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Almost half of patients recovering from open-chest surgery experience atrial fibrillation (AF) that results principally from inflammation in the pericardial space surrounding the heart. Given that postoperative AF is associated with increased mortality, effective measures to prevent AF after open-chest surgery are highly desirable. In this study, we tested the concept that extracellular vesicles (EVs) isolated from human atrial explant-derived cells can prevent postoperative AF. Middle-aged female and male rats were randomized to undergo sham operation or induction of sterile pericarditis followed by trans-epicardial injection of human EVs or vehicle into the atrial tissue. Pericarditis increased the probability of inducing AF while EV treatment abrogated this effect in a sex-independent manner. EV treatment reduced infiltration of inflammatory cells and production of pro-inflammatory cytokines. Atrial fibrosis and hypertrophy seen after pericarditis were markedly attenuated by EV pretreatment, an effect attributable to suppression of fibroblast proliferation by EVs. Our study demonstrates that injection of EVs at the time of open-chest surgery shows prominent antiinflammatory effects and prevents AF due to sterile pericarditis. Translation of this finding to patients might provide an effective new strategy to prevent postoperative AF by reducing atrial inflammation and fibrosis.

Background/purpose: Atrial fibrillation (AF) recurs post-ablation in 30-40% of patients. The approach to a repeat ablation, beyond isolation of reconnected pulmonary veins (PVs), is not well established. We sought to prospectively assess outcomes and predictors of recurrence among consecutive patients who underwent repeat AF ablation with a standardized approach., Methods: This was a single-center prospective study of consecutive patients who underwent repeat AF ablation. Our protocol consisted of six steps: PV re-isolation, ablation of left atrial low-voltage areas (LVAs), ablation of isoproterenol-induced non-PV triggers, electrophysiology study (EPS) and ablation of induced AVNRT/AVRT, ablation of induced clinical atrial flutters, and lastly empiric ablation as per operator discretion if no other ablation was performed., Results: Among 725 AF ablations performed during the study period, 74 were repeat ablations. Of those undergoing repeat ablation, 53 (72%) had PV reconnection, 30 (41%) had LVAs, seven (10%) had non-PV triggers, five (7%) had AVNRT, and 15 (20%) had typical atrial flutter. Following repeat ablation, arrhythmia-free survival was 65% at 1 year. The absence of PV reconnection was the only factor independently associated with recurrence after repeat ablation (recurrence rate 71%, adjusted OR 7.91, 95% CI 2.31-27.16, p = 0.001)., Conclusions: A comprehensive approach to repeat AF ablation including PV re-isolation, LVA ablation, non-PV trigger ablation, EPS, and flutter ablation was associated with a 65% 1-year arrhythmia-free survival. The absence of PV reconnection was the only independent predictor of arrhythmia recurrence. Further research is needed to identify therapies beyond PV isolation for patients undergoing repeat ablation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The effectiveness, safety, and pulmonary vein (PV) reconnection patterns of point-by-point high-power, short-duration (HPSD) ablation relative to conventional force-time integral (FTI)-guided strategies for atrial fibrillation (AF) ablation are unknown., Objectives: To compare 1-year freedom from atrial arrhythmia (AA), complication rates, procedural times, and PV reconnection patterns with HPSD AF AF ablation versus an FTI-guided low-power, long-duration (LPLD) strategy., Methods: We compared consecutive patients undergoing a first ablation procedure for paroxysmal or persistent AF. The HPSD protocol utilized a power of 50 W and durations of 6-8 s posteriorly and 8-10 s anteriorly. The LPLD protocol was FTI-guided with a power of ≤25 W posteriorly (FTI ≥ 300g·s) and ≤35 W anteriorly (FTI ≥ 400g·s)., Results: In total, 214 patients were prospectively included (107 HPSD, 107 LPLD). Freedom from AA at 1 year was achieved in 79% in the HPSD group versus 73% in the LPLD group (p = .339; adjusted hazard ratio with HPSD, 0.67; 95% confidence interval, 0.36-1.23; p < .004 for non-inferiority). Procedure duration was shorter in the HPSD group (229 ± 60 vs. 309 ± 77 min; p < .005). Patients undergoing repeat ablation had a higher propensity for reconnection at the right PV carina in the HPSD group compared with the LPLD group (14/30 = 46.7% vs. 7/34 = 20.6%; p = .035). There were no differences in complication rates., Conclusion: HPSD AF ablation resulted in similar freedom from AAs at 1 year, shorter procedure times, and a similar safety profile when compared with an LPLD ablation strategy. Patients undergoing HPSD ablation required more applications at the right carina to achieve isolation, and had a significantly higher rate of right carinal reconnections at redo procedures., (© 2021 Wiley Periodicals LLC.)

