The global, regional, and national burden of myocarditis in 204 countries and territories, 1990-2021: Results from the Global Burden of Disease Study 2021.

AIMS: To estimate the global burden of myocarditis in the general population from 1990 to 2021. METHODS AND RESULTS: Data on myocarditis were retrieved from the Global Burden of Disease Study 2021. Incidence, deaths, and disability-adjusted life years (DALYs), along with their age-standardized rates (ASRs) per 100 000 population, were used to measure the burden of myocarditis. Global, regional, and national analyses were performed for the period between 1990 and 2021. Further sub-analyses were conducted based on age group, sex, and sociodemographic index (SDI). In 2021, there were 1.3 million (95% uncertainty interval [UI]: 1.1 to 1.6) incident cases, 31.7 thousand (95% UI: 25.5 to 37.1) deaths, and 96.3 thousand (95% UI: 79.6 to 114.8) DALY cases globally. The ASRs of incidence, death, and DALYs significantly decreased from 1990 to 2021, with percentage changes of -3.9% (95% UI: -4.7% to -2.9%), -28.2% (95% UI: -42.2% to -12.5%), and -37.8% (95% UI: -50.5% to -24.3%), respectively. The global burden of myocarditis was higher in males, children, and the elderly. Additionally, the burden of myocarditis varied widely across different SDI regions, with high SDI regions having the highest ASR of incidence, and high-middle SDI regions having the highest ASRs of deaths and DALYs. CONCLUSION: Although the ASRs of incidence, deaths, and DALYs significantly decreased from 1990 to 2021, the global number of incidences, deaths, and DALYs increased substantially. Certain populations, including males, children, the elderly, and regions with advanced sociodemographic levels, experienced a heavier burden of myocarditis.

ABLE-SCORE, a simplified risk score for major adverse cardiovascular outcomes in left ventricular hypertrabeculation: a multicenter longitudinal cohort study.

BACKGROUND: Left ventricular hypertrabeculation (LVHT) is a heterogeneous entity with life-threatening complications and variable prognosis. However, there are limited prediction models available to identify individuals at high risk of adverse outcomes, and the current risk score in LVHT is comparatively complex for clinical practice. This study aimed to develop and validate a simplified risk score to predict major adverse cardiovascular events (MACE) in LVHT. METHODS: This multicenter longitudinal cohort study consecutively enrolled morphologically diagnosed LVHT patients between January 2009 and December 2020 at Fuwai Hospital (derivation cohort, n = 300; internal validation cohort, n = 129), and between January 2014 and December 2022 at two national-level medical centers (external validation cohort, n = 95). The derivation/internal validation cohorts and the external validation cohort were followed annually until December 2022 and December 2023, respectively. MACE was defined as a composite of all-cause mortality, heart transplantation/left ventricular assist device implantation, cardiac resynchronization therapy, malignant ventricular arrhythmia, and thromboembolism. A simplified risk score, the ABLE-SCORE, was developed based on independent risk factors in the multivariable Cox regression predictive model for MACE, and underwent both internal and external validations to confirm its discrimination, calibration, and clinical applicability. RESULTS: A total of 524 LVHT patients (43.5 ± 16.6 years, 65.8% male) were included in the study. The ABLE-SCORE was established using four easily accessible clinical variables: age at diagnosis, N-terminal pro-brain natriuretic peptide levels, left atrium enlargement, and left ventricular ejection fraction ≤ 40% measured by echocardiography. The risk score showed excellent performance in discrimination, with Harrell's C-index of 0.821 [95% confidence interval (CI), 0.772-0.869], 0.786 (95%CI, 0.703-0.869), and 0.750 (95%CI, 0.644-0.856) in the derivation, internal validation, and external validation cohort, respectively. Calibration plots of the three datasets suggested accurate agreement between the predicted and observed 5-year risk of MACE in LVHT. According to decision curve analysis, the ABLE-SCORE displayed greater net benefits than the existing risk score for LVHT, indicating its strength in clinical applicability. CONCLUSIONS: A simplified and efficient risk score for MACE was developed and validated using a large LVHT cohort, making it a reliable and convenient tool for the risk stratification and clinical management of patients with LVHT.

