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Background: Irrigated radiofrequency (RF) ablation catheters may produce different lesion sizes dependent upon the electrode orientation to the tissue. This study examined the effect of irrigated electrode orientation on the lesion size and explores a potential mechanism for this effect. Methods and Results: Lesions were created in isolated porcine myocardium using an open irrigation, closed irrigation, and nonirrigated RF catheter (all 3.5-4 mm tips). Lesions were created with the electrodes with all permutations of electrode orientation (vertical or horizontal), contact pressure (6 or 20 g), and saline superfusate flow (0.2 or 0.4 m/sec) over tissue interface. The effect of electrode irrigation without RF delivery on tissue temperature was assessed with intramyocardial temperature probes and infrared thermal imaging. For both irrigated catheters, the horizontal orientation produced 25-30% smaller lesion volumes than the vertical orientation despite equal or greater power deliveries. The horizontal orientation produced larger lesion volumes for the nonirrigated catheter. Higher superfusate flow rates were associated with decreased lesion volumes for the irrigated catheters but greater lesion volumes for the nonirrigated catheter. Catheter irrigation alone without RF delivery reduced intramyocardial temperatures up to 4.9°C and the horizontal orientation produced a 2-fold greater area of tissue cooling than the vertical orientation. Conclusion: Horizontal electrode orientations reduce lesion volumes for irrigated RF catheters. This effect may be in part due to greater areas of active tissue cooling in the horizontal orientation. [ABSTRACT FROM AUTHOR]

The development of multitarget opioid drugs has emerged as an attractive approach for innovative pain management with reduced side effects. In the present study, a novel hybrid peptide BNT12 containing the opioid and neurotensin (NT)-like fragments was synthesized and pharmacologically characterized. In acute radiant heat paw withdrawal test, intracerebroventricular (i.c.v.) administration of BNT12 produced potent antinociception in mice. The central antinociceptive activity of BNT12 was mainly mediated by μ-, δ-opioid receptor, neurotensin receptor type 1 (NTSR1) and 2 (NTSR2), supporting a multifunctional agonism of BNT12 in the functional assays. BNT12 also exhibited significant antinociceptive effects in spared nerve injury (SNI)-neuropathic pain, complete Freund's adjuvant (CFA)-induced inflammatory pain, acetic acid-induced visceral and formalin-induced pain after i.c.v. administration. Furthermore, BNT12 exhibited substantial reduction of acute antinociceptive tolerance, shifted the dose-response curve to the right by only 1.3-fold. It is noteworthy that BNT12 showed insignificant chronic antinociceptive tolerance at the supraspinal level. In addition, BNT12 exhibited reduced or no opioid-like side effects on conditioned place preference (CPP) response, naloxone-precipitated withdrawal response, acute hyperlocomotion, motor coordination, gastrointestinal transit, and cardiovascular responses. The present investigation demonstrated that the novel hybrid peptide BNT12 might serve as a promising analgesic candidate with limited opioid-like side effects., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Artificial intelligence (AI) ECG arrhythmia mapping provides arrhythmia source localization using 12-lead ECG data; whether this information impacts procedural efficiency is unknown. We performed a retrospective, case-control study to evaluate the hypothesis that AI ECG mapping may reduce time to ablation, procedural duration, and fluoroscopy., Materials and Methods: Cases in which system output was used were retrospectively enrolled according to IRB-approved protocols at each site. Matched control cases were enrolled in reverse chronological order beginning on the last day for which the technology was unavailable. Controls were matched based upon physician, institution, arrhythmia, and a predetermined complexity rating. Procedural metrics, fluoroscopy data, and clinical outcomes were assessed from time-stamped medical records., Results: The study group consisted of 28 patients (age 65 ± 11 years, 46% female, left atrial dimension 4.1 ± 0.9 cm, LVEF 50 ± 18%) and was similar to 28 controls. The most common arrhythmia types were atrial fibrillation (n = 10), premature ventricular complexes (n = 8), and ventricular tachycardia (n = 6). Use of the system was associated with a 19.0% reduction in time to ablation (133 ± 48 vs. 165 ± 49 min, p = 0.02), a 22.6% reduction in procedure duration (233 ± 51 vs. 301 ± 83 min, p < 0.001), and a 43.7% reduction in fluoroscopy (18.7 ± 13.3 vs. 33.2 ± 18.0 min, p < 0.001) versus controls. At 6 months follow-up, arrhythmia-free survival was 73.5% in the study group and 63.3% in the control group (p = 0.56)., Conclusion: Use of forward-solution AI ECG mapping is associated with reductions in time to first ablation, procedure duration, and fluoroscopy without an adverse impact on procedure outcomes or complications., (© 2024 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background and Purpose: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent μ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined., Experimental Approach: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test., Key Results: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct μ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit., Conclusions and Implications: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects., (© 2023 British Pharmacological Society.)

Background: Frailty is associated with significant morbidity and mortality and may have clinical implications in an advanced age population with atrial fibrillation undergoing left atrial appendage occlusion (LAAO). We sought to develop a novel frailty scale to predict worse outcomes in patients undergoing LAAO., Methods: Patients in the NCDR LAAO Registry between 2016 and 2021 receiving percutaneous LAAO devices were categorized as non-frail (0 points), pre-frail (1-3 points), or frail (4-5 points) based on a 5-point scale representing multiple domains of frailty: hemoglobin <13.0 g/dL in male, <12.0 g/dL in female; creatinine ≥1.2 mg/dL; albumin <3.5 g/dL; body mass index <20 kg/m2; and increased risk of falls., Results: Of 57,728 patients, 44,360 (76.8%) were pre-frail and 7693 (13.3%) were frail. Compared to non-frail, pre-frail and frail patients were older, had a higher burden of co-morbidities, and more disability based on the Modified Rankin Scale. Compared to non-frail patients after adjustment, frail patients were at higher risk of in-hospital major complication (OR 1.29, 95% 1.02-1.62, p = 0.01), any complication (OR 1.29, 95% CI 1.09-1.52, p = 0.0005), and death (OR 5.79, 95% CI 1.75-19.17, p = 0.001), while no difference was observed in pre-frail patients. At 45-day follow-up, there was no difference in the risk of complications in frail patients as compared to non-frail, although mortality was significantly higher (OR 3.01, 95% CI 1.97-4.85, p < 0.0001)., Conclusion: A simple and practical frailty scale accurately predicts adverse events in patients undergoing LAAO. The 13% of patients considered frail were at significantly higher risk of in-hospital adverse events and 45-day mortality., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Pulsed field ablation (PFA) induces cell death through electroporation using ultrarapid electrical pulses. We sought to compare the procedural efficiency characteristics, safety, and efficacy of ablation of atrial fibrillation (AF) using PFA compared with thermal energy ablation., Methods: We performed an extensive literature search and systematic review of studies that compared ablation of AF with PFA versus thermal energy sources. Risk ratio (RR) 95% confidence intervals (CI) were measured for dichotomous variables and mean difference (MD) 95% CI were measured for continuous variables, where RR < 1 and MD < 0 favor the PFA group., Results: We included 6 comparative studies for a total of 1012 patients who underwent ablation of AF: 43.6% with PFA (n = 441) and 56.4% (n = 571) with thermal energy sources. There were significantly shorter procedures times with PFA despite a protocolized 20-min dwell time (MD - 21.95, 95% CI - 33.77, - 10.14, p = 0.0003), but with significantly longer fluroscopy time (MD 5.71, 95% CI 1.13, 10.30, p = 0.01). There were no statistically significant differences in periprocedural complications (RR 1.20, 95% CI 0.59-2.44) or recurrence of atrial tachyarrhythmias (RR 0.64, 95% CI 0.31, 1.34) between the PFA and thermal ablation cohorts., Conclusions: Based on the results of this meta-analysis, PFA was associated with shorter procedural times and longer fluoroscopy times, but no difference in periprocedural complications or rates of recurrent AF when compared to ablation with thermal energy sources. However, larger randomized control trials are needed., (© 2023. The Author(s).)

