Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure.

AIMS: The current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA. METHODS AND RESULTS: A total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the '2021 Universal Definition of HF' criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76-0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07-0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05). CONCLUSIONS: The improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.

Establishment and Validation of the Nomogram Model and the Probability of Silent Cerebral Infarction After Ablation Atrial Fibrillation.

BACKGROUND: The objective of this study is to establish and validate a nomogram model for predicting the probability of silent cerebral infarction following ablation of atrial fibrillation. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 238 patients with atrial fibrillation who underwent radiofrequency ablation in our hospital from October 2019 to December 2022. LASSO regression and multivariate logistics regression analysis were used to assess the independent risk factors for silent cerebral infarction after ablation. The AUC of the predictive model was 0.733 (95% CI, 0.649-0.816) and the internal validation (bootstrap = 1000) of the bootstrap method was 0.733 (95% CI 0.646-0.813). The Hosmer-Lemeshow test yields an insignificant p-value of X-squared = 10.212 and p-value = 0.2504, thus indicating an insignificant difference between predicted and observed values and good calibration results. The clinical impact curve (CIC) and clinical decision curve also prove that this graph is useful in the clinical setting. CONCLUSION: We developed an easy-to-use nomogram model to predict the probability of silent cerebral infarction following radiofrequency ablation of atrial fibrillation. This model can provide a valid assessment of the probability of postoperative silent cerebral infarction in patients undergoing radiofrequency ablation of atrial fibrillation.

Development and Validation of a Nomogram Model Affecting the ACT Targeting Rate During Radiofrequency Ablation of Atrial Fibrillation in China.

CONTEXT: A nomogram model affecting the activated clotting time (ACT) targeting rate during radiofrequency ablation of atrial fibrillation (RFCA) in China. PURPOSE: The aim of this study is to develop and validate a nomogram model for predicting the activated clotting time targeting rate after the initial bolus heparin dosages during the radiofrequency catheter ablation of atrial fibrillation in China. METHODS AND RESULTS: A retrospective observational study was conducted on the data of 465 patients with atrial fibrillation who underwent radiofrequency catheter ablation (RFCA) from October 2019 to June 2022. All patients were randomized into a training cohort (70%; n = 325) and a validation cohort (30%; n = 140). Independent risk factors were identified using univariate and multifactorial logistic regression analysis. The predictive nomogram model was established using R software. The nomogram was developed and evaluated based on differentiation, calibration, and clinical efficacy using concordance statistic (C-statistic), calibration plots, and decision curve analysis (DCA), respectively. The nomogram was established using three variables, including sex (OR 1.01, 95% CI 0.29-1.76, P = 0.007), heparin dose (OR 0.04; 95%CI 0.02-0.05, P < 0.001), and the baseline ACT (OR 0.03; 95%CI 0.02-0.04, P < 0.001). The C-statistic of the nomogram was 0.736 (95%CI 0.675-0.732) in the training cohort and 0.700 (95%CI 0.622-0.721) in the validation cohort. The calibration plots showed good agreement between the predictions and observations in the training and validation cohorts. The clinical decision curve also proves that the map is useful in clinical settings. CONCLUSION: The nomogram model has good discrimination and accuracy, which can screen attainment groups intuitively and individually, and has a certain predictive value for the probability of ACT reaching the target after the adequate dosage of initial heparin in Chinese patients with atrial fibrillation.

Cardioprotection of hydralazine against myocardial ischemia/reperfusion injury in rats.

This study aimed to investigate whether hydralazine could reduce cardiac ischemia/reperfusion (I/R) injury in rats. Anesthetized male Sprague-Dawley rats underwent myocardial I/R injury. Saline, hydralazine (HYD, 10-30 mg/kg) was administered intraperitoneally 10 min before reperfusion. After 30 min of ischemia and 24 h of reperfusion, the myocardial infarct size was determined using TTC staining. Heart function and oxidative stress were determined through biochemical assay and DHE staining. HE staining was used for histopathological evaluation. Additionally, the cardiomyocytes apoptosis and protein expression of PI3K-Akt-eNOS pathway marker were detected by TUNEL and Western blotting. The serum levels of malonaldehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and reactive oxygen species were significantly elevated in cardiac I/R group, but the superoxide dismutase (SOD) level was suppressed. However, intraperitoneal pretreatment with hydralazine at a dose of 10-30 mg/kg before cardiac I/R significantly limited the increase in CK-MB, LDH, oxidative stress, inflammatory factors, histological damage and apoptosis in the hearts. In addition, hydralazine also increased p-PI3K, p-AKT, p-eNOS expression and decreased Cleaved Caspase-3, Cleaved Caspase-9 expression in the hearts. Our results suggest that the cardioprotective effect of hydralazine against I/R injury might be a cooperation of the inhibition of oxidative stress, inflammatory response, apoptosis with the motivation of eNOS phosphorylation via activating the PI3K/AKT signal pathway.

