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Abstract Background The dominant frequency of the Fourier power spectrum is useful to analyze complex fractionated atrial electrograms (CFAE), but spectral resolution is limited and uniform from DC to the Nyquist frequency. Herein the spectral resolution of a recently described and relatively new spectral estimation technique is compared to the Fourier radix-2 implementation. Methods In 10 paroxysmal and 10 persistent atrial fibrillation patients, 216 CFAE were acquired from the pulmonary vein ostia and left atrial free wall (977 Hz sampling rate, 8192 sample points, 8.4 s duration). With these parameter values, in the physiologic range of 3–10 Hz, two frequency components can theoretically be resolved at 0.24 Hz using Fourier analysis and at 0.10 Hz on average using the new technique. For testing, two closely-spaced periodic components were synthesized from two different CFAE recordings, and combined with two other CFAE recordings magnified 2×, that served as interference signals. The ability to resolve synthesized frequency components in the range 3–4 Hz, 4–5 Hz, …, 9–10 Hz was determined for 15 trials each (105 total). Results With the added interference, frequency resolution averaged 0.29 ± 0.22 Hz for Fourier versus 0.16 ± 0.10 Hz for the new method (p p Conclusions Within the physiologically relevant frequency range for characterization of CFAE, the new method has approximately twice the spectral resolution of Fourier analysis, there is less error in estimating frequencies, and peaks appear more readily above the noise floor. Theoretically, when interference is not present, to resolve frequency components separated by 0.10 Hz using Fourier analysis would require an 18.2 s sequence duration, versus 8.4 s with the new method.

Abstract Background A biomedical signal can be defined by its extrinsic features (x-axis and y-axis shift and scale) and intrinsic features (shape after normalization of extrinsic features). In this study, an LMS algorithm utilizing the method of differential steepest descent is developed, and is tested by normalization of extrinsic features in complex fractionated atrial electrograms (CFAE). Method Equations for normalization of x-axis and y-axis shift and scale are first derived. The algorithm is implemented for real-time analysis of CFAE acquired during atrial fibrillation (AF). Data was acquired at a 977 Hz sampling rate from 10 paroxysmal and 10 persistent AF patients undergoing clinical electrophysiologic study and catheter ablation therapy. Over 24 trials, normalization characteristics using the new algorithm with four weights were compared to the Widrow-Hoff LMS algorithm with four tapped delays. The time for convergence, and the mean squared error (MSE) after convergence, were compared. The new LMS algorithm was also applied to lead aVF of the electrocardiogram in one patient with longstanding persistent AF, to enhance the F wave and to monitor extrinsic changes in signal shape. The average waveform over a 25 s interval was used as a prototypical reference signal for matching with the aVF lead. Results Based on the derivation equations, the y-shift and y-scale adjustments of the new LMS algorithm were shown to be equivalent to the scalar form of the Widrow-Hoff LMS algorithm. For x-shift and x-scale adjustments, rather than implementing a long tapped delay as in Widrow-Hoff LMS, the new method uses only two weights. After convergence, the MSE for matching paroxysmal CFAE averaged 0.46 ± 0.49μV2/sample for the new LMS algorithm versus 0.72 ± 0.35μV2/sample for Widrow-Hoff LMS. The MSE for matching persistent CFAE averaged 0.55 ± 0.95μV2/sample for the new LMS algorithm versus 0.62 ± 0.55μV2/sample for Widrow-Hoff LMS. There were no significant differences in estimation error for paroxysmal versus persistent data. From all trials, the mean convergence time was approximately 1 second for both algorithms. The new LMS algorithm was useful to enhance the electrocardiogram F wave by subtraction of an adaptively weighted prototypical reference signal from the aVF lead. The extrinsic weighting over 25 s demonstrated that time-varying functions such as patient respiration could be identified and monitored. Conclusions A new LMS algorithm was derived and used for normalization of the extrinsic features in CFAE and for electrocardiogram monitoring. The weighting at convergence provides an estimate of the degree of similarity between two signals in terms of x-axis and y-axis shift and scale. The algorithm is computationally efficient with low estimation error. Based on the results, proposed applications include monitoring of extrinsic and intrinsic features of repetitive patterns in CFAE, enhancement of the electrocardiogram F wave and monitoring of time-varying signal properties, and to quantitatively characterize mechanistic differences in paroxysmal versus persistent AF.

Abstract Background Identification of recurrent patterns in complex fractionated atrial electrograms (CFAE) has been used to differentiate paroxysmal from persistent atrial fibrillation (AF). Detection of the atrial CFAE patterns might therefore be assistive in guiding radiofrequency catheter ablation to drivers of the arrhythmia. In this study a technique for robust detection and classification of recurrent CFAE patterns is described. Method CFAE were obtained from the four pulmonary vein ostia, and from the anterior and posterior left atrium, in 10 patients with paroxysmal AF and 10 patients with longstanding persistent AF (216 recordings in total). Sequences 8.4 s in length were analyzed (8,192 sample points, 977 Hz sampling). Among the 216 sequences, two recurrent patterns A and B were substituted for 4 and 5 of the sequences, respectively. To this data, random interference, and random interference + noise were separately added. Basis vectors were constructed using a new transform that is derived from ensemble averaging. Patterns A and B were then detected and classified using a threshold level of Euclidean distance between spectral signatures as constructed with transform coefficients. Results In the presence of interference, sensitivity to detect and distinguish two patterns A and B was 96.2%, while specificity to exclude nonpatterns was 98.0%. In the presence of interference + noise, sensitivity was 89.1% while specificity was 97.0%. Conclusions Transform coefficients computed from ensemble averages can be used to succinctly quantify synchronized patterns present in AF data. The technique is useful to automatically detect recurrent patterns in CFAE that are embedded in interference without user bias. This quantitation can be implemented in real-time to map the AF substrate prior to and during catheter ablation.

Abstract Background Representation of independent biophysical sources using Fourier analysis can be inefficient because the basis is sinusoidal and general. When complex fractionated atrial electrograms (CFAE) are acquired during atrial fibrillation (AF), the electrogram morphology depends on the mix of distinct nonsinusoidal generators. Identification of these generators using efficient methods of representation and comparison would be useful for targeting catheter ablation sites to prevent arrhythmia reinduction. Method A data-driven basis and transform is described which utilizes the ensemble average of signal segments to identify and distinguish CFAE morphologic components and frequencies. Calculation of the dominant frequency (DF) of actual CFAE, and identification of simulated independent generator frequencies and morphologies embedded in CFAE, is done using a total of 216 recordings from 10 paroxysmal and 10 persistent AF patients. The transform is tested versus Fourier analysis to detect spectral components in the presence of phase noise and interference. Correspondence is shown between ensemble basis vectors of highest power and corresponding synthetic drivers embedded in CFAE. Results The ensemble basis is orthogonal, and efficient for representation of CFAE components as compared with Fourier analysis (p ≤ 0.002). When three synthetic drivers with additive phase noise and interference were decomposed, the top three peaks in the ensemble power spectrum corresponded to the driver frequencies more closely as compared with top Fourier power spectrum peaks (p ≤ 0.005). The synthesized drivers with phase noise and interference were extractable from their corresponding ensemble basis with a mean error of less than 10%. Conclusions The new transform is able to efficiently identify CFAE features using DF calculation and by discerning morphologic differences. Unlike the Fourier transform method, it does not distort CFAE signals prior to analysis, and is relatively robust to jitter in periodic events. Thus the ensemble method can provide a useful alternative for quantitative characterization of CFAE during clinical study.