Previously, we have investigated three C-terminal esterified endomorphin-2 (EM-2) analogs EM-2-Me, EM-2-Et and EM-2-Bu with methyl, ethyl and tert-butyl ester modifications, respectively. These analogs produced significant antinociception in acute pain at the spinal and supraspinal levels, with reduced tolerance and gastrointestinal side effects. The present study was undertaken to determine the analgesic effects and opioid mechanisms of these three analogs in the formalin pain test. Our results demonstrated that intracerebroventricular (i.c.v.) administration of 0.67-20 nmol EM-2 analogs EM-2-Me, EM-2-Et and EM-2-Bu produced dose-dependent antinociceptive effects in both phase Ⅰ and phase Ⅱ of formalin pain. EM-2-Me and EM-2-Bu displayed more potent antinociception than morphine. Especially, EM-2-Bu exhibited the highest antinociception in phase Ⅱ of formalin pain, with the ED 50 value being 2.1 nmol. Naloxone (80 nmol, i.c.v.) completely antagonized the antinociceptive effects of EM-2-Me, EM-2-Et and EM-2-Bu (20 nmol, i.c.v.) in both phase I and phase Ⅱ of formalin pain, suggesting a central opioid mechanism. Nevertheless, the antinociception induced by EM-2-Me might be involved in the release of dynorphin A, which subsequently acted on κ- opioid receptor. EM-2-Bu produced the antinociception probably by the direct activation of both μ- and δ-opioid receptors. EM-2-Me, EM-2-Et and EM-2-Bu also produced significant analgesic effects after peripheral administration, and the central opioid receptors were involved. Furthermore, EM-2-Bu had no influence on the locomotor activity after i.c.v. injection. The present investigation demonstrated that C-terminal esterified modifications of EM-2 will be beneficial for developing novel therapeutics in formalin pain., Competing Interests: Declarations of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Catheter ablation improves outcomes in symptomatic atrial fibrillation (AF) patients. However, its safety and efficacy in the very elderly (≥80 years old) is not well described., Hypothesis: Ablation of AF in the very elderly is safe and effective., Methods: We performed a retrospective study of all patients who underwent catheter ablation enrolled in the University of California, San Diego AF Ablation Registry. The primary outcome was freedom from atrial arrhythmias on or off antiarrhythmic drugs (AADs)., Results: Of 847 patients, 42 (5.0%) were 80 years of age or greater with a median age of 81.5 (80-82.3) and 805 (95.0%) were less than 80 years of age with a median age of 64.4 (57.6-70.2). Among those who were ≥80 years old, 29 were undergoing de novo ablation (69.0%), whereas in the younger cohort, 518 (64.5%) were undergoing de novo ablation (p = .548). There were no statistically significant differences in fluoroscopy (p = .406) or total procedure times (p = .076), AAD use (p = .611), or procedural complications (p = .500) between groups. After multivariable adjustment, there were no statistically significant differences in recurrence of any atrial arrhythmias on or off AAD (adjusted hazard ratio [AHR]: 0.75; 95% confidence interval [CI]: 0.45-1.23; p = .252), all-cause hospitalizations (AHR: 0.86; 95% CI: 0.46-1.60; p = .626), or all-cause mortality (AHR: 4.48; 95% CI: 0.59-34.07; p = .147) between the very elderly and the younger cohort., Conclusion: In this registry analysis, catheter ablation of AF appears similarly effective and safe in patients 80 years or older when compared to a younger cohort., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Pulsed field ablation (PFA) has emerged as a novel energy source for the ablation of atrial fibrillation (AF) using ultrarapid electrical pulses to induce cell death via electroporation., Objective: The purpose of this study was to compare the safety and acute efficacy of ablation for AF with PFA vs thermal energy sources., Methods: We performed an extensive literature search and systematic review of studies that evaluated the safety and efficacy of ablation for AF with PFA and compared them to landmark clinical trials for ablation of AF with thermal energy sources. Freeman-Tukey double arcsine transformation was used to establish variance of raw proportions followed by the inverse with the random-effects model to combine the transformed proportions and generate the pooled prevalence and 95% confidence interval (CI)., Results: We included 24 studies for a total of 5203 patients who underwent AF ablation. Among these patients, 54.6% (n = 2842) underwent PFA and 45.4% (n = 2361) underwent thermal ablation. There were significantly fewer periprocedural complications in the PFA group (2.05%; 95% CI 0.94-3.46) compared to the thermal ablation group (7.75%; 95% CI 5.40-10.47) ( P = .001). When comparing AF recurrence up to 1 year, there was a statistically insignificant trend toward a lower prevalence of recurrence in the PFA group (14.24%; 95% CI 6.97-23.35) compared to the thermal ablation group (25.98%; 95% CI 15.75-37.68) ( P = .132)., Conclusion: Based on the results of this meta-analysis, PFA was associated with lower rates of periprocedural complications and similar rates of acute procedural success and recurrent AF with up to 1 year of follow-up compared to ablation with thermal energy sources., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Background: High-dose isoproterenol infusion is a useful provocative maneuver to elicit triggers of atrial fibrillation (AF) during ablation. We evaluated whether the use of isoproterenol infusion to elicit triggers of AF after ablation is associated with differential outcomes., Methods: We performed a retrospective study of all patients who underwent de novo radiofrequency catheter ablation of AF enrolled in the University of California, San Diego AF Ablation Registry. The primary outcome was freedom from atrial arrhythmias on or off antiarrhythmic drugs (AAD)., Results: Of 314 patients undergoing AF ablation, 235 (74.8%) received isoproterenol while 79 (25.2%) did not. Among those who received isoproterenol, 11 (4.7%) had additional triggers identified. There were no statistically significant differences in procedure time (p = 0.432), antiarrhythmic drug use (p = 0.289), procedural complications (p = 0.279), recurrences of atrial arrhythmias on or off AAD [adjusted hazard ratio (AHR) 0.92 (95% CI 0.58-1.46); p = 0.714], all-cause hospitalizations [AHR 1.00 (95% CI 0.60-1.67); p = 0.986], or all-cause mortality [AHR 0.14 (95% CI 0.01-3.52); p = 0.229] between groups., Conclusions: In this registry analysis, use of isoproterenol is safe but was not associated with a reduction in recurrence of atrial arrhythmias., (© 2022. The Author(s).)