Global, Regional, and National Burden of Nonrheumatic Valvular Heart Disease and Its Attributable Risk Factors in 204 Countries and Territories, 1990 to 2019: Results From the Global Burden of Disease Study 2019.

BACKGROUND: Nonrheumatic valvular heart disease (NRVD) is increasingly becoming a significant public health concern, particularly among older people. In the context of population aging, a detailed report on the epidemiological trends of NRVD is crucial for policymakers to effectively allocate health care resources. This study aimed to explore these trends using data from the GBD (Global Burden of Disease) 2019 study. METHODS AND RESULTS: We assessed the changing trends of the incidence, mortality, and disability-adjusted life years rates for NRVD by calculating the estimated annual percentage change for each. Additionally, we examined the impact of a region's level of social development on NRVD epidemiological trends and identified key risk factors contributing to NRVD-related deaths. Between 1990 and 2019, the global incidence of NRVD showed a gradual increase, with an estimated annual percentage change of 0.39 (95% CI, 0.30-0.48). The data revealed that women and older people are more likely to develop NRVD. High-sociodemographic index countries exhibited higher age-standardized incidence and mortality rates compared with low- and middle-sociodemographic index countries. The most significant risk factor for NRVD-related mortality was identified as high systolic blood pressure. CONCLUSIONS: Over the past 3 decades, the burden of NRVD has intensified, indicating a need for more health care resources to address this issue, which is closely associated with an aging population. Currently, high-sociodemographic index countries report the highest incidences and deaths due to NRVD. However, low- and middle-sociodemographic index countries should also implement measures to manage the rapidly increasing burden of NRVD.

Hybrid Biatrial Ablation Versus Catheter Ablation for Patients With Nonparoxysmal Atrial Fibrillation and Enlarged Left Atrium.

OBJECTIVE: There is no consensus on the optimal ablation strategy for nonparoxysmal atrial fibrillation (NPAF) with enlarged left atrium. We aimed to explore whether hybrid ablation (HA) of combined thoracoscopic surgical ablation with catheter ablation (CA) was superior to CA alone in these patients. METHODS: Patients with NPAF and left atrial diameter (LAD) ≥45 mm who underwent hybrid biatrial ablation or CA procedure from June 2014 to July 2021 were included in this study. Propensity score matching was applied to select patients in each group. The primary endpoint was freedom from atrial tachyarrhythmias after procedures. RESULTS: After propensity score matching, 52 patients with enlarged left atrium (median LAD = 51 mm) were enrolled in each group. The median follow-up was 36 months. The probability of freedom from atrial tachyarrhythmias at 12, 24, and 36 months on antiarrhythmic drugs (AADs) was 70.1%, 65.4%, and 62.6% in the HA group and 34.3%, 29.4%, and 22.0% in the CA group, respectively (P < 0.001); off AADs was 57.1%, 52.7%, and 50.0% in the HA group and 25.0%, 16.2%, and 11.5% in the CA group (P < 0.001); on AADs after redo CA was 76.2%, 73.7%, and 73.7% in the HA group and 43.6%, 43.6%, and 38.2% in the CA group, respectively (P < 0.001); off AADs after redo CA was 62.5%, 60.1%, and 60.1% in the HA group and 30.4%, 25.1%, and 20.9% in the CA group, respectively (P < 0.001). CONCLUSIONS: For patients with NPAF and enlarged left atrium, hybrid biatrial ablation was superior to CA in sinus rhythm maintenance even if redo CA was performed.

Comparing simultaneous hybrid ablation with stand-alone thoracoscopic surgical ablation for the treatment of non-paroxysmal atrial fibrillation: a prospective randomized controlled trial.

