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Esophageal injury is a rare but serious complication of catheter ablation for atrial fibrillation using radiofrequency energy. Recent studies have begun to identify variables that may determine heat transfer to and thermal injury of the esophagus. There is significant variability in the relationship between the esophagus and left atrium among individuals. New imaging techniques can facilitate assessment of esophagus position relative to intended ablation targets. Strategies to minimize the risk of esophageal injury include avoidance of ablation near the esophagus, titration of RF energy delivery at the posterior left atrial endocardium, and the use of alternative ablation methods. [ABSTRACT FROM AUTHOR]

The currently available sudden cardiac death (SCD) risk prediction tools fail to identify most at-risk patients and cannot delineate a specific patient's SCD risk. We sought to develop a tool to improve the risk stratification of patients with coronary artery disease. Clinical, demographic, and angiographic characteristics were evaluated among 37,258 patients who had undergone coronary angiography from January 1, 1985 to May 31, 2005, and who were found to have at least one native coronary artery stenosis of > or =75%. After a median follow-up of 6.2 years, SCD had occurred in 1,568 patients, 14,078 patients had died from other causes, and 21,612 patients remained alive. A Cox proportional hazards model identified 10 independent patient characteristic variables significantly associated with SCD. A simplified model accounting for 97% of the predictive capacity of the full model included the following 7 variables: depressed left ventricular ejection fraction, number of diseased coronary arteries, diabetes mellitus, hypertension, heart failure, cerebrovascular disease, and tobacco use. The Duke SCD risk score was created from the simplified model to predict the likelihood of SCD among patients with coronary artery disease. It was internally validated with bootstrapping (c-index = 0.75, chi-square = 1,220.8) and externally validated in patients with ischemic cardiomyopathy from the Sudden Cardiac Death Heart Failure Trial (SCD-HeFT) database (c-index = 0.64, chi-square = 14.1). In conclusion, the Duke SCD risk score represents a simple, validated method for predicting the risk of SCD among patients with coronary artery disease and might be useful for directing treatment strategies designed to mitigate the risk of SCD. [ABSTRACT FROM AUTHOR]

Background: The majority of data on left bundle branch area pacing (LBBAP) are on a lumenless lead. Data on the safety and effectiveness of stylet driven leads are comparatively lacking., Methods: We retrospectively analyzed 265 patients who underwent attempted LBBAP with an 7842 (Boston Scientific, Marlborough, MA) lead in the Duke University Health System between 1/1/2020 and 9/1/2023. Outcomes of interest included post-operative 7842 helix extension (≥2 helix rotations beyond the lead tip), complications, and lead parameters. A nested analysis of single and dual chamber LBBAP attempts was performed to compare outcomes among similar patients who underwent attempted LBBAP with the lumenless 3830 (Medtronic, Mineappolis, MN) lead., Results: LBBAP success with 7842 was 89.8%. Characteristics were similar among patients with (n = 238) and without (n = 27) successful implants. Helix extension was evaluable for 222 of 238 successful 7842 implants. Of evaluable leads, helix extension was complete for 174 leads (78%), and partial for 48 (21.6%). A trend towards lower dislodgement rates was observed in patients with full versus partial extension (2.9% vs. 8.3%, p = 0.0895) and the rate of full helix extension increased over time (64.1% over 24 months vs. 81.4% over 21 months, p = 0.0162). The success rate of 3830 LBBAP implants (n = 140) was 92.8% (p = 0.069 vs. 7842). At implant, R waves were similar for 7842 and 3830 leads but were greater for 7842 during follow-up (14.4 + /-0.77 vs. 11.3 + /-0.68, p = 0.004). Pacing impedances were higher with 7842 compared with 3830 at baseline (838 + /-10.44 ohms vs. 772 + /-14.58 ohms, p < 0.001) and during follow-up (652 + /-11.0 ohms vs. 513 + /-9.18 ohms, p < 0.001); similarly, 7842 pacing thresholds (@ 0.4 ms) were slightly higher at baseline (0.85 V + /-0.03 vs. 0.68 V + /-0.03, p < 0.001) and 6 months (0.95 V + /-0.03 vs. 0.80 V + /-0.03, p < 0.001) compared with those for the lumenless 3830., Conclusion: LBBAP implant success rates, complications, and pacing parameters using the 7842 lead are stable over time, and appeared overall similar to the 3830 lead. Incomplete 7842 helix extension is a modifiable risk factor for lead dislodgement., (© 2025 Wiley Periodicals LLC.)

Background: Clinically detected atrial fibrillation (AF) is associated with a significant increase in mortality and other adverse cardiovascular events. Since the advent of effective methods for AF rhythm control, investigators have attempted to determine how much these adverse prognostic AF effects could be mitigated by the restoration of sinus rhythm (SR) and whether the method used mattered., Methods: The CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) randomized 2204 AF patients to ablation versus drug therapy, of which 1240 patients were monitored in follow-up using the CABANA ECG rhythm monitoring system. To assess the prognostic benefits of SR, we performed a prespecified analysis using Cox survival modeling with heart rhythm as a time-dependent variable and randomized treatment group as a stratification factor., Results: In the 1240 patient study cohort, 883 (71.2%) had documented AF at some point during their postblanking follow-up. Among the 883 patients, 671 (76.0%) experienced AF within the first year of postblanking follow-up, and 212 (24.0%) experienced their first AF after ≥1 year of postblanking follow-up. The primary CABANA end point (death, disabling stroke, serious bleeding, or cardiac arrest) occurred in 95 (10.8%) of the 883 patients with documented AF and in 29 (8.1%) of the 357 patients with no AF recorded during follow-up. In multivariable time-dependent analysis, the presence of SR (compared with non-SR) was associated with a significantly reduced risk of the primary end point (adjusted hazard ratio, 0.57 [95% CI, 0.38-0.85]; P =0.006; independent of treatment strategy [ablation versus drugs]). Corresponding results for all-cause mortality were adjusted hazard ratio of 0.59 [95% CI, 0.35-1.01]; P =0.053)., Conclusions: In patients in the CABANA trial with detailed long-term rhythm follow-up, increased time in SR was associated with a clinically consequential decrease in mortality and other adverse prognostic events. The predictive value of SR was independent of the therapeutic approach responsible for reducing the burden of detectable AF., Registration: URL: https://clinicaltrials.gov; Unique Identifier: NCT00911508., Competing Interests: Disclosures Dr Packer reports grants from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI), St. Jude Medical Corporation and Foundation, Biosense Webster Inc, Medtronic Corp, and Boston Scientific Corp during the conduct of the study; grants from Abbott, Biosense Webster Inc, Boston Scientific Corp, CardioFocus, Medtronic Inc, St. Jude Medical, CardioInsight, NIH, Siemens, Thermedical, Endosense, Robertson Foundation, and Hansen Medical; advisory board without compensation from Abbott, Biosense Webster Inc, Boston Scientific Corp, CardioFocus, Medtronic Inc, St. Jude Medical, Spectrum Dynamics, Siemens, Thermedical, Johnson & Johnson, and SigNum Preemptive Healthcare Inc; speaking with honorarium from Biotronik and MediaSphere Medical, LLC; and royalties from Wiley & Sons, Oxford, and St. Jude Medical. Dr Packer and Mayo Clinic jointly have equity in a privately held company, External Beam Ablation Medical Devices, outside the submitted work. In addition, Dr Packer has mapping technologies with royalties paid. Dr Piccini reports grants from ARCA Biopharma, Boston Scientific, Gilead Sciences, Janssen Pharmaceuticals, Abbott, and Verily; consulting from Allergan, Bayer, Johnson & Johnson, Medtronic, Sanofi, and Philips outside the submitted work. Dr Al-Khalidi reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study. Dr Poole reports grants from ATriCure outside the submitted work. Dr Bahnson reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study; grants from St. Jude Medical Inc, Abbott Medical, Biosense Webster Inc, Johnson & Johnson, NIH, and Boston Scientific, Corp; and consulting from Cardiofocus Inc, and Ventrix outside the submitted work. Dr Lee reports grants from the NIH/NHLBI and Mayo Clinic, as well as Data Safety Monitoring Board service on studies funded by AstraZeneca, Medtronic, Merck, Amgen, and the Cardiovascular Research Foundation during the conduct of the study. Dr Mark reports grants from NIH/NHLBI and Mayo Clinic during the conduct of the study; grants from Merck, Oxygen Therapeutics, Bristol Myers Squibb, AstraZeneca, University of Calgary, Eli Lilly & Company, AGA Medical, St. Jude Medical, and Tufts University; and personal fees from CeleCor outside the submitted work. The other authors report no conflicts.

