Search

Abstract Background Many adult patients with secundum-type atrial septal defects (ASDs) are able to have these defects fixed percutaneously. Traditionally, this has involved an assessment of ASD size, geometry and atrial septal margins by transoesophageal echocardiography (TOE) prior to percutaneous closure. This is a semi-invasive technique, and all of the information obtained could potentially be obtained by non-invasive cardiovascular magnetic resonance (CMR). We compared the assessment of ASDs in consecutive patients being considered for percutaneous ASD closure using CMR and TOE. Methods Consecutive patients with ASDs diagnosed on transthoracic echocardiography (TTE) were invited to undergo both CMR and TOE. Assessment of atrial septal margins, maximal and minimal defect dimensions was performed with both techniques. Analyses between CMR and TOE were made using simple linear regression and Bland Altman Analyses. Results Total CMR scan time was 20 minutes, and comparable to the TOE examination time. A total of 20 patients (M:F = 5:15, mean age 42.8 years ± 15.7) were included in the analyses. There was an excellent agreement between CMR and TOE for estimation of maximum defect size (R = 0.87). The anterior inferior, anterior superior and posterior inferior margins could be assessed in all patients with CMR. The posterior superior margin could not be assessed in only one patient. Furthermore, in 1 patient in whom TOE was unable to be performed, CMR was used to successfully direct percutaneous ASD closure. Conclusions CMR agrees with TOE assessment of ASDs in the work-up for percutaneous closure. Potentially CMR could be used instead of TOE for this purpose.

Abstract Background Pericardial adipose tissue (PAT) has been shown to be an independent predictor of coronary artery disease. To date its assessment has been restricted to the use of surrogate echocardiographic indices such as measurement of epicardial fat thickness over the right ventricular free wall, which have limitations. Cardiovascular magnetic resonance (CMR) offers the potential to non-invasively assess total PAT, however like other imaging modalities, CMR has not yet been validated for this purpose. Thus, we sought to describe a novel technique for assessing total PAT with validation in an ovine model. Methods 11 merino sheep were studied. A standard clinical series of ventricular short axis CMR images (1.5T Siemens Sonata) were obtained during mechanical ventilation breath-holds. Beginning at the mitral annulus, consecutive end-diastolic ventricular images were used to determine the area and volume of epicardial, paracardial and pericardial adipose tissue. In addition adipose thickness was measured at the right ventricular free wall. Following euthanasia, the paracardial adipose tissue was removed from the ventricle and weighed to allow comparison with corresponding CMR measurements. Results There was a strong correlation between CMR-derived paracardial adipose tissue volume and ex vivo paracardial mass (R2 = 0.89, p < 0.001). In contrast, CMR measurements of corresponding RV free wall paracardial adipose thickness did not correlate with ex vivo paracardial mass (R2 = 0.003, p = 0.878). Conclusion In this ovine model, CMR-derived paracardial adipose tissue volume, but not the corresponding and conventional measure of paracardial adipose thickness over the RV free wall, accurately reflected paracardial adipose tissue mass. This study validates for the first time, the use of clinically utilised CMR sequences for the accurate and reproducible assessment of pericardial adiposity. Furthermore this non-invasive modality does not use ionising radiation and therefore is ideally suited for future studies of PAT and its role in cardiovascular risk prediction and disease in clinical practice.

Abstract Background Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing left-to-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function. Furthermore, atrial changes post-ASD closure have been poorly understood and may be important for understanding risk of atrial arrhythmia post-ASD closure. Cardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using CMR. Methods Consecutive patients (n = 23) underwent CMR pre- and 6 months post-ASD closure. Steady state free precession cine CMR was performed using contiguous slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial, ventricular end diastolic volumes (EDV) and end systolic volumes (ESV). Data is presented as mean ± SD, volumes as mL, and paired t-testing performed between groups. Statistical significance was taken as p < 0.05. Results There was a significant reduction in right ventricular volumes at 6 months post-ASD closure (RVEDV: 208.7 ± 76.7 vs. 140.6 ± 60.4 mL, p < 0.0001) and RVEF was significantly increased (RVEF 35.5 ± 15.5 vs. 42.0 ± 15.2%, p = 0.025). There was a significant increase in the left ventricular volumes (LVEDV 84.8 ± 32.3 vs. 106.3 ± 38.1 mL, p = 0.003 and LVESV 37.4 ± 20.9 vs. 46.8 ± 18.5 mL, p = 0.016). However, there was no significant difference in LVEF and LV mass post-ASD closure. There was a significant reduction in right atrial volumes at 6 months post-ASD closure (pre-closure 110.5 ± 55.7 vs. post-closure 90.7 ± 69.3 mL, p = 0.019). Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant (84.5 ± 34.8 mL to 81.8 ± 44.2 mL, p = NS). Conclusion ASD closure leads to normalisation of ventricular volumes and also a reduction in right atrial volume. Further follow-up is required to assess how this predicts outcomes such as risk of atrial arrhythmias after such procedures.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society., Competing Interests: Data availability No new data were generated or analyzed in support of this research., (Copyright © 2024. Published by Elsevier Inc.)

Background: Leadless left ventricular (LV) endocardial pacing is an emerging cardiac resynchronization therapy (CRT) technology. Predictors of response to leadless CRT are poorly understood. Implanting the LV endocardial pacing electrode in sites with increased electrical latency (Q-LV) may improve response rates., Objective: To examine the association between Q-LV and echocardiographic remodelling response to leadless CRT delivered with the WiSE-CRT system., Methods: A post-hoc analysis (n=122) of the SOLVE-CRT trial examined the relationship between LV pacing site Q-LV with rate of LV end-systolic volume (LVESV) reduction >15% at 6 months. Multivariable regression analysis, adjusting for age, sex, prior CRT non-response, cardiomyopathy aetiology, QRS morphology and QRS duration was performed, followed by ROC analysis and analysis of variance by Q-LV quartile. A subgroup analysis of the ischaemic cardiomyopathy cohort was undertaken., Results: Complete Q-LV data was available in 122/153 (80%) of patients in the active arms SOLVE-CRT. Overall, the 6-month LVESV response rate was 46%. Logistic regression identified Q-LV as an independent response predictor with borderline significance (adjusted odds ratio 1.015, p=0.05). Analysis by Q-LV quartile demonstrated a significant improvement in response rate in quartile 4 (longest Q-LV, 64%) compared to quartile 1 (shortest Q-LV, 28%), p<0.01. This association was primarily driven by strong Q-LV-response correlation in patients with ischaemic cardiomyopathy, demonstrated by subgroup logistic regression (adjusted odds ratio 1.034, p=0.004)., Conclusion: Increased Q-LV was associated with improved reverse remodelling following leadless CRT. Targeting LV endocardial sites of high Q-LV may deliver additional benefit compared to empirical LV electrode implantation., (Copyright © 2024. Published by Elsevier Inc.)