Background: An early rhythm control strategy is the preferred management for patients newly diagnosed with atrial fibrillation (AF). A rhythm control strategy, however, has been historically underused for patients from underrepresented racial and ethnic groups (UREGs)., Objective: We aimed to determine whether disparities in rhythm control are present at the initial diagnosis with AF., Methods: We used the Get With the Guidelines (GWTG)-Atrial Fibrillation registry to compare the use of a rhythm control strategy among patients with different racial and ethnic backgrounds hospitalized with a new diagnosis of AF from January 2013 through December 2023., Results: Among 21,567 patients hospitalized for newly detected AF across 249 hospitals, 17,659 patients (81.9%) identified as non-Hispanic White (NHW), 1,860 patients (8.6%) identified as Black, 1,232 patients (5.7%) identified as Hispanic, and 255 patients (1.2%) identified as Asian. After adjusting for age, sex, and year of presentation, NHW patients were more likely to receive rhythm control (odds ratio [OR], 1.19 [1.07, 1.33], P = .0013) compared with non-White patients at the time of initial diagnosis with AF. Black patients were less likely to receive rhythm control compared with all other racial and ethnic groups (OR, 0.80 [0.71, 0.91], P = .0005). These differences persisted after fully adjusting for demographic characteristics, clinical variables, hospital characteristics, and socioeconomic factors., Conclusions: Differences in rhythm management exist amongst patients from different racial and ethnic groups. Efforts to mitigate disparities in AF management should include an emphasis on rhythm control at the time of initial diagnosis., Competing Interests: Disclosure Dr Jackson serves as a consultant to Biosense Webster, Johnson and Johnson, Sanofi, Bristol Myers Squibb, and Pfizer and receives honoraria from PRIME Education. Dr Piccini is supported by R01AG074185 from the National Institutes of Aging. He also receives grants for clinical research from Abbott, the American Heart Association, Bayer, Boston Scientific, iRhythm, and Philips and serves as a consultant to Abbott, Abbvie, Bayer, Boston Scientific, Element Science, Milestone, ElectroPhysiology Frontiers, Medtronic, Sanofi, Pacira, Philips, and Up-to-Date. Dr Reddy reports the following disclosures with medical companies not related to this manuscript: Abbott (Consultant), Ablacon (Consultant, Equity), Acutus Medical (Consultant, Equity), Affera (Consultant, Equity), Apama Medical (Consultant, Equity), Aquaheart (Consultant, Equity), Autonomix (Consultant, Equity), Axon (Consultant), Backbeat (Consultant, Equity), BioSig (Consultant, Equity), Biosense-Webster (Consultant), Biotronik (Consultant), Boston Scientific (Consultant), Cardiofocus (Consultant), Cardionomic (Consultant), CardioNXT / AFTx (Consultant), Circa Scientific (Consultant, Equity), Corvia Medical (Consultant, Equity), East End Medical (Consultant, Equity), EBR (Consultant), EPD (Consultant, Equity), Epix Therapeutics (Consultant, Equity), EpiEP (Consultant, Equity), Eximo (Consultant, Equity), Farapulse (Consultant, Equity), Fire1 (Consultant, Equity), Impulse Dynamics (Consultant), Javelin (Consultant, Equity), Keystone Heart (Consultant, Equity), LuxCath (Consultant, Equity), Manual Surgical Sciences (Equity), Medlumics (Consultant, Equity), Medtronic (Consultant), Middlepeak (Consultant, Equity), Newpace (Equity), Nuvera (Consultant, Equity), Philips (Consultant), Stimda (Consultant), Surecor (Equity), Thermedical (Consultant), Valcare (Consultant, Equity), Vizara (Equity), and VytronUS (Consultant, Equity). Dr Curtis has the following disclosures: Medtronic: advisory board, honoraria for speaking; Abbott: advisory board, honoraria for speaking; Janssen Pharmaceuticals: advisory board; Milestone Pharmaceuticals: advisory board. The Get With The Guidelines–AFib (GWTG-AF) program is provided by the American Heart Association. GWTG-AF is sponsored, in part, by BMS Pfizer, Tylenol, and Philips Image Guided Therapy. None of the coauthors received funding for this project. The funders of this project had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors have stated their conflicts of interest, none of which were related to this project. No company or agency had any role in this manuscript., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Rapid technologic development and expansion of procedural expertise have led to widespread proliferation of catheter-based electrophysiology procedures. It is unclear whether these advances come at cost to patient safety., Objective: This meta-analysis aimed to assess complication rates after modern electrophysiology procedures during the lifetime of the procedures., Methods: A comprehensive search was performed to identify relevant data published before May 30, 2023. Studies were included if they met the following inclusion criteria: prospective trials or registries, including comprehensive complications data; and patients undergoing atrial fibrillation ablation, ventricular tachyarrhythmia ablation, leadless cardiac pacemaker implantation, and percutaneous left atrial appendage occlusion. Pooled incidences of procedure-related complications were individually assessed by random effects models to account for heterogeneity. Temporal trends in complications were investigated by clustering trials by publication year (2000-2018 vs 2019-2023)., Results: A total of 174 studies (43,914 patients) met criteria for analysis: 126 studies of atrial fibrillation ablation (n = 24,057), 25 studies of ventricular tachyarrhythmia ablation (n = 1781), 21 studies of leadless cardiac pacemaker (n = 8896), and 18 studies of left atrial appendage occlusion (n = 9180). The pooled incidences of serious procedure-related complications (3.49% [2000-2018] vs 3.05% [2019-2023]; P < .001), procedure-related stroke (0.46% vs 0.28%; P = .002), pericardial effusion requiring intervention (1.02% vs 0.83%; P = .037), and procedure-related death (0.15% vs 0.06%; P = .003) significantly decreased over time. However, there was no significant difference in the incidence of vascular complications over time (1.86% vs 1.88%; P = .888)., Conclusion: Despite an increase in cardiac electrophysiology procedures, procedural safety has improved over time., Competing Interests: Disclosures Dr Reddy reports no disclosures related to this manuscript; but unrelated to this manuscript, he serves as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical–Boston Scientific, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics–Medtronic, EpiEP, Eximo, Farapulse–Boston Scientific, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, Laminar Medical, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera–Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; unrelated to this work, has served as a consultant for Abbott, Adagio Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Boston Scientific, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, Pulse Biosciences; and has equity in DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. Dr Koruth has received grant support and stock options from Affera-Medtronic; unrelated to this manuscript, he has also served as a consultant to and has received grant support from Cardiofocus; has served as a consultant for Abbott, Boston Scientific, Biosense Webster, and Medtronic; and has received grant support from Pulse Bioscience. All other authors report no conflicts., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Prior studies have indicated that the frequency of premature ventricular complexes (PVC) increases after catheter ablation for atrial fibrillation (AF). However, these studies have primarily focused on patients whose PVC burden increased rather than including the full spectrum of outcomes., Methods and Results: We performed a single-center retrospective cohort study of consecutive patients who underwent first-time AF ablation from 1/2018 to 12/2022 for paroxysmal or persistent AF and had both preablation and postablation rhythm monitoring within 6 months of the procedure. Patients were excluded if they had prior AF or PVC ablation or were prescribed a class I or III antiarrhythmic medication. Among 2945 patients who underwent AF ablation during the study period, 130 patients underwent first-time AF ablation and received both pre and post ambulatory monitoring. The median PVC burden before ablation was <1%. Most patients (63%) had no change in PVC burden after AF ablation compared with preablation, and patients who had an increase in PVC burden were offset by those with reductions in PVCs. A paired analysis pre- and post-AF ablation showed no significant change in PVC burden (p = .495)., Conclusion: Although an elevated PVC burden after AF ablation may be seen clinically, the majority of patients have no change in burden. Studies that suggest an increase in PVC burden after AF ablation may suffer from incomplete sample selection and thus omit the important effect of regression to the mean., (© 2024 Wiley Periodicals LLC.)