Background: The finding of unexpected variations in treatment benefits by geographic region in international clinical trials raises complex questions about the interpretation and generalizability of trial findings. We observed such geographical variations in outcome and in the effectiveness of atrial fibrillation (AF) ablation versus drug therapy in the Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial. This paper describes these differences and investigates potential causes., Methods: The examination of treatment effects by geographic region was a prespecified analysis. CABANA enrolled patients from 10 countries, with 1,285 patients at 85 North American (NA) sites and 919 at 41 non-NA sites. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Death and first atrial fibrillation recurrence were secondary endpoints., Results: At least 1 primary endpoint event occurred in 157 patients (12.2%) from NA and 33 (3.6%) from non-NA sites over a median 54.9 and 40.5 months of follow-up, respectively (NA/non-NA adjusted hazard ratio (HR) 2.18, 95% confidence interval (CI) 1.48-3.21, P < .001). In NA patients, 78 events occurred in the ablation and 79 in the drug arm, (HR 0.91, 95% CI 0.66, 1.24) while 11 and 22 events occurred in non-NA patients (HR 0.51, 95% CI 0.25,1.05, interaction P = .154). Death occurred in 53 ablation and 51 drug therapy patients in the NA group (HR 0.96, 95% CI 0.65,1.42) and in 5 ablation and 16 drug therapy patients in the non-NA group (HR 0.32, 95% CI 0.12,0.86, interaction P = .044). Adjusting for baseline regional differences or prognostic risk variables did not account for the regional differences in treatment effects. Atrial fibrillation recurrence was reduced by ablation in both regions (NA: HR 0.54, 95% CI 0.46, 0.63; non-NA: HR 0.44, 95% CI 0.30, 0.64, interaction P = .322)., Conclusions: In CABANA, primary outcome events occurred significantly more often in the NA group but assignment to ablation significantly reduced all-cause mortality in the non-NA group only. These differences were not explained by regional variations in procedure effectiveness, safety, or patient characteristics., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT0091150; https://clinicaltrials.gov/study/NCT00911508., Competing Interests: Disclosures Riccardio Cappato: reports consulting for Boston Scientific; Medtronic; St. Jude; Biosense Webster; ELA Sorin; Boehringer Ingelheim; Bayer HealthCare; Abbott; Pfizer. Speaker's Bureau for Boston Scientific; Medtronic; St. Jude; Biosense Webster; BARD; Sanofi; Boehringer Ingelheim; Bayer HealthCare; Abbott. Investigator for Medtronic; Biosense Webster; Sanofi; Cameron Health, BARD; Bayer HealthCare; Abbott; Pfizer. Grants from Boston Scientific; Medtronic; St. Jude; Biosense Webster; BARD; ELA Sorin Equity and Intellectual Property Rights: Cameron Health, Atacor Inc. Daniel B. Mark: reports grants from the NIH/NHLBI, Mayo Clinic, Merck, NovoNordisk, and HeartFlow; and consulting fees from Novartis, Boehringer Ingelheim, and CeleCor Therapeutics. Peter A. Noseworthy: reports research funding from National Institutes of Health (NIH, including the National Heart, Lung, and Blood Institute [NHLBI, R21AG 62580-1, R01HL 131535-4, R01HL 143070-2] the National Institute on Aging [NIA, R01AG 062436-1]), Agency for Healthcare Research and Quality (AHRQ, R01HS 25402-3), Food and Drug Administration (FDA, FD 06292), and the American Heart Association (18SFRN34230146, AHA). Dr. Noseworthy and Mayo Clinic have filed patents related to the application of AI to the ECG for diagnosis and risk stratification and have licensed several A-ECG algorithms to Anumana. Dr. Noseworthy and Mayo Clinic are involved in potential equity/royalty relationship with AliveCor. Dr. Noseworthy is a study investigator in an ablation trial sponsored by Medtronic. Dr. Noseworthy has served on an expert advisory panel for OptumLabs. Jeanne E. Poole: reports research grants paid directly to the University of Washington from Biotonik, Boston Scientific, Kestra Medical and AtriCure. Jonathan P. Piccini: is supported by R01AG074185 from the National Institutes of Aging. He also receives grants for clinical research from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips and serves as a consultant to Abbott, Abbvie, ARCA biopharma, Bayer, Boston Scientific, Bristol Myers Squibb (Myokardia), Element Science, Itamar Medical, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, ReCor, Sanofi, Philips, and Up-to-Date. Tristram D. Bahnson: reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study; grants from St. Jude Medical, Inc, Abbott Medical, Biosense Webster Inc, Johnson & Johnson, and Boston Scientific Corp; consulting from Cardiofocus, Inc. outside of the submitted work. Hussein R. Al-Khalidi: reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study. Kerry L. Lee: reports grants from the NIH/NHLBI and Mayo Clinic; Data and Safety Monitoring Board service on studies funded by Astra-Zeneca, Medtronic, Merck, Amgen, and the Cardiovascular Research Foundation during the conduct of the study. Douglas L. Packer: in the past 12 months has provided consulting services for Abbott, Affera Inc., ArtFix, Biosense Webster, Inc., CathVision, Cardio Syntax, EBAmed, Johnson & Johnson, Maxwell Biomed, MediaSphere Medical, LLC, MedLumics, Medtronic, St. Jude Medical, Siemens, Sanofi, Spectrum Dynamics, Centrix, Thermedical, and Wave Strategy. Dr. Packer received no personal compensation for these consulting activities, unless noted. Dr. Packer receives research funding from the Abbott, Biosense Webster, Boston Scientific/EPT, CardioInsight, EBAmed, Medtronic, Inc, NeuCures, Siemens, St. Jude Medical, Inc, Thermedical, Inc., NIH, Robertson Foundation, Vital Project Funds, Inc., Xenter, Inc., Mr. and Mrs. J. Michael Cook/Fund. Mayo Clinic and Dr. Packer have a financial interest in Analyze-AVW technology that may have been used to analyze some of the heart images in this research. In accordance with the Bayh-Dole Act, this technology has been licensed to commercial entities, and both Mayo Clinic and Dr. Packer have received royalties less than $10,000, the federal threshold for significant financial interest. In addition, Mayo Clinic holds an equity position in the company to which the AVW technology has been licensed. Dr. Packer and Mayo Clinic jointly have equity in a privately held company, EBAmed. Royalties from Wiley & Sons, Oxford, and St. Jude Medical. Dr. Packer has a licensing agreement with the American Heart Association for the Mayo AF Symptom Inventory (MAFSI) Survey and has contractual rights to receive future royalties under this license. Dr. Packer has a licensing agreement with Medtronic for the Mayo AF Symptom Inventory (MAFSI) Survey and has contractual rights to receive future royalties under this license. Gianluca Bonitta: Adam Silverstein, MS, and Melanie R. Daniels, BA, report no disclosures during the conduct of the study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Catheter ablation of atrial fibrillation (AF) is an established therapy that reduces AF burden, improves quality of life, and reduces the risks of cardiovascular outcomes. Although there are clear guidelines for the application of de novo catheter ablation, there is less evidence to guide recommendations for repeat catheter ablation in patients who experience recurrent AF. In this review, we examine the rationale for repeat ablation, mechanisms of recurrence, patient selection, optimal timing, and procedural strategies. We discuss additional important considerations, including treatment of comorbidities and risk factors, risk of complications, and effectiveness. Mechanisms of recurrent AF are often due to non-pulmonary vein (non-PV) triggers; however, there is insufficient evidence supporting the routine use of empiric lesion sets during repeat ablation. The emergence of pulsed field ablation may alter the safety and effectiveness of de novo and repeat ablation. Extrapolation of data from randomized trials of de novo ablation does not optimally inform efficacy in cases of redo ablation. Additional large, randomized controlled trials are needed to address important clinical questions regarding procedural strategies and timing of repeat ablation., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There is evidence to suggest that colchicine reduces the risk of recurrent atrial fibrillation (AF) after catheter ablation; however, the tolerability and safety of colchicine in routine practice is unknown., Methods: Patients undergoing catheter ablation for AF who received colchicine after ablation were matched 1:1 to patients who did not by age, sex, and renal function. Recurrent AF was compared between groups categorically at 12 months and via propensity weighted Cox proportional hazards models with and without a 3-month blanking period., Results: Overall, 180 patients (n = 90 colchicine and n = 90 matched controls) were followed for a median (Q1, Q3) of 10.3 (7.0, 12.0) months. Mean age was 65.3 ± 9.1 years, 33.9% were women, mean CHA 2 DS 2 -VASc score was 2.9 ± 1.5, and 51.1% had persistent AF. Most patients (70%) received colchicine 0.6 mg daily for a median of 30 days. In the colchicine group, 55 patients (61.1%) were receiving at least one known interacting medication with colchicine. After ablation, one patient required colchicine dose reduction and four patients required discontinuation. After adjusting for covariate imbalance using propensity weighting, no significant association between colchicine use and AF recurrence was identified (adjusted hazard ratio 0.94, 95% confidence interval [CI] 0.48-1.85; p = 0.853). No significant association was found between colchicine use and all-cause hospitalizations (adjusted odds ratio 0.74, 95% CI 0.28-1.96; p = 0.548)., Conclusion: Despite the frequent presence of drug-drug interactions, a 30-day course of colchicine is well-tolerated after AF ablation; however, we did not observe any association between colchicine and lower rates of AF recurrence or hospitalization., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Accurate localization of septal outflow tract premature ventricular contractions (PVCs) is often difficult due to frequent mid-myocardial or protected origin. Compared with traditional activation mapping, CARTO Ripple mapping provides visualization of all captured electrogram data without assignment of a specific local activation time and thus may enhance PVC localization., Methods: Electroanatomic maps for consecutive catheter ablation procedures for septal outflow tract PVCs (July 2018-December 2020) were analyzed. For each PVC, we identified the earliest local activation point (EA), defined by the point of maximal -dV/dt in a simultaneously recorded unipolar electrogram, and the earliest Ripple signal (ERS), defined as the earliest point at which three grouped simultaneous Ripple bars appeared in late diastole. Immediate success was defined as full suppression of the clinical PVC., Results: Fifty-seven unique PVCs in 55 procedures were included. When ERS and EA were in the same chamber (RV, LV, or CS), the odds ratio for the successful procedure was 13.1 (95% confidence interval [CI] 2.2-79.9, p = .005). Discordance between sites was associated with a higher likelihood of needing multi-site ablation (odds ratio [OR] 7.9 [1.4-4.6; p = .020]). Median EA-ERS distance in successful versus unsuccessful cases was 4.6 mm (interquartile range 2.9-8.5) versus 12.5 mm (7.8-18.5); (p = .020)., Conclusion: Greater EA-ERS concordance was associated with higher odds of single-site PVC suppression and successful septal outflow tract PVC ablation. Visualization of complex signals via automated Ripple mapping may offer rapid localization information complementary to local activation mapping for PVCs of mid-myocardial origin., (© 2023 Wiley Periodicals LLC.)

