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An abstract of the article "The use of transthoracic dobutamine stress echocardiography for risk stratification in patients undergoing bariatric surgery," by S. Lerakis and colleagues is presented.

Importance: Patients with atrial fibrillation (AF) who have ischemic stroke despite taking oral anticoagulation therapy (OAT) have a very high risk of recurrence. Left atrial appendage occlusion (LAAO) is a mechanical stroke prevention strategy that may provide additional protection in patients with thromboembolic events under OAT., Objective: To compare percutaneous LAAO with continuing OAT alone regarding stroke prevention in patients with AF who had a thromboembolic event despite taking OAT., Design, Setting, and Participants: This cohort study was a propensity score-matched comparison of the STR-OAC LAAO cohort, an international collaboration of 21 sites combining patients from multiple prospective registries of patients who underwent LAAO between 2010 and 2022. STR-OAC LAAO cohort patients who had follow-up longer than 3 months were propensity score-matched to a previously published control cohort comprising patients from an established international collaboration of investigator-initiated prospective studies. This control cohort included patients with nonvalvular AF, recent ischemic stroke or transient ischemic attack, and follow-up longer than 3 months who were taking OAT before the index event. Analyses were adjusted for imbalances in gender, age, hypertension, diabetes, and CHA2 DS2-VASc score., Exposure: Left atrial appendage occlusion vs continuation of oral anticoagulation therapy alone (control group)., Main Outcomes and Measures: The primary outcome was time to first ischemic stroke., Results: Four hundred thirty-three patients from the STR-OAC LAAO cohort (mean [SD] age, 72 [9] years; 171 [39%] females and 262 [61%] males; mean [SD] CHA2 DS2-VASc score, 5.0 [1.6]) were matched to 433 of 1140 patients (38%) from the control group. During 2-year follow-up, 50 patients experienced ischemic stroke: an annualized event rate of 2.8% per patient-year in the STR-OAC LAAO group vs 8.9% per patient-year in the control group. Left atrial appendage occlusion was associated with a lower risk of ischemic stroke (hazard ratio, 0.33; 95% CI, 0.19-0.58; P < .001) compared with the control group. After LAAO, OAT was discontinued in 290 patients (67%), and the remaining 143 patients (33%) continued OAT after LAAO as an adjunctive therapy., Conclusions and Relevance: In patients with nonvalvular AF and a prior thromboembolic event despite taking OAT, LAAO was associated with a lower risk of ischemic stroke compared with continued OAT alone. Randomized clinical trial data are needed to confirm that LAAO may be a promising treatment option for this population with a very high risk of stroke.

Background: Human in vivo data on the chemical stability of different transvenous lead materials, particularly Optim TM leads, are lacking., Objectives: The purpose of this study was to determine the chemical reactivity of insulation materials by analyzing the molar mass of extracted pacing and defibrillator leads METHODS: We collected extracted leads at Emory University Hospitals and sent the leads with thermoplastic outer insulation material for molar mass analysis, a material characteristic that informs biostability. Leads were separated based on the chemical identity of the outer insulation material, and the molar mass was measured by an independent party. The extent of chemical reaction was compared across leads having different materials: poly(ether)urethane 55D, poly(ether)urethane 80A, and Optim., Results: A total of 70 leads were extracted. The subset of extracted leads having outer insulation materials composed of PEU or Optim were analyzed for molar mass, where implant times ranged from 0.12 to 16.26 years. The rate of chemical degradation was compared by plotting the extent of reaction [M n (t = 0)/M n (t)] as a function of implant time. The Optim molar mass decreased to 40% of its initial value at 10 years of implant. No change in the molar mass of the PEU insulations could be resolved over the same 10-year implant time., Conclusion: Because the molar mass of a polymer is directly related to its mechanical integrity, the observed decrease in molar mass of Optim likely translates into premature insulation defects and is consistent with the observed increased rate of electrical malfunction/noise in this subset of cardiac leads., Competing Interests: Disclosures Dr El-Chami reports honoraria/speaking/consulting fees from Boston Scientific and Medtronic. Dr Lloyd reports honoraria/speaking/consulting fees from Medtronic and Boston Scientific. Dr Chaffin is an employee of Medtronic. All other authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Left atrial appendage occlusion (LAAO) provides mechanical cardioembolic protection for atrial fibrillation (AF) patients who cannot use oral anticoagulation therapy (OAT). Patients