Background: Autonomic denervation is an ancillary phenomenon during thermal ablation of atrial fibrillation (AF), that may have synergistic effects on symptomatic improvement and long-term freedom from AF. Pulsed field ablation (PFA), a nonthermal ablation modality, was noninferior to thermal ablation in treating AF; however, PFA's relative myocardial selectivity may minimize autonomic effects., Objectives: This study sought to compare heart rate (HR) and heart rate variability (HRV) metrics as markers of autonomic function after ablation using PFA vs thermal ablation., Methods: ADVENT (FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation) was a randomized pivotal study comparing PFA (pentaspline catheter) with thermal ablation (radiofrequency [RF] or cryoballoon [CB]) for treating paroxysmal AF. Baseline HR was acquired from a pre-ablation 12-lead electrocardiogram, whereas follow-up HRs, as well as HRV (standard deviation of all normal to normal RR intervals, standard deviation of 5-minute average RR intervals) metrics, were derived from 72-hour Holter monitors at 6 and 12 months., Results: This study included 379 paroxysmal AF patients undergoing PFA (n = 194) or thermal ablation (n = 185; n = 102 RF, n = 83 CB) completing 6- and 12-month Holter monitoring. Compared with PFA, thermal patients had significantly greater increases in HR from baseline to 6 months (ΔHR; 10.1 vs 5.9 beats/min; P = 0.02) and 12 months (ΔHR; 8.8 vs 5.2 beats/min; P = 0.03). This increase in HR at 6 and 12 months was similar between CB and RF (P = 0.94 and 0.83, respectively). HRV, both standard deviation of all normal to normal RR intervals and standard deviation of 5-minute average RR intervals, were significantly lower at both 6 and 12 months after thermal ablation compared with PFA (P < 0.01)., Conclusions: PFA's effect on the autonomic nervous system was attenuated compared with thermal ablation. Whether this affects long-term freedom from AF or symptomatic bradycardia/pauses after AF ablation requires further study., Competing Interests: Funding Support and Author Disclosures The ADVENT study was funded by Boston Scientific, Inc. Dr Gerstenfeld has served on an advisory board (unpaid) for Boston Scientific; serves as a consultant for Abbott, Adagio Medical and Biosense Webster, unrelated to this work; has received lecture honoraria from Medtronic, Abbott, Boston Scientific, and Biosense Webster; and has received research funding from Abbott, Biosense Webster, and Adagio Medical. Dr Mansour has been a consultant for Boston Scientific, Biosense Webster, Abbott, Medtronic, Siemens Novartis, Janssen, Boehringer Ingelheim, Pfizer, and SentreHEART/AtriCure; and has equity in EPD-Philips (divested), and NewPace Ltd. Dr Ellis has received research grants (to VUMC), from Boston Scientific, AtriCure, and Medtronic; and has served on advisory boards or received consulting fees from Abbott Medical, Boston Scientific, AtriCure, and Medtronic. Dr Osorio has been a consultant for Boston Scientific, Biosense Webster, Medtronic, Volta, and Abbott Medical; and has served on advisory boards for Boston Scientific, Biosense Webster, and Volta. Dr DeLurgio has been a consultant and speaker for Boston Scientific. Dr McElderry has served as a consultant for Boston Scientific (formerly Farapulse), Abbott, Medtronic, Heamonetics, and Biosense Webster. Ms Richards, Dr Albrecht, Mr Schneider, and Dr Sutton are salaried employees of Boston Scientific. Dr Reddy has equity in Farapulse Inc (now divested), Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, AquaHeart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioFocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, Laminar Medical, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, and Valcare, and unrelated to this work, in Atraverse, DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Soundcath, Surecor, and Vizaramed; has served as a consultant for Boston Scientific Inc and Farapulse Inc, and unrelated to this work, Abbott, Adagio Medical, Append Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Novo Nordisk, Philips, Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, AquaHeart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioFocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, Laminar Medical, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare, and Pulse Biosciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Traditional right atrial appendage (RAA) pacing accentuates conduction disturbances as opposed to Bachmann bundle pacing (BBP)., Objective: The purpose of this study was to evaluate the feasibility, efficacy, and safety of routine anatomically guided high right atrial septal (HRAS) pacing with activation of Bachmann bundle combined with routine left bundle branch area pacing (LBBAP)., Methods: This retrospective single-center study included 96 consecutive patients who underwent 1 of 2 strategies: physiological pacing (PP) (n = 32) with HRAS and LBBAP leads and conventional pacing (CP) (n = 64) with traditional RAA and right ventricular apical leads. Baseline characteristics, sensing, pacing thresholds, and impedances were recorded at implantation and follow-up., Results: The PP and CP cohorts were of similar age (74.2 ± 13.8 years vs 73.9 ± 9.9 years) and sex (28.1% vs 40.6% female). There were no differences in procedural time (95.0 ± 31.4 minutes vs 86.5 ± 33.3 minutes; P = .19) or fluoroscopy time (12.1 ± 4.5 minutes vs 12.3 ± 13.5 minutes; P = .89) between cohorts. After excluding patients who received >2 leads, these parameters became significantly shorter in the CP cohort. The PP cohort exhibited higher atrial pacing thresholds (1.5 ± 1.1 mV vs 0.8 ± 0.3 mV; P <.001) and lower p waves (1.8 ± 0.8 mV vs 3.8 ± 2.3 mV; P <.001) at implantation and at follow-up. In the PP cohort, 72% of implants met criteria for BBP; of the ventricular leads, 94% demonstrated evidence of LBBAP. One lead-related complication occurred in each cohort., Conclusion: Routine placement of leads in the HRAS is a feasible and safe alternative to standard RAA pacing, allowing for BBP in 72% of patients. HRAS pacing can be combined with LBBAP as a routine strategy., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Aims: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation., Methods and Results: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location., Conclusion: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue., Competing Interests: Conflict of interest: M.M. is a consultant for Boston Scientific, Biosense Webster, Abbott, Medtronic, Siemens Novartis, Janssen, Boehringer Ingelheim, Pfizer, and SentreHEART/AtriCure and has equity in EPD-Philips (divested), and NewPace Ltd. E.P.G. is a consultant to Farapulse Inc and serves as an unpaid consultant to Boston Scientific Inc and scientific advisory board to Biosense Webster and Adagio Medical, has research support from Biosense-Webster, Adagio Medical, and Abbott, has lecture honoraria from Medtronic, Boston Scientific Inc and Abbott. C.P. is a consultant for Boston Scientific. A.N. is a consultant for Abbott, Baylis, Biotronik, Biosense Webster, Boston Scientific, and Medtronic. W.W. has no relevant disclosures. F.A.C. is a consultant to Boston Scientific and Biosense Webster. S.E.M. is a consultant to Medtronic and Boston Scientific Inc, has research support from Medtronic, Biotronik, Abbott, and CVRx, and has lecture honoraria from Biosense Webster, Medtronic, Boston Scientific Inc, Zoll, and Abbott. D.N.G. is a consultant to Abbott, Baylis, Biotronik, Biosense Webster, Boston Scientific, and Medtronic. J.D.H. has no relevant disclosures. S.K.H. is an employee of Medpace Core Laboratories. C.W.S., A.B.A., E.M.A., and K.M.S. are employees of Boston Scientific. A.S.M. is a consultant to Farapulse Inc and serves as a consultant to Boston Scientific Inc; unrelated to this manuscript, he has also provided statistical consulting and/or Data Safety Monitoring Board services for AtriCure, Abbott, Biosense Webster, and Medtronic. J.W.L. is a consultant to and received equity from Farapulse Inc (now divested) and serves as a consultant to Boston Scientific Inc. V.Y.R. is a Farapulse-Boston Scientific Inc: grant support, consultant, equity (now divested); and unrelated to this manuscript, V.Y.R. also serves as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, Anumana, APN Health, AquaHeart, AtaCor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, MedLumics, Middlepeak, NeuTrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; unrelated to this work, V.Y.R. has served as a consultant for Abbott, AtriAN, Biosense Webster, BioTel Heart, Biotronik, Cairdac, CardioFocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, and Pulse Biosciences and has equity in DRS Vascular, Manual Surgical Sciences, NewPace, Nyra Medical, SureCor, and VizaraMed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known., Methods: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events., Results: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999)., Conclusions: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Premature ventricular complexes (PVCs) are prevalent and, although often benign, they may lead to PVC-induced cardiomyopathy. We created a deep-learning algorithm to predict left ventricular ejection fraction (LVEF) reduction in patients with PVCs from a 12-lead electrocardiogram (ECG)., Objectives: This study aims to assess a deep-learning model to predict cardiomyopathy among patients with PVCs., Methods: We used electronic medical records from 5 hospitals and identified ECGs from adults with documented PVCs. Internal training and testing were performed at one hospital. External validation was performed with the others. The primary outcome was first diagnosis of LVEF ≤40% within 6 months. The dataset included 383,514 ECGs, of which 14,241 remained for analysis. We analyzed area under the receiver operating curves and explainability plots for representative patients, algorithm prediction, PVC burden, and demographics in a multivariable Cox model to assess independent predictors for cardiomyopathy., Results: Among the 14,241-patient cohort (age 67.6 ± 14.8 years; female 43.8%; White 29.5%, Black 8.6%, Hispanic 6.5%, Asian 2.2%), 22.9% experienced reductions in LVEF to ≤40% within 6 months. The model predicted reductions in LVEF to ≤40% with area under the receiver operating curve of 0.79 (95% CI: 0.77-0.81). The gradient weighted class activation map explainability framework highlighted the sinus rhythm QRS complex-ST segment. In patients who underwent successful PVC ablation there was a post-ablation improvement in LVEF with resolution of cardiomyopathy in most (89%) patients., Conclusions: Deep-learning on the 12-lead ECG alone can accurately predict new-onset cardiomyopathy in patients with PVCs independent of PVC burden. Model prediction performed well across sex and race, relying on the QRS complex/ST-segment in sinus rhythm, not PVC morphology., Competing Interests: Funding Support and Author Disclosures Dr Lampert has served as a consultant for Viz.AI. Dr Reddy has served as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Farapulse-Boston Scientific, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare unrelated to this work; has served as a consultant for Abbott, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Boston Scientific, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, and Pulse Biosciences; and has equity in Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. Dr Nadkarni reports consultancy agreements with AstraZeneca, BioVie, GLG Consulting, Pensieve Health, Reata, Renalytix, Siemens Healthineers and Variant Bio; has received research funding from Goldfinch Bio, and Renalytix; has received honoraria from AstraZeneca, BioVie, Lexicon, Daiichi Sankyo, Meanrini Health, and Reata; has patents or royalties with Renalytix; owns equity and stock options in Pensieve Health and Renalytix as a scientific cofounder; owns equity in Verici Dx; has received financial compensation as a scientific board member and advisor to Renalytix; has served on the advisory board of Neurona Health; and has served in an advisory or leadership role for Pensieve Health and Renalytix. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Interatrial block (IAB) is associated with thromboembolism and atrial arrhythmias. However, prior studies included small patient cohorts so it remains unclear whether IAB predicts adverse outcomes particularly in context of atrial fibrillation (AF)/atrial flutter (AFL)., Objectives: This study sought to determine whether IAB portends increased stroke risk in a large cohort in the presence or absence of AFAF/AFL., Methods: We performed a 5-center retrospective analysis of 4,837,989 electrocardiograms (ECGs) from 1,228,291 patients. IAB was defined as P-wave duration ≥120 ms in leads II, III, or aVF. Measurements were extracted as .XML files. After excluding patients with prior AF/AFL, 1,825,958 ECGs from 458,994 patients remained. Outcomes were analyzed using restricted mean survival time analysis and restricted mean time lost., Results: There were 86,317 patients with IAB and 355,032 patients without IAB. IAB prevalence in the cohort was 19.6% and was most common in Black (26.1%), White (20.9%), and Hispanic (18.5%) patients and least prevalent in Native Americans (9.2%). IAB was independently associated with increased stroke probability (restricted mean time lost ratio coefficient [RMTLRC]: 1.43; 95% CI: 1.35-1.51; tau = 1,895), mortality (RMTLRC: 1.14; 95% CI: 1.07-1.21; tau = 1,924), heart failure (RMTLRC: 1.94; 95% CI: 1.83-2.04; tau = 1,921), systemic thromboembolism (RMTLRC: 1.62; 95% CI: 1.53-1.71; tau = 1,897), and incident AF/AFL (RMTLRC: 1.16; 95% CI: 1.10-1.22; tau = 1,888). IAB was not associated with stroke in patients with pre-existing AF/AFL., Conclusions: IAB is independently associated with stroke in patients with no history of AF/AFL even after adjustment for incident AF/AFL and CHA 2 DS 2 -VASc score. Patients are at increased risk of stroke even when AF/AFL is not identified., Competing Interests: Funding Support and Author Disclosures This project was internally funded. Dr Reddy has served as a consultant to Kardium Inc (including Equity); is a consultant to Abbott, Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, APN Health, Aquaheart, Atacor, AtiAN, Autonomix, Axon Therapies, Backbeat, BioSig, Biosense-Webster, BioTel Heart, Biotronik, Boston Scientific, Cairdac, CardiaCare, Cardiofocus, Cardionomic, CardioNXT / AFTx, Circa Scientific, CoreMap, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EBR, EPD-Philips, EP Frontiers, Epix Therapeutics, EpiEP, Eximo, Farapulse-Boston Scientific, Fire1, Focused Therapeutics, Gore & Associates, HRT, Impulse Dynamics, Intershunt, Javelin, Keystone Heart, LuxMed, Medlumics, Medtronic, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Philips, Pulse Biosciences, Restore Medical, Sirona Medical, SoundCath, and Valcare; and has equity from Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT / AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics, EpiEP, Eximo, Farapulse-Boston Scientific, Focused Therapeutics, HRT, Intershunt, Javelin, Keystone Heart, LuxMed, Manual Surgical Sciences, Medlumics, Middlepeak, Neutrace, Newpace, Nuvera-Biosense Webster, Nyra Medical, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Surecor, Valcare, and Vizaramed. Dr Fuster serves as the Editor-in-Chief of JACC. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Multiple randomized controlled trials have demonstrated sodium-glucose cotransporter-2 inhibitors (SGLT2i) decrease the composite endpoint of cardiovascular death or heart failure hospitalizations in all heart failure patients. It is uncertain whether SGLT2i impacts the risk of sudden cardiac death in patients with heart failure., Methods: A comprehensive search was performed to identify relevant data published before August 28, 2022. Trials were included if: (1) all patients had clinical heart failure (2) SGLT2i and placebo were compared (3) all patients received conventional medical therapy and (4) reported outcomes of interest (sudden cardiac death [SCD], ventricular arrhythmias, atrial arrhythmias)., Results: SCD was reported in seven of the eleven trials meeting selection criteria: 10 796 patients received SGLT2i and 10 796 received placebo. SGLT2i therapy was associated with a significant reduction in the risk of SCD (risk ratios [RR]: 0.68; 95% confidence intervals [CI]: 0.48-0.95; p = .03; I 2  = 0%). Absent dedicated rhythm monitoring, there were no significant differences in the incidence of sustained ventricular arrhythmias not associated with SCD (RR: 1.03; 95% CI: 0.83-1.29; p = .77; I 2  = 0%) or atrial arrhythmias (RR: 0.91; 95% CI: 0.77-1.09; p = .31; I 2  = 29%) between patients receiving an SGLT2i versus placebo., Conclusion: SGLT2i therapy is associated with a reduced risk of SCD in patients with heart failure receiving contemporary medical therapy. Prospective trials are needed to determine the long-term impact of SGLT2i therapy on atrial and ventricular arrhythmias., (© 2023 Wiley Periodicals LLC.)