Background Women with atrial fibrillation (AF) demonstrate more AF-related symptoms and worse quality of life (QOL). Whether increased use of ablation in women reduces sex-related QOL differences is unknown. Sex-related outcomes for ablation versus drug therapy was a prespecified analysis in the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial. Methods and Results Symptoms were assessed periodically over 60 months with the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score, and QOL was assessed with the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary and component scores. Women had lower baseline QOL scores than men (mean AFEQT scores 55.9 and 65.6, respectively). Ablation patients improved more than drug therapy patients with similar treatment effect by sex: AFEQT 12-month mean adjusted treatment difference in women 6.1 points (95% CI, 3.5-8.6) and men 4.9 points (95% CI, 3.0-6.9). Participants with baseline AFEQT summary scores <70 had greater QOL improvement, with a mean treatment difference at 12 months of 7.6 points for women (95% CI, 4.3-10.9) and 6.4 points for men (95% CI, 3.3-9.4). The mean adjusted difference in MAFSI frequency score between women randomized to ablation versus drug therapy at 12 months was -2.5 (95% CI, -3.4 to -1.6); for men, the difference was -1.3 (95% CI, -2.0 to -0.6). Conclusions Compared with drug therapy for AF, ablation resulted in more QOL improvement in both sexes, primarily driven by improvements in those with lower baseline QOL. Ablation did not eliminate the AF-related QOL gap between women and men. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00911508.

Aims: Influence of atrial fibrillation (AF) type on outcomes seen with catheter ablation vs. drug therapy is incompletely understood. This study assesses the impact of AF type on treatment outcomes in the Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA)., Methods and Results: CABANA randomized 2204 patients ≥65 years old or <65 with at least one risk factor for stroke to catheter ablation or drug therapy. Of these, 946 (42.9%) had paroxysmal AF (PAF), 1042 (47.3%) had persistent AF (PersAF), and 215 (9.8%) had long-standing persistent AF (LSPAF) at baseline. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Symptoms were measured with the Mayo AF-Specific Symptom Inventory (MAFSI), and quality of life was measured with the Atrial Fibrillation Effect on Quality of Life (AFEQT). Comparisons are reported by intention to treat. Compared with drug therapy alone, catheter ablation produced a 19% relative risk reduction in the primary endpoint for PAF {adjusted hazard ratio [aHR]: 0.81 [95% confidence interval (CI): 0.50, 1.30]}, and a 17% relative reduction for PersAF (aHR: 0.83, 95% CI: 0.56, 1.22). For LSPAF, the ablation relative effect was a 7% reduction (aHR: 0.93, 95% CI: 0.36, 2.44). Ablation was more effective than drug therapy at reducing first AF recurrence in all AF types: by 51% for PAF (aHR: 0.49, 95% CI: 0.39, 0.62), by 47% for PersAF (aHR: 0.53, 95% CI: 0.43,0.65), and by 36% for LSPAF (aHR 0.64, 95% CI 0.41,1.00). Ablation was associated with greater improvement in symptoms, with the mean difference between groups in the MAFSI frequency score favouring ablation over 5 years of follow-up in all subgroups: PAF had a clinically significant -1.9-point difference (95% CI: -1.2 to -2.6); PersAF a -0.9 difference (95% CI: -0.2 to -1.6); LSPAF a clinically significant difference of -1.6 points (95% CI: -0.1 to -3.1). Ablation was also associated with greater improvement in quality of life in all subgroups, with the AFEQT overall score in PAF patients showing a clinically significant 5.3-point improvement (95% CI: 3.3 to 7.3) over drug therapy alone over 5 years of follow-up, PersAF a 1.7-point difference (95% CI: 0.0 to 3.7), and LSPAF a 3.1-point difference (95% CI: -1.6 to 7.8)., Conclusion: Prognostic treatment effects of catheter ablation compared with drug therapy on the primary and major secondary clinical endpoints did not differ consequentially by AF subtype. With regard to decreases in AF recurrence and improving quality of life, ablation was more effective than drug therapy in all three AF type subgroups., Clinicaltrials.gov Identifier: NCT00911508., Competing Interests: Conflict of interest: K.H.M. reports grants from the NIH/NHLBI, St. Jude Foundation and Corporation, Biosense Webster, Inc., Medtronic, Inc., and Boston Scientific Corp., during the conduct of the study; consulting without compensation from Biosense Webster, Inc.; and personal fees from Thermedical outside the submitted work. T.J.B. reports research grants from Boston Scientific, Altathera, Boehringer Ingelheim, no personal compensation received. D.B.M. reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study; grants from Merck and HeartFlow; and personal fees from Novartis outside the submitted work. J.E.P. reports research grants paid directly to the University of Washington from Biotonik, Kestra Medical and AtriCure. T.D.B. reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study; grants from St. Jude Medical, Inc, Abbott Medical, Biosense Webster Inc, Johnson & Johnson, and Boston Scientific Corp and consulting from Cardiofocus, Inc, outside of the submitted work. H.R.A.-K. reports grants from the NIH/NHLBI and Mayo Clinic during the conduct of the study. A.P.S. and M.R.D. report no disclosures during the conduct of the study. K.L.L. reports grants from the NIH/NHLBI and Mayo Clinic, as well as Data and Safety Monitoring Board service on studies funded by Astra-Zeneca, Medtronic, Merck, Amgen, and the Cardiovascular Research Foundation during the conduct of the study. D.L P. in the past 12 months has provided consulting services for Abbott, AtriFix, Biosense Webster, Inc., Cardio Syntax, EBAmed, Johnson & Johnson, MediaSphere Medical, LLC, MedLumics, Medtronic, NeuCures, St. Jude Medical, Siemens, Spectrum Dynamics, Centrix, Thermedical, and Xenter, Inc. D.L.P. received no personal compensation for these consulting activities, unless noted. D.L.P. receives research funding from Abbott, Biosense Webster, Boston Scientific/EPT, CardioInsight, EBAmed, Medtronic, Inc., NeuCures, Siemens, St. Jude Medical, Inc, Thermedical, Inc., NIH, Robertson Foundation, Vital Project Funds, Inc., Xenter, Inc., Mr. and Mrs. J. Michael Cook/Fund. Mayo Clinic and D.L.P. have a financial interest in Analyze-AVW technology that may have been used to analyze some of the heart images in this research. In accordance with the Bayh-Dole Act, this technology has been licensed to commercial entities, and both Mayo Clinic and D.L.P. have received royalties greater than $10 000, the federal threshold for significant financial interest. In addition, Mayo Clinic holds an equity position in the company to which the AVW technology has been licensed. D.L.P. and Mayo Clinic jointly have equity in a privately held company, EBAmed. Royalties from Wiley & Sons, Oxford, and St. Jude Medical. D.L.P. has a licensing agreement with the American Heart Association for the Mayo AF Symptom Inventory (MAFSI) Survey and has contractual rights to receive future royalties under this license., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup, ablation improved both survival and quality of life. Cost-effectiveness was a prespecified CABANA secondary end point., Methods: Medical resource use data were collected for all CABANA patients (N=2204). Costs for hospital-based care were assigned using prospectively collected bills from US patients (n=1171); physician and medication costs were assigned using the Medicare Fee Schedule and National Average Drug Acquisition Costs, respectively. Extrapolated life expectancies were estimated using age-based survival models. Quality-of-life adjustments were based on EQ-5D-based utilities measured during the trial. The primary outcome was the incremental cost-effectiveness ratio, comparing ablation with drug therapy on the basis of intention-to-treat, and assessed from the US health care sector perspective., Results: Costs in the first 3 months averaged $20 794±SD 1069 higher with ablation compared with drug therapy. The cumulative within-trial 5-year cost difference was $19 245 (95% CI, $11 360-$27 170) and the lifetime mean cost difference was $15 516 (95% CI, -$2963 to $35,512) higher with ablation than with drug therapy. The drug therapy arm accrued an average of 12.5 life-years (LYs) and 10.7 quality-adjusted life-years (QALYs). For the ablation arm, the corresponding estimates were 12.6 LYs and 11.0 QALYs. The incremental cost-effectiveness ratio was $57 893 per QALY gained, with 75% of bootstrap replications yielding an incremental cost-effectiveness ratio < $100 000 per QALY gained. With no quality-of-life/utility adjustments, the incremental cost-effectiveness ratio was $183 318 per LY gained., Conclusions: Catheter ablation of atrial fibrillation was economically attractive compared with drug therapy in the CABANA Trial overall at present benchmarks for health care value in the United States on the basis of projected incremental QALYs but not LYs alone.

