Association between estimated glucose disposal rate and atrial fibrillation recurrence in patients undergoing radiofrequency catheter ablation: a retrospective study.

OBJECTIVE: Previous studies have shown a clear link between insulin resistance (IR) and an elevated risk of atrial fibrillation (AF). However, the relationship between the estimated glucose disposal rate (eGDR), which serves as a marker for IR, and the risk of AF recurrence after radiofrequency catheter ablation (RFCA) remains uncertain. Therefore, this study aimed to examine the potential association between the eGDR and the risk of AF recurrence following RFCA. METHODS: This retrospective study was conducted at Nanchang University Affiliated Second Hospital. The study enrolled 899 patients with AF who underwent RFCA between January 2015 and January 2022. The formula used to calculate the eGDR was as follows: 19.02 - (0.22 * body mass index) - (3.26 * hypertension) - (0.61 * HbA1c). Cox proportional hazard regression models and exposure-effect curves were used to explore the correlation between the baseline eGDR and AF recurrence. The ability of the eGDR to predict AF recurrence was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: The study observed a median follow-up period of 11.63 months, during which 296 patients experienced AF recurrence. K‒M analyses revealed that the cumulative incidence AF recurrence rate was significantly greater in the group with the lowest eGDR (log-rank p < 0.01). Participants with an eGDR ≥ 8 mg/kg/min had a lower risk of AF recurrence than those with an eGDR < 4 mg/kg/min, with a hazard ratio (HR) of 0.28 [95% confidence interval (CI) 0.18, 0.42]. Additionally, restricted cubic spline analyses demonstrated a linear association between the eGDR and AF recurrence (p nonlinear = 0.70). The area under the curve (AUC) for predicting AF recurrence using the eGDR was 0.75. CONCLUSIONS: The study revealed that a decrease in the eGDR is associated with a greater AF recurrence risk after RFCA. Hence, the eGDR could be used as a novel biomarker for assessing AF recurrence risk.

Nonlinear associations between the ratio of family income to poverty and all-cause mortality among adults in NHANES study.

Socioeconomic status (SES) has been linked to mortality rates, with family income being a quantifiable marker of SES. However, the precise association between the family income-to-poverty ratio (PIR) and all-cause mortality in adults aged 40 and older remains unclear. A cross-sectional study was conducted using data from NHANES III, including 20,497 individuals. The PIR was used to assess financial status, and various demographic, lifestyle, and clinical factors were considered. Mortality data were collected from the NHANES III linked mortality file. The study revealed a non-linear association between PIR and all-cause mortality. The piecewise Cox proportional hazards regression model showed an inflection point at PIR 3.5. Below this threshold, the hazard ratio (HR) for all-cause mortality was 0.85 (95% CI 0.79-0.91), while above 3.5, the HR decreased to 0.66 (95% CI 0.57-0.76). Participants with lower income had a higher probability of all-cause mortality, with middle-income and high-income groups showing lower multivariate-adjusted HRs compared to the low-income group. This study provides evidence of a non-linear association between PIR and all-cause mortality in adults aged 40 and older, with an inflection point at PIR 3.5. These findings emphasize the importance of considering the non-linear relationship between family income and mortality when addressing socioeconomic health disparities.

Angiotensin receptor-neprilysin inhibitor delays progression from paroxysmal to persistent atrial fibrillation.