AIMS: Advanced atrial fibrillation (AF) is currently a dilemma for electrophysiologists when choosing a minimally invasive treatment strategy. Previous studies have demonstrated the outcome of either catheter ablation or thoracoscopic surgical ablation (SA) is unsatisfactory in these patients. Whether hybrid ablation (HA) could improve outcomes in these patients is unknown. The purpose of this study was to evaluate the clinical efficacy of HA for the treatment of advanced AF. METHODS AND RESULTS: A randomized controlled trial was designed to enrol patients with persistent AF (PerAF) and enlarged left atrium or long-standing persistent AF (LSPAF) who were randomized to HA or thoracoscopic SA at a 1:1 ratio. The primary endpoint was freedom from any recurrence of AF off antiarrhythmic drugs (AADs) 12 months after operation. The primary endpoint was monitored by 7-day electrocardiogram monitoring devices. One hundred patients were enrolled. The mean age was 58.5 ± 7.6 years, and the mean left atrial diameter (LAD) was 50.1 ± 6.1 mm. At 12 months, freedom from AF off AADs was recorded in 71.4% (35/49) of patients in HA group and 45.8% (22/48) in SA group [odds ratio 2.955, 95% confidence interval (1.275-6.848), P = 0.014]. HA significantly reduced patients' AF burden (30.2% in SA group and 14.8% in HA group, P = 0.048) and the LAD (mean differences: -5.53 ± 4.97 mm in HA group and -3.27 ± 5.20 mm in SA group, P = 0.037) at 12 months after operation. CONCLUSION: In patients with PerAF and enlarged left atrium or LSPAF, HA achieved better freedom from AF after 1 year of follow-up compared with thoracoscopic SA.

Effectiveness of cardioneuroablation in different subtypes of vasovagal syncope.

BACKGROUND: Cardioneuroablation (CNA) has shown encouraging results in patients with vasovagal syncope (VVS). However, data on different subtypes was scarce. METHODS: This observational study retrospectively enrolled 141 patients [mean age: 40 ± 18 years, 51 males (36.2%)] with the diagnosis of VVS. The characteristics among different types of VVS and the outcomes after CNA were analyzed. RESULTS: After a mean follow-up of 4.3 ± 1.5 years, 41 patients (29.1%) experienced syncope/pre-syncope events after CNA. Syncope/pre-syncope recurrence significantly differed in each subtype (P = 0.04). The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure (n = 6, 16.7%), followed by mixed (n = 26, 30.6%) and vasodepressive (n = 9, 45.0%). Additionally, a significant difference was observed in the analyses of the Kaplan-Meier survival curve (P = 0.02). Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type (P < 0.01). Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity (DC) level than those without (7.4 ± 1.0 ms vs. 9.0 ± 1.6 ms, P = 0.01). Patients with DC < 8.4 ms had an 8.1 (HR = 8.1, 95% CI: 2.2-30.0, P = 0.02) times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC ≥ 8.4 ms, and this association still existed after adjusting for age and sex (HR = 8.1, 95% CI: 2.2-30.1, P = 0.02). CONCLUSIONS: Different subtypes exhibit different event-free rates. The vasodepressive type exhibited the lowest event-free rate, but those patients with DC ≥ 8.4 ms might benefit from CNA.

Machine learning for the prediction of 1-year mortality in patients with sepsis-associated acute kidney injury.

INTRODUCTION: Sepsis-associated acute kidney injury (SA-AKI) is strongly associated with poor prognosis. We aimed to build a machine learning (ML)-based clinical model to predict 1-year mortality in patients with SA-AKI. METHODS: Six ML algorithms were included to perform model fitting. Feature selection was based on the feature importance evaluated by the SHapley Additive exPlanations (SHAP) values. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminatory ability of the prediction model. Calibration curve and Brier score were employed to assess the calibrated ability. Our ML-based prediction models were validated both internally and externally. RESULTS: A total of 12,750 patients with SA-AKI and 55 features were included to build the prediction models. We identified the top 10 predictors including age, ICU stay and GCS score based on the feature importance. Among the six ML algorithms, the CatBoost showed the best prediction performance with an AUROC of 0.813 and Brier score of 0.119. In the external validation set, the predictive value remained favorable (AUROC = 0.784). CONCLUSION: In this study, we developed and validated a ML-based prediction model based on 10 commonly used clinical features which could accurately and early identify the individuals at high-risk of long-term mortality in patients with SA-AKI.