with a thrombotic event despite OAT are at high risk for recurrence and may also benefit from LAAO., Objectives: This study sought to investigate the efficacy of LAAO in AF patients with a thrombotic event on OAT compared to: 1) LAAO in AF patients with a contraindication for OAT; and 2) historical data., Methods: The international LAAO after stroke despite oral anticoagulation (STR-OAC LAAO) collaboration included patients who underwent LAAO because of thrombotic events on OAT. This cohort underwent propensity score matching and was compared to the EWOLUTION (Evaluating Real-Life Clinical Outcomes in Atrial Fibrillation Patients Receiving the WATCHMAN Left Atrial Appendage Closure Technology) registry, which represents patients who underwent LAAO because of OAT contraindications. The primary outcome was ischemic stroke. Event rates were compared between cohorts and with historical data without OAT, yielding relative risk reductions based on risk scores., Results: Analysis of 438 matched pairs revealed no significant difference in the ischemic stroke rate between the STR-OAC LAAO and EWOLUTION cohorts (2.5% vs 1.9%; HR: 1.37; 95% CI: 0.72-2.61). STR-OAC LAAO patients exhibited a higher thromboembolic risk (HR: 1.71; 95% CI: 1.04-2.83) but lower bleeding risk (HR: 0.39; 95% CI: 0.18-0.88) compared to EWOLUTION patients. The mortality rate was slightly higher in EWOLUTION (4.3% vs 6.9%; log-rank P = 0.028). Relative risk reductions for ischemic stroke were 70% and 78% in STR-OAC LAAO and EWOLUTION, respectively, compared to historical data without OAT., Conclusions: LAAO in patients with a thrombotic event on OAT demonstrated comparable stroke rates to the OAT contraindicated population in EWOLUTION. The thromboembolic event rate was higher and the bleeding rate lower, reflecting the intrinsically different risk profile of both populations. Until randomized trials are available, LAAO may be considered in patients with an ischemic event on OAT., Competing Interests: Funding Support and Author Disclosures Dr Maarse has received an educational grant from Boston Scientific. Dr Tondo serves on the advisory board of Boston Scientific; and has received lecture and tutoring fees from Boston Scientific and Abbott Medical. Dr Demkow has received proctoring fees from Boston Scientific and Abbott. Dr de Backer has received institutional research grants and consulting fees from Abbott and Boston Scientific. Dr Nielsen-Kudsk has received grants from Abbott and Boston Scientific. Dr Estevez-Loureiro is a proctor for Abbott Vascular, Boston Scientific, and Lifetech. Dr de Prado is a proctor for Boston Scientific. Dr Nombela-Franco is a proctor for Abbott Vascular, Edwards Lifesciences, and Boston Scientific. Dr Salinas is a proctor for Abbott Vascular. Dr Berti is a proctor for Edwards Lifesciences, Boston Scientific, and Abbott. Dr Millan has received consultant fees/honoraria from Abbott Laboratories and Boston Scientific. Dr Arzamendi has received consultant fees/honoraria from Abbott Laboratories and Boston Scientific. Dr Agarwal is a member of the Speaker Bureau and proctor for Medtronics, Abbott, Edwards Lifesciences, and Boston Scientific. Dr Spoon is a speaker for Medtronic, Abiomed, and Abbott. Dr El-Chami is a consultant for Medtronic and Boston Scientific. Dr Adamo has received speaker honoraria from Abbott Structural Heart. Dr van Dijk is a proctor for Boston Scientific. Dr Swaans is a proctor/lecturer for Abbott Vacular, Bioventrix Inc, Boston Scientific, Cardiac Dimensions, Edwards Lifesciences, GE Healthcare, and Philips Healthcare. Dr Vireca is an employee of Boston Scientific. Dr Bergmann has received speaker honoraria from Boston Scientific and Abbott; and has received research support from Boston Scientific and Abbott. Dr Boersma is a consultant for Boston Scientific; and is a proctor for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Rao reports receiving research funding from NIH grant and AHRQ. Dr El-Chami consults for Medtronic, Boston Scientific, and Biotronik. Dr Knops reports consultancy fees and research grants from Boston Scientific, Medtronic, and Abbott and has stock options from AtaCor Medical. Dr Lloyd has served as a consultant for and received research support from Medtronic, Boston Scientific, Biosense Webster, and Abbott.

Introduction: The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre-existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score., Methods: We prospectively evaluated all patients without pre-existing pacemakers, ICD, or pre-existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision-making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis., Results: A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05-3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74-0.88], p < 0.001)., Conclusions: The ERS prospectively predicted the need for PPM in a serial, real-world cohort of patients undergoing TAVR with a balloon-expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR., (© 2023 Wiley Periodicals LLC.)