Progression from paroxysmal to persistent atrial fibrillation (AF) is linked to adverse clinical outcomes. The present study sought to clarify whether angiotensin receptor-neprilysin inhibitor (ARNI) can delay AF progression. A retrospective cohort study was conducted on consecutive patients with paroxysmal AF admitted at the Second Affiliated Hospital of Nanchang University between January 2017 and January 2022. The risk of AF progression from paroxysmal to persistent was compared between paroxysmal patients treated with ARNI and those who received an angiotensin receptor blocker (ARB). Seven-day Holter monitoring was performed to identify persistent AF. Propensity-score matched analysis was performed to compare the two groups. Cox-regression was used to estimate the hazard ratio (HR) for AF progression events. A total of 1083 patients were screened, and 113 patients in the ARB group and 57 patients in the ARNI group were eligible for analysis. Before propensity-score matching, the ARNI therapy was associated with a lower risk of AF progression than the ARB therapy (HR 0.34; 95% confidence interval [CI] 0.14-0.81; P = 0.015) after a median follow-up of 705 (interquartile range [IQR] 512 to 895) days. Among 170 patients, 47 ARNI-treated patients were successfully matched to 47 ARB-treated patients. After a median follow-up of 724 (541-929) days, compared to ARB, ARNI significantly reduced the risk of AF progression (HR 0.32; 95% CI 0.12-0.88; P = 0.016). ARNI may be superior to ARB in reducing the risk of progression from paroxysmal to persistent AF.

Development and Validation of a Novel Prognostic Model Predicting the Atrial Fibrillation Recurrence Risk for Persistent Atrial Fibrillation Patients Treated with Nifekalant During the First Radiofrequency Catheter Ablation.

BACKGROUND: This study aimed to establish and assess a prediction model for patients with persistent atrial fibrillation (AF) treated with nifekalant during the first radiofrequency catheter ablation (RFCA). METHODS: In this study, 244 patients with persistent AF from January 17, 2017 to December 14, 2017, formed the derivation cohort, and 205 patients with persistent AF from December 15, 2017 to October 28, 2018, constituted the validation cohort. The least absolute shrinkage and selection operator regression was used for variable screening and the multivariable Cox survival model for nomogram development. The accuracy and discriminative capability of this predictive model were assessed according to discrimination (area under the curve [AUC]) and calibration. Clinical practical value was evaluated using decision curve analysis. RESULTS: Body mass index, AF duration, sex, left atrial diameter, and the different responses after nifekalant administration were identified as AF recurrence-associated factors, all of which were selected for the nomogram. In the development and validation cohorts, the AUC for predicting 1-year AF-free survival was 0.863 (95% confidence interval (CI) 0.801-0.926) and 0.855 (95% CI 0.782-0.929), respectively. The calibration curves showed satisfactory agreement between the actual AF-free survival and the nomogram prediction in the derivation and validation cohorts. In both groups, the prognostic score enabled stratifying the patients into different AF recurrence risk groups. CONCLUSIONS: This predictive nomogram can serve as a quantitative tool for estimating the 1-year AF recurrence risk for patients with persistent AF treated with nifekalant during the first RFCA.

Lowering serum homocysteine in H-type hypertensive patients with atrial fibrillation after radiofrequency catheter ablation to prevent atrial fibrillation recurrence.

Background: Prior investigation revealed that elevated serum total homocysteine (tHcy) are strongly correlated with atrial fibrillation (AF) recurrence. Herein, the goal of this study was to elucidate whether folic acid (FA) treatment reduced AF recurrence following radiofrequency catheter ablation (RFCA). Methods: To conduct this retrospective research, we included consecutive H-type hypertensive AF patients, who were treated with first RFCA, between January 2010 and January 2022. We assessed the AF recurrence risk between patients who were taking 10 mg enalapril and 0.8 mg FA in a single-pill combination (enalapril-FA) daily and those who were taking a pill of 10 mg enalapril only. Outcomes were compared using the propensity-score matched analysis. Cox regression model was employed for the evaluation of AF recurrence events. Results: Out of 2,714 patients, 645 patients receiving enalapril and 282 patients receiving enalapril-FA were included for analysis. Following propensity score matching, 239 patients remained in each group. These patients were followed-up for a median of 379 (137-596) days, and revealed that the enalapril-FA patients had drastically reduced AF recurrence, compared to the enalapril patients [adjusted hazard ratio (HR), 0.68; 95% confidence interval (CI), 0.48-0.97; P = 0.029]. Apart from this, no interactions were detected in the subgroup analysis. Conclusion: In H-type hypertensive AF patients who were treated with first RFCA, FA supplementation was correlated with a reduced AF recurrence risk.

