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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.

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

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 duration120 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, P0.001), 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.

Catheter ablation has been established to be an effective therapy for drug-refractory paroxysmal AF and is recommended as the treatment of choice for many patients, including those with a permanent pacemaker (PM). However, the clinical efficacy of catheter ablation of paroxysmal AF in patients with a permanent PM for atrioventricular block (AVB) is not clear. Twenty-nine patients with a permanent PM for AVB (AVB + PM group), and 145 age- and gender-matched control patients (on a 1:5 basis) without AVB and without a permanent PM (no-AVB + no-PM group), were included in this study. Atrial fibrillation (AF) recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 seconds beyond 3 months after catheter ablation in the absence of any antiarrhythmic treatment. During a mean follow-up period of 14.2 ± 8.6 months (range, 3-30 months), 54 patients (31.0%) developed recurrence of AF. The recurrence rate was higher in the AVB + PM group than in the no-AVB + no-PM group (48.3% versus 27.6%, P = 0.005). Cox regression analysis with adjustment for age, valvular heart disease, AVB and a PM together, left atrial (LA) diameter and PV isolation identified LA diameter (hazard ratio 1.054, 95% confidence interval 1.001-1.110, P = 0.047) and AVB and a PM together (hazard ratio 2.095, 95% confidence interval 1.109-3.960, P = 0.023) as two independent predictors of recurrence of AF. Patients with a permanent PM for AVB were at an increased risk of recurrence of AF after catheter ablation.

Objective To study the clinical efficacy of catheter ablation for paroxysmal atrial fibrillation (AF) in patients with a permanent pacemaker (PM) for sick sinus syndrome (SSS). Methods Our prospectively established database of patients who underwent circumferential pulmonary vein (PV) ablation for paroxysmal AF was retrospectively reviewed. A total of 41 patients with a permanent PM for the treatment of SSS (SSS+PM group) and 123 age- and gender-matched control subjects (on a 1: 3 basis) without SSS or a permanent PM (no-SSS+no-PM group) were included in this study. AF recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 seconds beyond three months after catheter ablation in the absence of any antiarrhythmic treatment. Results During a mean follow-up period of 18.3±10.6 months (range 3-30 months), 50 patients (30.5%) developed recurrence of AF. The recurrence rate was higher in the SSS+PM group than in the no-SSS+no-PM group (43.9% vs. 26.3%, p=0.011). A Cox regression analysis adjusted for age, valvular heart disease, left atrial (LA) diameter and PV isolation identified only SSS and the use of a PM together as an independent predictor of recurrence of AF (hazard ratio 2.02, 95% confidence interval 1.10-3.69, p=0.023). Conclusion Patients with a permanent PM for SSS are at an increased risk of recurrence of AF after catheter ablation.