Pioneering advanced security solutions for reinforcement learning-based adaptive key rotation in Zigbee networks.

In the rapidly evolving landscape of Internet of Things (IoT), Zigbee networks have emerged as a critical component for enabling wireless communication in a variety of applications. Despite their widespread adoption, Zigbee networks face significant security challenges, particularly in key management and network resilience against cyber attacks like distributed denial of service (DDoS). Traditional key rotation strategies often fall short in dynamically adapting to the ever-changing network conditions, leading to vulnerabilities in network security and efficiency. To address these challenges, this paper proposes a novel approach by implementing a reinforcement learning (RL) model for adaptive key rotation in Zigbee networks. We developed and tested this model against traditional periodic, anomaly detection-based, heuristic-based, and static key rotation methods in a simulated Zigbee network environment. Our comprehensive evaluation over a 30-day period focused on key performance metrics such as network efficiency, response to DDoS attacks, network resilience under various simulated attacks, latency, and packet loss in fluctuating traffic conditions. The results indicate that the RL model significantly outperforms traditional methods, demonstrating improved network efficiency, higher intrusion detection rates, faster response times, and superior resource management. The study underscores the potential of using artificial intelligence (AI)-driven, adaptive strategies for enhancing network security in IoT environments, paving the way for more robust and intelligent Zigbee network security solutions.

Comparative pharmacognosy and secondary metabolite analysis of Balanophorae herbs from different sources.

The Balanophorae are not only traditional Chinese herbal medicines but also functional foods with diverse sources. This study aimed to distinguish pharmacognostic characteristics and secondary metabolites among different species of Balanophorae. Eight species of Balanophorae herbs were harvested, including 21 batches with 209 samples. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze secondary metabolites of Balanophorae from 21 sources. Targeted metabolomic analysis was performed to compare differences among the groups. Rhopalocnemis phalloide and B. indica can be identified by their pharmacognostic characteristics. Then, 41 secondary metabolites were identified or characterized in the mixed extracts of the 209 samples, mainly phenolic acids, flavonoids, and their derivatives. The distribution of these secondary metabolites revealed apparent differences among different species. In addition, targeted metabolomic analysis suggested that the secondary metabolite profiles of seven species of Balanophorae showed noticeable differences, and differences were also observed among different growing regions. Finally, five important metabolic markers were screened to successfully distinguish B. laxiflora, B. harlandii, and B. polyandra, including three phenolic acids and two flavonoids. This is the first study to systematically compare both the morphology and secondary metabolites among different sources of Balanophorae, which could provide effective information for identifying diverse species.

Efficacy of catheter ablation for ventricular tachycardia in ischemic cardiomyopathy patients without an ICD implantation.

BACKGROUND: The implantable cardioverter-defibrillator (ICD) prevents sudden cardiac death in patients with ischemic cardiomyopathy (ICM). Catheter ablation has been shown to effectively reduce ventricular tachycardia (VT) recurrence, yet its efficacy in patients without an ICD implantation remains uncertain. OBJECTIVE: We aimed to investigate the outcomes of ablation for VT in patients with ICM without a backup ICD. METHODS: Patients with ICM who received ablation for VT without an ICD implantation were included in this study. Ablation was guided by either activation mapping or substrate mapping. Endocardial ablation was the primary strategy; epicardial access was considered when endocardial ablation failed. The primary end point was VT recurrence during follow-up; secondary end points included cardiovascular rehospitalization, all-cause mortality, and a composite of these events. RESULTS: A total of 114 patients were included, with the mean age of 58.2 ± 11.1 years, 102 of whom (89.5%) were male. Twelve patients (10.5%) underwent endo-epicardial ablation, whereas the rest received endocardial ablation. With a median follow-up of 53.8 months (24.8-84.2 months), VT recurred in 45 patients (39.5%), and 6 patients (5.3%) died, including 2 sudden cardiac deaths. The recurrence rate of VT was significantly lower in patients undergoing endo-epicardial ablation than in those with endocardial ablation only (8.3% vs 43.1%; log-rank P = .032). After multivariate adjustment, epicardial ablation remained associated with a reduced risk of VT recurrence (hazard ratio, 0.14; 95% confidential interval, 0.02-0.98; P = .048). CONCLUSION: Patients with ICM undergoing VT ablation without a backup ICD experienced a notably low rate of arrhythmic death. Most recurrences proved nonlethal.