Background: Post-operative atrial fibrillation (POAF) is a frequent cardiothoracic surgery complication that increases hospital stay, mortality and costs. Despite decades of research, there has been no systematic overview and meta-analysis of preclinical therapies for POAF in animal models., Methods: We performed a systematic search of MEDLINE and EMBASE from their inception through September 2020 to determine the effect of preclinical POAF therapies on primary efficacy outcomes using a prospectively registered protocol (CRD42019155649). Bias was assessed using the SYRCLE tool and CAMARADES checklist., Results: Within the 26 studies that fulfilled our inclusion criteria, we identified 4 prevention strategies including biological (n = 5), dietary (n = 2), substrate modification (n = 2), and pharmacological (n = 17) interventions targeting atrial substrate, cellular electrophysiology or inflammation. Only one study altered more than 1 pathophysiological mechanism. 73% comprised multiple doses of systemic therapies. Large animal models were used in 81% of the studies. Preclinical therapies altogether attenuated atrial fibrosis (SMD -2.09; 95% confidence interval [CI] -2.95 to -1.22; p < 0.00001; I2 = 47%), AF inducibility (RR 0.40; 95% CI 0.21 to 0.79; p = 0.008; I2 = 39%), and AF duration (SMD -2.19; 95% CI -3.05 to -1.32; p < 0.00001; I2 = 50%). However, all the criteria needed to evaluate the risk of bias was unclear for many outcomes and only few interventions were independently validated by more than 1 research group., Conclusion: Treatments with therapies targeting atrial substrate, cellular electrophysiology or inflammation reduced POAF in preclinical animal models compared to controls. Improving the quality of outcome reporting, independently validating promising approaches and targeting complimentary drivers of POAF are promising means to improve the clinical translation of novel therapies for this highly prevalent and clinically meaningful disease., Competing Interests: The authors have declared that no competing interests exist.

Biological therapies that increase or suppress the expression of transcripts underlying atrial fibrillation (AF) progression are increasingly being explored to create novel treatment paradigms beyond simply suppressing or destroying tissue. To date, there has been no systematic overview of the preclinical evidence exploring manipulation of fundamental biological principles in the treatment of AF. As such, the objective of this study was to establish the effect of biological approaches used in the treatment of AF within large and small animals. We performed a systematic search using predefined terms, which yielded 25 studies. We determined the effect of biological approaches on primary efficacy outcomes and assessed the quality of included studies or possible bias in the treatment of AF. Compared with non-transduced or transduced controls, biological therapies reduced AF inducibility (85% less AF; odds ratio 0.15; 95% confidence interval [CI] 0.07-0.35; P < .01) and atrial scar burden (6.7% smaller scars; 95% CI 4.2-9.2; P < .01) or increased number of days in sinus rhythm (6.4 more days in sinus rhythm; 95% CI 5.83-6.97; P < .01). Similar effects were seen in both large and small animals, while a minor tendency to higher risk of bias was observed in small animal studies. In conclusion, treatment with any biological therapy significantly improved AF in preclinical animal models compared with controls. Although biological therapies target markedly different fundamental mechanisms, we observed a consistent difference in their effect on AF outcomes., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Electrical cardioversion is commonly performed to restore sinus rhythm in patients with atrial fibrillation (AF), but it is unsuccessful in 10-12% of attempts. We sought to evaluate the effectiveness and safety of a novel cardioversion protocol for this arrhythmia., Methods and Results: Consecutive elective cardioversion attempts for AF between October 2012 and July 2017 at a tertiary cardiovascular centre before (Phase I) and after (Phase II) implementing the Ottawa AF cardioversion protocol (OAFCP) as an institutional initiative in July 2015 were evaluated. The primary outcome was cardioversion success, defined as ≥2 consecutive sinus beats or atrial-paced beats in patients with implanted cardiac devices. Secondary outcomes were first shock success, sustained success (sinus or atrial-paced rhythm on 12-lead electrocardiogram prior to discharge from hospital), and procedural complications. Cardioversion was successful in 459/500 (91.8%) in Phase I compared with 386/389 (99.2%) in Phase II (P < 0.001). This improvement persisted after adjusting for age, body mass index, amiodarone use, and transthoracic impedance using modified Poisson regression [adjusted relative risk 1.08, 95% confidence interval (CI) 1.05-1.11; P < 0.001] and when analysed as an interrupted time series (change in level +9.5%, 95% CI 6.8-12.1%; P < 0.001). The OAFCP was also associated with greater first shock success (88.4% vs. 79.2%; P < 0.001) and sustained success (91.6% vs 84.7%; P=0.002). No serious complications occurred., Conclusion: Implementing the OAFCP was associated with a 7.4% absolute increase in cardioversion success and increases in first shock and sustained success without serious procedural complications. Its use could safely improve cardioversion success in patients with AF., Clinical Trial Number: www.clinicaltrials.gov ID: NCT02192957., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aims: There is ongoing controversy about the need for routine transoesophageal echocardiography (TOE) prior to atrial fibrillation (AF) ablation. Recently, the debate was reignited by the publication of a large series of patients showing a prevalence of left atrial appendage thrombus (LAAT) on TOE of 4.4%. We sought to assess the prevalence of LAAT on TOE before AF ablation at our institution., Methods and Results: Consecutive patients scheduled for AF ablation at our institution between January 2009 and December 2016 were included. All patients were on oral anticoagulation for at least 4 weeks prior to TOE. Transoesophageal echocardiographies were performed 3-5 days prior to scheduled AF ablation. Data were collected utilizing a prospective database. In all, 668 patients and 943 AF ablation procedures were included. Mean age was 64 ± 11 years, 72% were male, average CHADS2 score was 1.0 ± 1.0, and 72% of the patients had paroxysmal AF. At the time of ablation, 496 (53%) were on non-vitamin K antagonist oral anticoagulants (NOACs) and 447 (47%) were on Warfarin. There were three cases with LAAT (3/943, 0.3%), all of whom had persistent AF and were on Warfarin. Two patients underwent surgical ablation and the third patient did not undergo ablation., Conclusion: In our experience, the prevalence of LAAT in patients on anticoagulation therapy undergoing TOE before catheter ablation of AF is 0.3%, which was much lower than recently reported. None of the patients with paroxysmal AF or on NOACs were found to have LAAT. Rather than routine use of TOE prior to AF ablation, a risk-based approach should be considered.