Aims: To determine outcomes in atrial fibrillation (AF) patients undergoing percutaneous left atrial appendage occlusion (LAAO) with concomitant heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF)., Methods and Results: Data were extracted from National Inpatient Sample for calendar years 2015-2019. LAAO device implantations were identified on the basis of ICD-10-CM code of 02L73DK. The outcomes assessed in our study included complications, in-patient mortality, and resource utilization. A total of 62 980 LAAO device implantations were studied. HFpEF (14.4%, n = 9040) and HFrEF (11.2%, n = 7100) were associated with a higher prevalence of major complications and in-patient mortality in crude analysis. In the multivariate model adjusted for potential confounders, HFpEF and HFrEF were not associated with major complications [adjusted odds ratio (aOR) 1.04, 95% confidence interval (CI) 0.93-1.16 and aOR 1.07, 95% CI 0.95-1.21] or in-patient mortality (aOR 1.48, 95% CI 0.85-2.55 and aOR 1.26, 95% CI 0.67-2.38). HFpEF and HFrEF were associated with prolonged length of stay (LOS) > 1 day (aOR 1.41, 95% CI 1.31-1.53 and aOR 1.66, 95% CI 1.53-1.80) and increased hospitalization costs > median cost 24 752$ (aOR 1.26, 95% CI 1.19-1.34 and aOR 1.21, 95% CI 1.13-1.29)., Conclusion: The prevalence of HF in AF patients undergoing percutaneous LAAO was approximately 26%. HF was not independently associated with major complications and in-patient mortality but was associated with prolonged LOS and higher hospitalization costs., Competing Interests: Conflict of interest: J.C.H. reports receiving honoraria from Medtronic, Abbott, Boston Scientific, Biotronik, Janssen Pharmaceuticals, Bristol-Myers Squibb, Pfizer, Sanofi, Hillrom, Baylis Medical, Acutus Medical, iRhythm, Zoll Medical, and Biosense-Webster, research grants from Biotronik and Biosense-Webster, and has equity interest in Vektor Medical. The remaining authors have no conflicts to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The mechanisms for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) catheter ablation are unclear. Non-PV organized atrial arrhythmias (PAC, AT, macro-reentrant AFL) are possible contributors; however the prevalence and effect of their ablation on recurrent AF are unknown. We hypothesize that the identification and ablation of non-PV organized atrial arrhythmias were associated with less AF recurrence., Methods: Patients who underwent repeat ablation for recurrent AF after prior PVI were retrospectively enrolled. The prevalence and characteristics of PV reconnections and non-PV organized atrial arrhythmias were identified. The outcomes of time to clinical AF recurrence, heart failure (HF) hospitalization, and mortality were analyzed in patients using multivariable adjusted Cox regression., Results: In 74 patients with recurrent AF (age 66 ± 9 years, left atrial volume index 38 ± 10 ml/m 2 , 59% persistent AF), PV reconnections were found in 46 patients (61%), macro-reentrant atrial flutter in 27 patients (36%), and focal tachycardia in 12 patients (16%). Mapping and ablation of non-PV organized atrial arrhythmias were associated with a reduced recurrence of late clinical AF (adjusted HR 0.26, CI 0.08-0.85, p = 0.03) and the composite outcome of recurrence of late AF, HF hospitalization, and mortality (adjusted HR 0.38, CI 0.17-0.85, p = 0.02), with median follow-up of 1.6 (IQR 0.7-6.3) years. The presence of PV reconnections or empiric linear ablation was not associated with reduction in clinical AF or composite endpoints., Conclusion: The ablation of non-PV organized atrial arrhythmias resulted in a reduction of late clinical AF recurrence and composite outcome. In this challenging population, alternate mechanisms beyond PV reconnections need to be considered. Prospective studies are needed., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: The accuracy of noninvasive arrhythmia source localization using a forward-solution computational mapping system has not yet been evaluated in blinded, multicenter analysis. This study tested the hypothesis that a computational mapping system incorporating a comprehensive arrhythmia simulation library would provide accurate localization of the site-of-origin for atrial and ventricular arrhythmias and pacing using 12-lead ECG data when compared with the gold standard of invasive electrophysiology study and ablation., Methods: The VMAP study (Vectorcardiographic Mapping of Arrhythmogenic Probability) was a blinded, multicenter evaluation with final data analysis performed by an independent core laboratory. Eligible episodes included atrial and ventricular: tachycardia, fibrillation, pacing, premature atrial and ventricular complexes, and orthodromic atrioventricular reentrant tachycardia. Mapping system results were compared with the gold standard site of successful ablation or pacing during electrophysiology study and ablation. Mapping time was assessed from time-stamped logs. Prespecified performance goals were used for statistical comparisons., Results: A total of 255 episodes from 225 patients were enrolled from 4 centers. Regional accuracy for ventricular tachycardia and premature ventricular complexes in patients without significant structural heart disease (n=75, primary end point) was 98.7% (95% CI, 96.0%-100%; P <0.001 to reject predefined H 0 <0.80). Regional accuracy for all episodes (secondary end point 1) was 96.9% (95% CI, 94.7%-99.0%; P <0.001 to reject predefined H 0 <0.75). Accuracy for the exact or neighboring segment for all episodes (secondary end point 2) was 97.3% (95% CI, 95.2%-99.3%; P <0.001 to reject predefined H 0 <0.70). Median spatial accuracy was 15 mm (n=255, interquartile range, 7-25 mm). The mapping process was completed in a median of 0.8 minutes (interquartile range, 0.4-1.4 minutes)., Conclusions: Computational ECG mapping using a forward-solution approach exceeded prespecified accuracy goals for arrhythmia and pacing localization. Spatial accuracy analysis demonstrated clinically actionable results. This rapid, noninvasive mapping technology may facilitate catheter-based and noninvasive targeted arrhythmia therapies., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04559061.

Purpose: Early recurrence of atrial tachyarrhythmia (ER) is predictive of late recurrence of atrial tachyarrhythmia (LR) after first-time atrial fibrillation (AF) ablation, but the association in patients undergoing repeat AF ablation is unknown. We aim to determine the incidence and prognostic significance of ER after repeat ablation., Methods: A total of 259 consecutive patients (mean age 64 years, 75.3% male) undergoing repeat AF ablation with complete follow-up data were included at a single institution from 2010 to 2015. ER and LR were defined as atrial tachyarrhythmia (AF, atrial flutter or atrial tachycardia) > 30 s within the 3-month blanking period (BP) and after the 3-month BP, respectively., Results: ER occurred in 79/259 (30.5%), and LR occurred in 138/259 (53%) at a median follow-up of 1221 (IQR: 523-1712) days. Four-year freedom from LR was 22% and 56% in patients with and without ER, respectively (p < 0.001). After multivariate adjustment, ER was strongly associated with LR, cardioversion post BP, and repeat ablation, but not associated with hospitalization. Compared to those with no ER, there was a higher risk of LR when ER occurred within the first month of the BP [month 1: hazard ratio (HR) 2.32, confidence interval (CI) 1.57-3.74, p < 0.001; month 2: HR 2.01, CI 1.13-3.83, p = 0.02; month 3: HR 1.46, CI 0.5-3.36, p = 0.37], however the prediction of LR based on timing within the BP was poor (area under curve 0.64)., Conclusion: Following repeat AF ablation, ER is strongly associated with LR, cardioversion post BP, and repeat ablation., (© 2021. The Author(s).)