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an accepted alternative to transvenous (TV) ICD to provide defibrillation therapy to treat life-threatening ventricular tachyarrhythmias in high-risk patients. S-ICD outcomes by age group have not been reported., Objectives: In this study, the authors sought to report S-ICD outcomes in different age groups in a multicenter S-ICD post-approval study (PAS) involving the largest cohort of patients ever reported., Methods: Patients were prospectively enrolled in the S-ICD PAS and stratified based on age: young, aged 15-34 years; adult, aged 35-69 years; and elderly, aged ≥70 years. Patient characteristics and clinical outcomes through 3 years of follow up after implantation were compared., Results: The S-ICD PAS enrolled 1,637 patients. Elderly patients were more likely to receive an S-ICD as a replacement of a TV-ICD (15.1% elderly vs 12.3% adult vs 7.4% young). Secondary prevention indication decreased with age (32.7% young vs 22.2% adult vs 20.5% elderly). Mortality rate was significantly higher in the elderly group (24.0% elderly vs 13.0% adult vs 7.4% young; P < 0.0001), whereas the complication rate did not differ significantly (12.3% young vs 11.3% adult vs 8.1% elderly). Rates of appropriate shock (12.7% young vs 13.0% adult vs 13.8% elderly) and inappropriate shock (7.8% young vs 9.1% adult vs 8.8% elderly) rates did not differ between groups (P = 0.96 and P = 0.98, respectively)., Conclusions: Implant complications and appropriate and inappropriate shock rates were similar among age groups. S-ICD for secondary prevention was more common in the young group. Replacing a TV-ICD for an S-ICD increases with age. (S-ICD System Post-Approval Study; NCT01736618)., Competing Interests: Funding Support and Author Disclosures Dr Weiss has received compensation for services from Boston Sci Advisory honoraria; Biosense Consulting and Educational Honoraria; Abbott Consulting Honoraria; S4 Travel; and Sanofi Consulting; research grants from Boston Scientific, Abbott, Biosense, and Medtronic; and fellowship support from Boston Scientific Corporation, Abbott, Biosense, and Medtronic. Dr Knight has received consulting and speaker fees, investigator compensation, and fellowship support from Abbott, Biosense Webster, Biotronic, Boston Scientific, Medtronic, Atricure, and CVRx. Dr El-Chami has received compensation for services from Boston Scientific and Medtronic. Dr Aasbo has received consulting fees Boston Scientific and Biotronik. Dr Sadhu has received compensation for services and Speaker fees from Boston Scientific. Dr Brisben is a full-time employee of Boston Scientific. Mr Carter is a full-time employee of Boston Scientific. Dr Burke has received honoraria and research grants from Boston Scientific, Biosense Webster, and AtaCor Medical; and holds equity in AtaCor Medical. Dr Gold has received compensation for services from Boston Scientific, Medtronic, and Abbott. 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.)

Aims: Cardiac pacing represents a key element in the field of electrophysiology and the treatment of conduction diseases. Since the first issue published in 1999, EP Europace has significantly contributed to the development and dissemination of the research in this area., Methods: In the last 25 years, there has been a continuous improvement of technologies and a great expansion of clinical indications making the field of cardiac pacing a fertile ground for research still today. Pacemaker technology has rapidly evolved, from the first external devices with limited longevity, passing through conventional transvenous pacemakers to leadless devices. Constant innovations in pacemaker size, longevity, pacing mode, algorithms, and remote monitoring highlight that the fascinating and exciting journey of cardiac pacing is not over yet., Conclusion: The aim of the present review is to provide the current 'state of the art' on cardiac pacing highlighting the most important contributions from the Journal in the field., Competing Interests: Conflict of interest: P.D. research grants and honoraria from Boston Scientific, Abbott and Microport CRM. J.P. 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, Medtronic, Milestone, ElectroPhysiology Frontiers, Medtronic, Sanofi, Pacira, Philips, and Up-to-Date. M.E.C. is consultant for Medtronic and Boston Scientific and S.B. is consultant for Medtronic, Boston Scientific, Microport, and Zoll. The remaining authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Bakuchiol is gaining major interest for treatments against skin photoaging. The kinetics of mushroom tyrosinase inhibition by bakuchiol, by real-time oxygen sensing and UV-vis monitoring (475 nm), showed competitive inhibition with average K i constant (µM, 30 °C, pH 6.8) of 6.71 ± 1.23 and 1.15 ± 0.34 for monophenolase and diphenolase reactions respectively, with respective IC 50 37.22 ± 5.18 and 6.91 ± 0.96 ∼ at 1 mM substrate, compared to kojic acid IC 50 34.02 ± 5.51 and 16.86 ± 3.28 μM. Fluorescence quenching showed a single binding mode with formation constant K a 1.02 × 10 6 M -1 . The antioxidant activity was studied by inhibited autoxidation of styrene and cumene (PhCl, 30 °C) affording inhibition constant k inh  = 18.1 ± 6.6 (10 4 M -1 s -1 , 30 °C) and of MeLin in Triton™ X-100 micelles giving k inh  = 0.16 ± 0.03 (10 4 M -1 s -1 , 37 °C). Stoichiometric factor was 1.9 ± 0.1. ReqEPR spectroscopy afforded the BDE(OH) as 81.7 ± 0.1 kcal/mol. Bakuchiol is a potent tyrosinase inhibitor with good antioxidant activity having major potential as natural food preservative against oxidation and food-browning., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major public health problem. Recently substantial new evidence has accumulated regarding AF care. Furthermore, advances in technology for AF diagnosis and management have been made. 2020 European Society of Cardiology AF guideline document reflects recent evidence and contains several major updates in various aspects of AF management including rhythm control, anticoagulation, and risk factor modification. The objective of this report is to provide a summary of the 2020 European Society of Cardiology AF guideline recommendations for the management of AF for Georgian clinicians and to help promote AF management in an evidence-based manner.