Background: The association of hospital and physician procedure volume with outcome has not been well evaluated for atrial fibrillation (AF) ablation in contemporary practice., Objective: This study aimed to determine the association between hospital and physician AF ablation volume and procedural success (isolation of all pulmonary veins) and major adverse events (MAEs)., Methods: Procedures reported to the National Cardiovascular Data Registry AFib Ablation Registry between July 2019 and June 2022 were included. Hospital and physician procedural volumes were annualized and stratified into quartiles to compare outcomes. Three-level hierarchical (patient, hospital, and physician) models were used to assess the procedural volume-outcome relationship., Results: A total of 70,296 first-time AF ablations at 186 US hospitals were included. Overall, procedural success and MAE rates were 98.5% and 1.0%, respectively. With hospital volume (Q4) as a reference, the likelihood of procedural success was lower for Q1 (odds ratio [OR], 0.44; 95% CI, 0.29-0.68), Q2 (OR, 0.50; 95% CI, 0.33-0.75), and Q3 (OR, 0.60; 95% CI, 0.40-0.89); the results were similarly significant for physician volume. With MAE for hospitals, there was an inverse procedural volume relationship for Q1 (OR, 1.78; 95% CI, 1.26-2.52) but not for Q2 (OR, 1.06; 95% CI, 0.77-1.46) or Q3 (OR, 1.19; 95% CI, 0.89-1.58) and similarly for physicians in Q1 and Q2 but not in Q3. An adjusted MAE ≤1% was predicted by an annual volume of approximately 190 for hospitals and 60 for physicians., Conclusion: In this national cohort, hospital and physician AF ablation procedural volumes were directly related to acute procedural success and inversely related to rates of MAE., Competing Interests: Disclosures Dr Freeman reports advisory board/consulting fees from Boston Scientific, Medtronic, Biosense Webster, and PaceMate; and equity in PaceMate. Dr Zeitler reports nonfinancial research support from Biosense Webster, Boston Scientific, and Sanofi; travel/speaking for Abbott, Biosense Webster, Medtronic, and Philips; and advisory board/consulting fees from Biosense Webster and Medtronic. Dr Zei reports consulting fees from Biosense Webster, Abbott, Volta Medical, and Medtronic. Dr Sanders served on the advisory board of Medtronic, Abbott, Boston Scientific, PaceMate, and CathRx; the University of Adelaide, Australia has received on his behalf lecture, research funding, and/or consulting fees from Medtronic, Abbott, Boston Scientific, and Becton-Dickenson., (Published by Elsevier Inc.)

Background: Early recurrence of atrial tachyarrhythmias (ERAT) within 3 months of thermal ablation for atrial fibrillation (AF) is common and often considered transient. Pulsed field ablation (PFA) is a nonthermal energy source in which ERAT is not well described., Objective: The purpose of this study was to analyze ERAT in patients with AF undergoing PFA in the Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF (PULSED AF) trial., Methods: This analysis included 154 (52.4%) paroxysmal AF and 140 (47.6%) persistent AF who had ≥10 rhythm assessments during the 90-day blanking period. ERAT was defined as any instance of ≥30 seconds of AF, atrial flutter, or atrial tachycardia on transtelephonic monitoring (weekly and symptomatic) or ≥10 seconds on electrocardiography (at 3 months), both within 90 days. Late recurrence of atrial tachyarrhythmias (LRAT) was defined as observed atrial tachyarrhythmias between 90 days and 12 months., Results: The overall prevalence of ERAT was 27.1% in patients with paroxysmal AF and 31.6% in patients with persistent AF. In patients with ERAT, 73% had ERAT onset within the first month of the procedure. The presence of ERAT was associated with LRAT in patients with paroxysmal AF (hazard ratio 6.4; 95% confidence interval 3.6-11.3) and patients with persistent AF (hazard ratio 3.8; 95% confidence interval 2.2-6.6). Yet, in 29.4% of patients with paroxysmal AF and 34.3% of patients with persistent AF with ERAT, LRAT was not observed. LRAT was positively correlated with the number of ERAT observations., Conclusion: ERAT after PFA predicted LRAT in patients with paroxysmal and persistent AF. However, the concept of a blanking period after PFA is still valid, as approximately one-third of patients with ERAT did not continue to have LRAT during follow-up and may not need reablation., Competing Interests: Disclosures Dr Tarakji, Mr Cerkvenik, and Dr van Bragt are employees and stockholders of Medtronic. Dr Boersma’s cardiology department receives consultation funds from Medtronic, Boston Scientific (BS), Abbott Medical (AM), Adagio Medical, and ZOLL. Dr Natale receives grants and/or consultation funds from Medtronic, Abbott, Biosense Webster (BW), Biotronik, BS, and iRhythm. Dr Haines receives grants and/or consultation funds from Medtronic. Dr DeLurgio receives grants, consultation funds, and/or honoraria funds from Medtronic, AtriCure, and BS. Dr Sood receives consultation or honoraria funds from Johnson & Johnson, Abbott, BS, AtriCure, Bristol Myers Squibb, and Pfizer. Dr Marchlinski receives grants, consultation funds, and/or honoraria funds from Medtronic, BW, AM, and Biotronik. Dr Calkins receives grants, consultation funds, and/or honoraria funds from Medtronic, BS, AM, AtriCure, and BW. Dr Hoyt receives grants and/or consultation funds from Medtronic and AM. Dr Sanders receives grants, consultation funds, and/or honoraria funds from Medtronic, BS, AM, Becton Dickinson, PaceMate, and CathRx. Dr Packer receives grants and/or consultation funds from Medtronic. Dr Mittal receives consultation funds from Medtronic and BS. Dr Di Biase is a consultant for BW, Stereotaxis, and iRhythm and has received speaker honoraria/travel from BW, AM, BS, Medtronic, Biotronik, AtriCure, Siemens, and ZOLL. Dr Tada receives honoraria and/or grants from Medtronic, Daiichi Sankyo, AM, Nippon Boehringer Ingelheim, Eli Lilly, Otsuka Pharmaceutical, Marubun Tsusyo, Biotronik, Bristol Myers Squibb, BS, and Novartis Pharma. Dr Tomita receives research funding from Boehringer Ingelheim, Bayer, Daiichi Sankyo, BS, AM, and Biotronik and speakers’ honorarium from Boehringer Ingelheim, Bayer, Daiichi Sankyo, and Bristol Myers Squibb. Dr Tomita is also a concurrent professor of an endowment department supported by Medtronic Japan, Japan Lifeline, and Fukuda Denshi Kitatohoku Hanbai. Dr Kuck receives grants and/or consultation funds from Medtronic and Cardiovalve. Dr Verma receives grants and/or consultation funds from Medtronic, BW, Bayer, MedLumics, Adagio Medical, and BS. The others have nothing to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with atrial fibrillation (AF) represents a significant clinical challenge. Two diagnostic scoring tools have been developed to aid the noninvasive diagnosis of HFpEF: the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology) and the H 2 FPEF scoring systems., Objectives: The purpose of this study was to evaluate the performance of these 2 scoring tools for the diagnosis of HFpEF against a gold standard of invasive evaluation in a cohort of patients with AF., Methods: The authors recruited consecutive patients with symptomatic AF and preserved ejection fraction who were scheduled for an AF ablation procedure. Gold-standard invasive diagnosis of HFpEF was performed at the AF ablation procedure using mean left atrial pressure at rest and following infusion of 500 mL fluid. Each participant was scored according to the noninvasive HFA-PEFF and H 2 FPEF scoring systems. Sensitivity and specificity analyses were performed to assess the accuracy of these scoring systems in diagnosing HFpEF., Results: In total, 120 participants were recruited. HFpEF was diagnosed invasively in 88 (73.3%) participants, whereas 32 (26.7%) had no HFpEF. Using the HFA-PEFF score, 38 (31.7%) participants had a high probability of HFpEF and 82 (68.3%) had low/intermediate probability of HFpEF. Using the H 2 FPEF tool, 72 (60%) participants had a high probability of HFpEF and 48 (40%) had intermediate probability. A high HFA-PEFF (≥5 points) score could diagnose HFpEF with a sensitivity of 40% and a specificity of 91%, and a high H 2 FPEF score (≥6 points) could diagnose HFpEF with a sensitivity of 69% and specificity of 66%. Overall diagnostic accuracy was similar using both tools (AUC: 0.663 vs 0.707, respectively; P = 0.636)., Conclusions: Against a gold standard of invasively diagnosed HFpEF, the HFA-PEFF and H 2 FPEF scores demonstrate only moderate accuracy in patients with AF and should be utilized with caution in this cohort of patients. