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Fibrosis serves a critical role in driving atrial remodelling‐mediated atrial fibrillation (AF). Abnormal levels of the transcription factor PU.1, a key regulator of fibrosis, are associated with cardiac injury and dysfunction following acute viral myocarditis. However, the role of PU.1 in atrial fibrosis and vulnerability to AF remain unclear. Here, an in vivo atrial fibrosis model was developed by the continuous infusion of C57 mice with subcutaneous Ang‐II, while the in vitro model comprised atrial fibroblasts that were isolated and cultured. The expression of PU.1 was significantly up‐regulated in the Ang‐II‐induced group compared with the sham/control group in vivo and in vitro. Moreover, protein expression along the TGF‐β1/Smads pathway and the proliferation and differentiation of atrial fibroblasts induced by Ang‐II were significantly higher in the Ang‐II‐induced group than in the sham/control group. These effects were attenuated by exposure to DB1976, a PU.1 inhibitor, both in vivo and in vitro. Importantly, in vitro treatment with small interfering RNA against Smad3 (key protein of TGF‐β1/Smads signalling pathway) diminished these Ang‐II‐mediated effects, and the si‐Smad3‐mediated effects were, in turn, antagonized by the addition of a PU.1‐overexpression adenoviral vector. Finally, PU.1 inhibition reduced the atrial fibrosis induced by Ang‐II and attenuated vulnerability to AF, at least in part through the TGF‐β1/Smads pathway. Overall, the study implicates PU.1 as a potential therapeutic target to inhibit Ang‐II‐induced atrial fibrosis and vulnerability to AF.

Background Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff‐Parkinson‐White (WPW) syndrome and paroxysmal AF, in other patients it can recur. Hypothesis Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. Methods We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P‐wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12‐lead electrocardiography (ECG). Results During the mean follow‐up period of 30.9 ± 9.2 months (range, 3‐36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26‐1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). Conclusions PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12‐lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

Background Paroxysmal atrial fibrillation (AF) frequently occurs in patients with Wolff‐Parkinson‐White (WPW) syndrome. Although successful ablation of the accessory pathway (AP) eliminates paroxysmal AF in some patients, in other patients it can recur. Hypothesis We investigated the clinical utility of advanced interatrial block (IAB) for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation. Methods This retrospective study included 103 patients (70 men, 33 women; mean age, 44 ± 16 years) with WPW syndrome who had paroxysmal AF. A resting 12‐lead electrocardiogram was performed immediately after successful AP ablation to evaluate the presence of advanced IAB, which was defined as a P‐wave duration of >120 ms and biphasic [±] morphology in the inferior leads. Results During the mean follow‐up period of 30.9 ± 20.0 months (range, 2‐71 months), 16 patients (15.5%) developed AF recurrence. Patients with advanced IAB had significantly reduced event‐free survival from AF (P 50 years (hazard ratio, 12.64; 95% CI, 1.33‐119.75; P = .027) as independent predictors of AF recurrence. Conclusions Advanced IAB was an independent predictor of AF recurrence after successful AP ablation in patients with WPW syndrome.

Background: The efficacy of catheter ablation for atrial fibrillation (AF) in patients with functional mitral regurgitation (MR) and left ventricular (LV) systolic dysfunction (LVSD) is not known. The aim of the study is to determine the efficacy of catheter ablation for AF in patients with functional MR and LVSD, and to validate its effects on the severity of MR and cardiac reverse remodeling.Methods: We performed a retrospective study of 54 patients with functional MR who underwent AF ablation, including 21 (38.9%) with LVSD and 33 (61.1%) with normal LV systolic function (LVF). The primary outcomes evaluated were freedom from recurrent atrial tachyarrhythmia (ATa), severity of MR, and left atrial (LA) and LV remodeling.Results: During a mean follow-up of 20.7 ± 16.8 months, freedom from recurrent ATa was not significantly different between patients with LVSD and those with normal LVF after the first ablation (P = 0.301) and after multiple ablations (P = 0.728). Multivariable predictors of recurrent ATa were AF duration [hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.01–1.25; P = 0.039), previous stroke (HR 5.28, 95% CI 1.46–19.14; P = 0.011), and estimated glomerular filtration rate (HR 0.97, 95% CI 0.95–0.99; P = 0.012). Compared with baseline, there was a significant reduction in severity of MR (P = 0.007), LA size (P < 0.001) and LV end-systolic dimension (P = 0.008), and improvement in the LV ejection fraction (P = 0.001) after restoring sinus rhythm in patients with LVSD.Conclusion: Catheter ablation is a valid option for the treatment of AF in patients with functional MR and LVSD, even though multiple procedures may be required.