Background: Pulmonary vein (PV) isolation using radiofrequency ablation (RFA) to treat atrial fibrillation (AF) requires delivery of contiguous transmural lesions at the PV antra while avoiding injury to the esophagus. Continuous 2-dimensional phased-array intracardiac echocardiography (ICE) from within the left atrium (LA) can provide consistent high-resolution images of catheter tip contact and location during ablation., Objective: The purpose of this study was to compare near-term safety outcomes of therapeutic AF ablation with and without ICE imaging from within the LA., Methods: The study cohort included 590 consecutive patients undergoing RFA for AF including continuous ICE imaging during ablation from within either the right atrium (RA) or the LA. Subjects were followed prospectively, and periprocedural complications within 30 days were identified and recorded., Results: All subjects had RA ICE imaging to guide transseptal catheterization. Ultrasound imaging from both RA and LA was used in 243 (41.2%). Respectively, the LA vs RA only imaging cohorts were comparable with respect to age (median 64 [interquartile range 57.4-71.2] years vs 64 [56.2-70.6] years; P = .425); history of hypertension (64.0% vs 67.2%; P = .421); diabetes mellitus (23.1% vs 19.4%; P = .268); previous cerebrovascular accident/transient ischemic attack (10.8% vs 8.4%; P = .331); and AF type ( P = .241). There were no significant differences in major complications within 30 days between the 2 cohorts ( P = .649) and no identified cases of esophageal or phrenic nerve injury or PV stenosis., Conclusions: Routine continuous LA ICE imaging seems to be safe and holds potential to facilitate lesion delivery during RFA for AF., (© 2022 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Background: Atrial pacing and right ventricular (RV) pacing are both associated with adverse outcomes among patients with first-degree atrioventricular block (1°AVB). His-bundle pacing (HBP) provides physiological activation of the ventricle and may be able to improve both atrioventricular (AV) and inter-ventricular synchrony in 1°AVB patients. This study evaluates the acute echocardiographic and hemodynamic effects of atrial, atrial-His-bundle sequential (AH), and atrial-ventricular (AV) sequential pacing in 1°AVB patients., Methods: Patients with 1°AVB undergoing atrial fibrillation ablation were included. Following left atrial (LA) catheterization, patients underwent atrial, AH- and AV-sequential pacing. LA/left ventricular (LV) pressure and echocardiographic measurements during the pacing protocols were compared., Results: Thirteen patients with 1°AVB (mean PR 221 ± 26 ms) were included. The PR interval was prolonged with atrial pacing compared to baseline (275 ± 73 ms, p = .005). LV ejection fraction (LVEF) was highest during atrial pacing (62 ± 11%), intermediate with AH-sequential pacing (59 ± 7%), and lowest with AV-sequential pacing (57 ± 12%) though these differences were not statistically significant. No significant differences were found in LA or LV mean pressures or LV dP/dT. LA and LV volumes, isovolumetric times, electromechanical delays, and global longitudinal strains were similar across pacing protocols., Conclusion: Despite pronounced PR prolongation, the acute effects of atrial pacing were not significantly different than AH- or AV-sequential pacing. Normalizing atrioventricular and/or inter-ventricular dyssynchrony did not result in acute improvements in cardiac output or loading conditions., (© 2022 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Background: Observational data suggest that catheter ablation may be safe and effective to treat younger and older patients with atrial fibrillation. No large, randomized trial has examined this issue. This report describes outcomes according to age at entry in the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation)., Methods: Patients with atrial fibrillation ≥65 years of age, or <65 with ≥1 risk factor for stroke, were randomly assigned to catheter ablation versus drug therapy. The primary outcome was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause mortality, the composite of mortality or cardiovascular hospitalization, and recurrence of atrial fibrillation. Treatment effect estimates were adjusted for baseline covariables using proportional hazards regression models., Results: Of 2204 patients randomly assigned in CABANA, 766 (34.8%) were <65 years of age, 1130 (51.3%) were 65 to 74 years of age, and 308 (14.0%) were ≥75 years of age. Catheter ablation was associated with a 43% reduction in the primary outcome for patients <65 years of age (adjusted hazard ratio [aHR], 0.57 [95% CI, 0.30-1.09]), a 21% reduction for 65 to 74 years of age (aHR, 0.79 [95% CI, 0.54-1.16]), and an indeterminate effect for age ≥75 years of age (aHR, 1.39 [95% CI, 0.75-2.58]). Four-year event rates for ablation versus drug therapy across age groups, respectively, were 3.2% versus 7.8%, 7.8% versus 9.6%, and 14.8% versus 9.0%. For every 10-year increase in age, the primary outcome aHR increased (ie, less favorable to ablation) an average of 27% (interaction P value=0.215). A similar pattern was seen with all-cause mortality: for every 10-year increase in age, the aHR increased an average of 46% (interaction P value=0.111). Atrial fibrillation recurrence rates were lower with ablation than with drug therapy across age subgroups (aHR 0.47, 0.58, and 0.49, respectively). Treatment-related complications were infrequent for both arms (<3%) regardless of age., Conclusions: We found age-based variations in clinical outcomes for catheter ablation compared with drug therapy, with the largest relative and absolute benefits of catheter ablation in younger patients. No prognostic benefits for ablation were seen in the oldest patients. No differences were found by age in treatment-related complications or in the relative effectiveness of catheter ablation in preventing recurrent atrial arrhythmias., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT00911508.

Background: Cardiac implanted electronic device (CIED) pocket and systemic infection remain common complications with traditional CIEDs and are associated with high morbidity and mortality. Leadless pacemakers may be an attractive pacing alternative for many patients following complete hardware removal for a CIED infection by eliminating surgical pocket-related complications as well as lower risk of recurrent complications., Objective: To describe use and outcomes associated with leadless pacemaker implantation following extraction of a CIED system due to infection., Methods: Patient characteristics and postprocedural outcomes were described in patients who underwent leadless pacemaker implantation at Duke University Hospital between November 11, 2014 and November 18, 2019, following CIED infection and device extraction. Outcomes of interest included procedural complications, pacemaker syndrome, need for system revision, and recurrent infection., Results: Among 39 patients, the mean age was 71 ± 17 years, 31% were women, and the most frequent primary pacing indication was complete heart block (64.1%) with 9 (23.1%) patients being pacemaker dependent at the time of Micra implantation. The primary organism implicated in the CIED infection was Staphylococcus aureus (43.6%). Nine of the 39 patients had a leadless pacemaker implanted before or on the same day as their extraction procedure, and the remaining 30 patients had a leadless pacemaker implanted after their extraction procedure. During follow-up (mean 24.8 ± 14.7 months) after leadless pacemaker implantation, there were a total of 3 major complications: 1 groin hematoma, 1 femoral arteriovenous fistula, and 1 case of pacemaker syndrome. No patients had evidence of recurrent CIED infection after leadless pacemaker implantation., Conclusions: Despite a prior CIED infection and an elevated risk of recurrent infection, there was no evidence of CIED infection with a mean follow up of over 2 years following leadless pacemaker implantation at or after CIED system removal. Larger studies with longer follow-up are required to determine if there is a long-term advantage to implanting a leadless pacemaker versus a traditional pacemaker following temporary pacing when needed during the periextraction period in patients with a prior CIED infection., (© 2022 Wiley Periodicals LLC.)

Background: Atrioventricular (AV)-synchronous single-chamber leadless pacing using a mechanical atrial sensing algorithm produced high AV synchrony in clinical trials, but clinical practice experience with these devices has not yet been described., Objective: To describe pacing outcomes and programming changes with AV-synchronous leadless pacemakers in clinical practice., Methods: Consecutive patients without persistent atrial fibrillation who received an AV-synchronous leadless pacemaker and completed follow-up between February 2020 and April 2021 were included. We evaluated tracking index (atrial mechanical sense followed by ventricular pace [AM-VP] divided by total VP), total AV synchrony (sum of AM-ventricular sense [AM-VS], AM-VP, and AV conduction mode switch), use of programming optimization, and improvement in AV synchrony after optimization., Results: Fifty patients met the inclusion criteria. Mean age was 69 ± 16.8 years, 24 (48%) were women, 24 (48%) had complete heart block, and 17 (34%) required ≥50% pacing. Mean tracking index was 41% ± 34%. Thirty-five patients (70%) received ≥1 programming change. In 36 patients with 2 follow-up visits, tracking improved by +9% ± 28% ( P value for improvement = .09) and +18% ± 19% ( P = .02) among 15 patients with complete heart block. Average total AV synchrony increased from 89% [67%, 99%] to 93% [78%, 100%] in all patients ( P = .22), from 86% [52%, 98%] to 97% [82%, 99%] in those with complete heart block ( P = .04), and from 73% [52%, 80%] to 78% [70%, 85%] in those with ≥50% pacing ( P = .09)., Conclusion: In patients with AV-synchronous leadless pacemakers, programming changes are frequent and are associated with increased atrial tracking and increased AV synchrony in patients with complete heart block., (© 2021 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Background: Rhythm control strategies for atrial fibrillation (AF), including catheter ablation, are substantially underused in racial/ethnic minorities in North America., Objectives: This study sought to describe outcomes in the CABANA trial as a function of race/ethnicity., Methods: CABANA randomized 2,204 symptomatic participants with AF to ablation or drug therapy including rate and/or rhythm control drugs. Only participants in North America were included in the present analysis, and participants were subgrouped as racial/ethnic minority or nonminority with the use of National Institutes of Health definitions. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest., Results: Of 1,280 participants enrolled in CABANA in North America, 127 (9.9%) were racial and ethnic minorities. Compared with nonminorities, racial and ethnic minorities were younger with median age 65.6 versus 68.5 years, respectively, and had more symptomatic heart failure (37.0% vs 22.0%), hypertension (92.1% vs 76.8%, respectively), and ejection fraction <40% (20.8% vs 7.1%). Racial/ethnic minorities treated with ablation had a 68% relative reduction in the primary endpoint (adjusted hazard ratio [aHR]: 0.32; 95% confidence interval [CI]: 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR: 0.28; 95% CI: 0.10-0.79). Primary event rates in racial/ethnic minority and nonminority participants were similar in the ablation arm (4-year Kaplan-Meier event rates 12.3% vs 9.9%); however, racial and ethnic minorities randomized to drug therapy had a much higher event rate than nonminority participants (27.4% vs. 9.4%)., Conclusion: Among racial or ethnic minorities enrolled in the North American CABANA cohort, catheter ablation significantly improved major clinical outcomes compared with drug therapy. These benefits, which were not seen in nonminority participants, appear to be due to worse outcomes with drug therapy. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508)., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Institutes of Health (U01HL89709, U01HL089786, U01HL089907, and U01HL089645), St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific Corporation. The content of this paper does not necessarily represent the views of the National Heart, Lung, and Blood Institute or the Department of Health and Human Services. Dr. Thomas has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health), Patient-Centered Outcomes Research Institute, and American Heart Association; and has received consulting fees from Sanofi, Boehringer Ingelheim, Janssen, Bristol Myers Squibb, and Medtronic during the conduct of the study. Dr. Al-Khalidi has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health) and the Mayo Clinic during the conduct of the study. Dr. Monahan has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health), St. Jude Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific during the conduct of the study; has consulted without compensation from Biosense Webster; and has received personal fees from Thermedical outside the submitted work. Dr. Bahnson has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health) and the Mayo Clinic for conduct of the study; has received grants from Boston Scientific, St. Jude Medical Corporation, Biosense Webster, and Medtronic; and has received compensation for consulting from Cardiofocus and Ventrix during the conduct of the study but outside of the submitted work. Dr. Poole has received grants from ATriCure outside the submitted work. Dr. Mark has received grants from the National Heart, Lung, and Blood Institute (National Institutes of Health), the Mayo Clinic during the conduct of the study; and has received grants from Merck and HeartFlow outside the submitted work. Dr. Packer in the past 12 months has provided consulting services for Biosense Webster, Inc., Boston Scientific, CyberHeart, Medtronic, Inc., nContact, Sanofi, St. Jude Medical, and Toray Industries but has received no personal compensation for these consulting activities; has received grants from Abbott, Biosense Webster, Boston Scientific, CardioFocus, Medtronic, St. Jude Medical, CardioInsight, National Institutes of Health, Siemens, Thermedical, Endosense, Robertson Foundation, and Hansen Medical; has served on the advisory board without compensation for Abbott, Biosense Webster, Boston Scientific, CardioFocus, Medtronic, St. Jude Medical, Spectrum Dynamics, Siemens, Thermedical, Johnson & Johnson, and SigNum Preemptive Healthcare; has received speaking fees and honoraria from Biotronik and MediaSphere Medical; has received royalties from Wiley & Sons, Oxford, and St. Jude Medical; has joint equity with the Mayo Clinic in a privately held company, External Beam Ablation Medical Devices, outside the submitted work; and has received research funding from the NIH, Medtronic, Inc., Cryo Cath, Siemens AG, EP Limited, Minnesota Partnership for Biotechnology and Medical Genomics/University of Minnesota, Biosense Webster, Inc., and Boston Scientific. Mayo Clinic and Drs. Packer and Robb have a financial interest in mapping technology that may have been used at some of the 10 centers participating in this pilot research; in accordance with the Bayh-Dole Act, this technology has been licensed to St. Jude Medical, and Mayo Clinic and Drs. Packer and Robb received annual royalties >$10,000, the federal threshold for significant financial interest. Dr. Silverstein has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