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921)., Competing Interests: Funding Support and Author Disclosures Drs Ariyaratnam, Mishima, Kadhim, Emami, Fitzgerald, Stokes, and Thiyagarajah are supported by Postgraduate Scholarships from the University of Adelaide. Dr Sanders is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia; and the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Boston Scientific, and Abbott Medical, and research funding from Medtronic, Abbott Medical, Boston Scientific, and Microport CRM. Dr Elliott is supported by a Future Leader Fellowship from the National Heart Foundation of Australia. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Sex-specific outcomes after catheter ablation (CA) for atrial fibrillation (AF) have reported conflicting findings., Objective: We examined the impact of female sex on outcomes in patients with persistent AF (PsAF) from the Catheter Ablation for Persistent Atrial Fibrillation: A Multicentre Randomized Trial of Pulmonary Vein Isolation vs PVI with Posterior Left Atrial Wall Isolation (CAPLA) randomized trial., Methods: A total of 338 patients with PsAF were randomized to pulmonary vein isolation (PVI) or PVI with posterior wall isolation (PWI). The primary outcome was arrhythmia recurrence at 12 months. Clinical and electroanatomical characteristics, arrhythmia recurrence, and quality of life were compared between women and men., Results: Seventy-nine women (23.4%; PVI 37; PVI + PWI 42) and 259 men (76.6%; PVI 131; PVI + PWI 128) underwent AF ablation. Women were older {median age 70.4 (interquartile range [IQR] 64.8-74.6) years vs 64.0 (IQR 56.7-69.7) years; P < .001} and had more advanced left atrial electroanatomical remodeling. At 12 months, arrhythmia-free survival was lower in women (44.3% vs 56.8% in men; hazard ratio 1.44; 95% confidence interval 1.02-2.04; log-rank, P = .036). PWI did not improve arrhythmia-free survival at 12 months (hazard ratio 1.02; 95% confidence interval 0.74-1.40; log-rank, P = .711). The median AF burden was 0% in both groups (women: IQR 0.0%-2.2% vs men: IQR 0.0%-2.8%; P = .804). Health care utilization was comparable between women (36.7%) and men (30.1%) (P = .241); however, women were more likely to undergo a repeat procedure (17.7% vs 6.9%; P = .007). Women reported more severe baseline anxiety (average Hospital Anxiety and Depression Scale [HADS] anxiety score 7.5 ± 4.9 vs 6.3 ± 4.3 in men; P = .035) and AF-related symptoms (baseline Atrial Fibrillation Effect on Quality-of-Life Questionnaire [AFEQT] score 46.7 ± 20.7 vs 55.9 ± 23.0 in men; P = .002), with comparable improvements in psychological symptoms (change in HADS anxiety score -3.8 ± 4.6 vs -3.0 ± 4.5; P = .152 (change in HADS depression score -2.9 ± 5.0 vs -2.6 ± 4.0; P = .542) and greater improvement in AFEQT score compared with men at 12 months (change in AFEQT score +45.9 ± 23.1 vs +39.2 ± 24.8; P = .048)., Conclusion: Women undergoing CA for PsAF report more significant symptoms and poorer quality of life at baseline than men. Despite higher arrhythmia recurrence and repeat procedures in women, the AF burden was comparably low, resulting in significant improvements in quality of life and psychological well-being after CA in both sexes., Competing Interests: Disclosures The following industry funding sources regarding activities outside the submitted work have been declared in accordance with the ICMJE guidelines. Dr Segan has received a combined National Heart Foundation/National Health and Medical Research Council (NHMRC) PhD scholarship. Dr Kistler is a recipient of the investigator grant from the NHMRC and has received funding from Abbott Medical for consultancy and speaking engagements and has served on the advisory board with fellowship support from Biosense Webster. Dr Kalman has received fellowship support from Medtronic and Biosense Webster. Dr Sanders has served on the advisory board of Medtronic, Abbott Medical, Boston Scientific, CathRx, and PaceMate and has received funding for research and consultancy from Medtronic, Abbott Medical, Boston Scientific, and MicroPort. Dr Lee has received consulting fees from Biosense Webster. Dr Sterns has received consulting fees from Biosense Webster. Dr Ginks has received funding for speaking engagements from Abbott and Biosense Webster. Dr Prabhu has received fellowship and training support from the National Heart Foundation, Abbott Medical, and Boston Scientific. He has also received speaker fees and advisory fees from Abbott Medical and Biosense Webster. The remaining authors have nothing to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) is typically attempted with biventricular (BiV) pacing. One-third of patients are nonresponders. Left bundle branch area pacing (LBBAP) has been evaluated as an alternative means., Objective: The purpose of this study was to assess the feasibility and clinical response of permanent LBBAP as an alternative to BiV pacing., Methods: Of 479 consecutive patients referred with heart failure, 50 with BiV-CRT and 51 with LBBAP-CRT were included in this analysis after study exclusions. Quality-of-Life (QoL) assessments, echocardiographic measurements, and New York Heart Association (NYHA) class were obtained at baseline and at 6-monthly intervals., Results: There were no differences in baseline characteristics between groups (all P > .05). Clinical outcomes such as left ventricular ejection fraction, left ventricular end-systolic volume, QoL, and NYHA class were significantly improved for both pacing groups compared to baseline. The LBBAP-CRT group showed greater improvement in left ventricular ejection fraction at 6 months (P = .001) and 12 months (P = .021), accompanied by greater reduction in left ventricular end-systolic volume (P = .007). QRS duration < 120 ms (baseline 160.82 ± 21.35 ms vs 161.08 ± 24.48 ms) was achieved in 30% in the BiV-CRT group vs 71% in the LBBAP-CRT group (P ≤ .001). Improvement in NYHA class (P = .031) and QoL index was greater (P = .014). Reduced heart failure admissions (P = .003) and health care utilization (P < .05) and improved lead performance (P < .001) were observed in the LBBAP-CRT group., Conclusion: LBBAP-CRT is feasible and effective CRT. It results into a meaningful improvement in QoL and reduction in health care utilization. This can be offered as an alternative to BiV-CRT or potentially as first-line therapy., Competing Interests: Disclosures Dr Pathak reports having served on the advisory board of Medtronic, Abbott, Boston Scientific, and Biotronik. Dr Pathak reports that Canberra Heart Rhythm