Aims: Electrical cardioversion is commonly performed to restore sinus rhythm in patients with atrial fibrillation (AF), but it is unsuccessful in 10-12% of attempts. We sought to evaluate the effectiveness and safety of a novel cardioversion protocol for this arrhythmia.Methods and Results: Consecutive elective cardioversion attempts for AF between October 2012 and July 2017 at a tertiary cardiovascular centre before (Phase I) and after (Phase II) implementing the Ottawa AF cardioversion protocol (OAFCP) as an institutional initiative in July 2015 were evaluated. The primary outcome was cardioversion success, defined as ≥2 consecutive sinus beats or atrial-paced beats in patients with implanted cardiac devices. Secondary outcomes were first shock success, sustained success (sinus or atrial-paced rhythm on 12-lead electrocardiogram prior to discharge from hospital), and procedural complications. Cardioversion was successful in 459/500 (91.8%) in Phase I compared with 386/389 (99.2%) in Phase II (P < 0.001). This improvement persisted after adjusting for age, body mass index, amiodarone use, and transthoracic impedance using modified Poisson regression [adjusted relative risk 1.08, 95% confidence interval (CI) 1.05-1.11; P < 0.001] and when analysed as an interrupted time series (change in level +9.5%, 95% CI 6.8-12.1%; P < 0.001). The OAFCP was also associated with greater first shock success (88.4% vs. 79.2%; P < 0.001) and sustained success (91.6% vs 84.7%; P=0.002). No serious complications occurred.Conclusion: Implementing the OAFCP was associated with a 7.4% absolute increase in cardioversion success and increases in first shock and sustained success without serious procedural complications. Its use could safely improve cardioversion success in patients with AF.Clinical Trial Number: www.clinicaltrials.gov ID: NCT02192957. [ABSTRACT FROM AUTHOR]

Aims: There is ongoing controversy about the need for routine transoesophageal echocardiography (TOE) prior to atrial fibrillation (AF) ablation. Recently, the debate was reignited by the publication of a large series of patients showing a prevalence of left atrial appendage thrombus (LAAT) on TOE of 4.4%. We sought to assess the prevalence of LAAT on TOE before AF ablation at our institution.Methods and Results: Consecutive patients scheduled for AF ablation at our institution between January 2009 and December 2016 were included. All patients were on oral anticoagulation for at least 4 weeks prior to TOE. Transoesophageal echocardiographies were performed 3-5 days prior to scheduled AF ablation. Data were collected utilizing a prospective database. In all, 668 patients and 943 AF ablation procedures were included. Mean age was 64 ± 11 years, 72% were male, average CHADS2 score was 1.0 ± 1.0, and 72% of the patients had paroxysmal AF. At the time of ablation, 496 (53%) were on non-vitamin K antagonist oral anticoagulants (NOACs) and 447 (47%) were on Warfarin. There were three cases with LAAT (3/943, 0.3%), all of whom had persistent AF and were on Warfarin. Two patients underwent surgical ablation and the third patient did not undergo ablation.Conclusion: In our experience, the prevalence of LAAT in patients on anticoagulation therapy undergoing TOE before catheter ablation of AF is 0.3%, which was much lower than recently reported. None of the patients with paroxysmal AF or on NOACs were found to have LAAT. Rather than routine use of TOE prior to AF ablation, a risk-based approach should be considered. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]