Resveratrol Inhibits the TGF-ß1-Induced Proliferation of Cardiac Fibroblasts and Collagen Secretion by Downregulating miR-17 in Rat.

Myocardial fibrosis (MF) can cause heart remodeling and it is an independent risk factor for malignant arrhythmias, sudden cardiac death, and other malignant cardiovascular events. It is often characterized by myocardial interstitial collagen deposition and hyperproliferation of cardiac fibroblasts (CFs). The transforming growth factor-ß1 (TGF-ß1) is the most influential profibrogenic factor. Resveratrol (RSV) is an active polyphenol substance that inhibits myocardial fibrosis. The mechanism of RSV-mediated inhibition of the proliferation of CFs at the microRNA level is not fully understood. We used TGF-ß1 to induce CFs proliferation to simulate the pathogenesis of myocardial fibrosis. Neonatal rat CFs were treated with TGF-ß1 in the presence or absence of resveratrol. Cell proliferation was measured using the CCK-8 and EdU assay. Collagen secretion was measured using hydroxyproline kit. Further, qPCR analysis was performed to determine microRNA levels after TGF-ß1 or resveratrol treatment. To identify the target gene for miR-17, miR-17 was overexpressed or silenced, and the mRNA and protein levels of Smad7 were assessed. The effects of miR-17 silencing or Smad7 overexpression on cell proliferation and collagen secretion were also examined. Resveratrol treatment significantly decreased the TGF-ß1-induced CF proliferation and collagen secretion. Resveratrol also decreased the levels of miR-17, miR-34a, and miR-181a in TGF-ß1-treated CFs. Overexpression of miR-17 decreased the Smad7 mRNA and protein levels while silencing miR-17 increased them. Additionally, silencing miR-17 or overexpressing Smad7 decreased the TGF-ß1-induced CFs proliferation and collagen secretion. In conclusion, resveratrol inhibits TGF-ß1-induced CFs proliferation and collagen secretion. This inhibitory effect of resveratrol is orchestrated by the downregulation of miR-17 and the regulation of Smad7.

Suppression of Oxidative Stress and Apoptosis in Electrically Stimulated Neonatal Rat Cardiomyocytes by Resveratrol and Underlying Mechanisms.

PURPOSE: We explored the effects of resveratrol on oxidative stress in cardiomyocytes subjected to rapid electrical stimulation (RES) and also investigated the underlying mechanisms. METHODS: Cultured ventricular myocytes of neonatal rat were subjected to RES at 4.0 Hz, with or without resveratrol, an NADPH oxidase inhibitor apocyanin (APO) or a Ca/calmodulin-dependent protein kinase II (CaMKII) inhibitor autocamtide-2-inhibitory peptide (AIP). Cell counts, to optimize resveratrol concentration, and angiotensin II content were evaluated. Reactive oxygen species (ROS), intracellular Ca in cardiomyocytes, and cardiomyocyte apoptosis were also assessed. Levels of methionine sulfoxide reductase A (MsrA), Nox, oxidative CaMKII (OX-CaMKII), and cleaved caspase-3 in cardiomyocytes were examined. RESULTS: Resveratrol treatment, as compared with APO and AIP, significantly decreased ROS levels, improved Ca amplitudes, and intracellular Ca transient decay rates, and inhibited cardiomyocyte apoptosis. Resveratrol also increased MsrA protein levels. In cardiomyocytes subjected to RES, after pretreatment with resveratrol or APO, protein levels of Nox4, Nox2, OX-CaMKII, and cleaved caspase-3 were decreased. In comparison, with AIP pretreatment, only Nox2, OX-CaMKII, and cleaved caspase-3 were decreased. However, in the presence of dimethyl sulfoxide, a competitive inhibitor of MsrA function, a decrease in cleaved caspase-3 did not occur. CONCLUSIONS: Resveratrol decreased ROS, partially through the inhibition of NADPH oxidase activity and upregulation of MsrA expression.