Foundation/Australian National University has received on his behalf lecture and/or consulting fees and research funding from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. Dr Sanders reports having served on the advisory board of Medtronic, Abbott Medical, Boston Scientific, CathRx, and PaceMate. Dr Sanders reports that the University of Adelaide has received on his behalf lecture/consulting fees and/or research funding from Medtronic, Abbott Medical, Boston Scientific, and MicroPort. All other authors have no disclosures., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Implantable cardioverter-defibrillators last longer, and interest in reliable leads with targeted lead placement is growing. The OmniaSecure™ defibrillation lead is a novel small-diameter, catheter-delivered lead designed for targeted placement, based on the established SelectSecure SureScan MRI Model 3830 lumenless pacing lead platform., Objective: This trial assessed safety and efficacy of the OmniaSecure defibrillation lead., Methods: The worldwide LEADR pivotal clinical trial enrolled patients indicated for de novo implantation of a primary or secondary prevention implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator, all of whom received the study lead. The primary efficacy end point was successful defibrillation at implantation per protocol. The primary safety end point was freedom from study lead-related major complications at 6 months. The primary efficacy and safety objectives were met if the lower bound of the 2-sided 95% credible interval was >88% and >90%, respectively., Results: In total, 643 patients successfully received the study lead, and 505 patients have completed 12-month follow-up. The lead was placed in the desired right ventricular location in 99.5% of patients. Defibrillation testing at implantation was completed in 119 patients, with success in 97.5%. The Kaplan-Meier estimated freedom from study lead-related major complications was 97.1% at 6 and 12 months. The trial exceeded the primary efficacy and safety objective thresholds. There were zero study lead fractures and electrical performance was stable throughout the mean follow-up of 12.7 ± 4.8 months (mean ± SD)., Conclusion: The OmniaSecure lead exceeded prespecified primary end point performance goals for safety and efficacy, demonstrating high defibrillation success and a low occurrence of lead-related major complications with zero lead fractures., Competing Interests: Disclosures G.H.C.: speaker at Medtronic and Philips; consultant for Medtronic and Boston Scientific. P.S.: reports having served on the advisory boards of Medtronic, Abbott, Boston Scientific, PaceMate, and CathRx; the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Abbott, and Boston Scientific; and the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, and Becton-Dickson. B.H.: reports funding from Medtronic and CVRx. P.D.F.: consultant fees and travel support from Medtronic, Boston Scientific, Abbott, and Biotronik as well as honoraria and advisory board participation for Medtronic, Abbott, and Biotronik. M.S.: consultant for Medtronic and Tenaya Therapeutics. M.S.: speaker honorarium from Medtronic Japan and financial endowments to our clinical research division from Biotronik Japan, Medtronic Japan, Boston Scientific Japan, and Abbott Japan. S.K.K.: member of the speakers bureau for Bayer/Schering Pharma, Boston Scientific, Medtronic, and Pfizer; speaker fees, honoraria, consultancy, advisory board fees, investigator, committee member for Novartis, Medtronic, Boehringer-Ingelheim, Boston Scientific, and Bayer. T.R.: consultant for Medtronic, Johnson and Johnson, and Philips; research funding from Medtronic and Abbott. F.P.: speaker at Medtronic and Boston Scientific; consultant for Medtronic and Boston Scientific; research funding from Medtronic and Boston Scientific. J.S.Z.: consultant for Medtronic. H.F.T.: consultant and speaker fee and research grant from Abbott, BMS/Pfizer, Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi-Sankyo, Medtronic, and Sanofi. D.P.S.: institutional funding from Medtronic. C.S.: received scientific grants from Medtronic. R.K.P.: reports that Canberra Heart Rhythm Foundation has received on his behalf lecture and/or consulting fees from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. G.M.: received honoraria from Medtronic. J.S.C.: consultant for Medronic, Biosense Webster, and Boston Scientific. B.T.: honorarium from Boston scientific. M.B.W.: consultant for Medtronic. B.M.R.: consultant for Medtronic. X.H.: consultant for Medtronic. B.B.: consultant for Medtronic. R.C., M.P., A.H., T.G, and A.E.T.: employees of Medtronic, Inc. P.M.: consultant for Medtronic, Boston Scientific, and Cook as well as honoraria from Medtronic and Cook., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Endocardial electrogram (EGM) characteristics in nonischemic cardiomyopathy (NICM) have not been explored adequately for prognostication., Objective: We aimed to study correlation of bipolar and unipolar EGM characteristics with left ventricular ejection fraction (LVEF) and ventricular tachycardia (VT) in NICM., Methods: Electroanatomic mapping of the left ventricle was performed. EGM characteristics were correlated with LVEF. Differences between groups with and without VT and predictors of VT were studied., Results: In 43 patients, unipolar EGM variables had better correlation with baseline LVEF than bipolar EGM variables: unipolar voltage (r = +0.36), peak negative unipolar voltage (r = -0.42), peak positive unipolar voltage (r = +0.38), and percentage area of unipolar low-voltage zone (LVZ; r = -0.41). Global mean unipolar voltage (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2-0.8), extent of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3), and percentage area of unipolar LVZ (HR, 1.6; 95% CI, 1.1-2.3) were significant predictors of VT. For classification of patients with VT, extent of unipolar LVZ had an area under the curve of 0.82 (95% CI, 0.69-0.95; P < .001), and percentage area of unipolar LVZ had an area under the curve of 0.83 (95% CI, 0.71-0.96; P = .01). Cutoff of >3 segments for extent of unipolar LVZ had the best diagnostic accuracy (sensitivity, 90%; specificity, 67%) and cutoff of 33% for percentage area of unipolar LVZ had the best diagnostic accuracy (sensitivity, 95%; specificity, 60%) for VT., Conclusion: In NICM, extent and percentage area of unipolar LVZs are significant predictors of VT. Cutoffs of >3 segments of unipolar LVZ and >33% area of unipolar LVZ have good diagnostic accuracies for association with VT., Competing Interests: Disclosures Dr Sanders reports having served on the advisory boards of Medtronic, Abbott Medical, Boston Scientific, CathRx, and PaceMate and that the University of Adelaide has received on his behalf research funding and/or lecture and/or consulting fees from Medtronic, Abbott Medical, and Boston Scientific. Dr Pathak reports having served on the advisory boards of Medtronic, Abbott Medical, and Boston Scientific and that Canberra Heart Rhythm Foundation has received on his behalf research funding and/or lecture and/or consulting fees from Medtronic, Abbott Medical, Boston Scientific, and Biotronik. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. We hypothesize that patients with symptomatic AF but without overt clinical HF commonly exhibit subclinical HFpEF according to established hemodynamic criteria., Objectives: The authors sought to use invasive hemodynamics to investigate the prevalence and implications of subclinical HFpEF in AF ablation patients., Methods: Consecutive symptomatic AF ablation patients were prospectively recruited. Diagnosis of subclinical HFpEF was undertaken by invasive assessment of left atrial pressure (LAP). Participants had HFpEF if the baseline mean LAP was >15 mm Hg and early HFpEF if the mean LAP was >15 mm Hg after a 500-mL fluid challenge. LA compliance was assessed invasively by monitoring the LAP and LA diameter during direct LA infusion of 15 mL/kg normal saline. LA compliance was calculated as Δ LA diameter/ΔLAP. LA cardiomyopathy was further studied with exercise echocardiography and electrophysiology study. Functional impact was evaluated using cardiopulmonary exercise testing and the AF Symptom Severity questionnaire., Results: Of 120 participants, 57 (47.5%) had HFpEF, 31 (25.8%) had early HFpEF, and 32 (26.7%) had no HFpEF. Both HFpEF and early HFpEF were associated with lower LA compliance compared with those without HFpEF (P < 0.001). Participants with HFpEF and early HFpEF also displayed decreased LA emptying fraction (P = 0.004), decreased LA voltage (P = 0.001), decreased VO 2peak (P < 0.001), and increased AF symptom burden (P = 0.002) compared with those without HFpEF., Conclusions: Subclinical HFpEF is common in AF ablation patients and is characterized by a LA cardiomyopathy, decreased cardiopulmonary reserve and increased symptom burden. The diagnosis of HFpEF may identify patients with AF with the potential to benefit from novel HFpEF therapies. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921)., Competing Interests: Funding Support and Author Disclosures Drs Ariyaratnam, Mishima, Kadhim, Emami, Malik, and Fitzgerald are supported by Postgraduate Scholarships from the University of Adelaide. Dr Elliott is supported by a Future Leader Fellowship from the National Heart Foundation of Australia. Dr Gallagher is supported by a Postdoctoral Fellowship from the University of Adelaide. Dr Lau is supported by a Mid-career fellowship from The Hospital Research Foundation. Dr Sanders is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia. Dr Lau reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott Medical, Bayer, Biotronik, BMS Pfizer, Boehringer Ingelheim, Medtronic, and MicroPort CRM. Dr Sanders has served on the advisory board of Medtronic, Abbott Medical, Boston-Scientific, Pacemate, and CathRx. Dr Sanders reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Boston-Scientific, and Abbott Medical; and reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott Medical, Boston Scientific, and Microport CRM. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Fidelity of electrogram sensing may reduce false alerts from an insertable cardiac monitor (ICM)., Objective: The purpose of this study was to assess the effect of vector length, implant angle, and patient factors on electrogram sensing using surface electrocardiogram (ECG) mapping., Methods: Twelve separate precordial single-lead surface ECGs were acquired from 150 participants at 2 interelectrode distances (75 and 45 mm), at 3 vector angles (vertical, oblique, and horizontal), and in 2 postures (upright and supine). A subset of 50 patients also received a clinically indicated ICM implant in 1:1 ratio (Reveal LINQ [Medtronic, Minneapolis, MN]/BIOMONITOR III [Biotronik, Berlin, Germany]). All ECGs and ICM electrograms were analyzed by blinded investigators using DigitizeIt software (V2.3.3, Braunschweig, Germany). The P-wave visibility threshold was set at > 0.015 mV. Logistic regression was used to identify factors affecting P-wave amplitude., Results: A total of 1800 tracings from 150 participants (44.5% [n = 68] female; median age 59 [35-73] years) were assessed. The median P- and R-wave amplitudes were 45% and 53% larger with vector lengths of 75 and 45 mm, respectively (P < .001 for both). The oblique orientation yielded the best P- and R-wave amplitudes, while posture change did not affect P-wave amplitude. Mixed effects modeling found that visible P-waves occur more frequently with a vector length of 75 mm than with 45 mm (86% vs 75%, respectively; P < .0001). A longer vector length improved both P-wave amplitude and visibility in all body mass index categories. There was a moderate correlation of P- and R-wave amplitudes from the ICM electrograms to those from surface ECG recordings (intraclass correlation coefficient 0.74 and 0.80, respectively)., Conclusion: Longer vector length and oblique implant angle yielded the best electrogram sensing and are relevant considerations for ICM implantation procedures., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Freedom from atrial arrhythmia (AA) recurrence ≥30 seconds after pulsed field ablation (PFA) in patients with atrial fibrillation (AF) was reported in PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF; ClinialTrials.gov Identifier: NCT04198701). AA burden may be a more clinically meaningful endpoint., Objective: The purpose of this study was to determine the influence of monitoring strategies on AA detection and AA burden association with quality of life (QoL) and health care utilization (HCU) after PFA., Methods: Patients underwent 24-hour Holter monitoring at 6 and 12 months and weekly, and symptomatic transtelephonic monitoring (TTM). AA burden post-blanking was calculated as the greater of (1) percentage of AA on total Holter time; or (2) percentage of weeks with ≥1 TTM with AA out of all weeks with ≥1 TTM., Results: Freedom from all AAs varied by >20% when differing monitoring strategies were used. PFA resulted in zero burden in 69.4% of paroxysmal atrial fibrillation (PAF) and 62.2% of persistent atrial fibrillation (PsAF) patients. Median burden was low (<9%). Most PAF and PsAF patients had ≤1 week of AA detection on TTM (82.6% and 75.4%) and <30 minutes of AA per day of Holter monitoring (96.5% and 89.6%), respectively. Only PAF patients with <10% AA burden averaged a clinically meaningful (>19 point) QoL improvement. PsAF patients experienced clinically meaningful QoL improvements irrespective of burden. Repeat ablations and cardioversions significantly increased with higher AA burden (P <.01)., Conclusion: The ≥30-second AA endpoint is dependent on the monitoring protocol used. PFA resulted in low AA burden for most patients, which was associated with clinically relevant improvement in QoL and reduced AA-related HCU., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of data on the association between respiratory function and atrial fibrillation (AF). This study aimed to assess the relationship between forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC and incident AF., Methods: We performed an analysis of prospectively collected data from the UK Biobank. We included all participants with available spirometry and excluded those with prior AF. Incident AF was ascertained through hospitalisation and death records, and dose-response associations were assessed by means of multivariable Cox regression analysis with adjustment for known AF risk factors., Results: We studied 348,219 white individuals (54.1% female) with a median age of 58.1 years (interquartile range [IQR] 50.8-63.5 years). Over a median follow-up time of 11.5 years (IQR 11.0-12.6 years), a total of 18,188 incident AF events occurred. After standardisation to sex, age, and height, the risk of AF consistently increased with decreasing FEV1 percentage predicted, FEV1 z score, and FVC z score. The risk of AF linearly increased with decreasing FEV1/FVC ratio, and those that had airway obstruction as defined by FEV1/FVC ratio < 0.70 had a 23% greater risk of incident AF (adjusted hazard