Permanent Left Bundle Branch Area Pacing for High-Degree Atrioventricular Block in a 6-Year-Old Child with 2-Year Follow-Up.

The feasibility and safety of left bundle branch area pacing (LBBAP) used in pediatric patients with atrioventricular block (AVB) have not been well demonstrated. Currently, only several case reports for pediatric patients have been published since the advent of LBBAP, with 3 months to 1 year follow-up. Here, we present a case of LBBAP in a 6-year-old child with a high-degree AVB secondary to the transcatheter device closure of congenital ventricular septal defect. No procedure-related complications were observed, and the electrical parameters were stable at 2-year follow-up. Additionally, we performed a systematic literature review on pediatric patients with LBBAP. Fifteen cases were retrieved after systematically searching PubMed and Embase databases. No complications have been reported among these published cases. In conclusion, consistent with previous cases, our case with 2-year follow-up has demonstrated that LBBAP may be an alternative pacing modality from a very early age. However, given the limited evidence, the long-term outcomes of LBBAP in pediatric patients should be further investigated.

SIRT4 Suppresses Doxorubicin-Induced Cardiotoxicity by Regulating the AKT/mTOR/Autophagy Pathway.

Doxorubicin (DOX) is a potent anthracycline chemotherapeutic drug. DOX-induced cardiotoxicity (DIC) limits its application in cancer treatment, as this complication is detrimental and fatal. Reactive oxygen species (ROS) production, autophagic dysfunction and cell death are crucial factors related to DIC. Previous studies have shown that SIRT4 is associated with cardiac energy metabolism, cardiac mitochondrial dysfunction and cardiac cell death, but it is unclear whether SIRT4 affects DOX-induced cardiac injury. Our data suggested that SIRT4 overexpression in vivo and in vitro could alleviate DIC by improving cardiac function and reducing cardiomyocyte apoptosis and autophagy. However, autophagy activation by rapamycin abolished the protective effect of SIRT4 overexpression on DIC. Furthermore, in the context of DOX treatment, SIRT4 overexpression activated the Akt/mTOR signaling pathway and inhibited autophagy through the Akt/mTOR signaling pathway. Our findings indicate that SIRT4 overexpression protects against DIC by inhibiting Akt/mTOR-dependent autophagy. These findings may provide a prospective therapeutic target for DIC.

Long-term outcomes of left bundle branch area pacing versus biventricular pacing in patients with heart failure and complete left bundle branch block.

Left bundle branch area pacing (LBBAP) has developed in an effort to improve cardiac resynchronization therapy (CRT). We aimed to compare the long-term clinical outcomes between LBBAP and biventricular pacing (BIVP) in patients with heart failure (HF) and complete left bundle branch block (CLBBB). Consecutive patients with HF and CLBBB requiring CRT received either LBBAP or BIVP were recruited at the Second Affiliated Hospital of Nanchang University from February 2018 to May 2019. We assessed their implant parameters, electrocardiogram (ECG), clinical outcomes at implant and during follow-up at 1, 3, 6, 12, and 24 months. Forty-one patients recruited including 21 for LBBAP and 20 for BIVP. Mean follow-up duration was 23.71 ± 4.44 months. LBBAP produced lower pacing thresholds, shorter procedure time and fluoroscopy duration compared to BIVP. The QRS duration was significantly narrower after LBBAP than BIVP (129.29 ± 31.46 vs. 156.85 ± 26.37 ms, p = 0.005). Notably, both LBBAP and BIVP significantly improved LVEF, LVEDD, NYHA class, and BNP compared with baseline. However, LBBAP significantly lowered BNP compared with BIVP (416.69 ± 411.39 vs. 96.07 ± 788.71 pg/ml, p = 0.007) from baseline to 24-month follow-up. Moreover, patients who received LBBAP exhibited lower number of hospitalizations than those in the BIVP group (p = 0.019). In addition, we found that patients with moderately prolonged left ventricular activation time (LVAT) and QRS notching in limb leads in baseline ECG respond better to LBBAP for CLBBB correction. LBBAP might be a relative safe and effective resynchronization therapy and as a supplement to BIVP for patients with HF and CLBBB.