[Figure: see text].

Localized changes in myocardial conduction velocity (CV) are pro-arrhythmic, but high-resolution mapping of local CV is not yet possible during clinical electrophysiology procedures. This is in part because measurement of local CV at small spatial scales (1 mm) requires accurate annotation of local activation time (LAT) differences with very high temporal resolution (≤1 ms), beyond that of standard clinical methods. We sought to develop a method for high-resolution measurement of LAT differences and validate against existing techniques. First, we use a simplified theoretical model to identify a quantitative relationship between the LAT difference of a pair of electrodes and the peak amplitude of the bipolar EGM measured between them. This allows LAT differences to be calculated from bipolar EGM peak amplitude, by a novel "Determination of EGM Latencies by Transformation of Amplitude" (DELTA) method. Next, we use simulated EGMs from a computational model to validate this method. With 1 kHz sampling, LAT differences less than 4 ms were more accurately measured with DELTA than by standard LAT annotation (mean error 3.8% vs. 22.9%). In a 1-dimensional and a 2-dimension model, CV calculations were more accurate using LAT differences found by the DELTA method than by standard LAT annotation (by unipolar dV/dt timing). DELTA-derived LAT differences were more accurate than standard LAT annotation in simulated complex fractionated EGMs from a model incorporating fibrosis. Finally, we validated the DELTA method in vivo using 18,740 bipolar EGMs recorded from the left atrium of 10 atrial fibrillation patients undergoing catheter ablation. Using clinical EGMs, there was agreement in LAT differences found by DELTA, standard LAT annotation, and unipolar waveform cross-correlation. These results demonstrate an underlying relationship between a bipolar EGM's peak amplitude and the activation time difference between its two electrodes. Our computational modeling and clinical results suggest this relationship can be leveraged clinically to improve measurement accuracy for small LAT differences, which may improve CV measurement at small spatial scales., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gaeta, Bahnson and Henriquez.)

Background: In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation)., Methods: The CABANA trial randomized 2204 patients with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke at 126 sites to ablation with pulmonary vein isolation or drug therapy including rate or rhythm control drugs. Of these, 778 (35%) had New York Heart Association class >II at baseline and form the subject of this article. The CABANA trial's primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest., Results: Of the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction <40%, whereas 11.7% had ejection fractions between 40% and 50%. In the intention-to-treat analysis, the ablation arm had a 36% relative reduction in the primary composite end point (hazard ratio, 0.64 [95% CI, 0.41-0.99]) and a 43% relative reduction in all-cause mortality (hazard ratio, 0.57 [95% CI, 0.33-0.96]) compared with drug therapy alone over a median follow-up of 48.5 months. AF recurrence was decreased with ablation (hazard ratio, 0.56 [95% CI, 0.42-0.74]). The adjusted mean difference for the AFEQT (Atrial Fibrillation Effect on Quality of Life) summary score averaged over the entire 60-month follow-up was 5.0 points, favoring the ablation arm (95% CI, 2.5-7.4 points), and the MAFSI (Mayo Atrial Fibrillation-Specific Symptom Inventory) frequency score difference was -2.0 points, favoring ablation (95% CI, -2.9 to -1.2)., Conclusions: In patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification. Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT00911508; Unique identifier: NCT0091150.

Background: Among patients with atrial fibrillation (AF), women are less likely to receive catheter ablation and may have more complications and less durable results. Most information about sex-specific differences after ablation comes from observational data. We prespecified an examination of outcomes by sex in the 2204-patient CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation)., Methods: CABANA randomized patients with AF age ≥65 years or <65 years with ≥1 risk factor for stroke to a strategy of catheter ablation with pulmonary vein isolation versus drug therapy with rate/rhythm control agents. The primary composite outcome was death, disabling stroke, serious bleeding, or cardiac arrest, and key secondary outcomes included AF recurrence., Results: CABANA randomized 819 (37%) women (ablation 413, drug 406) and 1385 men (ablation 695, drug 690). Compared with men, women were older (median age, 69 years versus 67 years for men), were more symptomatic (48% Canadian Cardiovascular Society AF Severity Class 3 or 4 versus 39% for men), had more symptomatic heart failure (42% with New York Heart Association Class ≥II versus 32% for men), and more often had a paroxysmal AF pattern at enrollment (50% versus 39% for men) ( P <0.0001 for all). Women were less likely to have ancillary (nonpulmonary vein) ablation procedures performed during the index procedure (55.7% versus 62.2% in men, P =0.043), and complications from treatment were infrequent in both sexes. For the primary outcome, the hazard ratio for those who underwent ablation versus drug therapy was 1.01 (95% CI, 0.62-1.65) in women and 0.73 (95% CI, 0.51-1.05) in men (interaction P value=0.299). The risk of recurrent AF was significantly reduced in patients undergoing ablation compared with those receiving drug therapy regardless of sex, but the effect was greater in men (hazard ratio, 0.64 [95% CI, 0.51-0.82] for women versus hazard ratio, 0.48 [95% CI, 0.40-0.58] for men; interaction P value=0.060)., Conclusions: Clinically relevant treatment-related strategy differences in the primary and secondary clinical outcomes of CABANA were not seen between men and women, and there were no sex differences in adverse events. The CABANA trial results support catheter ablation as an effective treatment strategy for both women and men. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00911508.

Background: Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT)., Methods: We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics, and outcomes were determined by manual chart review., Results: A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and three atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs 40%, P = .003). Cardiac amyloid was diagnosed based on the results of preablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60 ± 15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69 ± 18 ms vs 57 ± 14 ms, P = .36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, whereas patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, P = .014). Arrhythmia-free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at 1 year and 20% at 2 years., Conclusions: Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid-stage CA, whereas AV node ablation may be more appropriate in patients with advanced-stage CA., (© 2020 Wiley Periodicals LLC.)