Competing Interests: Conflict of interest: The authors have provided declaration of interest information for all relationships that might be perceived as real or potential sources of conflicts of interest. The full disclosures can be viewed in the supplementary material for this article, available online at http://academic.oup.com/europace/article-lookup/doi/10.1093/europace/euac066#supplementary-data.

Importance: The safety and efficacy of leadless VVI pacemakers have been demonstrated in multiple clinical trials, but the comparative performance of the device in a large, real-world population has not been examined., Objective: To compare patient characteristics and complications among patients implanted with leadless VVI and transvenous VVI pacemakers., Design, Setting, Participants: The Longitudinal Coverage With Evidence Development Study on Micra Leadless Pacemakers (Micra CED) is a continuously enrolling observational cohort study evaluating complications, utilization, and outcomes of leadless VVI pacemakers in the US Medicare fee-for-service population. Patients implanted between March 9, 2017, and December 1, 2018, were identified and included. All Medicare patients implanted with leadless VVI and transvenous VVI pacemakers during the study period were enrolled. Patients with less than 12 months of continuous enrollment in Medicare prior to leadless VVI or transvenous VVI implant and with evidence of a prior cardiovascular implantable electronic device were excluded, leaving 5746 patients with leadless VVI pacemakers and 9662 patients with transvenous VVI pacemakers. Data were analyzed from May 2018 to April 2021., Exposures: Medicare patients implanted with leadless VVI pacemakers or transvenous VVI pacemakers., Main Outcomes and Measures: The main outcomes were acute (30-day) complications and 6-month complications., Results: Of 15 408 patients, 6701 (43.5%) were female, and the mean (SD) age was 81.0 (8.7) years. Compared with patients with transvenous VVI pacemakers, patients with leadless VVI pacemakers were more likely to have end-stage kidney disease (690 [12.0%] vs 226 [2.3%]; P < .001) and a higher mean (SD) Charlson Comorbidity Index score (5.1 [3.4] vs 4.6 [3.0]; P < .001). The unadjusted acute complication rate was higher in patients with leadless VVI pacemakers relative to transvenous VVI pacemakers (484 of 5746 [8.4%] vs 707 of 9662 [7.3%]; P = .02). However, there was no significant difference in overall acute complication rates following adjustment for patient characteristics (7.7% vs 7.4%; risk difference, 0.3; 95% CI, -0.6 to 1.3; P = .49). Pericardial effusion and/or perforation within 30 days was significantly higher among patients with leadless VVI pacemakers compared with patients with transvenous VVI pacemakers in both unadjusted and adjusted models (unadjusted, 47 of 5746 [0.8%] vs 38 of 9662 [0.4%]; P < .001; adjusted, 0.8% vs 0.4%; risk difference, 0.4; 95% CI, 0.1 to 0.7; P = .004). Patients implanted with leadless VVI pacemakers had a lower rate of 6-month complications compared with patients implanted with transvenous VVI pacemakers (unadjusted hazard ratio, 0.84; 95% CI, 0.68-1.03; P = .10; adjusted hazard ratio, 0.77; 95% CI, 0.62-0.96; P = .02)., Conclusions and Relevance: In this study, despite significant differences in patient characteristics, patients in whom a leadless pacemaker was implanted were observed to have higher rates of pericardial effusion and/or perforation but lower rates of other device-related complications and requirements for device revision at 6 months. Understanding the benefits and risks associated with leadless VVI pacemakers compared with transvenous VVI pacemakers can help clinicians and patients make informed treatment decisions.