Ferroptosis Is a Potential Novel Diagnostic and Therapeutic Target for Patients With Cardiomyopathy.

Cardiomyocyte death is a fundamental progress in cardiomyopathy. However, the mechanism of triggering the death of myocardial cells remains unclear. Ferroptosis, which is the nonapoptotic, iron-dependent, and peroxidation-driven programmed cell death pathway, that is abundant and readily accessible, was not discovered until recently with a pharmacological approach. New researches have demonstrated the close relationship between ferroptosis and the development of many cardiovascular diseases, and several ferroptosis inhibitors, iron chelators, and small antioxidant molecules can relieve myocardial injury by blocking the ferroptosis pathways. Notably, ferroptosis is gradually being considered as an important cell death mechanism in the animal models with multiple cardiomyopathies. In this review, we will discuss the mechanism of ferroptosis and the important role of ferroptosis in cardiomyopathy with a special emphasis on the value of ferroptosis as a potential novel diagnostic and therapeutic target for patients suffering from cardiomyopathy in the future.

Comparison of the efficacy and safety of different doses of nifekalant in the instant cardioversion of persistent atrial fibrillation during radiofrequency ablation.

Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single-centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end-point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end-point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end-point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end-point: The rates of the majority of other common drug-related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit-risk profile.

The Efficacy of Beta-Blockers in Patients With Long QT Syndrome 1-3 According to Individuals' Gender, Age, and QTc Intervals: A Network Meta-analysis.

Long QT syndrome (LQTS) is an arrhythmic heart disease caused by congenital genetic mutations, and results in increased occurrence rates of polymorphic ventricular tachyarrhythmias and sudden cardiac death (SCD). Clinical evidence from numerous previous studies suggested that beta blockers (BBs), including atenolol, propranolol, metoprolol, and nadolol, exhibit different efficacies for reducing the risk of cardiac events (CEs), such as syncope, arrest cardiac arrest (ACA), and SCD, in patients with LQTS. In this study, we identified relevant studies in MEDLINE, PubMed, embase, and Cochrane databases and performed a meta-analysis to assess the relationship between the rate of CEs and LQTS individuals with confounding variables, including different gender, age, and QTc intervals. Moreover, a network meta-analysis was not only established to evaluate the effectiveness of different BBs, but also to provide the ranked efficacies of BBs treatment for preventing the recurrence of CEs in LQT1 and LQT2 patients. In conclusion, nadolol was recommended as a relatively effective strategy for LQT2 in order to improve the prognosis of patients during a long follow-up period.

Identification of atrial fibrillation-related circular RNAs and constructing the integrative regulatory network of circular RNAs, microRNAs and mRNAs by bioinformatics analysis.