Purified protein glutaminase from Chryseobacterium proteolyticum enhances the properties of wheat gluten.

Protein glutaminase (PG), originating from Chryseobacterium proteolyticum, can catalyze the deamidation of glutamine residues in plant proteins into glutamic acid, thus enhancing its functional properties. However, the low yield of PG limits its industrial production. In this study, the yield of PG in C. proteolyticum TM1040 increased by 121 %, up to 7.30 U/mL in a 15 L fermenter after medium optimization. Subsequently, purified PG was obtained by cation exchange chromatography (CEX) coupled with hydrophobic interaction chromatography (HIC). The degree of deamidation (DD) of wheat gluten after purified PG deamidation was 87.11 %, which is superior to chemical deamidation in safety and DD. The emulsifying and foaming properties of deamidated wheat gluten were 2.67 and 18.86 times higher, and the water- and oil-holding properties were 4.23 and 18.77 times higher, respectively. The deamidated wheat gluten with enhanced functional properties was used to improve the flavor and texture in baking cakes.

Prognostic value of cardiac deceleration capacity in patients with atrial fibrillation after catheter ablation: A systematic review and meta-analysis.

INTRODUCTION: Cather ablation (CA) is a well-recognized treatment alternative for atrial fibrillation (AF) patients despite more than 20% ablation-treated patients suffering from AF recurrence. The underlying mechanism of AF recurrence postablation is probably associated with high cardiac parasympathetic activity, which can be assessed with deceleration capacity (DC) of heart rate. Given that the relationship between DC and AF recurrence is still controversial, this systematic review and meta-analysis was performed to investigate the characteristics of DC in patients with and without AF recurrence, evaluating the prognostic value of DC in AF patients after CA. METHODS: A literature search was systematically performed in the Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases until October 01, 2023. The observational studies reporting either the pre- and postablation DC in both recurrence and non-recurrence groups or the ratios based on DC for predicting AF recurrence were mainly included. Weighted mean differences (WMD) or odds ratios (OR) based on DC would be calculated with a random-effect model, if heterogeneity estimated with the I2 index and Q statistic was significant (I2 > 50% or p < .05); otherwise, a fixed-effect model would be utilized. RESULTS: A total of eight observational studies involving 914 AF patients treated with radiofrequency or cryoballoon ablation were included in this study. Ablation-treated patients with AF recurrence had the higher DC postablation in relation to those without recurrence (WMD, 1.00; 95% confidence interval [CI], 0.33-1.67; p < .01), which was present up to 3 months of follow-up (WMD, 1.54; 95% CI, 1.11-1.96; p < .01), whereas there was no statistical significance in DC before ablation between recurrence and non-recurrence groups (WMD, 0.34; 95% CI, -0.12 to 0.79; p = .15). The high DC postablation was a risk factor for AF recurrence in ablation-treated patients (OR, 2.17; 95% CI, 1.44-3.25; p < .01). CONCLUSION: The high DC postablation was associated with the risk of AF recurrence, suggesting that DC may act as a prognostic indicator in AF patients treated with CA.

Catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy and biventricular involvement.