Interatrial block (IAB) is associated with a multitude of medical conditions. The aim of this retrospective study was to investigate whether CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) score is positively associated with the development of IAB. A total of 1072 patients (men, 555; women, 517; mean age, 61 ± 14 years) were included in the study. P-wave duration was measured manually using a caliper. IAB was defined as a P-wave duration of ≥ 120 ms on a 12-lead electrocardiogram. CHADS2 scores were calculated retrospectively. Among the 1072 patients, the prevalence of IAB was 36.1% (387/1072). In multivariate analysis, increased CHADS2 score (odds ratio [OR], 1.810; 95% confidence interval [CI], 1.577-2.077; P < 0.001), coronary artery disease (OR, 1.536; 95% CI, 1.065-2.216; P = 0.022), and increased left atrial diameter (OR, 1.039; 95% CI, 1.008-1.071; P = 0.013) were independently associated with IAB. The percentages of patients with IAB among those with a CHADS2 score of 0, 1, 2, 3, 4, 5, and 6 were 20.6%, 33.0%, 45.0%, 55.9%, 61.9%, 77.8%, and 100%, respectively (P < 0.001). There was a greater percentage of patients with a CHADS2 score of ≥ 2 with IAB compared with a CHADS2 score of < 2 (26.5% vsrsus 52.0%; P < 0.001). In receiver operating curve (ROC) analysis, CHADS2 score (area under the curve, 0.670; 95% CI, 0.636-0.704; P < 0.001) was predictive of IAB. In conclusion, CHADS2 score was significantly associated with the development of IAB in this study population.

Oxidative stress and apoptosis serve an essential role in cisplatin-induced cardiotoxicity, which limits its clinical use, and increases the risk of cardiovascular disease. As a natural drug, the antioxidant and antitumor effects of cyanidin have been recognized, but its protective effect on cisplatin-induced cardiomyocyte cytotoxicity remains unclear. H9c2 cells were treated with cisplatin (1-40 µM) in the presence or absence of cyanidin (40-80 µM), subsequently; oxidative stress, apoptosis and mitochondrial function were assessed using several techniques. The results demonstrated that cyanidin was able to dose-dependently reverse cisplatin-induced cell damage and apoptosis, attenuate the accumulation of reactive oxygen species (ROS), and mitochondrial membrane potential depolarization, downregulate the expression of Bcl-2 homologous antagonist/killer, upregulate the expression of apoptosis regulator Bcl-2, and reduce the activation of caspase 3, caspase 9, but not caspase 8. Furthermore, the results revealed that the translocation of apoptosis regulator Bax (Bax) from the cytoplasm to the mitochondrial membrane serves an essential role in cisplatin-induced apoptosis. Cyanidin was able to block the translocation of Bax and reduce the release of cytochrome c from cytoplasm. These data indicate that cyanidin attenuates cisplatin-induced cardiotoxicity by inhibiting ROS-mediated apoptosis, while the mitochondrial and extracellular regulated kinase signaling pathways may also serve important roles.