Background: This case report demonstrates acute myeloid leukemia causing acute thrombosis of coronary arteries with anterolateral ST elevation myocardial infarction and ventricular tachycardia in an otherwise healthy woman. Few case reports have been documented on patients with concomitant conditions of acute myeloid leukemia and acute myocardial infarction, and it is important to note that prognosis for patients with both is worse than that of either condition. While both conditions together are rare, other non-atherosclerotic causes of acute coronary syndromes are likewise important considerations in the context of myocardial ischemia., Case Presentation: A 59-year-old Caucasian woman with no notable past medical history presented to her primary care provider with 2 weeks of severe fatigue, anorexia, and malaise, associated with chills, night sweats, and myalgias. Peripheral blood smear identified 92% blasts consistent with acute myeloid leukemia and computed tomography identified a right segmental pulmonary embolism and thrombotic infarcts in the spleen, bilateral kidneys, right lung, and liver. Laboratory testing also demonstrated disseminated intravascular coagulopathy. She was admitted to the intensive care unit for treatment and subsequently developed ventricular tachycardia, anterolateral ST segment elevation, acute dysarthria, and nonreactive pupils. Pulseless electrical activity developed with unsuccessful resuscitative measures. The patient died secondary to presumed cerebrovascular and coronary thromboses causing stroke and anterolateral infarct complicated by ventricular tachycardia and pulseless electrical activity., Conclusion: This case is notable as a case of acute myeloid leukemia causing acute thrombosis of coronary arteries with anterolateral ST elevation myocardial infarction, ventricular tachycardia, and pulseless electrical activity. Prognosis of concomitant acute myeloid leukemia and acute myocardial infarction is poor. Management is challenging due to thrombocytopenia, platelet dysfunction, and systemic coagulopathy, and administration of thrombolytic agents can be fatal. This is an extreme presentation of a case of acute myocardial infarction with disseminated intravascular coagulopathy causing acute coronary thrombosis and sudden death with dramatic electrocardiogram and telemetry findings recorded with rapid progression from normal sinus rhythm to acute myocardial infarction to terminal rhythm., (© 2022. The Author(s).)

Purpose: Mitral annular flutter (MAF) is a common arrhythmia after atrial fibrillation ablation. We sought to compare the efficacy and safety of catheter ablation utilizing either a left atrial anterior wall (LAAW) line or a lateral mitral isthmus (LMI) line., Methods: We performed a systematic review for all studies that compared LAAW versus LMI lines. Risk ratio (RR) and mean difference (MD) 95% confidence intervals were measured for dichotomous and continuous variables, respectively., Results: Four studies with a total of 594 patients were included, one of which was a randomized control trial. In the LMI ablation group, 40% of patients required CS ablation. There were no significant differences in bidirectional block (RR 1.26; 95% CI, 0.94-1.69) or ablation time (MD -1.5; 95% CI, -6.11-3.11), but LAAW ablation was associated with longer ablation line length (MD 11.42; 95% CI, 10.69-12.14) and longer LAA activation delay (MD 67.68; 95% CI, 33.47-101.89.14) when compared to LMI. There was no significant difference in pericardial effusions (RR 0.36; 95% CI, 0.39-20.75) between groups and more patients were maintained sinus rhythm (RR 1.19; 95% CI, 1.03-1.37, p = 0.02) who underwent LAAW compared to LMI., Conclusion: Ablation of mitral annular flutter with a LAAW line compared to a LMI line showed no difference in rates of acute bidirectional block, ablation time, or pericardial effusion. However, LAAW ablation required a longer ablation line length, resulted in greater LAA activation delayed and was associated with more sinus rhythm maintenance, with the added advantage of avoiding ablation in the CS., (© 2021. The Author(s).)

Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent μ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.

Importance: Left atrial appendage occlusion (LAAO) has emerged as an alternative to anticoagulation for select patients with atrial fibrillation; however, women have been underrepresented in clinical trials of LAAO, and sex-specific subanalyses are limited., Objective: To evaluate the sex differences in the baseline characteristics of patients undergoing LAAO implant and in the in-hospital outcomes after LAAO implant., Design, Setting, and Participants: A total of 49 357 patients in the National Cardiovascular Data Registry LAAO Registry undergoing LAAO with the Watchman device between January 1, 2016, and June 30, 2019, were included in this study., Exposure: Female or male sex., Main Outcomes and Measures: The primary outcomes were aborted or canceled procedure, major adverse event, any adverse event, prolonged hospital stay longer than 1 day, and death. Unadjusted and multivariable adjusted logistic regression analyses were performed to assess sex differences in in-hospital adverse events., Results: In this cohort study of 49 357 patients (mean [SD] age, 76.1 [8.0] years), 20 388 women (41.3%) and 28 969 (58.7%) men underwent LAAO. Compared with men, women were older and had a higher prevalence of paroxysmal atrial fibrillation, prior stroke, and uncontrolled hypertension but a lower prevalence of congestive heart failure, diabetes, and coronary artery disease. After multivariable adjustment, there were no differences in aborted or canceled procedures between women and men (613 [3.0%] vs 851 [2.9%]; odds ratio [OR] 1.01, 95% CI, 0.90-1.13). Women were more likely than men to experience any adverse event (1284 [6.3%] vs 1144 [3.9%]; P < .001; OR, 1.63; 95% CI, 1.49-1.77; P < .001) or major adverse event (827 [4.1%] vs 567 [2.0%]; P < .001; OR, 2.06; 95% CI, 1.82-2.34; P < .001) owing to pericardial effusion requiring drainage (241 [1.2%] vs 144 [0.5%]) or major bleeding (349 [1.7%] vs 244 [0.8%]). Women were also more likely than men to experience a hospital stay longer than 1 day (3272 [16.0%] vs 3355 [11.6%]; P < .001; adjusted OR, 1.46; 95% CI, 1.38-1.54; P < .001) or death (adjusted OR, 2.01; 95% CI, 1.31-3.09; P = .001), although death was rare and absolute differences were minimal (58 [0.3%] vs 37 [0.1%]; P < .001)., Conclusions and Relevance: This study suggests that, compared with men, women have a significantly higher risk of in-hospital adverse events after LAAO. Further research aimed at risk reduction, particularly strategies to reduce the risk of pericardial effusion and major bleeding, in women undergoing LAAO is warranted.