AIMS: Catheter ablation of ventricular tachycardia (VT) improves VT-free survival in 'classic' arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to investigate electrophysiological features and ablation outcomes in patients with ARVC and biventricular (BiV) involvement. METHODS AND RESULTS: We assembled a retrospective cohort of definite ARVC cases with sustained VTs. Patients were divided into the BiV (BiV involvement) group and the right ventricular (RV) (isolated RV involvement) group based on the left ventricular systolic function detected by cardiac magnetic resonance. All patients underwent electrophysiological mapping and VT ablation. Acute complete success was non-inducibility of any sustained VT, and the primary endpoint was VT recurrence. Ninety-eight patients (36 ± 14 years; 87% male) were enrolled, including 50 in the BiV group and 48 in the RV group. Biventricular involvement was associated with faster clinical VTs, a higher VT inducibility, and more extensive arrhythmogenic substrates (all P < 0.05). Left-sided VTs were observed in 20% of the BiV group cases and correlated with significantly reduced left ventricular systolic function. Catheter ablation achieved similar acute efficacy between these two groups, whereas the presence of left-sided VTs increased acute ablation failure (40 vs. 5%, P = 0.012). Over 51 ± 34 months [median, 48 (22-83) months] of follow-up, cumulative VT-free survival was 52% in the BiV group and 58% in the RV group (P = 0.353). A multivariate analysis showed that younger age, lower RV ejection fraction (RVEF), and non-acute complete ablation success were associated with VT recurrence in the BiV group. CONCLUSION: Biventricular involvement implied a worse arrhythmic phenotype and increased the risk of left-sided VTs, while catheter ablation maintained its efficacy for VT control in this population. Younger age, lower RVEF, and non-acute complete success predicted VT recurrence after ablation.

A novel method for high level production of protein glutaminase by sfGFP tag in Bacillus subtilis.

Protein glutaminase (PG; EC 3.5.1.44) is a novel deamidase that helps to improve functional properties of food proteins. Currently, the highest activated PG enzyme activity was 26 U/mg when recombinantly expressed via the twin-arginine translocation (Tat) pathway in Corynebacterium glutamicum. In this study, superfolder green fluorescent protein (sfGFP) was used to replace traditional signal peptides to facilitate efficient heterologous expression and secretion of Propeptide-Protein glutaminase (PP) in Bacillus subtilis. The fusion protein, sfGFP-PP, was secreted from 12 h of fermentation and reached its highest extracellular expression at 28 h, with a secretion efficiency of about 93 %. Moreover, when fusing sfGFP with PP at the N-terminus, it significantly enhances PG expression up to 26 U/mL by approximately 2.2-fold compared to conventional signal-peptides- guided PP with 11.9 U/mL. Finally, the PG enzyme activity increased from 26 U/mL to 36.9 U/mL after promoter and RBS optimization. This strategy not only provides a new approach to increase PG production as well as extracellular secretion but also offers sfGFP as an effective N-terminal tag for increased secreted production of difficult-to-express proteins.

Relationship between stress hyperglycemia ratio and acute kidney injury in patients with congestive heart failure.

BACKGROUND: The stress hyperglycemia ratio (SHR) has been demonstrated as an independent risk factor for acute kidney injury (AKI) in certain populations. However, this relationship in patients with congestive heart failure (CHF) remains unclear. Our study sought to elucidate the relationship between SHR and AKI in patients with CHF. METHODS: A total of 8268 patients with CHF were included in this study. We categorized SHR into distinct groups and evaluated its association with mortality through logistic or Cox regression analyses. Additionally, we applied the restricted cubic spline (RCS) analysis to explore the relationship between SHR as a continuous variable and the occurrence of AKI. The primary outcome of interest in this investigation was the incidence of AKI during hospitalization. RESULTS: Within this patient cohort, a total of 5,221 (63.1%) patients experienced AKI during their hospital stay. Upon adjusting for potential confounding variables, we identified a U-shaped correlation between SHR and the occurrence of AKI, with an inflection point at 0.98. When the SHR exceeded 0.98, for each standard deviation (SD) increase, the risk of AKI was augmented by 1.32-fold (odds ratio [OR]: 1.32, 95% CI: 1.22 to 1.46). Conversely, when SHR was below 0.98, each SD decrease was associated with a pronounced increase in the risk of AKI. CONCLUSION: Our study reveals a U-shaped relationship between SHR and AKI in patients with CHF. Notably, we identified an inflection point at an SHR value of 0.98, signifying a critical threshold for evaluating AKI in this population.