Background: During atrial fibrillation ablations using thermal energy, the treatment effect is attributed to not just pulmonary vein isolation (PVI), but also to modulation of the autonomic nervous system by ablation of cardiac ganglionated plexi (GP)., Objectives: This study sought to assess the impact of pulsed field ablation (PFA) on the GP in patients undergoing PVI., Methods: In the retrospective phase, heart rate was assessed pre- versus post-PVI using PFA, cryoballoon ablation, or radiofrequency ablation. In the prospective phase, a pentaspline PFA catheter was used in a protocol: 1) pre-PFA, high-frequency stimulation (HFS) identified GP sites by vagal effects; 2) PVI was performed assessing for repetitive vagal effects over each set of PF applications; 3) mapping defined PVI extent to identify those GP in the ablation zone; and 4) repeat HFS at GP sites to assess for persistence of vagal effects., Results: Between baseline and 3 months, heart rates in the retrospective radiofrequency ablation (n = 40), cryoballoon (n = 40), and PFA (n = 40) cohorts increased by 8.9 ± 11.4, 11.1 ± 9.4, and -0.1 ± 9.2 beats/min, respectively (P= 0.01 PFA vs radiofrequency ablation; P= 0.01 PFA vs cryoballoon ablation). In the prospective phase, pre-PFA HFS in 20 additional patients identified 65 GP sites. During PFA, vagal effects were noted in 45% of first PF applications, persisting through all applications in 83%. HFS post-PFA reproduced vagal effects in 29 of 38 sites (76%) in low-voltage tissue., Conclusions: PFA has minimal effect on GP. Unlike with thermal ablation, the mechanism by which PFA treats atrial fibrillation is mediated solely by durable PVI., Competing Interests: Funding Support and Author Disclosures Dr Neuzil has received grant support from, and has served as a consultant to Farapulse Inc. Dr Dukkipati has equity in Farapulse Inc. Dr Reddy has served as a consultant to and owns equity in Farapulse Inc, Ableton, Acutus Medical, Affera, Apama Medical–Boston Scientific, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNOVA EP Technology, East End Medical, EPD-Philips, EP Frontiers, EPIX Therapeutics, EpiEP, Eximo, HRT, Intershunt, Javelin, Kardium, Keystone heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Weber, Oracle Health, Restore Medical, Sirona Medical, and Valcare, is a consultant to Abbott, AtiAN, Biosense-Webster, BioTel Heart, Biotronik, Boston Scientific, Cardiofocus, Cardionomic, CoreMap, EBR, Fire1, W. L. Gore and Associates, Impulse Dynamics, Medtronic, Philips, and Pulse Biosciences, and holds equity in Manual Surgical Sciences, Newpace, Surecor, and Vizaramed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background: Depression after acute coronary syndrome (ACS) is common and increases risks of adverse outcomes, but it remains unclear which depression features are most associated with major adverse cardiac events (MACE) and all-cause mortality (ACM)., Purpose: To examine whether a subtype of depression characterized by anhedonia and major depressive disorder (MDD) predicts 1-year MACE/ACM occurrence in ACS patients compared to no MDD history. We also consider other depression features in the literature as predictors., Methods: Patients (N = 1,087) presenting to a hospital with ACS completed a self-report measure of current depressive symptoms in-hospital and a diagnostic interview assessing MDD within 1 week post-hospitalization. MACE/ACM events were assessed at 1-, 6-, and 12-month follow-ups. Cox regression models were used to examine the association of the anhedonic depression subtype and MDD without anhedonia with time to MACE/ACM, adjusting for sociodemographic and clinical covariates., Results: There were 142 MACE/ACM events over the 12-month follow-up. The 1-year MACE/ACM in patients with anhedonic depression, compared to those with no MDD, was somewhat higher in an age-adjusted model (hazard ratio [HR] = 1.63, p = .08), but was not significant after further covariate adjustment (HR = 1.24, p = .47). Of the additional depression features, moderate-to-severe self-reported depressive symptoms significantly predicted the risk of MACE/ACM, even in covariate-adjusted models (HR = 1.72, p = .04), but the continuous measure of self-reported depressive symptoms did not., Conclusion: The anhedonic depression subtype did not uniquely predict MACE/ACM as hypothesized. Moderate-to-severe levels of total self-reported depressive symptoms, however, may be associated with increased MACE/ACM risk, even after accounting for potential sociodemographic and clinical confounders., (© Society of Behavioral Medicine 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Frequent premature ventricular contractions (PVCs) are often amenable to catheter ablation. However, a deep intramural focus may lead to failure due to inability of standard ablation techniques to penetrate the focus. We sought to assess the efficacy and safety of infusion needle ablation (INA) for PVCs that are refractory to standard radiofrequency ablation., Methods: Under 2 Food and Drug Administration approved protocols, INA was evaluated in patients with frequent PVCs that were refractory to standard ablation. Initial targets for ablation were selected by standard mapping techniques. INA was performed with a deflectable catheter equipped with an extendable/retractable needle at the tip that can be extended up to 12 mm into the myocardium and is capable of pacing and recording. After contrast injection for location assessment, radiofrequency ablation was performed with the needle tip using a temperature-controlled mode (maximum temperature 60 °C) with saline infusion from the needle. The primary end point was a decrease in PVC burden to <5000/24 hours at 6 months. The primary safety end point was incidence of procedure- or device-related serious adverse events., Results: At 4 centers, 35 patients (age 55.3±16.9 years, 74.2% male) underwent INA. The baseline median PVC burden was 25.4% (interquartile range, 18.4%-33.9%) and mean left ventricular ejection fraction was 37.7±12.3%. Delivering 10.3±8.0 INA lesions/patient (91% had adjunctive standard radiofrequency ablation also) resulted in acute PVC elimination in 71.4%. After a mean follow-up of 156±109 days, the primary efficacy end point was met in 73.3%. The median PVC burden decreased to 0.8% (interquartile range, 0.1%-6.0%; P <0.001). The primary safety end point occurred in 14.3% consisting of 1 (2.9%) heart block, 1 (2.9%) femoral artery dissection, and 3 (8.6%) pericardial effusions (all treated percutaneously)., Conclusions: INA is effective for the elimination of frequent PVCs that are refractory to conventional ablation and is associated with an acceptable safety profile., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01791543 and NCT03204981.