Background: Stereotactic ablative radiotherapy (SAbR) is an emerging therapy for refractory ventricular tachycardia (VT). However, the current workflow is complicated, and the precision and safety in patients with significant cardiorespiratory motion and VT targets near the stomach may be suboptimal., Objective: We hypothesized that automated 12-lead electrocardiogram (ECG) mapping and respiratory-gated therapy may improve the ease and precision of SAbR planning and facilitate safe radiation delivery in patients with refractory VT., Methods: Consecutive patients with refractory VT were studied at 2 hospitals. VT exit sites were localized using a 3-D computational ECG algorithm noninvasively and compared to available prior invasive mapping. Radiotherapy (25 Gy) was delivered at end-expiration when cardiac respiratory motion was ≥0.6 cm or targets were ≤2 cm from the stomach., Results: In 6 patients (ejection fraction 29% ± 13%), 4.2 ± 2.3 VT morphologies per patient were mapped. Overall, 7 out of 7 computational ECG mappings (100%) colocalized to the identical cardiac segment when prior invasive electrophysiology study was available. Respiratory gating was associated with smaller planning target volumes compared to nongated volumes (71 ± 7 vs 153 ± 35 cc, P < .01). In 2 patients with inferior wall VT targets close to the stomach (6 mm proximity) or significant respiratory motion (22 mm excursion), no GI complications were observed at 9- and 12-month follow-up. Implantable cardioverter-defibrillator shocks decreased from 23 ± 12 shocks/patient to 0.67 ± 1.0 ( P < .001) post-SAbR at 6.0 ± 4.9 months follow-up., Conclusions: A workflow including computational ECG mapping and protocol-guided respiratory gating is feasible, is safe, and may improve the ease of SAbR planning. Studies to validate this workflow in larger populations are required.

Background: Left atrial appendage occlusion has shown promise in mitigating the risk of stroke in selected patients with atrial fibrillation., Objective: The purpose of this study was to determine the real-world prevalence and in-hospital outcomes in left atrial appendage occlusion (Watchman) recipients complicated by pericardial effusion requiring percutaneous drainage or open cardiac surgery-based intervention., Methods: Data were derived from the National Inpatient Sample database from January 2015 to December 2017. The primary outcomes assessed were the prevalence of pericardial effusion requiring intervention and in-hospital outcomes including mortality, other major complications, hospital stay > 1 day, and hospitalization costs. Predictors of pericardial effusion requiring intervention were also analyzed., Results: Pericardial effusion requiring intervention occurred in 220 total patients (1.24%). After multivariable adjustment, pericardial effusion requiring intervention was associated with in-hospital mortality (adjusted odds ratio [aOR] 511.6; 95% confidence interval [CI] 122-2145.3), other Watchman-related major complications (aOR 1.35; 95% CI 0.83-2.19), length of stay > 1 day (aOR 17.64; 95% CI 12.56-24.77), and hospitalization cost above the median of $24,327 (aOR 3.58; 95% CI 2.61-4.91). Independent patient predictors of pericardial effusion requiring intervention from the procedure included advanced age (aOR 1.029 per 1-year increase; 95% CI 1.009-1.05 per 1-year increase), higher CHA 2 DS 2 -VASc score (aOR 1.221 per 1-point increase; 95% CI 1.083-1.377 per 1-point increase), and obesity (aOR 2.033; 95% CI 1.464-2.823)., Conclusion: In a large, contemporary real-world cohort of Watchman recipients in US practice, the prevalence of pericardial effusion requiring intervention was 1.24%. Pericardial effusion requiring intervention was associated with several adverse events including increased in-hospital mortality, other major complications, prolonged hospital stay, and hospitalization costs., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Left atrial appendage occlusion (LAAO) has emerged as an alternative strategy to oral anticoagulation for mitigating ischemic stroke risk in selected patients with atrial fibrillation (AF), but safety data in patients with significant kidney disease are limited., Objective: To determine the association of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with procedural complications and in-hospital outcomes after LAAO in AF patients., Methods: Data were extracted from National Inpatient Sample for calendar years 2015-2018. Watchman implantations were identified on the basis of International Classification of Diseases, 9th and 10th Revision, Clinical Modification codes of 37.90 and 02L73DK. The outcomes assessed in our study included complications, inpatient mortality, and resource utilization with LAAO., Results: A total of 36,065 Watchman recipients were included in the final analysis. CKD (9.8%, n = 3545) and ESRD (3%, n = 1155) were associated with a higher prevalence of major complications and mortality in crude analysis compared to no CKD. After multivariate adjustment for potential confounders, CKD was associated with length of stay (LOS) >1 day (adjusted odds ratio [aOR] 1.355; 95% confidence interval [CI] 1.234-1.488), median cost >$24,663 (aOR 1.267; 95% CI 1.176-1.365), and acute kidney injury (aOR 4.134; 95% CI 3.536-4.833), while ESRD was associated with in-patient mortality (aOR 7.156; 95% CI 3.294-15.544)., Conclusion: The prevalence of CKD and ESRD was approximately 13% in AF patients undergoing Watchman LAAO implantations. CKD was independently associated with prolonged LOS, higher hospitalization costs, and acute kidney injury, while ESRD was independently associated with in-patient mortality., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

Purpose: To evaluate if specific AADs prescribed in the blanking period (BP) after catheter ablation of atrial fibrillation (AF) may be associated with reduced risk of early recurrence (ER) and/or late recurrence (LR) of atrial arrhythmias., Methods: A total of 478 patients undergoing first-time ablation at a single institution were included. Outcomes were: ER, LR, discontinuation of AAD less than 90 days post-ablation, and second ablation. ER was defined as AF, atrial flutter (AFL), or atrial tachycardia (AT) > 30 seconds within BP. LR was defined as AF/AFL/AT > 30 seconds after BP., Results: Of 478 patients, 14.9% were prescribed no AAD, 26.4% propafenone/flecainide, 34.5% sotalol/dofetilide, 10.7% dronedarone, and 13.6% amiodarone. Patients prescribed amiodarone were more likely to have persistent AF, hypertension, diabetes, and other comorbidities. In unadjusted analyses, there were no differences between groups in relation to ER (log rank P = 0.171), discontinuation of AAD before ninety days post-ablation (log rank P = 0.235), or freedom from second ablation (log rank P = 0.147). After multivariable adjustment, patients prescribed amiodarone or dronedarone were more likely to experience LR than those prescribed no AAD [Adjusted Hazard Ratio (AHR) 1.83, 95% CI 1.10-3.04, p = 0.02; AHR 1.79, 95% CI 1.05-3.05, p = 0.03, respectively]., Conclusion: Following first-time catheter ablation, there were no differences between specific AAD prescription and risk of ER, while those prescribed amiodarone or dronedarone in the BP were more likely to experience LR than those prescribed no AAD, which may represent an association due to confounding by indication., Competing Interests: Dr. Hsu reports receiving honoraria from Medtronic, Abbott, Boston Scientific, Biotronik, Janssen Pharmaceuticals, Bristol-Myers Squibb, Alathera Pharmaceuticals, Zoll Medical, and Biosense-Webster, equity in Acutus Medical and Vektor Medical, and research grants from Biotronik and Biosense-Webster. Dr. Ho receives grant support from the American Heart Association (AHA 19CDA34760021), National Institutes of Health (NIH 1KL2TR001444), and reports equity in Vektor Medical Inc unrelated to this work. Dr. Krummen receives grant support from the UCSD Galvanizing Engineering in Medicine Foundation. He also reports equity in Vektor Medical unrelated to this work. Dr. Feld reports equity in Acutus Medical and Vektor Medical, and Perminova, has received honoraria from Alathera Pharmaceuticals, Vektor Medical and Acutus Medical, and as EP Fellowship Training Program Director indirectly receives fellowship stipend support from Abbott, Boston Scientific, Biotronik, and Biosense-Webster. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

[Figure: see text].