Characteristics of deceleration capacity and deceleration runs in vasovagal syncope.

PURPOSE: Increased vagal activity plays a prominent role in vasovagal syncope (VVS). The aim of this study was to characterize vagal function in VVS by evaluating the heart rate (HR) deceleration capacity (DC) and the HR deceleration runs (DRs) in patients with VVS between attacks. METHODS: A total of 188 consecutive VVS patients were enrolled in the study, of whom 129 had positive head-up tilt test (HUTT); 132 healthy participants were enrolled as controls. DC, DRs (DR2, i.e., episodes of 2 consecutive beat-to-beat HR decelerations), and the sum of DR8-10 (very long DR [VLDR]) were calculated using 24-h electrograms. Clinical characteristics, DC, and DRs were compared among syncope groups and controls. RESULTS: Patients with VVS had higher DC (10.63 ± 2.1 vs. 6.58 ± 1.7 ms; P < 0.001) and lower minimum HR and DR6-10 than controls. No significant differences in DC or DR6-10 were found between the patients with positive and those with negative HUTT results. In multivariate logistic regression analysis, minimum HR ≥ 40 bpm (odds ratio [OR] 0.408, 95% confidence interval [CI] 0.167-0.989; P = 0.048), daytime DC ≥ 7.37 ms (OR 3.040, 95% CI 1.220-7.576; P = 0.013), and VLDR ≥ 0.046% (OR 0.306, 95% CI 0.138-0.679; P = 0.004) were demonstrated to be risk factors significantly associated with VVS. CONCLUSION: Compared to healthy controls, patients with VVS demonstrated distinct HR deceleration profiles between attacks, including overall higher DC and lower DR6-10.

Lupeol alleviates autoimmune myocarditis by suppressing macrophage pyroptosis and polarization via PPARα/LACC1/NF-κB signaling pathway.

BACKGROUND: Autoimmune myocarditis, with increasing incidence and limited therapeutic strategies, is in urgent need to explore its underlying mechanisms and effective drugs. Pyroptosis is a programmed cell death that may contribute to the pathogenesis of myocarditis. Nonetheless, no direct evidence validated the role of pyroptosis in autoimmune myocarditis. Lupeol (Lup), a pentacyclic triterpene, possesses various biological activities such as antidiabetic properties. However, the effects of Lup on autoimmune myocarditis and pyroptosis remain unelucidated. PURPOSE: This study aimed to reveal the role of pyroptosis in autoimmune myocarditis and explore the protective effects of Lup, and its engaged mechanisms. METHODS: The experimental autoimmune myocarditis (EAM) mouse model was established by immunization with a fragment of cardiac myosin in Balb/c mice. Lup and MCC950 were administered after EAM induction. The protective effects were assessed by inflammation score, cardiac injury, chronic fibrosis, and cardiac function. Mechanistically, the effects of Lup on the M1 polarization and pyroptosis of macrophages were evaluated. Transcriptome sequencing and molecular docking were subsequently employed, and the underlying mechanisms of Lup were further explored in vitro with small interfering RNA and adenovirus. RESULTS: Administration of Lup and MCC950 alleviated EAM progression. Western blotting and immunofluorescence staining identified macrophages as the primary cells undergoing pyroptosis. Lup inhibited the expression of pyroptosis-associated proteins in macrophages during EAM in a dose-dependent manner. Furthermore, Lup suppressed pyroptosis in both bone marrow-derived macrophages (BMDMs) and THP-1-derived macrophages in vitro. In addition, Lup inhibited the M1 polarization of macrophages both in vivo and in vitro. Mechanistically, the protective effects of Lup were demonstrated via the suppression of the nuclear factor-κΒ (NF-κB) signaling pathway. Transcriptome sequencing and molecular docking revealed the potential involvement of peroxisome proliferator-associated receptor α (PPARα). Subsequently, we demonstrated that Lup activated PPARα to reduce the expression level of LACC1, thereby inhibiting the NF-κB pathway and pyroptosis. CONCLUSION: Our findings indicated the crucial role of macrophage pyroptosis in the pathogenesis of EAM. Lup ameliorated EAM by inhibiting the M1 polarization and pyroptosis of macrophages through the PPARα/LACC1/NF-κB signaling pathway. Thus, our results provided a novel therapeutic target and agent for myocarditis.