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a high incidence of stroke. Many circular RNAs (circRNAs) have been demonstrated they are elated to various heart diseases and may play important roles in diagnostics or many pathophysiological processes. Nevertheless, there is Few studies on circRNAs functions in persistent AF. To identify AF-related circRNAs and construct the integrative regulatory network of circular RNAs, miRNAs, and mRNAs, we collected human right atrial appendage tissues from 5 patients suffering persistent AF (AF group) and 5 patients with normal sinus rhythm (NSR group) and characterized the global changes in circRNA expression with high-throughput sequencing technology. The differential expression of circRNAs and the interactions between circRNAs and microRNAs were analyzed. The microRNA expression file GSE68475 dataset was downloaded from the Gene Expression Omnibus (GEO) database to explore the differentially expressed microRNAs. The target genes of overlapped miRNAs were predicted by using DIANA-TarBase v8. We constructed the circRNA- miRNA-mRNA network using Cytoscape (version 3.4.0) and the network topology was analyzed by utilizing CentiScaPe app. Results showed that all of 600 differentially expressed circRNAs related to AF were screened, including 340 up-regulated and 260 down-regulated circRNAs. An integrative regulatory network was constructed, which included 30 circRNAs, 9 miRNAs and 130 target mRNAs of these miRNAs. It was concluded that that 30 circRNAs, including 8 upregulated circRNAs and 22 downregulated circRNAs, were predicted to highly possibly function as sponges of 9 miRNAs to regulate gene expression by using bioinformatics analysis. Moreover, the interactions of hsa-miR-339-5p with its related circRNAs and target mRNAs constructed the hub regulatory network in persistent AF by utilizing topology analysis. Our proposed regulatory network of circRNAs-miRNAs-mRNAs may provide new insight into the potential mechanism underlying persistent AF. Additionally, these important molecular may become novel biomarkers providing a new strategy in diagnosis and therapy of AF.

Homocysteine-induced electrical remodeling via the mediation of IP3R1/Nav1.5 signaling pathway.

Inositol-1,4,5-triphosphate-receptor 1 (IP3R1), a Ca2+ channel in the sarcoplasmic reticulum membrane, is an effective regulator of Ca2+ release involved in the pathology of most cardiovascular diseases. Our study aim to investigate the underlying mechanism by which IP3R1 signaling mediates the process of homocysteine (Hcy)-induced Ca2+ accumulation via interaction with sodium current (Nav1.5) in atrium. We utilized whole-cell patch-clamp analysis and flow cytometry to detect the abnormal electrical activity in mouse atrial myocytes (MACs) obtained from C57B6 mice fed with high-Hcy diet. The results represented not only an increase in protein levels of Nav1.5 and IP3R1, but also an enhanced intracellular levels of Ca2+, and prolonged action potential duration (APD). However, the inhibition of IP3R1 or Nav1.5 gene could both attenuate Ca2+ accumulation in MACs triggered by Hcy, as well as abnormal electrical activity. In addition, Hcy increased the interaction between IP3R1 and Nav1.5. These data suggest that Hcy induced Ca2+ accumulation is mediated by the IP3R1/Nav1.5 signaling pathway, accompanied with the influx of Na+ and Ca2+, which act as triggers for electrical remodeling.

Efficacy of Nifekalant in Patients With Wolff-Parkinson-White Syndrome and Atrial Fibrillation: Electrophysiological and Clinical Findings.

Background The efficacy of nifekalant in preexcited atrial fibrillation ( AF ) has not been assessed. Methods and Results The study populations consisted of patients with sustained preexcited AF (n=51), paroxysmal supraventricular tachycardia (n=201), and persistent AF (n=87). Effects of intravenous infusion of nifekalant were assessed on electrophysiological and clinical parameters. Nifekalant prolonged the shortest preexcited R-R, the average preexcited R-R, and the average R-R intervals from 290±35 to 333±44 ms, 353±49 to 443±64 ms, and 356±53 to 467±75 ms, respectively, in patients with preexcited AF (all P<0.001). Nifekalant also decreased the percentage of preexcited QRS complexes, heart rate, and increased systolic pressure (all P<0.001). Nifekalant terminated AF in 33 of 51 patients (65%). Similar effects were also observed in a subgroup of 12 patients with preexcited AF and impaired left ventricular function. In patients with paroxysmal supraventricular tachycardia, nifekalant significantly prolonged the effective refractory period, the block cycle length of the antegrade accessory pathway, and the atrial effective refractory period (all P<0.001). Nifekalant had no effect on the effective refractory period of the antegrade atrioventricular node. Finally, in patients with persistent AF without an accessory pathway, nifekalant did not significantly decrease the ventricular rate of AF . One patient developed Torsades de Pointes. No other adverse effects were observed. Conclusions Nifekalant prolongs the effective refractory period of the antegrade accessory pathway and atrium without blocking antegrade conduction through the atrioventricular node, leading to slowing and/or to termination of preexcited AF . Thus, nifekalant might be an effective and a relatively safe drug in patients with preexcited AF .

FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways.

High fibroblast growth factor 23 (FGF23) concentrations are a strong predictor of atrial fibrillation (AF), but researchers have not clearly determined the mechanism by which FGF23 causes atrial fibrosis in patients with AF. This study aims to elucidate the mechanism by which FGF23 induces atrial fibrosis in patients with AF. Immunohistochemistry was used to study the expression of FGF23, FGFR4, and fibrotic factors in patients with a normal sinus rhythm (SR) and patients with AF. Cardiac fibroblasts (CFs) were cocultured with different concentrations of the recombinant FGF23 protein. Compared with the SR group, the levels of FGF23, FGFR4, α-smooth muscle actin (α-SMA), and collagen-1 were significantly increased in the AF group. Exposure to high concentrations of the recombinant FGF23 protein increased the accumulation of reactive oxygen species (ROS) and activated α-SMA, collagen-1, signal transducer and activator of transcription 3 (STAT3) and SMAD3 signaling in cultured CFs. The levels of fibrotic proteins in CFs stimulated with high concentrations of the recombinant FGF23 protein were reversed by N-acetylcysteine (NAC, a ROS inhibitor), ship information system 3 (a SMAD3 inhibitor), and Stattic (a STAT3 inhibitor). Furthermore, compared to untreated CFs, CFs treated with the recombinant FGF23 protein were characterized by an increased interaction between STAT3 and SMAD3. Based on these results, FGF23 induces atrial fibrosis in patients with AF by increasing ROS production and subsequently activating STAT3 and SMAD3 signaling.

Retracted Article: Knockdown of TUG1 aggravates hypoxia-induced myocardial cell injury via regulation of miR-144-3p/Notch1.

Myocardial infarction is a common cause of mortality in cardiovascular diseases. Long noncoding RNA taurine-upregulated gene 1 (TUG1) has been reported to play an important role in the regulation of myocardial injury; however, the mechanism via which TUG1 participates in myocardial infarction is unknown. In this study, hypoxia-treated cardiomyoblast H9c2 cells were used as a model of myocardial infarction. Cell transfection was conducted using Lipofectamine 2000 for 48 h. Hypoxia-induced injury was investigated by cell viability and apoptosis using the trypan blue exclusion method, flow cytometry and Western blot. The expressions of TUG1, microRNA-144-3p (miR-144-3p) and the Notch1 pathway were investigated by a quantitative real-time polymerase chain reaction and Western blot. The association between miR-144-3p and TUG1 or Notch1 was analyzed by bioinformatics analysis and luciferase reporter assay. Our results showed that hypoxia-induced H9c2 cell injury led to the inhibition of cell viability and promotion of apoptosis. Moreover, hypoxia could cause the up-regulation of TUG1 and Notch1 expression and down-regulation of miR-144-3p. The knockdown of TUG1 or overexpression of miR-144-3p aggravated the hypoxia-induced viability suppression and apoptosis production in the H9c2 cells. Moreover, miR-144-3p was indicated to be bound to TUG1, and its abrogation reversed the silencing of TUG1-mediated promotion of hypoxia-induced injury. In addition, Notch1 was a target of miR-144-3p, and its restoration attenuated the miR-144-3p-mediated promotion of hypoxia-induced injury. Moreover, TUG1 interference alleviated the hypoxia-induced activation of the Notch1/Hes-1 pathway via the regulation of miR-144-3p. In conclusion, the interference of TUG1 contributed to hypoxia-induced injury via the regulation of the miR-144-3p/Notch1/Hes-1 pathway; this indicated a novel mechanism for understanding the pathogenesis of myocardial infarction.