Background: The CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial randomized 2,204 patients with atrial fibrillation (AF) to catheter ablation or drug therapy. Analysis by intention-to-treat showed a nonsignificant 14% relative reduction in the primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest., Objectives: The purpose of this study was to assess recurrence of AF in the CABANA trial., Methods: The authors prospectively studied CABANA patients using a proprietary electrocardiogram recording monitor for symptom-activated and 24-h AF auto detection. The AF recurrence endpoint was any post-90-day blanking atrial tachyarrhythmias lasting 30 s or longer. Biannual 96-h Holter monitoring was used to assess AF burden. Patients who used the CABANA monitors and provided 90-day post-blanking recordings qualified for this analysis (n = 1,240; 56% of CABANA population). Treatment comparisons were performed using a modified intention-to-treat approach., Results: Median age of the 1,240 patients was 68 years, 34.4% were women, and AF was paroxysmal in 43.0%. Over 60 months of follow-up, first recurrence of any symptomatic or asymptomatic AF (hazard ratio: 0.52; 95% confidence interval: 0.45 to 0.60; p < 0.001) or first symptomatic-only AF (hazard ratio: 0.49; 95% confidence interval: 0.39 to 0.61; p < 0.001) were both significantly reduced in the catheter ablation group. Baseline Holter AF burden in both treatment groups was 48%. At 12 months, AF burden in ablation patients averaged 6.3%, and in drug-therapy patients, 14.4%. AF burden was significantly less in catheter ablation compared with drug-therapy patients across the 5-year follow-up (p < 0.001). These findings were not sensitive to the baseline pattern of AF., Conclusions: Catheter ablation was effective in reducing recurrence of any AF by 48% and symptomatic AF by 51% compared with drug therapy over 5 years of follow-up. Furthermore, AF burden was also significantly reduced in catheter ablation patients, regardless of their baseline AF type. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). Few studies have compared clinical outcomes after catheter ablation between patients with and those without DM., Objective: The purpose of this study was to compare AF ablation outcomes in patients with and those without DM., Methods: We performed a retrospective analysis of 351 consecutive patients who underwent first-time AF ablation. Clinical outcomes included freedom from recurrent atrial arrhythmia, symptom burden (Mayo AF Symptom Inventory score), cardiovascular and all-cause hospitalizations, and periprocedural complications., Results: Patients with DM (n = 65) were older, had a higher body mass index, more persistent AF, more hypertension, and larger left atrial diameter ( P <.05 for all). Median (Q1, Q3) total radiofrequency duration [64.0 (43.6, 81.4) minutes vs 54.3 (39.2, 76.4) minutes; P = .132] and periprocedural complications ( P = .868) did not differ between patients with and those without DM. After a median follow-up of 29.5 months, arrhythmia recurrence was significantly higher in the DM group compared to the no-DM group after adjustment for baseline differences (adjusted hazard ratio [HR] 2.24; 95% confidence [CI] 1.42-3.55; P = .001). There was a nonsignificant trend toward higher AF recurrence with worse glycemic levels (HR 1.29; 95% CI 0.99-1.69; P = .064)., Conclusion: Although safety outcomes associated with AF ablation were similar between patients with and those without DM, arrhythmia-free survival was significantly lower among patients with DM. Poor glycemic control seems to an important risk factor for AF recurrence., (© 2020 Heart Rhythm Society. Published by Elsevier Inc.)

Background: The amplitude of bipolar electrograms (EGMs) is directionally sensitive, decreasing when measured from electrode pairs oriented oblique to a propagating wavefront., Objective: The purpose of this study was to use a computational model and clinical data to establish the mechanism and magnitude of directional sensitivity., Methods: Simulated EGMs were created using a computational model with electrode pairs rotated relative to a passing wavefront. A clinical database of 18,740 EGMs with varying electrode separation and orientations was recorded from the left atrium of 10 patients with atrial fibrillation during pacing. For each EGM, the angle of incidence between the electrodes and the wavefront was measured using local conduction velocity (CV) mapping., Results: A theoretical model was derived describing the effect of the changing angle of incidence, electrode spacing, and CV on the local activation time difference between a pair of electrodes. Model predictions were validated using simulated and clinical EGMs. Bipolar amplitude measured by an electrode pair is decreased (directionally sensitive) at angles of incidence resulting in local activation time differences shorter than unipolar downstroke duration. Directional sensitivity increases with closer electrode spacing, faster CV, and longer unipolar EGM duration. For narrowly spaced electrode pairs (<5 mm), it is predicted at all orientations., Conclusion: Directional sensitivity occurs because bipolar amplitude is reduced when the component unipolar EGMs overlap, such that neither electrode is "indifferent." At the electrode spacing of clinical catheters, this is predicted to occur regardless of catheter orientation. This suggests that bipolar directional sensitivity can be lessened but not overcome by recently introduced catheters with additional rotated electrode pairs., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Catheter ablation is an important rhythm control therapy in patients with atrial fibrillation (AF) with concomitant heart failure (HF). The objective of this study was to assess the comparative efficacy of AF ablation patients with ischemic vs nonischemic heart failure., Methods: We conducted a retrospective, observational cohort study of patients with HF who underwent AF ablation. Outcomes were compared based on HF etiology and included in-hospital events, symptoms (Mayo AF Symptom Inventory [MAFSI]), and functional status (New York Heart Association class) and freedom from atrial arrhythmias at 12 months., Results: Among 242 patients (n = 70 [29%] ischemic, n = 172 [71%] nonischemic), patients with nonischemic cardiomyopathy were younger (mean age 64 ± 11.5 vs 69 ± 9.1, P  = .002), more often female (36% vs 17%, P  = .004), and had higher mean left-ventricular ejection fraction (47% vs 42%, P  = .0007). There were no significant differences in periprocedural characteristics, including mean procedure time (243 ± 74.2 vs 259 ± 81.8 minutes, P  = .1) and nonleft atrial ablation (17% vs 20%, P  = .6). All-cause adverse events were similar in each group (15% vs 17%, P  = .7). NYHA and MAFSI scores improved significantly at follow-up and did not differ according to HF etiology ( P  = .5; P  = .10-1.00 after Bonferroni correction). There were no significant differences in freedom from recurrent atrial arrhythmia at 12-months between ischemic (74%) and nonischemic patients (78%): adjusted RR 0.63, 95% confidence interval 0.33-1.19., Conclusions: Catheter ablation in patients with AF and concomitant heart failure leads to significant improvements in functional and symptom status without significant differences between patients with ischemic vs nonischemic HF etiology., Competing Interests: E. Black‐Maier: None. BA Steinberg: Fellowship Support; Medtronic, Inc, St. Jude Medical, Biotronik, Boston Scientific Corp. Fellowship Support; Biosense Webster, Inc.; Boston Scientific Corp., Janssen Pharmaceuticals. Other; Bristol Meyers Squibb. K. Trulock: None. F. Wang: None.. Y. Lokhnygina: None. W. O 'Neal: None. SM Al‐Khatib: None. BD Atwater: Research Grants; St. Jude Medical. JP Daubert: consulting fees/honoraria from Medtronic, St. Jude Medical, Boston Scientific, Sorin Group, and CardioFocus' research grants from Boston Scientific, Biosense Webster, Medtronic, and Gilead Sciences. C. Frazier‐M ills: None. DD Hegland: None. KP Jackson: None. LR Jackson: None. JI Koontz: None. RK Lewis: None. AY Sun: None. KL Thomas: None. TD Bahnson: Research Grants: Medtronic; St. Jude Medical; Consultant to Boehringer Ingelheim, ChanRX, Sequel Pharma, and Sanofi‐Aventis. JP Piccini: research grants from Abbott, American Heart Association, Bayer, Boston Scientific, Gilead, Janssen Pharmaceuticals, NHLBI, and Philips and consultant fees from Abbott, Allergan, ARCA Biopharma, Biotronik, Boston Scientific, Johnson & Johnson, LivaNova, Medtronic, Milestone, Sanofi, and Philips., (© 2020 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Background: Compared with medical therapy, catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) improves cardiovascular outcomes. Risk scores (CAAP-AF and APPLE) have been developed to predict the likelihood of AF recurrence after ablation, have not been validated specifically in patients with AF and HF., Methods: We analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in a cohort of 230 consecutive patients with AF and HF undergoing PVI in the Duke Center for Atrial Fibrillation registry from 2009-2013., Results: During a follow-up period of 12 months, 76 of 230 (33%) patients with HF experienced recurrent AF after ablation. The median APPLE and CAAP-AF scores were 1.5 ([Q1, Q3]: [1.0, 2.0]) and 4.0 ([Q1, Q3]: [3.0, 5.0]), respectively and were not different from those patients with and without recurrent AF. Freedom from AF was not different according to APPLE and CAAP-AF scores. Discrimination for recurrent AF with the CAAP-AF score was modest with a C-statistic of 0.60 (95% CI 0.52-0.67). Discrimination with the APPLE score was similarly modest, with a C-statistic of 0.54 (95% CI: 0.47-0.62)., Conclusions: Validated predictive risk scores for recurrent AF after catheter ablation exhibit limited predictive ability in cohorts of AF and HF. Additional tools are needed to facilitate risk stratification and patient selection for AF ablation in patients with concomitant HF., (© 2019 Wiley Periodicals, Inc.)

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain., Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF., Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017., Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines., Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence., Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001)., Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial., Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.

Importance: Catheter ablation is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on long-term quality of life (QOL) is uncertain., Objective: To determine whether catheter ablation is more beneficial than conventional drug therapy for improving QOL in patients with AF., Design, Setting, and Participants: An open-label randomized clinical trial of catheter ablation vs drug therapy in 2204 symptomatic patients with AF older than 65 years or 65 years or younger with at least 1 risk factor for stroke. Patients were enrolled from November 2009 to April 2016 from 126 centers in 10 countries. Follow-up ended in December 2017., Interventions: Pulmonary vein isolation, with additional ablation procedures at the discretion of the investigators, for the catheter ablation group (n = 1108) and standard rhythm and/or rate-control drugs selected and managed by investigators for the drug therapy group (n = 1096)., Main Outcomes and Measures: Prespecified co-primary QOL end points at 12 months, including the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score (range, 0-100; 0 indicates complete disability and 100 indicates no disability; patient-level clinically important difference, ≥5 points) and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score (range, 0-40; 0 indicates no symptoms and 40 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.6 points) and severity score (range, 0-30; 0 indicates no symptoms and 30 indicates the most severe symptoms; patient-level clinically important difference, ≤-1.3 points)., Results: Among 2204 randomized patients (median age, 68 years; 1385 patients [63%] were men, 946 [43%] had paroxysmal AF, and 1256 [57%] had persistent AF), the median follow-up was 48.5 months, and 1968 (89%) completed the trial. The mean AFEQT summary score was more favorable in the catheter ablation group than the drug therapy group at 12 months (86.4 points vs 80.9 points) (adjusted difference, 5.3 points [95% CI, 3.7-6.9]; P < .001). The mean MAFSI frequency score was more favorable for the catheter ablation group than the drug therapy group at 12 months (6.4 points vs 8.1 points) (adjusted difference, -1.7 points [95% CI, -2.3 to -1.2]; P < .001) and the mean MAFSI severity score was more favorable for the catheter ablation group than the drug therapy group at 12 months (5.0 points vs 6.5 points) (adjusted difference, -1.5 points [95% CI, -2.0 to -1.1]; P < .001)., Conclusions and Relevance: Among patients with symptomatic atrial fibrillation, catheter ablation, compared with medical therapy, led to clinically important and significant improvements in quality of life at 12 months. These findings can help guide decisions regarding management of atrial fibrillation., Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.