Background: Increasing interest in physiological pacing has been countered with challenges such as accurate lead deployment and increasing pacing thresholds with His-bundle pacing (HBP). More recently, left bundle branch area pacing (LBBAP) has emerged as an alternative approach to physiologic pacing., Objective: To compare procedural outcomes and pacing parameters at follow-up during initial adoption of HBP and LBBAP at a single center., Methods: Retrospective review, from September 2016 to January 2020, identified the first 50 patients each who underwent successful HBP or LBBAP. Pacing parameters were then assessed at first follow-up after implantation and after approximately 1 year, evaluating for acceptable pacing parameters defined as sensing R-wave amplitude >5 mV, threshold <2.5 V @ 0.5 ms, and impedance between 400 and 1200 Ω., Results: The HBP group was younger with lower ejection fraction compared to LBBAP (73.2 ± 15.3 vs. 78.2 ± 9.2 years, p = .047; 51.0 ± 15.9% vs. 57.0 ± 13.1%, p = .044). Post-procedural QRS widths were similarly narrow (119.8 ± 21.2 vs. 116.7 ± 15.2 ms; p = .443) in both groups. Significantly fewer patients with HBP met the outcome for acceptable pacing parameters at initial follow-up (56.0% vs. 96.4%, p = .001) and most recent follow-up (60.7% vs. 94.9%, p ≤ .001; at 399 ± 259 vs. 228 ± 124 days, p ≤ .001). More HBP patients required lead revision due to early battery depletion or concern for pacing failure (0% vs. 13.3%, at a mean of 664 days)., Conclusion: During initial adoption, HBP is associated with a significantly higher frequency of unacceptable pacing parameters, energy consumption, and lead revisions compared with LBBAP., (© 2021 Wiley Periodicals LLC.)

During the clinical care of hospitalized patients with COVID-19, diminished QRS amplitude on the surface electrocardiogram (ECG) was observed to precede clinical decompensation, culminating in death. This prompted investigation into the prognostic utility and specificity of low QRS complex amplitude (LoQRS) in COVID-19. We retrospectively analyzed consecutive adults admitted to a telemetry service with SARS-CoV-2 (n = 140) or influenza (n = 281) infection with a final disposition-death or discharge. LoQRS was defined as a composite of QRS amplitude <5 mm or <10 mm in the limb or precordial leads, respectively, or a ≥50% decrease in QRS amplitude on follow-up ECG during hospitalization. LoQRS was more prevalent in patients with COVID-19 than influenza (24.3% vs 11.7%, p = 0.001), and in patients who died than survived with either COVID-19 (48.1% vs 10.2%, p <0.001) or influenza (38.9% vs 9.9%, p <0.001). LoQRS was independently associated with mortality in patients with COVID-19 when adjusted for baseline clinical variables (odds ratio [OR] 11.5, 95% confidence interval [CI] 3.9 to 33.8, p <0.001), presenting and peak troponin, D-dimer, C-reactive protein, albumin, intubation, and vasopressor requirement (OR 13.8, 95% CI 1.3 to 145.5, p = 0.029). The median time to death in COVID-19 from the first ECG with LoQRS was 52 hours (interquartile range 18 to 130). Dynamic QRS amplitude diminution is a strong independent predictor of death over not only the course of COVID-19 infection, but also influenza infection. In conclusion, this finding may serve as a pragmatic prognostication tool reflecting evolving clinical changes during hospitalization, over a potentially actionable time interval for clinical reassessment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: We studied the extent/area of electrical pulmonary vein isolation (PVI) after either pulsed field ablation (PFA) using a pentaspline catheter or thermal ablation technologies., Methods and Results: In a clinical trial (NCT03714178), paroxysmal atrial fibrillation (PAF) patients underwent PVI with a multi-electrode pentaspline PFA catheter using a biphasic waveform, and after 75 days, detailed voltage maps were created during protocol-specified remapping studies. Comparative voltage mapping data were retrospectively collected from consecutive PAF patients who (i) underwent PVI using thermal energy, (ii) underwent reablation for recurrence, and (iii) had durably isolated PVs. The left and right PV antral isolation areas and non-ablated posterior wall were quantified. There were 20 patients with durable PVI in the PFA cohort, and 39 in the thermal ablation cohort [29 radiofrequency ablation (RFA), 6 cryoballoon, and 4 visually guided laser balloon]. Pulsed field ablation patients were younger with shorter follow-up. Left atrial diameter and ventricular systolic function were preserved in both cohorts. There was no significant difference between the PFA and thermal ablation cohorts in either the left- and right-sided PV isolation areas, or the non-ablated posterior wall area. The right superior PV isolation area was smaller with PFA than RFA, but this disappeared after propensity score matching. Notch-like normal voltage areas were seen at the posterior aspect of the carina in the balloon sub-cohort, but not the PFA or RFA cohorts., Conclusion: Catheter-based PVI with the pentaspline PFA catheter creates chronic PV antral isolation areas as encompassing as thermal energy ablation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Genetic channelopathies can predispose individuals to life-threatening arrhythmias. Two such channelopathies are long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). To the best of our knowledge, we present the first case of LQTS with novel combined genetic mutations of KCNH2 and cardiac ryanodine receptor (RYR2) genes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Lakhana et al.)

Objectives: The goal of this study is to determine the incidence, predictors, and outcomes of atrial fibrillation (AF) or atrial flutter (AFL) in patients hospitalized with coronavirus disease-2019 (COVID-19)., Background: COVID-19 results in increased inflammatory markers previously associated with atrial arrhythmias. However, little is known about their incidence or specificity in COVID-19 or their association with outcomes., Methods: This is a retrospective analysis of 3,970 patients admitted with polymerase chain reaction-positive COVID-19 between February 4 and April 22, 2020, with manual review performed of 1,110. The comparator arm included 1,420 patients with influenza hospitalized between January 1, 2017, and January 1, 2020., Results: Among 3,970 inpatients with COVID-19, the incidence of AF/AFL was 10% (n = 375) and in patients without a history of atrial arrhythmias it was 4% (n = 146). Patients with new-onset AF/AFL were older with increased inflammatory markers including interleukin 6 (93 vs. 68 pg/ml; p < 0.01), and more myocardial injury (troponin-I: 0.2 vs. 0.06 ng/ml; p < 0.01). AF and AFL were associated with increased mortality (46% vs. 26%; p < 0.01). Manual review captured a somewhat higher incidence of AF/AFL (13%, n = 140). Compared to inpatients with COVID-19, patients with influenza (n = 1,420) had similar rates of AF/AFL (12%, n = 163) but lower mortality. The presence of AF/AFL correlated with similarly increased mortality in both COVID-19 (relative risk: 1.77) and influenza (relative risk: 1.78)., Conclusions: AF/AFL occurs in a subset of patients hospitalized with either COVID-19 or influenza and is associated with inflammation and disease severity in both infections. The incidence and associated increase in mortality in both cohorts suggests that AF/AFL is not specific to COVID-19, but is rather a generalized response to the systemic inflammation of severe viral illnesses., Competing Interests: Funding Support and Author Disclosures Dr Koruth has received consulting fees from Abbott Laboratories, CardioFocus, Farapulse, and Vytron US, Inc. Dr Dukkipati has received grant support from Biosense Webster; and has equity with Farapulse and Manual Surgical Sciences, LLC. Dr Halperin has received consulting fees from Boehringer Ingelheim, Johnson & Johnson-Janssen Pharmaceuticals, and Medtronic. Dr Reddy is a consultant with Abbott, Ablacon, Acutus Medical, Affera, Apama Medical, Aquaheart, Atacor, Autonomix, Axon, Backbeat, BioSig, Biosense Webster, Biotronik, Boston Scientific, Cardiofocus, Cardionomic, CardioNXT/AFTx, Circa Scientific, Corvia Medical, Dinova-Hangzhou Nuomao Medtech Co., Ltd., East End Medical, EBR, EPD, Epix Therapeutics, EpiEP, Eximo, Fire1, Impulse Dynamics, Javelin, Kardium, Keystone Heart, LuxCath, Manual Surgical Sciences, Medlumics, Medtronic, Middlepeak, Newpace, Nuvera, Philips, Pulse Biosciences, Sirona Medical, Stimda, Surecor, Thermedical, and Valcare; and has equity in Ablacon, Acutus Medical, Affera, Apama, Aquaheart, Atacor, Autonomix, Backbeat, BioSig, Circa Scientific, Corvia Medical, Dinova-Hangzhou Nuomao Medtech Co., Ltd., East End Medical, EPD, Epix Therapeutics, EpiEP, Eximo, Fire 1, Javelin, Kardium, Keystone Heart, LuxCath, Manual Surgical Sciences, Medlumics, Middlepeak, Newpace, Nuvera, Sirona Medical, Surecor, Valcare, and Vizaramed. All other authors have reported that they have 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.)

Inflammation is increasingly recognized as a critical mediator of angiogenesis, and unregulated angiogenic responses often involve human diseases. The importance of regulating angiogenesis in inflammatory diseases has been demonstrated through some successful cases of anti-angiogenesis therapies in related diseases, including arthritis, but it has been reported that some synthetic types of antiangiogenic drugs have potential side effects. In recent years, the importance of finding alternative strategies for regulating angiogenesis has begun to attract the attention of researchers. Therefore, identification of natural ingredients used to prevent or treat angiogenesis-related diseases will play a greater role. Isookanin is a phenolic flavonoid presented in Bidens extract, and it has been reported that isookanin possesses some biological properties, including antioxidative and anti-inflammatory effects, anti-diabetic properties, and an ability to inhibit α-amylase. However, its antiangiogenic effects and mechanism thereof have not been studied yet. In this study, our results indicate that isookanin has an effective inhibitory effect on the angiogenic properties of microvascular endothelial cells. Isookanin shows inhibitory effects in multiple stages of PGE 2 -induced angiogenesis, including the growth, proliferation, migration, and tube formation of microvascular endothelial cells. In addition, isookanin induces cell cycle arrest in S phase, which is also the reason for subsequent inhibition of cell proliferation. The mechanism of inhibiting angiogenesis by isookanin is related to the inhibition of PGE 2 -mediated ERK1/2 and CREB phosphorylation. These findings make isookanin a potential candidate for the treatment of angiogenesis-related diseases.