[Figure: see text].

Catheter ablation improves clinical outcomes in atrial fibrillation (AF) patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, the role of catheter ablation in HF with a preserved ejection fraction (HFpEF) is less clear. We performed a literature search and systematic review of studies that compared AF recurrence at one year after catheter ablation of AF in patients with HFpEF versus those with HFrEF. Risk ratio (RR; where a RR <1.0 favors the HFpEF group) and mean difference (MD; where MD <0 favors the HFpEF group) 95% confidence intervals (CI) were measured for dichotomous and continuous variables, respectively. Six studies with a total of 1,505 patients were included, of which 764 (51%) had HFpEF and 741 (49%) had HFrEF. Patients with HFpEF experienced similar recurrence of AF 1 year after ablation on or off antiarrhythmic drugs compared with those with HFrEF (RR 1.01; 95% CI 0.76, 1.35). Fluoroscopy time was significantly shorter in the HFpEF group (MD -5.42; 95% CI -8.51, -2.34), but there was no significant difference in procedure time (MD 1.74; 95% CI -11.89, 15.37) or periprocedural adverse events between groups (RR 0.84; 95% CI 0.54,1.32). There was no significant difference in hospitalizations between groups (MD 1.18; 95% CI 0.90, 1.55), but HFpEF patients experienced significantly less mortality (MD 0.41; 95% CI 0.18, 0.94). In conclusion, based on the results of this meta-analysis, catheter ablation of AF in patients with HFpEF appears as safe and efficacious in maintaining sinus rhythm as in those with HFrEF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine trends in real-world utilization and in-hospital adverse events from Watchman implantation since its approval by the Food and Drug Administration in 2015., Background: The risk of embolic stroke caused by atrial fibrillation is reduced by oral anticoagulants, but not all patients can tolerate long-term anticoagulation. Left atrial appendage occlusion with the Watchman device has emerged as an alternative therapy., Methods: This was a retrospective cohort study utilizing data from National Inpatient Sample for calendar years 2015-2017. The outcomes assessed in this study were associated complications, in-hospital mortality, and resource utilization trends after Watchman implantation. Trends analysis were performed using analysis of variance. Multivariable adjusted logistic regression analysis was performed to determine predictors of mortality., Results: A total of 17 700 patients underwent Watchman implantation during the study period. There was a significantly increased trend in the number of Watchman procedures performed over the study years (from 1195 in 2015 to 11 165 devices in 2017, p < .01). A significant decline in the rate of complications (from 26.4% in 2015% to 7.9% in 2017, p < .01) and inpatient mortality (from 1.3% in 2015% to 0.1% in 2017, p < .01) were noted. Predictors of in-hospital mortality included a higher CHA 2 DS 2 -VASc score (odds ratio [OR]: 2.61 per 1-point increase, 95% confidence interval [CI]: 1.91-3.57), chronic blood loss anemia (OR: 3.63, 95% CI: 1.37-9.61) and coagulopathy (OR: 4.90, 95% CI: 2.32-10.35)., Conclusion: In contemporary United States clinical practice, Watchman utilization has increased significantly since approval in 2015, while complications and in-patient mortality have declined., (© 2020 Wiley Periodicals LLC.)

Catheter ablation improves outcomes in atrial fibrillation (AF) patients with heart failure (HF) with reduced ejection fraction (HFrEF). We sought to evaluate the efficacy and safety of catheter ablation of AF in HF patients with a preserved ejection fraction (HFpEF). We performed a retrospective study of all patients who underwent de novo radiofrequency catheter ablation enrolled in the UC San Diego AF Ablation Registry. The primary outcome was recurrence of all atrial arrhythmias on or off antiarrhythmic drugs (AAD). Of 547 total patients, 51 (9.3%) had HFpEF, 40 (7.3%) had HFrEF, and 456 (83.4%) were without HF. There was no difference in recurrence of atrial arrhythmias on or off AAD (Adjusted Hazard Ratio [AHR] 1.92 [95% CI 0.97 to 3.83] for HFpEF vs HFrEF and AHR 0.90 [95% CI 0.59 to 1.39] for HFpEF vs no HF) or off AAD (AHR 1.96 [95% CI 0.99 to 3.90] for HFpEF vs HFrEF and AHR 1.14 [95% CI 0.74 to 1.77] for HFpEF vs no HF). There was also no difference in rates of all-cause hospitalizations (AHR 1.80 [95% CI 0.97 to 3.33] for HFpEF vs HFrEF and AHR 2.05 [95% CI 1.30 to 3.23] for HFpEF vs no HF) or rates of all-cause mortality (AHR 0.53 [95% CI 0.05 to 6.11] for HFpEF vs HFrEF and AHR 2.46 [95% CI 0.34 to 17.92] for HFpEF vs no HF). There were no significant differences in AAD use (p = 0.176) or procedural complications between groups (p = 0.980). In conclusion, there were no significant differences in arrhythmia-free survival between patients with HFpEF and HFrEF that underwent catheter ablation of AF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The posterior wall of the left atrium may promote atrial fibrillation (AF) due to its propensity for fibrosis, in addition to a high prevalence of non-pulmonary vein triggers. Multiple smaller studies have assessed the incremental value of posterior wall isolation (PWI) in addition to standard atrial fibrillation. Similarly, this method has shown promise as an ablation strategy for patients with persistent AF, when PVI alone has shown only modest efficacy., Methods: We performed an extensive literature search and systematic review of studies that compared AF ablation plus PWI versus control. We separately assessed the recurrence rates of all atrial arrhythmias (AF/AFL/AT), as well as separate recurrence rates of AF and atrial tachycardia/atrial flutter (AT/AFL) after ablation. Risk ratio (RR) 95% confidence intervals were measured using the Mantel-Haenszel method. The random effects model was used due to heterogeneity (I 2 ) > 25%., Results: Seven studies with a total of 1151 patients were included. Patients who underwent concomitant PWI experienced less recurrence of all atrial arrhythmias post ablation (RR 0.77; 95% CI 0.62-0.96, p = 0.02) and less recurrence of AF (RR 0.55; 95% CI 0.39-0.77, p < 0.01). There was no difference in onset of AT/AFL (RR 0.96; 95% CI 0.62-1.48, p = 0.85) after ablation. These results were replicated in subgroup analysis of patients with persistent AF., Conclusions: Based on the results of this meta-analysis, concomitant PWI is associated with less recurrence of AF and all atrial arrhythmias after ablation, without an increase in the risk for post-ablation AFL/AT.