Aims: To assess whether obstructive sleep apnea (OSA) was associated with increased rotor burden among atrial fibrillation (AF) patients., Methods and Results: We studied 33 consecutive patients who were scheduled for focal impulse and rotor modulation (FIRM) ablation at our institution to describe the mapping, ablation, and outcomes, among patients with and without OSA. Patients underwent biatrial FIRM mapping in AF with ablation of stable rotors in addition to conventional ablation lesion sets. Differences between groups were tested with student's t-tests and Fisher's exact tests, as appropriate. Survival analyses were performed using the Kaplan-Meier method. Twelve of the 33 (36%) patients had OSA and 8 (66%) used continuous positive airway pressure ventilation (CPAP). Obstructive sleep apnea patients had a higher body mass index (BMI) (33.6 vs. 28.8 kg/m2, P = 0.01) and were more commonly on beta blockers (67% vs. 29%, P = 0.03) but were otherwise similar regarding baseline characteristics, medication use, and prior AF treatments, including antiarrhythmic drugs and prior ablation. Focal impulse and rotor modulation mapping demonstrated increased rotor burden in the OSA patients (2.6 ± 0.9 vs. 2.0 ± 1.0, P =0.03). The increased rotor burden was more evident in the right atrium (RA) (1.0 ± 0.7 vs. 0.5 ± 0.7, P =0.04 compared with left atrium (1.7 ± 0.8 vs. 1.4 ± 0.7, P = 0.15). There was no correlation between BMI and total number of rotors (r = 0.0961, P = 0.59). Among the population of patients with OSA, CPAP therapy was associated with a lower number of RA rotors (0.8 ± 0.7 vs. 1.5 ± 0.6, P = 0.05) but no significant difference in overall rotors (P = 0.33)., Conclusion: Obstructive sleep apnea patients demonstrate increased rotor prevalence, driven predominantly by an increase in RA rotors. CPAP therapy was associated with fewer RA rotors.

The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA,NCT00911508)(1) trial is testing the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) is superior to current state-of-the-art pharmacologic therapy. This international 140-center clinical trial was designed to randomize 2200 patients to a strategy of catheter ablation versus state-of-the-art rate or rhythm control drug therapy. Inclusion criteria include: 1) age> 65, or ≤65 with≥ 1 risk factor for stroke, 2) documented AF warranting treatment, and 3) eligibility for both catheter ablation and≥ 2 anti-arrhythmic or≥ 2 rate control drugs. Patients were followed every 3 to 6 months (median 4 years) and underwent repeat trans-telephonic monitoring, Holter monitoring, and CT/MR in a subgroup of patient studies to assess the impact of treatment on AF recurrence and atrial structure. With 1100 patients in each treatment arm, CABANA is projected to have 90% power for detecting a 30% relative reduction in the primary composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest. Secondary endpoints include total mortality; mortality or cardiovascular hospitalization; a combination of mortality, stroke, hospitalization for heart failure or acute coronary artery events; cardiovascular death alone; and heart failure death, as well as AF recurrence, quality of life, and cost effectiveness. At a time when AF incidence is rising rapidly, CABANA will provide critical evidence with which to guide therapy and shape health care policy related to AF for years to come., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Few studies have examined outcomes of catheter ablation for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF)., Objective: The purpose of this study was to compare outcomes of AF ablation in patients with HFpEF vs HF with reduced ejection fraction (HFrEF)., Methods: We performed a retrospective study of 230 patients with HF who underwent AF ablation, including 97 (42.2%) with HFrEF and 133 (57.8%) with HFpEF. Outcomes included adverse events, symptoms (Mayo AF Symptom Inventory [MAFSI]), New York Heart Association (NYHA) functional class, and freedom from recurrent atrial arrhythmia at 12 months., Results: Overall, 150 of 230 patients had nonparoxysmal AF (62.8% HFpEF vs 63.0% HFrEF). Patients with HFpEF had a smaller mean left atrial diameter (4.4 ± 0.8 cm vs 4.7 ± 0.7 cm; P = .013) and were less likely to be taking a beta-blocker at baseline (72.9% vs 85.6%; P = .022). Median (Q1, Q3) procedure times (233 minutes [192, 290] vs 233.5 minutes [193.0, 297.5]; P = .780) and adverse events such as acute HF (3.8% vs 6.2%; P = .395) were similar between HFpEF and HFrEF patients. Freedom from recurrent atrial arrhythmia was not significantly different in HFpEF vs HFrEF patients (33.9% vs 32.6%; adjusted hazard ratio 1.47; 95% confidence interval 0.72-3.01), with similar improvements in NYHA functional class (-0.32 vs -0.19; P = .135) and MAFSI symptom severity (-0.23 vs -0.09; P = .116) after ablation., Conclusion: Catheter ablation of AF seems to have similar effectiveness in patients with HF, regardless of presence of systolic dysfunction. There were no significant differences in procedural characteristics, arrhythmia-free recurrence, or functional improvements between patients with HFpEF and those with HFrEF., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Compared with men, women have longer corrected QT (QTc) intervals, lower clearance of dofetilide, and higher rates of drug-induced torsades de pointes, but the dofetilide dosing algorithm is the same for men and women., Objective: The purpose of this study was to evaluate the tolerability of the 500 μg twice daily dose of dofetilide for men and women., Methods: Men and women admitted to Duke University Medical Center (January 1, 2006, to October 19, 2012) for the initiation of dofetilide 500 μg twice daily were matched 1:1 on age and estimated creatinine clearance. Electrocardiograms throughout dosing were analyzed, and rates of dofetilide discontinuations and dose reductions were compared in unadjusted and adjusted analyses., Results: For 220 matched men and women, the median age was 62.5 years (interquartile range 55-69 years) and the median eCrCl was 98.1 mL/min (interquartile range 77.6-126.2 mL/min). Women were less likely than men to have hypertension and interventricular conduction delay but were otherwise similar. During dofetilide initiation, women were more likely than men to have their dofetilide dose discontinued or reduced (55% vs 32%; P < .001). In most women (82%) and men (69%), the reason for dose adjustment was significant QTc prolongation. In the adjusted analysis, female sex was associated with higher rates of dofetilide dose discontinuations or reductions (odds ratio 3.01; 95% confidence interval 1.58-5.71; P < .01)., Conclusion: More than half of women who initiated on 500 μg twice daily of dofetilide required medication discontinuations or dose reductions, mostly because of QTc prolongation. Additional studies are needed to evaluate the optimal dosing algorithm of dofetilide in women., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: In this study, the authors sought to perform a meta-analysis of controlled studies assessing the relationship between left atrial appendage (LAA) electrical isolation (EI) and recurrent atrial fibrillation (AF)., Background: LAA triggers could play an important role in AF and can be treated with complete EI of the LAA via surgical or percutaneous approaches., Methods: We conducted a meta-analysis of all controlled studies published as of November 21, 2016, assessing the relationship between left atrial appendage electrical isolation (LAAEI) and recurrent AF. The primary endpoint was atrial tachycardia (AT) or AF recurrence after the post-procedure blanking period. The association between LAAEI and AT/AF was estimated using random-effects modeling. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the DerSimonian and Laird method., Results: We identified 7 studies including 1,037 patients; LAAEI was performed in 566 patients (55%). LAAEI was associated with a significantly lower rate of AT/AF recurrence in the primary analysis (OR: 0.38; 95% CI: 0.16 to 0.90; p = 0.02). The association between LAAEI and recurrent AT/AF was strongest in a sensitivity analysis restricted to studies of percutaneous LAAEI (OR: 0.22; 95% CI: 0.11 to 0.46; p < 0.001; 5 studies, n = 623). LAAEI was not associated with thromboembolism (OR: 0.50; 95% CI: 0.18 to 1.39; p = 0.18; 5 studies, n = 767), although these studies either incorporated LAA occlusion (3 studies, n = 552 patients) or follow-up echocardiography to assess LAA function (2 studies, n = 215 patients) to inform antithrombotic strategies., Conclusions: LAAEI is associated with a significant reduction in recurrent AT/AF. Randomized trials are required to confirm the efficacy and long-term safety of LAAEI and to determine the optimal concomitant antithrombotic strategy., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrioesophageal fistula formation is a rare but life-threatening complication of atrial fibrillation ablation. Contact force (CF)-sensing catheters improve procedural effectiveness. However, the impact of the implementation of CF-sensing technology on the risk of atrioesophageal fistula formation has not been explored., Objective: The purpose of this study was to determine the association between the use of CF-sensing catheters and atrioesophageal fistula development., Methods: We searched the Manufacturer and User Facility Device Experience database for adverse event reports involving Food and Drug Administration-approved ablation catheters., Results: Among 2689 device reports, we identified 78 atrioesophageal fistula cases, 65 of which involved CF-sensing catheters and 13 non-CF-sensing catheters. The percentage of total reports involving atrioeosphageal fistula was 5.4% for CF-sensing catheters (65 of 1202) and 0.9% for non-CF-sensing catheters (13 of 1487) (P < .0001). Procedural details (CF and power settings) were not consistently reported. Esophageal temperature increases were detected in only 2.5% of cases (2 of 78). The mean time to presentation was 16 ± 9 days. Overall mortality was at least 56%, with patients who underwent surgical repair more likely to survive than those treated with stenting or no intervention., Conclusion: Atrioesophageal fistula formation accounted for a much higher proportion of reported adverse events with CF-sensing catheters compared with non-CF-sensing catheters. Improved understanding of the relationship between power/force delivery and esophageal damage is needed to minimize the risk of atrioesophageal fistula formation., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The utility of routine transesophageal echocardiography (TEE) to exclude left atrial appendage (LAA) thrombus before atrial fibrillation (AF) ablation in patients treated with nonvitamin K oral anticoagulant (NOAC) therapy is unclear. This single-center retrospective study sought to investigate the incidence of LAA thrombus in patients undergoing routine TEE before AF ablation treated with warfarin or NOAC therapy. We included 937 routine pre-AF ablation TEE procedures performed in patients treated with warfarin (n = 517) or NOAC (n = 420). Patients were anticoagulated without interruption for at least 4 consecutive weeks before the TEE. Patients treated with warfarin had lower LAA velocity and underwent TEE earlier in the study period than those treated with NOAC (p <0.05). The incidence of LAA thrombus was higher in patients treated with warfarin (1.55%, 8 of 517) compared with patients treated with NOAC (0.24%, 1 of 420, p = 0.0473 for difference). No LAA thrombus was identified in NOAC-treated patients with a CHA 2 DS 2 -VASC score <5 and in warfarin-treated patients with a CHA 2 DS 2 -VASC score <2. TEE-related complications occurred in 3 of 937 procedures (0.3%). In conclusion, LAA thrombus is detected rarely during pre-AF ablation TEE. Treatment with an NOAC is associated with a lower incidence of pre-AF ablation LAA thrombus compared with warfarin., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This article reviews methods for lesion set assessment during radiofrequency catheter ablation for atrial fibrillation (AF). Pulmonary vein isolation (PVI) is the foundation for AF ablation, but PV reconnection can lead to treatment failure. Testing for entrance block can help confirm PVI, although complex electrograms that consist of both near- and far-field potentials may make assessment of entrance block challenging. Differential pacing maneuvers can help appropriately identify PV potentials. After entrance block has been achieved, pacing within the PVs to demonstrate capture of PV musculature with exit block may also help to confirm completeness of lesion sets for PVI. Employing a waiting period of at least 30 min or administering adenosine or isoproterenol can reveal dormant conduction, warranting adjunctive ablation. Additional techniques to confirm durable PVI include testing the ablation lines for excitability with high amplitude pacing, and automated waveform analysis of local electrogram morphology. Newer techniques like real-time magnetic resonance imaging and acoustic radiation force impulse elastography may have a role in testing the completeness of lesion sets in the future., Competing Interests: Dr. Sze reports grants from Medtronic, outside the scope of the submitted work. Dr. Bahnson reports grants received from the National Institutes of Health and St. Jude Medical, Inc. during the course of the study., (Copyright: © 2017 Innovations in Cardiac Rhythm Management.)