Importance: Early rhythm control of atrial fibrillation (AF) with either antiarrhythmic drugs (AADs) or catheter ablation has been reported to improve cardiovascular outcomes compared with usual care; however, the optimal therapeutic modality to achieve early rhythm control is unclear., Objective: To assess the safety and efficacy of AF ablation as first-line therapy when compared with AADs in patients with paroxysmal AF., Data Sources: PubMed/MEDLINE, Scopus, Google Scholar, and various major scientific conference sessions from January 1, 2000, through November 23, 2020., Study Selection: Randomized clinical trials (RCTs) published in English that had at least 12 months of follow-up and compared clinical outcomes of ablation vs AADs as first-line therapy in adults with AF. The quality of individual studies was assessed using the Cochrane risk of bias tool. Six RCTs met inclusion criteria, including 1212 patients., Data Extraction and Synthesis: Two investigators independently extracted data. Reporting was performed in compliance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines. Analysis was performed using a random-effects model with the Mantel-Haenszel method, and results are presented as 95% CIs., Main Outcomes and Measures: Main outcomes were safety and efficacy of AF ablation as first-line therapy when compared with AADs. Trials were evaluated as having low risk of selection and attrition biases, high risk of performance bias, and with unclear risk for detection biases due to unblinding and open-label designs., Results: A total of 6 RCTs involving 1212 patients with AF were included (609 were randomized to AF ablation and 603 to drug therapy; mean [SD] age, 56 [11] years). Compared with AADs, catheter ablation use was associated with reductions in recurrent atrial arrhythmia (32.3% vs 53%; risk ratio [RR], 0.62; 95% CI, 0.51-0.74; P < .001; I2 = 40%), with a number needed to treat with ablation to prevent 1 arrhythmia of 5. Use of ablation was also associated with reduced symptomatic atrial arrhythmia (11.8% vs 26.4%; RR, 0.44; 95% CI, 0.27-0.72; P = .001; I2 = 54%) and hospitalization (5.6% vs 18.7%; RR, 0.32; 95% CI, 0.19-0.53; P < .001) with no significant difference in serious adverse events between the groups (4.2% vs 2.8%; RR, 1.52; 95% CI, 0.81-2.85; P = .19)., Conclusions and Relevance: In this meta-analysis of randomized clinical trials including first-line therapy of patients with paroxysmal AF, catheter ablation compared with antiarrhythmic drugs was associated with reductions in recurrence of atrial arrhythmias and hospitalizations, with no difference in major adverse events.

Background: Left atrial appendage closure (LAAC) has proven to be an effective alternative to long-term oral anticoagulation in the prevention of thromboembolic events in patients with atrial fibrillation. In a minority of patients, inadequate seal may result in persistent peridevice flow and inability of the appendage to fully thrombose, thereby representing a potential source for thromboembolism., Objective: The purpose of this study was to study the use of endovascular coiling of the appendage to address persistent peridevice leak in patients undergoing LAAC with the Watchman device., Methods: This is a retrospective single-center analysis involving patients who underwent placement of a LAAC device and returned for endovascular coiling to address persistent device leak between 2018 and 2020. Baseline characteristics, procedural outcomes, and follow-up echocardiograms were analyzed to demonstrate the feasibility and safety of this technique., Results: Patients (N = 20) were identified with a mean leak size of 3.8 ± 1.3 mm (range 2.5-7 mm), all of whom had a non-thrombosed appendage. Acute procedural success was achieved in 95% of patients. Complete or significant reduction in flow beyond the LAAC device was achieved in 61% and 33% of patients, respectively. The 1 procedure-related adverse event was a pericardial effusion before coil deployment, requiring percutaneous drainage., Conclusion: The clinical impact of residual peridevice leak post-Watchman implantation is a matter of continuing investigation. However, appendage coiling represents a new therapeutic tool to address this potential source for thromboembolism. Further studies should address the clinical impact of this technique, including the safety of discontinuing anticoagulation after successful coiling., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Same-day discharge (SDD) after atrial fibrillation (AF) ablation is increasingly being considered. This study examined the barriers and financial impact associated with SDD in a contemporary cohort of patients undergoing elective AF ablation., Methods: A single center retrospective review was conducted of the 249 first case-of-the-day outpatient AF ablations performed in 2019 to evaluate the proportion of patients that could have undergone SDD. Barriers to SDD were defined as any intervention that prevented SDD by 8 p.m. The financial impact of SDD was based on savings from avoidance of the overnight hospital stay and revenue related to management of chest pain facilitated by a vacant hospital bed., Results: SDD could have occurred in 157 patients (63%) without change in management and in up to 200 patients (80%) if avoidable barriers were addressed. Barriers to SDD included non-clinical logistical issues (43%), prolonged post-procedure recovery (42%) and minor procedural complications (15%). On multivariate analysis, factors associated with barriers to SDD included increasing age (P = .01), left ventricular ejection fraction ≤ 35% (P = .04), and severely dilated left atrium (P = .04). The financial gain from SDD would have ranged from $1,110,096 (assuming discharge of 63% of eligible patients) to $1,480,128 (assuming 80% discharge) over the course of a year., Conclusions: Up to 80% of patients undergoing outpatient AF ablation were amenable to SDD if avoidable delays in care had been anticipated. Based on reduced hospital operating expenses and increased revenue from management of individuals with chest pain, this would translate to a financial savings of ∼$1.5 million., (© 2021 Wiley Periodicals LLC.)

Objectives: This study sought to determine the impact of adjunctive renal sympathetic denervation to catheter ablation in patients with atrial fibrillation (AF) and history of hypertension., Background: There are limited data regarding the impact of upstream adjunctive renal sympathetic denervation (RSDN) to pulmonary vein isolation (PVI) in patients with symptomatic atrial fibrillation (AF) and hypertension., Methods: The data for this study were obtained from 2 prospective randomized pilot studies, the HFIB (Adjunctive Renal Denervation to Modify Hypertension and Sympathetic tone as Upstream Therapy in the Treatment of Atrial Fibrillation)-1 (n = 30) and HFIB (Adjunctive Renal Denervation to Modify Hypertension and Sympathetic tone as Upstream Therapy in the Treatment of Atrial Fibrillation)-2 (n = 50) studies, and we performed a meta-analysis including all published studies comparing RSDN+PVI versus PVI alone up to January 25, 2020, in patients with AF and hypertension., Results: At 24 months, AF recurrence occurred in 53% and 38% in the PVI and PVI+RSDN groups (p = 0.43) in the HFIB-1 study, respectively, and 27% and 25% in the PVI and PVI+RSDN groups (p = 0.80) in the HFIB-2 study, respectively. When combined in a meta-analysis including 6 studies (n = 725), adjunctive RSDN significantly decreased the risk of AF recurrence (risk ratio [RR]: 0.68; 95% confidence interval [CI]: 0.55 to 0.83; p = 0.0002; I 2  = 0%) when compared with PVI. Six renal artery complications occurred in the HFIB-1 study and none occurred in the HFIB-2 study with RSDN. However, in the meta-analysis, there were no significant differences in overall complications between both groups (RR: 1.43; 95% CI: 0.63 to 3.22; p = 0.40; I 2  = 7%). When compared with baseline, RDSN significantly reduced the systolic blood pressure (-12.1 mm Hg; 95% CI: -20.9 to -3.3 mm Hg; p < 0.007; I 2  = 99%) and diastolic blood pressure (-5.60 mm Hg; 95% CI: -10.05 to -1.10 mm Hg; p = 0.01; I 2  = 98%) on follow-up., Conclusions: The pilot HFIB-1 and HFIB-2 studies did not demonstrate a benefit with RSDN as an adjunctive upstream therapy during PVI. However, in the meta-analysis, adjunctive RSDN to PVI appears to be safe, and improves clinical outcomes in AF patients with a history of hypertension., Competing Interests: Author Disclosures The HFIB-1 study was sponsored by Biosense Webster. The HFIB-2 study was sponsored by Boston Scientific. Dr. Cuoco has served as a consultant for St. Jude Medical and Boston Scientific. Dr. Mansour has received research grant support from Abbott, Biosense Webster, Johnson and Johnson, Boston Scientific, Medtronic, Pfizer, Boehringer Ingelheim, and Sentre Heart; has served as a consultant for Abbott, Biosense Webster, Jonhson and Johnson, Boston Scientific, Janssen, Medtronic, Philips, Novartis, and Sentre Heart; and owns equity interest in Affera, EPS Solutions, and NewPace Ltd. Dr. Lakkireddy has served as a steering committee member for the Amulet and Amaze IDE studies; and received consulting fees from Abbott. Dr. Michaud has served as a consultant for Biosense Webster, Boston Scientific, and Abbott; and has received honoraria from Biosense Webster, Boston Scientific, Biotronik, Medtronic, and Abbott. Dr. Dukkipati owns equity interest in Manual Surgical Sciences and Farapulse; and has received research grant support from Biosense Webster. Dr. Reddy has served as an unpaid consultant to and received grant support from Biosense Webster and Boston Scientific. Additional disclosures unrelated to this manuscript are listed in the Supplemental Appendix. All other authors have reported that they have 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.)