Background: Ablation of septal accessory pathways (SAPs) is associated with an increased risk of heart block. Data on outcomes of SAP ablation in adults are limited., Objectives: To describe outcomes of SAP ablation in our center., Methods: Patients with Wolff-Parkinson-White syndrome (WPW) undergoing an EP study at our center between January 2008 and August 2019 were identified from our institutional database. Location of the pathway was noted as anteroseptal (AS), midseptal (MS), or posteroseptal (PS). Outcomes of the ablation including success, complication rates, and recurrences were also recorded., Results: Thirty-three patients with SAP underwent 35 EP studies: AS (n = 13), MS (n = 5), and PS (n = 15). Thirty pathways were targeted for ablation, two of which required a 2nd procedure resulting in 32 attempts at ablation in 30 patients. In the remaining 3 patients, SAP did not have malignant features and were not targeted for ablation. Single-procedure success rate was 28/30 (93.33%): 9/10 AS, 5/5 MS, and 14/15 PS ablations. One AS pathway was successfully ablated during a 2nd procedure. Two complications were observed: 1 pericardial effusion in a patient who underwent epicardial mapping and ablation of both PS and right free wall APs. Additionally, transient 2:1 AV block occurred during an MS pathway ablation that recovered during follow-up and did not require permanent pacing procedure., Conclusion: In this single-center experience, ablation of manifest SAP was associated with high success rates and low complication rates. No instances of permanent heart block requiring pacing occurred., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Right free wall (RFW) accessory pathways (AP) typically present anatomical challenges to ablation leading to high rates of procedural failure and recovery of AP conduction., Methods: Patients with a diagnosis of Wolff-Parkinson-White Syndrome (WPW) and a manifest RFW AP undergoing an electrophysiology study (EPS) or an ablation at our center between 01/01/2008 and 08/01/2019 were identified from our databases using diagnosis codes and manual chart review., Results: Twenty-one patients with manifest RFW AP underwent EPS, all of which were targeted for ablation. Single procedure success rate was 19 / 21 (90.5%). Of the 19 successful cases, 4 (17.4%) patients were found to have recurrent right free wall pathway conduction at follow-up and each underwent a successful 2nd procedure (9.5%). Fluoroscopic and 3D electroanatomic mapping software was used in all cases to guide ablation. A 4 mm or 8 mm non-irrigated radiofrequency (RF) ablation catheter was used in 76% of cases while an 8 mm cryo-catheter was used in one case. More than one type of ablation catheter was used in four cases (16%). A steerable sheath was used in 68% of cases., Conclusions: In a tertiary center, RFW AP ablation has high acute success (>90%) but approximately 21% of patients with initially successful ablation required a 2nd procedure for recurrence of pathway conduction. A combination of a large tip ablation catheter and a steerable sheath were used in most cases.

Background: Traditionally, implantation of the subcutaneous implantable cardioverter defibrillator (S-ICD) requires incisions near the lateral chest wall, the xyphoid, and the superior sternal region (three-incision technique [3IT]). A two-incision technique (2IT) avoids the superior incision and has been shown to be a viable alternative in small studies with limited follow-up., Objectives: To report on the long-term safety and efficacy of the 2IT compared to the 3IT procedure in a large patient cohort., Methods: Patients enrolled in the S-ICD post approval study (PAS) were stratified by procedural technique (2IT vs. 3IT). Baseline demographics, comorbidities and procedural outcomes were collected. Complications and S-ICD effectiveness in treating ventricular arrhythmias through an average 3-year follow-up period were compared., Results: Of 1637 patients enrolled in the S-ICD PAS, 854 pts (52.2%) were implanted using the 2IT and 782 were implanted using the 3IT (47.8%). The 2IT became more prevalent over time, increasing from 40% to 69% of implants (Q1-Q4). Mean procedure time was shorter with 2IT (69.0 vs. 86.3 min, p < .0001). No other differences in outcomes were observed between the two groups, including rates of infection, electrode migration, inappropriate shocks and first shock efficacy for treating ventricular arrhythmias., Conclusion: In this large cohort of patients implanted with an S-ICD and followed for 3 years the 2IT was as safe and effective as the 3IT while significantly reducing procedure time., (© 2021 Wiley Periodicals LLC.)