ratio [aHR] 1.23, 95% confidence interval [CI] 1.19-1.28) compared with those without airway obstruction. Patients with known chronic obstructive pulmonary disease and asthma were at 40% (aHR 1.40, 95% CI 1.29-1.51) and 17% (aHR 1.17, 95% CI 1.12-1.22) increased risk of incident AF respectively., Conclusions: These findings indicate that reduced ventilatory function is associated with increased risk of AF independently from age, sex, smoking, and other known AF risk factors., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background: Methamphetamine-associated cardiomyopathy (MA-CMP) is an increasingly recognised aetiology of cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a specialised cardiac imaging modality commonly used in assessment of cardiomyopathy. We aimed to identify specific CMR features associated with MA-CMP., Methods: A retrospective cohort study of CMR scans was performed in a single centre between January 2015 and December 2020. Thirty patients with MA-CMP who had undergone CMR were identified. MA-CMP was defined as those with a history of significant methamphetamine use hospitalised with acute decompensated heart failure (other causes of cardiomyopathy excluded). A retrospective analysis of index admission CMRs was performed. All studies were performed on a 1.5 T CMR scanner., Results: The mean age of MA-CMP patients was 43.7 ± 7.5 years, and 86.7% were male. The mean left ventricular (LV) volume obtained in this cohort was consistent with severe LV dilatation (LV end-diastolic volume (334 ± 99 ml); LV end-systolic volume: 269 ± 98 ml), whilst the right ventricular (RV) volume indicated moderate-to-severe dilatation (RV end-diastolic volume: 272 ± 91 ml; RV end-systolic volume: 173 ± 82 ml). Mean LV ejection fraction (20.9 ± 9.2%) indicated severe LV dysfunction, with moderate-to-severe RV dysfunction also detected (RV ejection fraction: 29.4 ± 13.4%). 22 patients (73.3%) had myocardial late gadolinium enhancement (LGE), of which 59.1% were located in the mid-wall, with all of these involving the interventricular septum. 22.7% displayed localised regions of sub-endocardial LGE in a variety of locations, and 18.2% had transmural regions of LGE that were located in the inferior and inferolateral segments. 6 patients (20%) had intracardiac thrombus (4 LV, 2 both LV and RV)., Conclusion: MA-CMP was associated with severe biventricular dilatation and dysfunction, with a high prevalence of intraventricular thrombus. This cohort study highlights that MA-CMP patients have a high prevalence of CMR findings., (© 2022. The Author(s).)

Objective: To summarize data on the prevalence/incidence, risk factors and prognosis of atrial fibrillation (AF) in patients with acute pulmonary embolism (aPE)., Methods: MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through December 12, 2021. Random-effects meta-analysis method was used to pool estimates., Results: We included 27 studies reporting data from a pooled population of 819,380 patients. The prevalence rates were 11.3% for pre-existing AF, 4.7% for newly diagnosed AF, and 13.2% for prevalent (total) AF. Predictors of newly diagnosed AF (from one study) included congestive heart failure (adjusted odds ratio [aOR] 3.33, 95% CI: 1.81-6.12), ischemic heart disease (aOR 3.25, 95% CI: 1.65-6.39), massive PE (aOR 2.67, 95% CI: 1.19-5.99). Overall, AF was associated with increased risk of short-term (aOR 1.54, 95% CI: 1.44-1.64) and long-term mortality (aOR 1.58, 95% CI: 1.26-1.97). In subgroup analyses, all types of AF were associated with increased risk of short-term mortality: pre-existing AF (aOR 1.90, 95% CI: 1.59-2.27), newly diagnosed AF (aOR 1.51, 95% CI: 1.18-1.93), and prevalent AF (aOR 1.50, 95% CI: 1.42-1.60). Pre-existing AF (aOR 2.08, 95% CI: 1.27-3.42) and prevalent AF (aOR 1.29, 95% CI: 1.02-1.63) were also associated with higher long-term mortality., Conclusion: AF is present in about one in eight patients with aPE, and is associated with increased short- and long-term mortality. AF might improve risk stratification in patients with aPE., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Chronological aging is one of the major risk factors of cardiovascular (CV) disease (CVD); however, the effect of biological aging on CVD and outcomes remain poorly understood. Herein, we evaluated the association between leukocyte telomere length (LTL), a marker of biological age, and CV outcomes., Methods: We searched PubMed, Embase, Ovid Medline, and Web of Science Core Collection for the studies on the association between LTL and myocardial infarction (MI), CV death, and/or CVD risk factors from inception to July 2020. Extracted data were pooled in a random-effects meta-analysis and summarized as risk ratio (RR) and corresponding 95% confidence interval (CI) per LTL tertile., Results: A total of 32 studies (n = 144,610 participants) were included. In a pooled analysis of MI and LTL in a multivariate-adjusted model, the shortest LTL was associated with a 39% higher risk of MI (RR, 1.39; 95% CI, 1.16-1.67; P < 0.001). After adjusting for chronological age and traditional covariance, we showed a 28% increased risk of CV death in the shortest tertile of LTL (RR, 1.28; 95% CI, 1.05-1.56; P = 0.01). Analysis of the studies that investigated the association between CV risk factors and LTL (n = 7) showed that diabetes mellitus is associated with a 46% increased risk of LTL attrition (RR, 1.46; 95% CI, 1.46-2.09; P = 0.039)., Conclusions: This study shows a strong association between LTL, a marker of biological aging, and the risk of MI and CV death. Cardiometabolic risk factors contribute to telomere attrition and therefore accelerates biological aging., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Background: Although previous studies have demonstrated a U-shaped relationship between alcohol and sudden cardiac death (SCD), there is a paucity of evidence on the role of alcohol specifically on incident ventricular arrhythmias (VAs)., Objective: The purpose of this study was to characterize associations of total and beverage-specific alcohol consumption with incident VA and SCD using data from the UK Biobank., Methods: Alcohol consumption reported at baseline was calculated as UK standard drinks (8 g of alcohol) per week. Outcomes were assessed through hospitalization and death records. Alcohol consumption was modeled as restricted cubic splines in multivariate Cox regression models and corrected for regression dilution bias., Results: We studied 408,712 middle-aged individuals (52.1% female) over a median follow-up time of 11.5 years. A total of 1733 incident VA events and 2044 SCDs occurred. For incident VA, no clear association was seen with total alcohol consumption. Although consumption of greater amounts of spirits was associated with increased VA risk, no other significant beverage-specific associations were observed. For SCD, a U-shaped association was seen for total alcohol consumption, such that consumption of <26 drinks per week was associated with lowest risk. Consumption of greater amounts of beer, cider, and spirits was potentially associated with increasing SCD risk, whereas increasing red and white wine intake was associated with reduced risk., Conclusion: In this predominantly white cohort, no association of total alcohol consumption was observed with VA, whereas a U-shaped association was present for SCD. Additional studies utilizing accurately defined VA and SCD events are required to provide further insights into these contrasting findings., (Copyright © 2021 Heart Rhythm Society. All rights reserved.)

