting incomplete penetrance that is influenced by gender. Methods: Whole-exome sequencing (WES) was conducted on the proband to identify pathogenic variants. Subsequently, Sanger sequencing was employed to validate the identified likely pathogenic variants in all family members. Results: We analyzed a pedigree spanning three-generations afflicted by Long QT syndrome. WES revealed a novel KCNH2 missense variant (p.Val630Gly, c.1889 T>G) as the causative factor for the family's phenotype. Within this family, all three male carriers of the KCNH2 variant carriers exhibited the Long QT syndrome phenotype: one experienced sudden death during sleep, another received an implantable cardioverter defibrillator (ICD), and a younger man displayed a prolonged QTc interval without any instances of syncope or malignant arrhythmia to date. Interestingly, the middle-aged female carrier showed no Long QT Syndrome phenotype. However, her offspring, diagnosed with Turner syndrome (45, X) and also a carrier of this variant, experienced frequent syncope starting at 12 years old and was diagnosed with Long QT syndrome, leading to an ICD implantation when she was 15 years old. These observations suggest that the manifestation of Long QT syndrome associated with this KCNH2 variant exhibits incomplete penetrance influenced by gender within this family, indicating potential protective mechanisms against the syndrome in females affected by this variant. Conclusion: Our investigation has led to the identification of a novel pathogenic KCNH2 variant responsible for Long QT syndrome within a familial context characterized by gender-selective, incomplete penetrance. This discovery highlights a unique pathogenic inheritance pattern for the KCNH2 gene associated with Long QT syndrome, and could potentially shed light on the distinct penetrance behaviors and patterns of the KCNH2 gene. This discovery broadens our exploration of the KCNH2 gene in cardiac arrhythmias, highlighting the intricate genetic dynamics behind Long QT syndrome.

Fulminant myocarditis (FM) is an acute and severe form of myocarditis with rapid progression and poor clinical outcomes in the absence of acute or chronic coronary artery disease. Electrocardiogram (ECG) abnormalities can provide preliminary clues for diagnosis; however, there is a lack of systemic descriptions on ECG changes in FM populations. Thus, a retrospective analysis of 150 consecutive FM patients and 300 healthy controls was performed to determine the characteristic ECG findings in FM. All patients included had markedly abnormal ECG findings. Specifically, 83 (55.33%) patients had significantly lower voltage with remarkably decreased QRS amplitudes in all leads compared with healthy controls (p < 0.01), and 77 (51.33%) patients had a variety of arrhythmias with lethality ventricular tachycardia/ventricular fibrillation in 21 (14.00%) patients and third-degree atrioventricular block in 21 (14.00%) patients, whereas sinus tachycardia was only found in 43 (28.67%) patients with the median heart rate (HR; 88.00 bpm, IQR: 76.00–113.50) higher than that of controls (73.00 bpm, IQR: 68.00–80.00) (p = 0.000). Conduction and repolarization abnormalities were common in patients. A longer QTc interval (452.00 ms, IQR: 419.00–489.50) and QRS duration (94.00 ms, IQR: 84.00–119.00) were observed in patients compared to controls (QTc interval = 399.00 ms, IQR: 386.00–414.00; QRS duration = 90.00 ms, IQR: 86.00–98.00) (p < 0.05). Additionally, HR > 86.50 bpm, QTc > 431.50 ms, and RV5 + SV1 < 1.715 mV can be used to predict FM. Thus, marked and severe ECG abnormalities provide preliminary clues for the diagnosis of FM.

We describe a previously uncharacterized ATP-binding cassette A1 super enhancer RNA (ABCA1-seRNA)-mediated cholesterol efflux. In addition, it promoted macrophage inflammatory cytokine release, and was causally correlated with coronary artery disease severity. Mechanistically, ABCA1-seRNA upregulated cholesterol efflux by interacting with mediator complex subunit 23 and recruiting retinoid X receptor-alpha and liver X receptor-alpha to promote ABCA1 transcription in a cis manner. Meanwhile, ABCA1-seRNA induced P65 ubiquitination degradation, and thereby repressed the macrophage inflammatory response. Consistently, overexpression of ABCA1-seRNA in ApoE-/- mice decreased plasma lipids, cytokines, and atherosclerotic plaques. These findings indicate ABCA1-seRNA is a critical epigenetic regulator that maintains cholesterol homeostasis and modulates inflammation, thus promising a therapeutic target for atherosclerotic cardiovascular diseases.