Increased expression of adhesion molecules is thought to serve an important role in the pathogenesis of atherosclerosis. Myricitrin, a bioactive compound of Myrica cerifera, has been demonstrated to exhibit anti‑atherogenic effects. However, the effect of myricitrin on the expression of adhesion molecules in vascular smooth muscle cells (VSMCs) remains unknown. Therefore, the aim of the present study was to evaluate the inhibitory effects of myricitrin on tumor necrosis factor‑α (TNF‑α)‑induced expression of adhesion molecules in VSMCs in vitro. The results revealed that myricitrin inhibited the adhesion of human THP‑1 monocyte cells to TNF‑α‑stimulated mouse MOVAS‑1 VSMC cells, and reduced the expression of adhesion molecules in TNF‑α‑stimulated MOVAS‑1 cells. In addition, myricitrin significantly inhibited the TNF‑α‑induced expression of nuclear factor (NF)‑κB p65, and prevented the TNF‑α‑induced degradation of nuclear factor of κ light chain enhancer in B‑cells inhibitor α. Furthermore, myricitrin inhibited the production of intracellular reactive oxygen species in TNF‑α‑stimulated MOVAS‑1 cells. In conclusion, the results of the present study indicated that myricitrin inhibits the expression of vascular cell adhesion protein‑1 and intercellular adhesion molecule‑1 in TNF‑α‑stimulated MOVAS‑1 cells potentially via the NF‑κB signaling pathway. Therefore, myricitrin may be an effective pharmacological agent for the prevention or treatment of atherosclerosis.

AIM To evaluate the role of CHADS2 and CHA2DS2-VASc scores in predicting the risk of ischemic stroke or transient ischemic attack (TIA) outcomes in patients with interatrial block (IAB) without a history of atrial fibrillation (AF). METHODS A retrospective study was conducted, including 1,046 non-anticoagulated inpatients (612 males, 434 females; mean age: 63±10 years) with IAB and without AF. IAB was defined as P-wave duration ＞120 ms using a 12-lead electrocardiogram. CHADS2 and CHA2DS2-VASc scores were retrospectively calculated. The primary outcomes evaluated were ischemic stroke or TIA. RESULTS During the mean follow-up period of 4.9±0.7 years, 55 (5.3%) patients had an ischemic stroke or TIA. Receiver operating characteristic (ROC) curve analysis showed that the CHADS2 score [area under the curve (AUC), 0.638; 95% confidence interval (CI), 0.562-0.715; P=0.001] and the CHA2DS2-VASc score (AUC, 0.671; 95% CI, 0.599-0.744; P＜0.001) were predictive of ischemic strokes or TIA. Cut-off point analysis showed that a CHADS2 score ≥3 (sensitivity=0.455 and specificity=0.747) and a CHA2DS2-VASc score ≥4 (sensitivity=0.564 and specificity=0.700) provided the highest predictive value for ischemic stroke or TIA. The multivariate Cox regression analysis showed that CHADS2 [hazard ratio (HR), 1.442; 95% CI, 1.171-1.774; P=0.001] and CHA2DS2-VASc (HR, 1.420; 95% CI, 1.203-1.677; P＜0.001) scores were independently associated with ischemic stroke or TIA following adjustment for smoking, left atrial diameter, antiplatelet agents, angiotensin inhibitors, and statins. CONCLUSIONS CHADS2 and CHA2DS2-VASc scores may be predictors of risk of ischemic stroke or TIA in patients with IAB without AF.

Background It has been demonstrated that advanced interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF); however, the impact of advanced IAB on recurrence of paroxysmal AF after catheter ablation is not clear. Methods 204 consecutive patients with paroxysmal AF who underwent index circumferential pulmonary vein (PV) isolation were prospectively enrolled. In all patients, a resting electrocardiogram in sinus rhythm was evaluated for the presence of advanced IAB, defined as a P-wave duration >120 ms and biphasic (±) morphology in the inferior leads. Advanced IAB was detected in 20.1% of patients. AF recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 s beyond 3 months after the catheter ablation in the absence of any antiarrhythmic treatment. Results During the mean follow-up period of 13.9 ± 6.2 months (range, 3–27 months), 62 patients (30.4%) developed recurrence of AF. The recurrence rate was higher in patients with advanced IAB than those without advanced IAB (46.3% vs. 26.4%, p = 0.006). Cox regression analysis with adjustment for age, P-wave duration, CHADS2 score, and PV isolation identified advanced IAB (hazard ratio, 2.111; 95% confidence interval, 1.034–4.308; p = 0.040) and left atrial diameter (hazard ratio, 1.051; 95% confidence interval, 1.004–1.100; p = 0.034) as two independent predictors of recurrence of AF. Conclusions Patients with advanced IAB were at an increased risk of AF recurrence after catheter ablation.

Interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF). The aim of this retrospective study was to investigate the association of a combination of IAB and the CHADS2 score, an AF-related risk score for ischemic stroke, with new onset AF in patients in sinus rhythm. A total of 1,571 patients (803 males, 768 females; mean age: 58 ± 16 years) were included in this study. IAB was defined as a P-wave duration > 120 ms in the 12-lead electrocardiogram, and a high CHADS2 score as ≥ 2 points. During the mean follow-up period of 4.8 ± 0.7 years, new onset AF occurred in 122 patients (16.1 per 1,000 patient-years). The incidence of new onset AF was 4.0 per 1,000 patient-years in patients with no IAB and a low CHADS2 score, and 44.0 per 1,000 patient-years in patients with IAB and a high CHADS2 score. In multivariate Cox regression analysis, the hazard ratio for IAB and a high CHADS2 score compared with no IAB and a low CHADS2 score was 12.18 (95% confidence interval: 6.22-23.87, P < 0.001), after adjustment for age, sex, coronary artery disease, valvular heart disease, smoking, medications, and echocardiographic parameters. In conclusion, IAB and a high CHADS2 score independently and synergistically predict new onset AF in patients in sinus rhythm, indicating an approximately 12-fold higher risk in patients with both IAB and a high CHADS2 score. Patients meeting these criteria should have more aggressive early intervention to prevent AF.

A low resting heart rate (RHR) is associated with an increased risk of atrial fibrillation (AF), and this is common in older people. Whether a low RHR in older people can predict recurrence of AF after catheter ablation is unclear. A total of 329 consecutive patients ≥65 years of age with paroxysmal AF who underwent index circumferential pulmonary vein isolation were prospectively enrolled. A 10-second standard resting 12-lead electrocardiogram in sinus rhythm was recorded to measure the RR interval, P-wave duration, and PR interval. The RHR was calculated based on the mean RR interval. During a mean follow-up period of 17.0 ± 8.3 months (range, 3 to 32 months), 96 (29.2%) patients developed recurrence of AF. The AF recurrence rate was 46.2%, 32.3%, and 25.4% in patients with an RHR50, 50 to 59, and ≥60 beats/min, respectively (log-rank test, p = 0.009). Cox regression analysis with adjustment for P-wave duration and the CHADS

Hyperhomocysteine has become a critical risk for atherosclerosis and can stimulate proliferation and migration of vascular smooth muscle cells (VSMCs). N-methyl-D-aspartic acid receptor (NMDAR) is a receptor of homocysteine and mediates the effects of homocysteine on VSMCs. Bioinformatics analysis has shown NMDAR is a potential target of microRNA-217 (miR-217), which exerts multiple funct ions in cancer tumorigenesis and carotid plaque progression. In this study, we sought to investigate the role of miR-217 in VSMCs phenotype transition under homocysteine exposure and elucidate its effect on atherosclerotic plaque formation. After treating with several doses of homocysteine (0~8×10-4 M) for 24 h, the expression of miR-217 in HA-VSMCs and rat aortic VSMCs was not altered. Intriguingly, the expression of NMDAR mRNA and protein was reduced by homocysteine in a dose-dependent manner. Transfection of miR-217 mimic significantly inhibited the proliferation and migration of VSMCs with homocysteine treatment, while transfection of miR-217 inhibitor promoted VSMCs migration. Moreover, miR-217 mimic down-regulated while miR-217 inhibitor up-regulated NMDAR protein expression but not NMDAR mRNA expression. Through luciferase reporter assay, we showed that miR-217 could directly bind to the 3’-UTR of NMDAR. MiR-217 mimic transfection also released the inhibition of cAMP-response element-binding protein (CREB)-PGC-1α signaling induced by homocysteine. Additionally, restoration of PGC-1α expression via AdPGC-1α infection markedly suppressed VSMCs proliferation through the degradation of NADPH oxidase (NOX1) and reduction of reactive oxygen species (ROS). Collectively, our study identified the role of miR-217 in regulating VSMCs proliferation and migration, which might serve as a target for atherosclerosis therapy. This article is protected by copyright. All rights reserved.