U-shaped association between stress hyperglycemia ratio and risk of all-cause mortality in cardiac ICU.

BACKGROUND: Stress hyperglycemia has been associated with poor prognosis in patients admitted to the cardiac intensive care unit (ICU). Recently, the stress hyperglycemia ratio (SHR) has been proposed to reflect true acute hyperglycemic. This study aimed to investigate the relationship between SHR and prognosis of patients in the cardiac ICU. METHODS: A retrospective analysis was conducted on a cohort of 5,564 patients admitted to the cardiac ICU. The participants were divided into seven groups based on their SHR levels. SHR was calculated as admission blood glucose/[(28.7 × HbA1c %) - 46.7]. The primary outcomes of this study were 28-day all-cause mortality. RESULTS: During the follow-up period, 349 (6.3%) patients succumbed within 28 days. A U-shaped correlation between SHR and mortality persisted, even after adjusting for other confounding variables, with a discernible inflection point at 0.95. When SHR surpassed 0.95, each standard deviation (SD) increase corresponded to a 1.41-fold elevation in the risk of mortality (odds ratio [OR]: 1.41, 95% CI: 1.25 to 1.59). In contrast, when SHR fell below 0.95, each SD increment correlated with a significantly reduced risk of mortality (OR: 0.56, 95% CI: 0.34 to 0.91). CONCLUSION: There was a U-shaped association between SHR and short -term mortality in patients in the cardiac ICU. The inflection point of SHR for poor prognosis was identified at an SHR value of 0.95.

Electrophysiological Characteristics and Ablation Outcomes in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

BACKGROUND: Catheter ablation of premature ventricular contractions (PVCs) that trigger polymorphic ventricular tachycardia (PVT) or ventricular fibrillation has been reported as a novel therapy to reduce the syncope events in patients with catecholaminergic PVT, whereas the long-term ablation outcome and its value in improving exercise-induced ventricular arrhythmias remain unclear. METHODS AND RESULTS: Fourteen consecutive selected patients with catecholaminergic PVT (mean±SD age, 16±6 years; 43% male patients) treated with maximum ß-blockers with no possibility of adding flecainide were prospectively enrolled for catheter ablation. The primary end point was syncope recurrence, and the secondary end point was the reduction of the ventricular arrhythmia score during exercise testing. Twenty-six PVT/ventricular fibrillation-triggering PVCs were identified for ablation. The trigger beats arose from the left ventricle in 50% of the cases and from both ventricles in 36% of the cases. Purkinje potentials were observed at 27% of the targets. After a mean follow-up of 49 months after ablation, 8 (57%) patients were free from syncope recurrence. Ablation of trigger beat significantly reduced the syncope frequency (mean±SD, 4.3±1.6 to 0.5±0.8 events per year; P<0.001) and improved the ventricular arrhythmia scores at the 3-month (5 [range, 3-6] to 1.5 [range, 0-5]; P=0.002) and 12-month (5 [range, 3-6] to 2 [range, 0-5]; P=0.014) follow-ups. The induction of nontriggering PVCs postablation was closely associated with syncope recurrence (hazard ratio, 6.8 [95% CI, 1.3-35.5]; P=0.026). CONCLUSIONS: Catheter ablation of PVT/ventricular fibrillation-triggering PVCs in patients with catecholaminergic PVT who cannot receive flecainide treatment seems to be a safe and feasible adjunctive treatment that may reduce the syncope burden and improve exercise-related ventricular arrhythmias. Induction of nontriggering PVCs after ablation is associated with a higher risk of syncope recurrence.