Background: In this study, we sought to estimate the prevalence of concomitant sleep-disordered breathing (SDB) in patients with atrial fibrillation (AF) and to systematically evaluate how SDB is assessed in this population., Methods: We searched Medline, Embase and Cinahl databases through August 2020 for studies reporting on SDB in a minimum 100 patients with AF. For quantitative analysis, studies were required to have systematically assessed for SDB in consecutive AF patients. Pooled prevalence estimates were calculated with the use of the random effects model. Weighted mean differences and odds ratios were calculated when possible to assess the strength of association between baseline characteristics and SDB., Results: The search yielded 2758 records, of which 33 studies (n = 23,894 patients) met the inclusion criteria for qualitative synthesis and 13 studies (n = 2660 patients) met the meta-analysis criteria. The pooled SDB prevalence based on an SDB diagnosis cutoff of apnea-hypopnea index (AHI) ≥ 5/h was 78% (95% confidence interval [CI] 70%-86%; P < 0.001). For moderate-to-severe SDB (AHI ≥ 15/h), the pooled SDB prevalence was 40% (95% CI 32%-48%; P < 0.001). High degrees of heterogeneity were observed (I 2  = 96% and 94%, respectively; P < 0.001). Sleep testing with the use of poly(somno)graphy or oximetry was the most common assessment tool used (in 22 studies, 66%) but inconsistent diagnostic thresholds were used., Conclusions: SDB is highly prevalent in patients with AF. Wide variation exists in the diagnostic tools and thresholds used to detect concomitant SDB in AF. Prospective systematic testing for SDB in unselected cohorts of AF patients may be required to define the true prevalence of SDB in this population., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Objective: This review aimed to summarize the evidence on the risk of thromboembolism associated with carotid and aortic atherosclerosis in patients with AF, and the potential impact of their inclusion in current stroke risk stratification scores., Methods: MEDLINE, Web of Science and EMBASE were systematically searched to identify all published studies providing relevant data through 28 February 2021., Results: We identified 10 eligible studies. There was high heterogeneity across studies, precluding a meta-analysis. Carotid stenosis was not associated with incident ischemic stroke in three prospective studies, including the SPAF II trial and the ROCKET-AF trial. An association between carotid stenosis and thromboembolism was found in two studies, with a potential reporting bias due to their retrospective design. The evidence suggesting that carotid plaque predicts stroke or transient ischemic attack in AF patients were more consistent in the four studies evaluating this association. The inclusion of carotid plaque and carotid intima-media thickness (cIMT) into stroke risk stratification tools for AF patients improved their performance. Data on the association of aortic plaque with thromboembolism is scarce in patients with AF. The two studies reporting on this association suggest that aortic plaque alone does not predict incident ischemic stroke., Conclusion: Available data suggest an association of carotid atherosclerosis with the risk of stroke and transient ischemic attack in patients with AF. Future studies should evaluate whether incorporating cIMT and characteristics of carotid and aortic plaques into scoring systems would improve stroke prediction and prevention in patients with AF., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cardiac fibrosis in mitral valve prolapse (MVP) is implicated in the development of sudden cardiac death (SCD); however, the pattern remains poorly characterized., Objective: The purpose of this study was to systematically quantify left and right ventricular fibrosis in individuals with isolated MVP and SCD (iMVP-SCD), whereby other potential causes of death are excluded, compared to a control cohort., Methods: Individuals with iMVP-SCD were identified from the Victorian Institute of Forensic Medicine, Australia, and matched for age, sex, and body mass index to control cases with noncardiac death. Cardiac tissue sections were analyzed to determine collagen deposition in the left ventricular free wall (anterior, lateral, and posterior portions), interventricular septum, and right ventricle. Within the iMVP-SCD cases, the endocardial-to-epicardial distribution of fibrosis within the left ventricle was specifically characterized., Results: Seventeen cases with iMVP-SCD were matched 1:1 with 17 controls, yielding 149 samples and 1788 histologic regions. The iMVP-SCD group had increased left ventricular (anterior, lateral, and posterior; all P <.001) and interventricular septum fibrosis (P <.001), but similar amounts of right ventricular fibrosis (P = .62) compared to controls. In iMVP-SCD, left ventricular fibrosis was significantly higher in the lateral and posterior walls compared to the anterior wall and interventricular septum (all P <.001). Within the lateral and posterior walls, iMVP-SCD cases had a significant endocardial-to-epicardial gradient of cardiac fibrosis (P <.01) similar to other known conditions that cause cardiac remodeling., Conclusion: Our study indicates that nonuniform left ventricular remodeling with both localized and generalized left ventricular fibrosis is important in the pathogenesis of SCD in individuals with MVP., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Although physical activity (PA) is an important component of cardiovascular disease prevention and treatment, its role in atrial fibrillation (AF) risk is less well established., Objective: The purpose of this study was to systematically summarize the evidence pertaining to the relationship of PA and risk of AF., Methods: We searched the PubMed and Embase databases for prospective cohort studies reporting the risk of AF associated with a specific PA volume through March 2020. From each study, we extracted the risk associated with a given PA level, in comparison with insufficiently active ("inactive") individuals. The reported risk was normalized to metabolic equivalent of task (MET)-minutes per week. A random-effects meta-analysis was used to compare AF risk between those who met and those who did not meet PA recommendations (450 MET-minutes per week), and a dose-response analysis between the level of PA and the risk of AF was performed., Results: Fifteen studies reporting data from 1,464,539 individuals (median age 55.3 years; 51.7% female) were included. Individuals achieving guideline-recommended level of PA had a significantly lower risk of AF (hazard ratio 0.94; 95% confidence interval 0.90-0.97; P = .001). Dose-response analysis showed that PA levels up to 1900 MET-minutes per week were associated with a lower risk of AF, with less certainty beyond that level., Conclusion: PA at guideline-recommended levels and above are associated with a significantly lower AF risk. However, at 2000 MET-minutes per week and beyond, the benefit is less clear., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways., Objective: We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate., Methods: INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS)., Results: INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033)., Conclusion: Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The 3-dimensional (3D) nature of sinoatrial node (SAN) function has not been characterized in the intact human heart., Objective: The purpose of this study was to characterize the 3D nature of SAN function in patients with structural heart disease (SHD) using simultaneous endocardial-epicardial (endo-epi) phase mapping., Methods: Simultaneous intraoperative endo-epi SAN mapping was performed during sinus rhythm at baseline (SR baseline ) and postoverdrive suppression at 600 ms (SR post-pace600 ) and 400 ms (SR post-pace400 ) using 2 Abbott Advisor HD Grid Mapping Catheters. Unipolar and bipolar electrograms (EGMs) were exported for phase analysis to determine (1) activation exits; (2) wavefront