Background: Head-to-head comparative data for the postoperative care of patients undergoing left atrial ablation procedures are lacking., Objective: We sought to investigate complication and readmission rates between patients undergoing same-day (SD) or next-day (ND) discharges for ablative procedures in the left atrium, primarily atrial fibrillation (AF)., Methods: Two electrophysiology centers simultaneously perform left atrial ablations with differing discharge strategies. We identified all patients who underwent left atrial ablation from August 2017 to August 2019 (n = 409) undergoing either SD (n = 210) or ND (n = 199) discharge protocols. We analyzed any clinical events that resulted in procedural abortion, extended hospitalization, or readmission within 72 hours., Results: The primary endpoint of complication and readmission rate was similar between SD and ND discharge (14.3% vs 12.6%, p = 0.665). Rates of complications categorized as major (2.4% vs 3.0%, p = 0. 776) and minor (11.9% vs 9.5%, p = 0.524) were also similar.Multivariable regression modeling revealed no significant correlation between discharge strategy and complication/readmission occurrence (OR 1.565 [0.754 - 3.248], p = 0.23), but a positive association of hypertension and procedure duration (OR 3.428 [1.436 - 8.184], p = 0.006) and (OR 1.01 [1 - 1.019], p = 0.046) respectively., Conclusions: Left atrial ablation complication and readmission rates were similar between SD and ND discharge practices. Hypertension and procedural duration were associated with increased complication rates irrespective of discharge strategy. These data, which represent the first side-by-side comparison of discharge strategy, suggests same-day discharge is safe and feasible for left atrial ablation procedures.

Background: Cancer treatmentinduced arrhythmia (CTIA) is a well-recognized form of cardiotoxicity associated with chemotherapy. Immune checkpoint inhibitors (ICI) have been associated with important forms of cardiotoxicity, including myocarditis. However, the incidence of CTIA associated with ICI has not been well characterized., Methods: We reviewed all patients treated with ICIs at our institution from Jan. 2010 to Oct. 2015. CTIA was defined as a new diagnosis of clinically relevant arrhythmia within 6 months after ICI initiation., Results: During the study period, 268 patients were treated with immune checkpoint inhibitors, of whom 190 received monotherapy with ipilimumab (n=114), nivolumab (n=52) or pembrolizumab (n=24) and 78 received combination therapy: ipilimumab & nivolumab (n=37), ipilimumab & pembrolizumab (n=39) and nivolumab & pembrolizumab (n=2). Four patients (1.5%) developed CTIA. Of these, 3 patients developed a new diagnosis of atrial fibrillation (AF), one of whom required cardioversion. In 2 cases of new-onset AF, significant provoking factors were present in addition to ICI therapy including thyrotoxicosis in one and metabolic disarray in another. Six patients (2.2%) with a pre-existing diagnosis of paroxysmal AF experienced episodes within 6 months of initiating ICI therapy. None of the arrhythmic events were associated with known or suspected myocarditis., Conclusions: The incidence of arrhythmic complications associated with immune checkpoint inhibitors appears to be very low (~1.5%). Patients with a pre-existing diagnosis of AF may be at-risk of recurrence during ICI treatment and should be monitored accordingly. These suggest that from an arrhythmia perspective, ICIs appear to be very safe and well-tolerated.

Moderate acute intermittent hypoxia (mAIH) elicits a progressive increase in phrenic motor output lasting hours post-mAIH, a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). mAIH-induced pLTF is initiated by activation of spinally-projecting raphe serotonergic neurons during hypoxia and subsequent serotonin release near phrenic motor neurons. Since raphe serotonergic neurons are also sensitive to pH and CO 2 , the prevailing arterial CO 2 pressure (PaCO 2 ) may modulate their activity (and serotonin release) during hypoxic episodes. Thus, we hypothesized that changes in background PaCO 2 directly influence the magnitude of mAIH-induced pLTF. mAIH-induced pLTF was evaluated in anesthetized, vagotomized, paralyzed and ventilated rats, with end-tidal CO 2 (i.e., a PaCO 2 surrogate) maintained at: (1) ≤39 mmHg (hypocapnia); (2) ∼41 mmHg (normocapnia); or (3) ≥48 mmHg (hypercapnia) throughout experimental protocols. Although baseline phrenic nerve activity tended to be lower in hypocapnia, short-term hypoxic phrenic response, i.e., burst amplitude (Δ = 5.1 ± 1.1 μV) and frequency responses (Δ = 21 ± 4 bpm), was greater than in normocapnic (Δ = 3.6 ± 0.6 μV and 8 ± 4, respectively) or hypercapnic rats (Δ = 2.0 ± 0.6 μV and -2 ± 2, respectively), followed by a progressive increase in phrenic burst amplitude (i.e., pLTF) for at least 60 min post mAIH. pLTF in the hypocapnic group (Δ = 4.9 ± 0.6 μV) was significantly greater than in normocapnic (Δ = 2.8 ± 0.7 μV) or hypercapnic rats (Δ = 1.7 ± 0.4 μV). In contrast, although hypercapnic rats also exhibited significant pLTF, it was attenuated versus hypocapnic rats. When pLTF was expressed as percent change from maximal chemoreflex stimulation, all pairwise comparisons were found to be statistically significant ( p < 0.05). We conclude that elevated PaCO 2 undermines mAIH-induced pLTF in anesthetized rats. These findings contrast with well-documented effects of PaCO 2 on ventilatory LTF in awake humans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Perim, El-Chami, Gonzalez-Rothi and Mitchell.)