Background: Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias. However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality., Methods: We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block., Results: Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88). The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P =0.01)-a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event., Conclusions: Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

Background: Because device-related thrombus (DRT) portends a poor prognosis after left atrial appendage closure with the Watchman device, surveillance transesophageal echocardiography (TEE) is recommended at 45 days and 1 year. However, oral anticoagulants are just discontinued at 45 days, rendering this early TEE unlikely to detect DRT. Indeed, DRT is most likely to occur after instituting aspirin monotherapy., Objective: The purpose of this study was to evaluate the alternative strategy of first TEE imaging (or computed tomography) at 4 months post-Watchman implantation., Methods: After Food and Drug Administration approval, consecutive patients undergoing Watchman implantation at 2 centers received TEE or CT at 4 months and 1 year, along with a truncated drug regimen: 6 weeks of an oral anticoagulant (or clopidogrel in a subset) plus aspirin, then 6 weeks of dual antiplatelet therapy, and finally aspirin monotherapy., Results: Of the 530-patient cohort (mean age 78.7±7.9 years; 65.5% (n = 347) male; CHA 2 DS 2 -VASc score 4.5±1.4), 465 patients (87.7%) received 4-month imaging: 83.0% (440 of 530) TEE and 4.7% (25 of 530) computed tomography. Over a median follow-up of 12 months, 16 ischemic strokes (ISs), 8 transient ischemic attacks, and 1 systemic embolization occurred. Importantly, no IS occurred between 45 days and 4 months; the sole transient ischemic attack in this period (at ∼2 months) occurred 1 week after transcatheter aortic valve replacement. DRT was detected in 2.4% (11 of 465) at 4 months and 0.9% (2 of 214) at 1 year. No IS, but 1 leg embolization, was observed after DRT detection., Conclusion: Delaying the first imaging post-Watchman implantation to 4 months was associated with no IS between 45 days and 4 months, the "vulnerable" period of this follow-up strategy., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Recent studies have described several cardiovascular manifestations of COVID-19 including myocardial ischemia, myocarditis, thromboembolism, and malignant arrhythmias. However, to our knowledge, syncope in COVID-19 patients has not been systematically evaluated. We sought to characterize syncope and/or presyncope in COVID-19., Methods: This is a retrospective analysis of consecutive patients hospitalized with laboratory-confirmed COVID-19 with either syncope or presyncope. This "study" group (n = 37) was compared with an age and gender-matched cohort of patients without syncope ("control") (n = 40). Syncope was attributed to various categories. We compared telemetry data, treatments received, and clinical outcomes between the two groups., Results: Among 1000 COVID-19 patients admitted to the Mount Sinai Hospital, the incidence of syncope/presyncope was 3.7%. The median age of the entire cohort was 69 years (range 26-89+ years) and 55% were men. Major comorbidities included hypertension, diabetes, and coronary artery disease. Syncopal episodes were categorized as (a) unspecified in 59.4% patients, (b) neurocardiogenic in 15.6% patients, (c) hypotensive in 12.5% patients, and (d) cardiopulmonary in 3.1% patients with fall versus syncope and seizure versus syncope in 2 of 32 (6.3%) and 1 of 33 (3.1%) patients, respectively. Compared with the "control" group, there were no significant differences in both admission and peak blood levels of d-dimer, troponin-I, and CRP in the "study" group. Additionally, there were no differences in arrhythmias or death between both groups., Conclusions: Syncope/presyncope in patients hospitalized with COVID-19 is uncommon and is infrequently associated with a cardiac etiology or associated with adverse outcomes compared to those who do not present with these symptoms., (© 2020 Wiley Periodicals LLC.)

Background: Pulmonary vein (PV) stenosis is an important potential complication of PV isolation using thermal modalities such as radiofrequency ablation (RFA). Pulsed field ablation (PFA) is an alternative energy that causes nonthermal myocardial cell death., Objective: The purpose of this study was to compare the effect of PFA vs RFA on the incidence and severity of PV narrowing or stenosis., Methods: Data were analyzed from 4 paroxysmal atrial fibrillation ablation trials using either PFA or RFA; because of absent CT scans or poor computed tomography scan quality, 73 of 153 patients (47.7%) were excluded. Baseline and 3-month cardiac computed tomography scans were reconstructed into 3-dimensional images, and the long and short axes of the PV ostia were quantitatively and qualitatively assessed in a randomized blinded manner by 2 physicians., Results: A total of 299 PVs from 80 patients after either PFA (n = 37) or RFA (n = 43) were enrolled. PV ostial diameters decreased significantly less with PFA than with RFA (% change; long axis: 0.9% ± 8.5% vs -11.9% ± 16.3%; P < .001 and short axis: 3.4% ± 12.7% vs -12.9% ± 18.5%; P < .001). After a combined quantitative/qualitative analysis, mild (30%-49%), moderate (50%-69%), or severe (70%-100%) PV narrowing was observed, respectively, in 9.0% (15 of 166), 1.8% (3 of 166), and 1.2% (2 of 166) of PVs in the RFA cohort but in none of the PVs after PFA (P < .001). Overall, PV narrowing/stenosis was present in 0% and 0% vs 12.0% and 32.5% of PVs and patients who underwent PFA and RFA, respectively., Conclusion: This study indicates that unlike after RFA, the incidence and severity of PV narrowing/stenosis after PV isolation is virtually eliminated with PFA., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Catheter ablation for atrial fibrillation (AF) using point-by-point radiofrequency energy or single-application one-shot balloons is either technically challenging or have limited ability to accommodate variable patient anatomy to achieve acute and durable pulmonary vein (PV) isolation. A novel ablation system employs low intensity collimated ultrasound (LICU)-guided anatomic mapping and robotic ablation to isolate PVs. In this first-in-human, single-center, multioperator trial, VALUE trial (VytronUS Ablation System for Treatment of Paroxysmal Atrial Fibrillation; NCT03639597) in patients with paroxysmal atrial fibrillation, this LICU system was evaluated to determine its safety, effectiveness in PV isolation, and freedom from recurrent atrial arrhythmias., Methods: In the enrolled 52 patients with paroxysmal atrial fibrillation, ultrasound M-mode-based left atrial anatomies were successfully created, and ablation was performed under robotic control along an operator-defined lesion path. The LICU system software advanced over the course of the study: the last 13 patients were ablated with enhanced software., Results: Acute PV isolation was achieved in 98% of PVs-using LICU-only in 77.3% (153/198) of PVs and requiring touch-up with a standard radiofrequency ablation catheter in 22.7% (45/198) PVs. The touch-up rate decreased to 5.8% (3/52) in patients undergoing LICU-ablation with enhanced software. Freedom from atrial arrhythmia recurrence was 79.6% (39/49 patients) at 12 months or 92.3% (12/13 patients) with the enhanced software. Major adverse events occurred in 3 patients (5.8%): one had transient diaphragmatic paralysis, one vascular access complication, and one had transient ST-segment elevation from air-embolism, without sequelae., Conclusions: In this first-in-human study, low- intensity collimated ultrasound-guided anatomic mapping and robotic ablation allows PV isolation with good chronic safety; PV isolation success is improving with device enhancements. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03639597.

Background: Pulmonary vein isolation is insufficient to treat all patients with persistent atrial fibrillation (AF), and effective adjunctive ablation strategies are needed. Ablation of AF drivers holds promise, but current technologies to identify drivers are limited by spatial resolution. In a single-arm, first-in-human, investigator-initiated Food and Drug Administration Investigational Device Exemption study, we used a novel system for real-time, high-resolution identification of AF drivers in persistent AF., Methods: Patients with persistent or long-standing persistent AF underwent ablation using the RADAR (Real-Time Electrogram Analysis for Drivers of Atrial Fibrillation) system in conjunction with a standard electroanatomical mapping system. After pulmonary vein isolation, electrogram and spatial information was streamed to the RADAR system and analyzed to identify driver domains to target for ablation., Results: Across 4 centers, 64 subjects were enrolled: 73% male, age, 64.7±9.5 years; body mass index, 31.7±6.0 kg/m 2 ; left atrium size, 54±10 mm, with persistent/long-standing persistent AF in 53 (83%)/11 (17%), prior AF ablation (re-do group) in 26 (41%). After 12.6±0.8 months follow-up, 68% remained AF-free off all antiarrhythmics; 74% remained AF-free and 66% remained AF/atrial tachycardia/atrial flutter-free on or off AADs (antiarrhythmic drugs). AF terminated with ablation in 35 patients (55%) overall and in 23/38 (61%) of de novo ablation patients. For patients with AF termination during ablation, 82% remained AF-free and 74% AF/atrial tachycardia/atrial flutter-free during follow-up on or off AADs. Patients undergoing first-time ablation generally had higher rates of freedom from AF than the re-do group., Conclusions: This novel technology for panoramic mapping of AF drivers showed promising results in a persistent/long-standing persistent AF population. These data provide the scientific basis for a randomized trial., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03263702; IDE#G170049.