propagation sequence; (3) endo-epi dissociation; and (4) fractionation. Comparison of these variables was made among the 3 rhythms from an endo-epi perspective., Results: Sixteen patients with SHD were included. SR baseline activations were unicentric and predominantly exited cranially (87.5%) with endo-epi synchrony. However, with overdrive suppression, a tendency for caudal exit shift and endo-epi asynchrony was observed: SR post-pace600 vs SR baseline : cranial endo 75% vs 87.5% (P = .046); cranial epi 68.8% vs 87.5% (P = 0.002); caudal endo 12.5% vs 6.2% (P = 0.215); caudal epi 25% vs 6.2% (P = .0003); and SR post-pace400 vs SR baseline : cranial endo 81.3% vs 87.5% (P = 0.335); cranial epi 68.7% vs 87.5% (P = 0.0034; caudal endo 12.5% vs 6.2% (P = .148); caudal epi 31.2% vs 6.2% (P = 0.0017), consistent with multicentricity. EGM fractionation was more prevalent with overdrive suppression., Conclusion: During mapping of the intact human heart, SAN demonstrated redundancy of sinoatrial exits with postoverdrive shift in sites of earliest activation and epi-endo dissociation of sinoatrial exits., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Traditional methods for the quantification of OSA severity may not encapsulate potential relationships between hypoxemia in OSA and cardiovascular risk., Research Question: Do novel nocturnal oxygen saturation (Spo 2 ) metrics have prognostic value in patients with OSA and high cardiovascular event risk?, Study Design and Methods: We conducted post hoc analyses of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. In 2687 individuals, Cox proportional hazards models that were stratified for treatment allocation were used to determine the associations between clinical characteristics, pulse oximetry-derived metrics that were designed to quantify sustained and episodic features of hypoxemia, and cardiovascular outcomes. Metrics included oxygen desaturation index, time <90% Spo 2 , average Spo 2 for the entire recording (mean Spo 2 ), average Spo 2 during desaturation events (desaturation Spo 2 ), average baseline Spo 2 interpolated across episodic desaturation events (baseline Spo 2 ), episodic desaturation event duration and desaturation/resaturation-time ratio, and mean and SD of pulse rate., Results: Neither apnea-hypopnea index, oxygen desaturation index, nor any of the novel Spo 2 metrics were associated with the primary SAVE composite cardiovascular outcome. Mean and baseline Spo 2 were associated with heart failure (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .009; and HR, 0.78; 95% CI, 0.67-0.90; P = .001, respectively) and myocardial infarction (HR, 0.86; 95% CI, 0.77-0.95; P = .003; and HR, 0.81; 95% CI, 0.73-0.90; P < .001, respectively). Desaturation duration and desaturation/resaturation time ratio, with established risk factors, predicted future heart failure (area under the curve, 0.86; 95% CI, 0.79-0.93)., Interpretation: Apnea-hypopnea index and oxygen desaturation index were not associated with cardiovascular outcomes. In contrast, the pattern of oxygen desaturation was associated with heart failure and myocardial infarction. However, concomitant risk factors remained the predominant determinants for secondary cardiovascular events and thus deserve the most intensive management., (Copyright © 2020. Published by Elsevier Inc.)

Background: Atrial fibrillation (AF) management guidelines recommend screening for symptoms of sleep-disordered breathing (SDB). We aimed to assess the role of self-reported daytime sleepiness in detection of patients with SDB and AF., Methods: A total of 442 consecutive ambulatory patients with AF who were considered candidates for rhythm control and underwent polysomnography comprised the study population. The utility of daytime sleepiness (quantified by the Epworth Sleepiness Scale [ESS]) to predict any (apnea-hypopnea index [AHI] ≥ 5), moderate-to-severe (AHI ≥ 15), and severe (AHI ≥ 30) SDB on polysomnography was tested., Results: Mean age was 60 ± 11 years and 69% patients were men. SDB was present in two-thirds of the population with 33% having moderate-to-severe SDB. Daytime sleepiness was low (median ESS = 8/24) and the ESS poorly predicted SDB, regardless of the degree of SDB tested (area under the curve: 0.48-0.56). Excessive daytime sleepiness (ESS ≥ 11) was present in 11.9% of the SDB population and had a negative predictive value of 43.1% and a positive predictive value of 67.5% to detect moderate-to-severe SDB. Male gender (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.4-3.8, P = 0.001), obesity (OR: 3.5, 95% CI: 2.3-5.5, P < 0.001), diabetes (OR: 2.3, 95% CI: 1.2-4.4, P = 0.08), and stroke (OR: 4.6, 95% CI: 1.7-12.3, P = 0.002) were independently associated with an increased likelihood of moderate-to-severe SDB., Conclusions: In an ambulatory AF population, SDB was common but most patients reported low daytime sleepiness levels. Clinical features, rather than daytime sleepiness, were predictive of patients with moderate-to-severe SDB. Lack of excessive daytime sleepiness should not preclude patients from being investigated for the potential presence of concomitant SDB., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is common after pacemaker implantation. However, the impact of pacemaker algorithms in AF prevention is not well understood., Objective: The purpose of this study was to evaluate the role of pacing algorithms in preventing AF progression., Methods: A systematic search of articles using the PubMed and Embase databases resulted in a total of 754 references. After exclusions, 21 randomized controlled trials (8336 patients) were analyzed, comprising studies reporting ventricular pacing percentage (VP%) (AAI vs DDD, n = 1; reducing ventricular pacing [RedVP] algorithms, n = 2); and atrial pacing therapies (atrial preference pacing [APP], n = 14; atrial antitachycardia pacing [aATP]+APP, n = 3; RedVP+APP+aATP, n = 1)., Results: Low VP% (<10%) lead to a nonsignificant reduction in the progression of AF (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.57-1.13; P = .21; I 2 = 67%) compared to high VP% (>10%). APP algorithm reduced premature atrial complexes (PAC) burden (mean difference [MD] -1117.74; 95% CI -1852.36 to -383.11; P = .003; I 2 = 67%) but did not decrease AF burden (MD 8.20; 95% CI -5.39 to 21.80; P = .24; I 2 = 17%) or AF episodes (MD 0.00; 95% CI -0.24 to 0.25; P = .98; I 2 = 0%). Similarly, aATP+APP programming showed no significant difference in AF progression (odds ratio 0.65; 95% CI 0.36-1.14; P = .13; I 2 = 61%). No serious adverse events related to algorithm were reported., Conclusion: This meta-analysis of randomized controlled trials demonstrated that algorithms to reduce VP% can be considered safe. Low burden VP% did not significantly suppress AF progression. The atrial pacing therapy algorithms could suppress PAC burden but did not prevent AF progression., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation is the most common sustained arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system has a significant role in the milieu predisposing to the triggers, perpetuators and substrate for atrial fibrillation. It has direct electrophysiological effects and causes alterations in atrial structure. In a significant portion of patients with atrial fibrillation, the autonomic nervous system activity is likely a composite of reflex excitation due to atrial fibrillation itself and contribution of concomitant risk factors such as hypertension, obesity and sleep-disordered breathing. We review the role of autonomic nervous system activation, with focus on changes in reflex control during atrial fibrillation and the role of combined sympatho-vagal activation for atrial fibrillation initiation, maintenance and progression. Finally, we discuss the potential impact of combined aggressive risk factor management as a strategy to modify the autonomic nervous system in patients with atrial fibrillation and to reverse the arrhythmogenic substrate., (Copyright © 2018 Elsevier B.V. All rights reserved.)