We investigated whether time of day affects loop gain (LG) and the arousal threshold (AT) during non-rapid eye movement (NREM) sleep. Eleven men with obstructive sleep apnea (apnea-hypopnea index > 5 events/h) completed a constant-routine protocol that comprised 3-h sleep sessions in the evening [10 PM (1) to 1 AM], morning (6 AM to 9 AM), afternoon (2 PM to 5 PM), and subsequent evening [10 PM (2) to 1 AM]. During each sleep session LG and the AT were measured during NREM sleep with a model-based approach. Our results showed the presence of a rhythmicity in both LG ( P < 0.0001) and the AT ( P < 0.001) over a 24-h period. In addition, LG and the AT were greater in the morning compared with both evening sessions [6 AM vs. 10 PM (1) vs. 10 PM (2): LG (1 cycle/min): 0.71 ± 0.23 vs. 0.60 ± 0.22 ( P = 0.01) vs. 0.56 ± 0.10 ( P < 0.001), AT (fraction of eupneic breathing): 1.45 ± 0.47 vs. 1.28 ± 0.36 ( P = 0.02) vs. 1.20 ± 0.18 ( P = 0.001)]. No difference in LG and the AT existed between the evening sessions (LG: P = 0.27; AT: P = 0.24). LG was correlated to measures of the hypocapnic ventilatory response (i.e., a measure of chemoreflex sensitivity) ( r  = 0.72 and P = 0.045) and the critical closing pressure (i.e., a measure of airway collapsibility) ( r  = 0.77 and P = 0.02) that we previously published. We conclude that time of day, independent of hallmarks of sleep apnea, affects LG and the AT during NREM sleep. These modifications may contribute to increases in breathing instability in the morning compared with other periods throughout the day/night cycle in individuals with obstructive sleep apnea. In addition, efficaciousness of treatments for obstructive sleep apnea that target LG and the AT may be modified by a rhythmicity in these variables. NEW & NOTEWORTHY Loop gain and the arousal threshold during non-rapid eye movement (NREM) sleep are greater in the morning compared with the afternoon and evening. Loop gain measures are correlated to chemoreflex sensitivity and the critical closing pressure measured during NREM sleep in the evening, morning, and afternoon. Breathing (in)stability and efficaciousness of treatments for obstructive sleep apnea may be modulated by a circadian rhythmicity in loop gain and the arousal threshold.