Objective Emerging evidence highlights the pivotal roles of long non-coding RNAs (lncRNAs) in lipid metabolism. Apoprotein C3 (ApoC3) is a well-established therapeutic target for hypertriglyceridemia and exhibits a strong association with cardiovascular disease. However, the exact mechanisms via which the lncRNAs control ApoC3 expression remain unclear. Methods We identified a novel long noncoding RNA (lncRNA), GM47544, within the ApoA1/C3/A4/A5 gene cluster. Subsequently, the effect of GM47544 on intracellular triglyceride metabolism was analyzed. The diet-induced mouse models of hyperlipidemia and atherosclerosis were established to explore the effect of GM47544 on dyslipidemia and plaque formation in vivo. The molecular mechanism was explored through RNA sequencing, immunoprecipitation, RNA pull-down assay, and RNA immunoprecipitation. Results GM47544 was overexpressed under high-fat stimulation. GM47544 effectively improved hepatic steatosis, reduced blood lipid levels, and alleviated atherosclerosis in vitro and in vivo. Mechanistically, GM47544 directly bound to ApoC3 and facilitated the ubiquitination at lysine 79 in ApoC3, thereby facilitating ApoC3 degradation via the ubiquitin-proteasome pathway. Moreover, we identified AP006216.5 as the human GM47544 transcript, which fulfills a comparable function in human hepatocytes. Conclusions The identification of GM47544 as a lncRNA modulator of ApoC3 reveals a novel mechanism of post-translational modification, with significant clinical implications for the treatment of hypertriglyceridemia and atherosclerosis.

Review Brief Version of Chinese Society of Cardiology Guidelines on the Diagnosis and Treatment of Adult Fulminant Myocarditis Hongyang Shu, Chen Chen, Luyun Wang, Jiangang Jiang and Daowen Wang * Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China * Correspondence: dwwang@tjh.tjmu.edu.cn Received: 3 April 2024; Revised: 6 June 2024; Accepted: 25 June 2024; Published: 20 August 2024 Abstract: Fulminant myocarditis is an acute and severe diffuse inflammatory disease of the heart with a high mortality rate. Its pathogenesis is driven by overactivation of the innate immunity and inflammatory storms. Based on China’s practical experience, the clinical guidelines for the management of the disease recommend adoption of a “life support-based comprehensive treatment regimen” which comprises mechanical circulatory support and immunomodulatory therapy at optimized doses of glucocorticoids and immunoglobin rather than immunosuppression to improve survival rates and long-term prognosis. The application experience of this treatment regimen in China provides evidence upon which the guidelines are formulated. This regimen emphasizes the importance of early identification, diagnosis, prediction, and treatment in patients with fulminant myocarditis. This is a brief introduction of the guidelines.

Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients, and has poor prognosis. However, the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave. We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital. The results indicated that the myocardial injury accounted for 30.8% of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching (PSM) [adjusted hazard ratio (HR), 10.61; 95% confidence interval (CI), 7.76-14.51; P < 0.001; adjusted HR, 2.70; 95% CI, 1.86-3.93; P < 0.001; respectively]. Further, the levels of cytokines (IL-1 ss, IL-6, IL-10, and TNF-a) in patients with myocardial injury were higher than those without injury, and the higher levels of cytokines in the myocardial injury group were associated with increased mortality. Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) could significantly reduce the mortality in patients with myocardial injury (adjusted HR, 0.52; 95% CI, 0.38-0.71; P < 0.001). Additionally, the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury. Collectively, the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China, and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.