Background: Atrial fibrillation (AF) is frequently present in patients with heart failure (HF) and an implantable cardioverter-defibrillator (ICD). This study aims to identify clinical factors associated with a baseline history of AF in ICD recipients, and compares subsequent clinical outcomes in those with and without a baseline history of AF., Methods: We studied 566 consecutive first-time ICD recipients at an academic center between 2011 and 2018. Logistic regression multivariable analyses were used to identify clinical factors associated with a baseline history of AF at the time of ICD implant. Cox-proportional hazard regression models were constructed for multivariate analysis to examine associations between a baseline history of AF with subsequent clinical outcomes, including ICD therapies, HF readmission, and all-cause mortality., Results: Of all patients, 201 (36%) had a baseline history of AF at the time of ICD implant. In multivariate analyses, clinical factors associated with a baseline history of AF included hypertension, valvular heart disease, body weight, PR interval, and serum creatinine level. After multivariate adjustment for potential confounders, a baseline history of AF was associated with an increased risk of anti-tachycardia pacing (HR = 1.84, 95% CI = 1.19-2.85, P = .006), appropriate ICD shocks (HR = 1.80, 95% CI = 1.05-3.09, P = .032), and inappropriate ICD shocks (HR = 3.72, 95% CI = 1.7-7.77, P = .0001), but not other adverse outcomes., Conclusion: Among first-time ICD recipients, specific clinical characteristics were associated with a baseline history of AF at the time of ICD implant. After adjustment for potential confounders, a baseline history of AF was associated with a higher risk of all ICD therapies in follow-up., (© 2020 Wiley Periodicals LLC.)

Background: Nodoventricular and nodofascicular accessory pathways (AP) are uncommon connections between the atrioventricular node and the fascicles or ventricles., Methods: Five patients with nodofascicular or nodoventricular tachycardia were studied., Results: We identified 5 patients with concealed, left-sided nodoventricular (n=4), and nodofascicular (n=1) AP. We proved the participation of AP in tachycardia by delivering His-synchronous premature ventricular contractions that either delayed the subsequent atrial electrogram or terminated the tachycardia (n=3), and by observing an increase in VA interval coincident with left bundle branch block (n=2). The APs were not atrioventricular pathways because the septal VA interval during tachycardia was <70 ms in 3, 1 had spontaneous atrioventricular dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing. Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of the AP was suspected after failed ablation of the right inferior extension of atrioventricular node in 3 cases and by observing a VA increase with left bundle branch block in 2 cases. The nodofascicular and 3 of the nodoventricular AP were successfully ablated from within the proximal coronary sinus (CS) guided by recorded potentials at the roof of the CS, and 1 nodoventricular AP was ablated via a transseptal approach near the CS os., Conclusions: Left-sided nodofascicular and nodoventricular AP appear to connect the ventricles with the CS musculature in the region of the CS os. Mapping and successful ablation sites can be guided by recording potentials within or near the CS os.

Aims: Incorporating patient-reported outcomes (PROs) into routine care of atrial fibrillation (AF) enables direct integration of symptoms, function, and health-related quality of life (HRQoL) into practice. We report our initial experience with a system-wide PRO initiative among AF patients., Methods and Results: All patients with AF in our practice undergo PRO assessment with the Toronto AF Severity Scale (AFSS), and generic PROs, prior to electrophysiology clinic visits. We describe the implementation, feasibility, and results of clinic-based, electronic AF PRO collection, and compare AF-specific and generic HRQoL assessments. From October 2016 to February 2019, 1586 unique AF patients initiated 2379 PRO assessments, 2145 of which had all PRO measures completed (90%). The median completion time for all PRO measures per visit was 7.3 min (1st, 3rd quartiles: 6, 10). Overall, 38% of patients were female (n = 589), mean age was 68 (SD 12) years, and mean CHA2DS2-VASc score was 3.8 (SD 2.0). The mean AFSS symptom score was 8.6 (SD 6.6, 1st, 3rd quartiles: 3, 13), and the full range of values was observed (0, 35). Generic PROs of physical function, general health, and depression were impacted at the most severe quartiles of AF symptom score (P < 0.0001 for each vs. AFSS quartile)., Conclusion: Routine clinic-based, PRO collection for AF is feasible in clinical practice and patient time investment was acceptable. Disease-specific AF PROs add value to generic HRQoL instruments. Further research into the relationship between PROs, heart rhythm, and AF burden, as well as PRO-guided management, is necessary to optimize PRO utilization., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Variable-capacitance electrostatic motors are ideal for driving the test mass in ultra-low-noise electrostatic accelerometers. Such devices are essential for testing the new equivalence principle (NEP) with rotating extended masses. However, as the air-film damping is greatly reduced by placing the sensor core assembly in a high-vacuum housing, this synchronous motor may easily fall out of step and suffer spin-up failures with traditional open-loop excitation. In this study, a synchronous electronic phase commutation scheme is proposed by sensing the three-phase position change of the rotor poles and activating the stator electrodes in careful correlation with the instantaneous rotor position. Experiments on a ground-test NEP instrument prototype show that the proposed closed-loop excitation scheme can spin-up the rotor synchronously and maintain stable constant-speed operation of this macroscale variable capacitance motor operated in a high-vacuum environment. This rotation control method is also applicable to the synchronous operation of micromachined variable-capacitance electrostatic motors.

Variant accessory pathways include atriofascicular, nodofascicular, nodoventricular, atrio-Hisian, and fasciculoventricular pathways. Atriofascicular pathways are the most common with others occurring rarely. The anatomical descriptions, electrocardiographic findings, electrophysiologic findings, and clincial manifestations are discussed., (© 2019 Wiley Periodicals, Inc.)

Obesity and atrial fibrillation (AF) are growing epidemics with significant overlap in co-morbidities. Multiple smaller studies have evaluated the effects of weight loss and risk factor modification on recurrence of AF, reduction in AF burden and improvement in AF symptom severity. The objective of this study was to determine if a modest weight loss of ≥10% of initial body weight is enough to improve outcomes in overweight or obese patients with established AF. We performed an extensive literature search and systematic review of studies that compared weight loss of ≥10% versus weight loss of less than 10% or weight gain and assessed outcomes including recurrence of AF as determined through a Holter monitor, AF burden and improvement in AF symptom severity. Risk ratio 95% confidence intervals (CI) were measured for dichotomous variables and mean difference (MD) 95% CI were measured for continuous variables, where MD >0 favors the group with ≥10% weight loss. Five studies with a total of 548 patients were included. Patients who lost ≥10% of their initial body weight experienced less recurrence of AF (risk ratio 0.29; 95% CI 0.19 to 0.44) and a larger reduction in reported event frequency (MD 1.74; 95% CI 0.70 to 2.79), episode duration (MD 2.14; 95% CI 0.04 to 4.23), global episode severity (MD 1.89; 95% CI 1.34 to 2.45), and symptom severity (MD 5.36; 95% CI 3.75 to 6.97). In conclusion, weight loss is associated with less risk of recurrent AF, reduction in AF burden, and improvement in AF symptom severity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Patients with severe cardiomyopathy often have chronotropic incompetence, which is predominantly managed by activating rate-adaptive pacing in patients implanted with an implantable cardioverter-defibrillator (ICD) capable of atrial pacing. The purpose of this study was to determine predictors of rate-adaptive pacing activation, the cumulative incidence of activation, and the association of rate-adaptive pacing activation with subsequent clinical outcomes in an ICD population., Methods: The authors evaluated 228 patients implanted with an ICD between 2011 and 2015. Multivariable logistic regression was used to evaluate predictors of rate-adaptive pacing activation. Cox proportional-hazards regression was used to examine associations of rate-adaptive pacing activation and clinical outcomes., Results: Rate-adaptive pacing was turned on in 38.5% (n = 88) of patients during follow-up. Several statistically significant predictors of rate-adaptive pacing activation were found, particularly previous atrial fibrillation (odds ratio [OR] = 8.27, 95% confidence interval [CI] = 2.96-23.06, p < 0.001), previous myocardial infarction (OR = 4.17, 95% CI = 1.38-12.58, p = 0.01), and non-ischemic cardiomyopathy (OR = 3.83, 95% CI = 1.22-12.00, p = 0.02). In multivariable adjusted analyses, rate-adaptive pacing activation within 30 days of implantation was not associated with the risk of device therapy for tachyarrhythmias (hazard ratio [HR] = 1.52, 95% CI = 0.71-3.28, p = 0.29), atrial fibrillation (HR = 1.42, 95% CI = 0.71-2.87, p = 0.32), HF re-admission (HR = 1.39, 95% CI = 0.80-2.43, p = 0.25), nor all-cause mortality (HR = 2.34, 95% CI = 0.80-6.84, p = 0.12)., Conclusions: During follow-up, more than one in three HF patients implanted with an ICD developed the need for rate-adaptive pacing. Atrial fibrillation, prior myocardial infarction, and non-ischemic cardiomyopathy were statistically significant baseline clinical predictors of rate-adaptive pacing activation. Rate-adaptive pacing activation was not associated with subsequent adverse clinical outcomes.