Background: Experience with retrieval of a Watchman left atrial (LA) appendage (LAA) closure device (WD) is limited. An embolized or grossly malpositioned WD warrants retrieval to minimize the risk of thromboembolic complications and vascular occlusion., Objective: The purpose of this study was to report approaches for percutaneous retrieval of a WD from multicenter experience., Methods: Data on successful WD retrievals were obtained from high-volume operators. Data included clinical characteristics; structural characteristics of the LA and LAA; and procedural details of the deployment and retrieval procedure, type of retrieval (immediate: during the same procedure; delayed: during a separate procedure after the successful deployment), equipment used, complications, and postretrieval management., Results: Ten successful percutaneous and 1 surgical retrievals comprised this study. Seven patients had immediate retrieval, while 4 had delayed retrieval. The median duration before delayed retrieval was 45 days (range 1-45 days). The median LAA diameter and size of a successfully deployed WD was 16 mm (range 14-24 mm) and 21 mm (range 21-30 mm), respectively. A WD was retrieved from the LA (n = 1), LAA (n = 2), left ventricle (n = 2), and aorta (n = 6). The reason for retrieval from the LAA was inadequate deployment, resulting in a significant peri-device leak. Retrieval from the LA or LAA was successfully performed using snares (n = 2) and a Raptor grasping device (n = 1). Retrieval from the left ventricle was achieved with a snare (n = 1) and surgery (n = 1). Retrieval from the aorta required snares (n = 5) and retrieval forceps (n = 1). Five patients were successfully reimplanted with a larger size WD. The only complication during percutaneous retrieval was a pseudoaneurysm., Conclusion: Retrieval of an embolized or malpositioned WD is feasible, and familiarity with snares and grasping tools can facilitate a successful removal., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to define risk factors and develop a predictive risk score for new pacemaker implantation (PMI) after transcatheter aortic valve replacement (TAVR)., Background: TAVR has become an accepted treatment alternative for patients with severe aortic stenosis at elevated surgical risk. New PMI is a common occurrence after TAVR and is associated with poorer outcomes., Methods: All patients without prior valve procedures undergoing elective TAVR with the Edwards SAPIEN 3 at a single institution (n = 1,266) were evaluated. Multivariate analysis was performed to evaluate for predictors of PMI in this population in a derivation cohort of patients with complete data (n = 778), and this model was used to develop the Emory risk score (ERS), which was tested in a validation cohort (n = 367)., Results: Fifty-seven patients (7.3%) in the derivation cohort required PMI. In a regression model, history of syncope (odds ratio [OR]: 2.5; p = 0.026), baseline right bundle branch block (OR: 4.3; p < 0.001), QRS duration ≥138 ms (OR: 2.5; p = 0.017), and valve oversizing >15.6% (OR: 1.9; p = 0.041) remained independent predictors of PMI and were included in the ERS. The ERS was strongly associated with PMI (per point increase OR: 2.2; p < 0.001) with an area under the receiver-operating characteristic curve of 0.778 (p < 0.001), which was similar to its performance in the derivation cohort., Conclusions: A history of syncope, right bundle branch block, longer QRS duration, and higher degree of oversizing are predictive of the need for PMI after TAVR. Additionally, the ERS for PMI was developed and validated, representing a simple bedside tool to aid in risk stratification for patients for undergoing TAVR., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In transvenous implantable cardioverter-defibrillator (TV-ICD) implants, routine defibrillation testing (DFT) does not improve shock efficacy or reduce arrhythmic death but patients are exposed to the risk of complications related to DFT. The conversion rate of DFT in subcutaneous ICD (S-ICD) is high and first shock efficacy is similar to TV-ICD efficacy rates. STUDY DESIGN: The PRAETORIAN-DFT trial is an investigator-initiated, randomized, controlled, multicenter, prospective two-arm trial designed to demonstrate non-inferiority of omitting DFT in patients undergoing S-ICD implantation in which the S-ICD system components are optimally positioned. Positioning of the S-ICD will be assessed with the PRAETORIAN score. The PRAETORIAN score is developed to systematically evaluate implant position of the S-ICD system components which determine the defibrillation threshold on post-operative chest X-ray. A total of 965 patients, scheduled to undergo a de novo S-ICD implantation without contra-indications for either DFT strategy, will be randomized to either standard of care S-ICD implantation with DFT, or S-ICD implantation without DFT but with evaluation of the implant position using the PRAETORIAN score. The study is powered to claim non-inferiority of S-ICD implantation without DFT in de novo S-ICD patients in respect to the primary endpoint of first shock efficacy in spontaneous arrhythmia episodes. Patients with a high PRAETORIAN score (≥90) in the interventional arm of this study will undergo DFT according to the same DFT protocol as in the control arm. CONCLUSION: The PRAETORIAN-DFT trial is a randomized trial that aims to gain scientific evidence to safely omit a routine DFT after S-ICD implantation in patients with correct device positioning., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The following review explores the effect that intermittent or sustained hypercapnia coupled to intermittent hypoxia has on respiratory plasticity. The review explores published work which suggests that intermittent hypercapnia leads to long-term depression of respiration when administered in isolation and prevents the initiation of long-term facilitation when administered in combination with intermittent hypoxia. The review also explores the impact that sustained hypercapnia alone and in combination with intermittent hypoxia has on the magnitude of long-term facilitation. After exploring the outcomes linked to intermittent hypoxia/hypercapnia and intermittent hypoxia/sustained hypercapnia the translational relevance of the outcomes as it relates to breathing stability during sleep is addressed. The likelihood that naturally induced cycles of intermittent hypoxia, coupled to oscillations in carbon dioxide that range between hypocapnia and hypercapnia, do not initiate long-term facilitation is addressed. Moreover, the conditions under which intermittent hypoxia/sustained hypercapnia could serve to improve breathing stability and mitigate co-morbidities associated with sleep apnea are considered., (Published by Elsevier B.V.)