Background: Balloon catheters have been designed to facilitate pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). The visually guided laser balloon (VGLB) employs laser energy to ablate tissue under direct visual guidance., Objectives: This study compared the efficacy and safety of VGLB ablation with standard irrigated radiofrequency ablation (RFA) during catheter ablation of AF., Methods: Patients with drug-refractory paroxysmal AF were enrolled in a multicenter, randomized controlled study of PV isolation using either the VGLB or RFA (control). The primary efficacy endpoint was freedom from protocol-defined treatment failure at 12 months, including symptomatic AF occurring after the 90-day blanking period. The primary efficacy and safety endpoints were powered for noninferiority., Results: A total of 353 patients (178 VGLB, 175 control) were randomized at 19 clinical sites. The mean procedure, ablation, and fluoroscopy times were longer with VGLB compared with controls. The primary efficacy endpoint was met in 61.1% in the VGLB group versus 61.7% in controls (absolute difference -0.6%; lower limit of 95% confidence interval [CI]: -9.3%; p = 0.003 for noninferiority). The primary adverse event rate was 11.8% in the VGLB group versus 14.5% in controls (absolute difference -2.8%; upper limit of 95% CI: 3.5; p = 0.002 for noninferiority), and was mainly driven by cardioversions. Diaphragmatic paralysis was higher (3.5% vs. 0.6%; p = 0.05), but PV stenosis was lower (0.0% vs. 2.9%; p = 0.03) with VGLB., Conclusions: Despite minimal prior experience, the safety and efficacy of VGLB ablation proved noninferior to RFA for the treatment of paroxysmal AF. (Pivotal Clinical Study of the CardioFocus Endoscopic Ablation System-Adaptive Contact [EAS-AC] [HeartLight] in Patients With Paroxysmal Atrial Fibrillation [PAF] [HeartLight]; NCT01456000)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Restoration of sinus rhythm (SR) in patients with atrial fibrillation/atrial flutter (AF/AFL) is limited principally to direct current cardioversion. The multi-ion channel blocker vanoxerine may prove an effective alternative., Objective: The purpose of this study was to assess vanoxerine, a 1,4-dialkylpiperazine derivative, for acute conversion of recent-onset, symptomatic AF and AFL., Methods: One hundred four subjects with symptomatic AF/AFL for <7 days were randomized sequentially to single oral doses of vanoxerine 200, 300, and 400 mg or placebo. Holter monitors were examined for conversion to SR and proarrhythmia through ≥24 hours., Results: Conversion to SR was dose related: 18.2%, 44.0%, and 52.0% within 4 hours, and 59.1%, 64.0%, and 84.0% within 24 hours, for the 200-, 300-, and 400-mg groups, respectively. This was significantly higher than placebo for the 300- and 400-mg groups within 4 hours (12.5% for placebo; P = .0138 and P = .0028, respectively) and for all doses within 24 hours (31.3% for placebo; P = .0421, P = .0138, P = .0001 for 200-, 300-, and 400-mg vanoxerine groups, respectively). Although vanoxerine caused significant dose-dependent QTcF (QT correction by Fridericia) prolongation, monomorphic or polymorphic ventricular tachycardia did not occur. Adverse events were mild and self-limited, with only the highest dose having a greater frequency than placebo., Conclusion: Oral vanoxerine converted AF/AFL to SR at a high rate, was well tolerated, and caused no ventricular proarrhythmia., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Geometric analysis of the left atrium and pulmonary veins is important for assessing reverse structural remodeling following cardiac ablation therapy. Most volumetric analysis techniques, however, require laborious manual tracing of image cross-sections. Pulmonary vein diameters are typically measured at the junction between the left atrium and pulmonary veins, called the pulmonary vein ostia, with manually drawn lines on volume renderings or in image slices. In this work, we describe a technique for making semi-automatic measurements of left atrial volume and pulmonary vein diameters from high resolution CT scans and demonstrate its use for analyzing reverse structural remodeling following cardiac ablation therapy., Methods: The left atrium and pulmonary veins are segmented from high-resolution computed tomography (CT) volumes using a 3D volumetric approach and cut planes are interactively positioned to separate the pulmonary veins from the body of the left atrium. Left atrial volume and pulmonary vein ostial diameters are then automatically computed from the segmented structures. Validation experiments are conducted to evaluate accuracy and repeatability of the measurements. Accuracy is assessed by comparing left atrial volumes computed with the proposed methodology to a manual slice-by-slice tracing approach. Repeatability is assessed by making repeated volume and diameter measurements on duplicated and randomized datasets. The proposed techniques were then utilized in a study of 21 patients from the Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA) pilot study who were scanned both before and approximately 3 months following ablation therapy., Results: In the high resolution CT scans the left atrial volume measurements show high accuracy with a mean absolute difference of 2.3±1.9 cm(3) between volumes computed with the proposed methodology and a manual slice-by-slice tracing approach. In the intra-rater repeatability study, the mean absolute difference in left atrial volume was 4.7±2.5 cm(3) and 4.4±3.4 cm(3) for the two raters. Intra-rater repeatability for pulmonary vein diameters ranged from 0.9 to 2.3 mm. The inter-rater repeatability for left atrial volume was 5.8±5.1 cm(3) and inter-rater repeatability for pulmonary vein diameter measurements ranged from 1.4 to 2.3 mm. In the patient study, significant (p<.05) decreases in left atrial volume and all four pulmonary vein diameters were observed. The absolute change in LA volume was 20.0 cm(3), 95%CI [12.6, 27.5]. The left inferior pulmonary vein diameter decreased 2.1 mm, 95%CI [0.4, 3.7], the left superior pulmonary vein diameter decreased 3.2 mm, 95%CI [1.0, 5.4], the right inferior pulmonary vein diameter decreased 1.5 mm, 95%CI [0.3, 2.7], and the right superior pulmonary vein diameter decreased 2.8 mm, 95%CI [1.4, 4.3]., Conclusions: Using the proposed techniques, we demonstrate high accuracy of left atrial volume measurements as well as high repeatability for left atrial volume and pulmonary vein diameter measurements. Following cardiac ablation therapy, a significant decrease was observed for left atrial volume as well as all four pulmonary vein diameters., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)