Background The PROTECT-AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trials demonstrated noninferiority of left atrial appendage closure (LAAC) to warfarin for the composite end point of stroke, systemic embolism, or cardiovascular death. This study aims to quantify the net clinical benefit (NCB) of LAAC versus warfarin, accounting for differences in clinical impact of different event types. Methods and Results We performed a post hoc analysis of the PROTECT-AF and PREVAIL trials, which randomized atrial fibrillation patients to LAAC or warfarin in a 2:1 fashion. The trials enrolled patients in the United States and Europe between 2005 and 2012 with paroxysmal, persistent, or permanent atrial fibrillation and CHADS 2 risk scores ≥1. Relative to an index weight for death (1.0), events were assigned weights based on their disabling effect: (1) stroke event weights were based on modified Rankin scores in the base case analyses, and (2) major bleed (0.05) and pericardial effusion (0.05). NCB was calculated as the sum of weight-adjusted events per 100 patient-years. Among 1114 randomized subjects, the NCB of LAAC was 1.42% per year (95% CI 0.01-2.82, P =0.04) and a relative risk of 0.74 (95% CI 0.56-1.00). NCB point estimates favored warfarin early in follow-up, but trended in favor of LAAC after 1 to 2 years. The benefit of LAAC was preserved across subgroups, with particular benefit observed in the subgroup of prior stroke and without diabetes mellitus. Conclusions This analysis demonstrates long-term NCB of LAAC with Watchman over warfarin therapy, as the upfront risk of periprocedural events is counterbalanced over time by reduced bleeding events and mortality. Clinical Trial Registration UR: http://www.clinicaltrials.gov. Unique identifiers: NCT01182441 and NCT00129545.

Objective: This study evaluated the impact of daily ECG (electrocardiogram) self-recordings on time to documented recurrent atrial fibrillation (AF) or atrial flutter (AFL) and time to treatment of recurrent arrhythmia in patients undergoing catheter radiofrequency ablation (RFA) or direct current cardioversion (DCCV) for AF/AFL., Background: AF recurrence rates after RFA and DCCV are 20% to 45% and 60% to 80%, respectively. Randomized trials comparing mobile ECG devices to standard of care have not been performed in an AF/AFL population after treatment., Methods: Of 262 patients consented, 238 were randomized to either standard of care (123) or to receive the iHEART intervention (115). Patients in the intervention group were provided with and trained to use an AliveCor KardiaMobile ECG monitor, and were instructed to take and transmit daily ECG recordings. Data were collected from transmitted ECG recordings and patients' electronic health records., Results: In a multivariate Cox model, the likelihood of recurrence detection was greater in the intervention group (hazard ratio = 1.56, 95% confidence interval [CI]: 1.06-2.30, P = .024). Hazard ratios did not differ significantly for RFA and DCCV procedures. Recurrence during the first month after ablation strongly predicted later recurrence (hazard ratio = 4.53, 95% CI: 2.05-10.00, P = .0006). Time from detection to treatment was shorter for the control group (hazard ratio = 0.33, 95% CI: 0.57-2.92, P < .0001)., Conclusions: The use of mobile ECG self-recording devices allows for earlier detection of AF/AFL recurrence and may empower patients to engage in shared health decision-making., (© 2019 The Authors. Journal of Cardiovascular Electrophysiology Published by Wiley Periodicals, Inc.)

Despite considerable advances in guidance of radiofrequency ablation (RFA) therapy for the treatment of cardiac arrhythmias, success rates have been hampered by a lack of tools for precise intraoperative evaluation of lesion extent. Near-infrared spectroscopic (NIRS) techniques are sensitive to tissue structural and biomolecular properties, characteristics that are directly altered by radiofrequency (RF) treatment. In this work, a combined NIRS-RFA catheter is developed for real-time monitoring of tissue reflectance during RF energy delivery. An algorithm is proposed for processing NIR spectra to approximate nonirrigated lesion depth in both atrial and ventricular tissues. The probe optical geometry was designed to bias measurement influence toward absorption enabling enhanced sensitivity to changes in tissue composition. A set of parameters termed "lesion optical indices" are defined encapsulating spectral differences between ablated and unablated tissue. Utilizing these features, a model for real-time tissue spectra classification and lesion size estimation is presented. Experimental validation conducted within freshly excised porcine cardiac specimens showed strong concordance between algorithm estimates and post-hoc tissue assessment., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: This study sought to determine the electrophysiological predictors of acute procedural success and of post-ablation recurrence of atrial tachyarrhythmias (ATs) in our adult congenital heart disease (ACHD) population undergoing catheter ablation for treatment of AT., Background: Catheter ablation is frequently performed to treat persistent AT in ACHD. The predictors of post-ablation AT recurrence have not been well studied in the ACHD population., Methods: The authors performed a retrospective study of all catheter ablations for treatment of AT performed in ACHD patients between December 1, 2005, and July 20, 2017, at Columbia University Medical Center. Pre-specified clinical and procedural data of interest and the time from ablation to recurrence were determined by chart and procedure report review., Results: A total of 140 patients (mean age: 45 years) underwent catheter ablation for 182 AT. Of the AT, 179 (93%) were intra-atrial macro-re-entrant tachycardia, and 12 (7%) had a focal origin. The presence of a single mechanism was a predictor of acute procedural success that could be achieved in 89% of the patients. At a median of 49.9 months, 62 patients (44%) had recurrent AT. Time to recurrence was significantly shorter (12.5 months) for recurrent AT in 13 of the 20 patients with previous Fontan procedure. By multivariable analysis, acute procedural success was a positive predictor and prior surgical maze procedure was a negative predictor of AT-free survival. Of the 62 patients with recurrent AT, 42 (68%) had a second catheter ablation procedure, and in 22 of these, the AT mechanism was different than previously observed., Conclusions: Catheter ablation for AT in ACHD patients is an effective method of arrhythmia control. More than 1 AT mechanism per patient is common. Acute procedural success is a predictor of freedom from AT recurrence. The majority of patients achieve multiple arrhythmia-free years., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Catheter ablation is commonly performed to treat atrial arrhythmias in adult congenital heart disease (ACHD). Despite the frequency of ablations in the ACHD population, predictors of recurrence remain poorly defined., Objective: We sought to determine predictors of arrhythmia recurrence in ACHD patients following catheter ablation for atrial arrhythmias., Methods: We performed a retrospective study of all catheter ablations for atrial arrhythmias performed in ACHD patients between January 12, 2005 and February 11, 2015 at our institution. Prespecified exposures of interest and time from ablation to recurrence were determined via chart review., Results: Among 124 patients (mean age: 45 years) who underwent catheter ablation, 96 (77%) were treated for macro-reentrant atrial tachycardia, 10 (7%) for focal atrial tachycardia, 9 (7%) for atrial fibrillation, 7 (6%) for atrioventricular nodal reentrant tachycardia, and 2 (2%) for atrioventricular reentrant tachycardia. 15 (12%) required transseptal/transbaffle puncture. Fifty-one percent of patients recurred with a median time to recurrence of 1639 days. By univariate and multivariable analysis, body mass index (BMI) and Fontan status were the only variables associated with recurrence. Dose-dependent effect was observed with overweight (HR = 2.37, P = .012), obese (HR = 2.67, P = .009), and morbidly obese (HR = 4.23, P = .003) patients demonstrating an increasing risk for arrhythmia recurrence postablation. There was no significant different in recurrence rates by gender, age, non-Fontan diagnosis, or need for transseptal puncture., Conclusions: In our cohort of ACHD patients, BMI was a significant risk factor for arrhythmia recurrence postablation, independent of Fontan status. These findings may help guide treatment decisions for persistent arrhythmias in the ACHD population., (© 2018 Wiley Periodicals, Inc.)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement., Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and are associated with increased morbidity and mortality risk., Purpose: To compare benefits and harms between catheter ablation and drug therapy in adult patients with AF and HF., Data Sources: ClinicalTrials.gov, PubMed, Web of Science (Clarivate Analytics), EBSCO Information Services, Cochrane Central Register of Controlled Trials, Google Scholar, and various scientific conference sessions from 1 January 2005 to 1 October 2018., Study Selection: Randomized controlled trials (RCTs) published in English that had at least 6 months of follow-up and compared clinical outcomes of catheter ablation versus drug therapy in adults with AF and HF., Data Extraction: 2 investigators independently extracted data and assessed study quality., Data Synthesis: 6 RCTs involving 775 patients met inclusion criteria. Compared with drug therapy, AF ablation reduced all-cause mortality (9.0% vs. 17.6%; risk ratio [RR], 0.52 [95% CI, 0.33 to 0.81]) and HF hospitalizations (16.4% vs. 27.6%; RR, 0.60 [CI, 0.39 to 0.93]). Ablation improved left ventricular ejection fraction (LVEF) (mean difference, 6.95% [CI, 3.0% to 10.9%]), 6-minute walk test distance (mean difference, 20.93 m [CI, 5.91 to 35.95 m]), peak oxygen consumption (Vo2max) (mean difference, 3.17 mL/kg per minute [CI, 1.26 to 5.07 mL/kg per minute]), and quality of life (mean difference in Minnesota Living with Heart Failure Questionnaire score, -9.02 points [CI, -19.75 to 1.71 points]). Serious adverse events were more common in the ablation groups, although differences between the ablation and drug therapy groups were not statistically significant (7.2% vs. 3.8%; RR, 1.68 [CI, 0.58 to 4.85])., Limitation: Results driven primarily by 1 clinical trial, possible patient selection bias in the ablation group, lack of patient-level data, open-label trial designs, and heterogeneous follow-up length among trials., Conclusion: Catheter ablation was superior to conventional drug therapy in improving all-cause mortality, HF hospitalizations, LVEF, 6-minute walk test distance, Vo2max, and quality of life, with no statistically significant increase in serious adverse events., Primary Funding Source: None.