Background Late gadolinium enhancement magnetic resonance imaging is an effective tool for assessment of atrial fibrosis. The degree of left atrial fibrosis is a good predictor of atrial fibrillation ( AF ) ablation success at 1 year, but the association between left atrial fibrosis and long-term ablation success has not been studied. Methods and Results Late gadolinium enhancement magnetic resonance images of sufficient quality to quantify atrial fibrosis were obtained before the first AF ablation in 308 consecutive patients. Left atrial fibrosis was classified in 4 Utah stages (I, 0-10%; II , 10-20%; III , 20-30%; and IV , >30%). Patients were followed up for up to 5 years until the time of first arrhythmia recurrence or second ablation. A total of 308 patients were included; the mean age was 64.5±12.1 years, and 63.4% were men. During follow-up, 157 patients experienced an arrhythmia recurrence and 106 patients underwent a repeated ablation. A graded effect was observed in which patients with more advanced atrial fibrosis were more likely to experience recurrent AF (hazard ratio for stage IV versus stage I, 2.73; 95% confidence interval, 1.57-4.75) and undergo a repeated ablation (proportional odds ratio for stage IV versus stage I, 5.19; 95% confidence interval, 2.12-12.69). Conclusions The degree of left atrial fibrosis predicts the success of AF ablation at up to 5 years follow-up. In patients with advanced atrial fibrosis, AF ablation is associated with a high procedural failure rate.

Objectives: This study retrospectively evaluated the feasibility and esophageal thermal injury (ETI) patterns of high-power short-duration (HPSD) radiofrequency atrial fibrillation (AF) ablation., Background: ETI following AF ablation can lead to serious complications. Little consensus exists on the optimal radiofrequency power setting or on the optimal strategy to assess ETI., Methods: A total of 687 patients undergoing first-time AF ablation with either HPSD ablation (50 W for 5 s, n = 574) or low-power long-duration ablation (LPLD, ≤35 W for 10 to 30 s, n = 113) were analyzed. ETI was assessed by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) within 24 h post-ablation. Patients with moderate or severe esophageal LGE had a follow-up MRI within 24 h to 1 week, and esophagogastroduodenoscopies were performed when significant gastrointestinal symptoms or persistent LGE on repeat MRI was present. AF recurrence adjusted for potential confounders was analyzed., Results: The average age was 69.0 ± 11.8 years in the group undergoing HPSD ablation versus 68.3 ± 11.6 years in the LPLD group (p = 0.554), with 67.1% versus 59.3% male (p = 0.111). Esophageal LGE patterns were similar (64.8% vs. 57.5% none, 21.0% vs. 28.3% mild, 11.5% vs. 11.5% moderate, 2.8% vs. 2.7% severe for HPSD vs. LPLD, respectively; p = 0.370) with no atrioesophageal fistulas. Mean procedure length was significantly shorter in the HPSD group (149 ± 65 min vs. 251 ± 101 min; p < 0.001). AF recurrence rates were similar in the 2 groups for the mean 2.5-year follow-up period (adjusted, 42% vs. 41%; p = 0.571)., Conclusions: HPSD ablation results in similar ETI patterns, as assessed by same-day LGE MRI, compared with the LPLD setting but with significantly shorter procedure times. Recurrence rates at 2.5-year follow-up are similar., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Electrostatic accelerometers have extremely high sensitivity and are ideal scientific instruments for measuring very weak acceleration. In particular, a single-sensitive-axis electrostatic accelerometer can be used for testing the equivalence principle in space. Sensitive-axis capacitances formed by axial electrodes and a cylindrical proof mass vary with the axial motion of the mass and are also affected by radial motion, which results in cross-axis coupling disturbances. A quantitative model is built to analyze the cross-axis coupling effect on the sensitive axis from the radial suspension loop, including a nonlinear model for large radial motion and a linear model for small radial motion. Frequency response simulation shows that the cross-axis coupling effect for a small signal case arises mostly in the high-frequency range. Experiments are carried out with a ground-based electrostatic accelerometer made of a single, non-rotating test cylinder, and in this case, the experimental results are utilized to verify the mathematical model. Cross-axis coupling for small signal perturbations is virtually removed if the equilibrium position of the proof mass is calibrated to the null position of the sensor cage. In addition, data post-processing can further attenuate the cross-axis coupling disturbances when dealing with large radial motion. The cross-axis coupling disturbances on both the position and the acceleration measurement signals in the sensitive axis are mostly removed in ground-based experiments. The proposed model and compensation can be extended to space equivalence principle instruments and other electrostatic accelerometers with a cylindrical proof mass.

Ventricular tachycardia (VT), which can lead to sudden cardiac death, occurs frequently in patients with myocardial infarction. Catheter-based radiofrequency ablation of cardiac tissue has achieved only modest efficacy, owing to the inaccurate identification of ablation targets by current electrical mapping techniques, which can lead to extensive lesions and to a prolonged, poorly tolerated procedure. Here we show that personalized virtual-heart technology based on cardiac imaging and computational modelling can identify optimal infarct-related VT ablation targets in retrospective animal (5 swine) and human studies (21 patients) and in a prospective feasibility study (5 patients). We first assessed in retrospective studies (one of which included a proportion of clinical images with artifacts) the capability of the technology to determine the minimum-size ablation targets for eradicating all VTs. In the prospective study, VT sites predicted by the technology were targeted directly, without relying on prior electrical mapping. The approach could improve infarct-related VT ablation guidance, where accurate identification of patient-specific optimal targets could be achieved on a personalized virtual heart prior to the clinical procedure., Competing Interests: Competing Interests. NAT holds partial ownership of CardioSolv Ablation Technologies LLC. SN is a scientific advisor to CardioSolv Ablation Technologies LLC. The other authors declare no competing financial and non-financial interests.