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Summary: Background: Drug development for atrial fibrillation (AF) has failed to yield new approved compounds. We sought to identify and prioritise potential druggable targets with support from human genetics, by integrating the available evidence with bioinformatics sources relevant for AF drug development. Methods: Genetic hits for AF and related traits were identified through structured search of MEDLINE. Genes derived from each paper were cross-referenced with the OpenTargets platform for drug interactions. Confirmation/validation was demonstrated through structured searches and review of evidence on MEDLINE and ClinialTrials.gov for each drug and its association with AF. Findings: 613 unique drugs were identified, with 21 already included in AF Guidelines. Cardiovascular drugs from classes not currently used for AF (e.g. ranolazine and carperitide) and anti-inflammatory drugs (e.g. dexamethasone and mehylprednisolone) had evidence of potential benefit. Further targets were considered druggable but remain open for drug development. Interpretation: Our systematic approach, combining evidence from different bioinformatics platforms, identified drug repurposing opportunities and druggable targets for AF. Funding: KK is supported by Barts Charity grant G-002089 and is mentored on the AFGen 2023-24 Fellowship funded by the AFGen NIH/NHLBI grant R01HL092577. RP is supported by the UCL BHF Research Accelerator AA/18/6/34223 and NIHR grant NIHR129463. AFS is supported by the BHF grants PG/18/5033837, PG/22/10989 and UCL BHF Accelerator AA/18/6/34223 as well as the UK Research and Innovation (UKRI) under the UK government’s Horizon Europe funding guarantee EP/Z000211/1 and by the UKRI-NIHR grant MR/V033867/1 for the Multimorbidity Mechanism and Therapeutics Research Collaboration. AF is supported by UCL BHF Accelerator AA/18/6/34223. CF is supported by UCL BHF Accelerator AA/18/6/34223.

Background: Mechanisms sustaining persistent atrial fibrillation (AF) remain unclear. Objectives: The study sought to evaluate both the clinical outcomes and response to ablation of potential drivers in patients with recurrent persistent AF recurrence following pulmonary vein isolation (PVI). Methods: A total of 100 patients with persistent AF of 1.5 revolutions or focal activations. Cycle lengths were measured pre- and postablation. The primary outcome was freedom from atrial arrhythmia off antiarrhythmic drugs at 1 year as per guidelines. Results: Of 37 patients recruited, 26 had recurrent AF and underwent ECGI-guided ablation of PDs. An average of 6.4 ± 2.7 PDs were targeted per patient. The mean ablation time targeting PDs was 15.5 ± 6.9 minutes. An ablation response occurred in 20 patients (AF termination in 6, cycle length prolongation ≥10% in 14). At 1 year, 14 (54%) of 26 patients were free from arrhythmia, and 12 (46%) of 26 were off antiarrhythmic drugs. Considering the 96 patients who completed follow-up out of the original cohort of 100 patients undergoing cryoablation in this staged strategy, freedom from arrhythmia at 1 year following the last procedure was 72 (75%) of 96, or 70 (73%) of 96 off antiarrhythmic drugs. Conclusions: In patients with recurrent AF despite PVI, ECGI-guided ablation caused an acute response in a majority with reasonable long-term outcomes.

Background: The value of antitachycardia pacing (ATP) in the overall cohort of primary prevention patients who receive implantable cardioverter-defibrillators (ICDs) remains uncertain. ATP success reported in prior trials potentially included a large number of patients receiving unnecessary ATP for arrhythmias that may have self-terminated owing to the prematurity of the intervention. Although some patients derive benefit from initial ATP in terminating rapid ventricular arrhythmias and thereby preventing shocks, there are limited data allowing us to identify those patients a priori. Objective: The purpose of APPRAISE ATP is to understand the role of ATP in primary prevention patients currently indicated for ICD therapy in a large prospective randomized controlled trial with modern programming parameters. Methods: The study is a global, prospective, randomized, multicenter clinical trial conducted at up to 150 sites globally, enrolling approximately 2600 subjects The primary endpoint of the trial is time to first all-cause shock in a 2-arm study with an equivalent study design in which the incidence of all-cause shocks will be compared between primary prevention subjects programmed with shocks only vs subjects programmed to standard therapy (ATP and shock). Results: An Electrogram and Device Interrogation Core Laboratory will review interrogation data to determine primary endpoints that occur in APPRAISE ATP. Their decisions are based on independent physician review of the data from device interrogation. Conclusion: The ultimate purpose of the study is to aid clinicians in the selection of ICD technologies based on hard endpoint evidence across the spectrum of indications for primary prevention implantation.

Background: The presence of dynamic substrate changes may facilitate functional block and reentry in ventricular tachycardia (VT). Objective: We aimed to study dynamic ventricular repolarization changes in critical regions of the VT circuit during sensed single extrastimulus pacing known as the Sense Protocol (SP). Methods: Twenty patients (aged 67 ± 9 years, 17 male) underwent VT ablation. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular SP pacing at 20 ms above ventricular effective refractory period. Ventricular repolarization maps were constructed. Ventricular repolarization time (RT) was calculated from unipolar electrogram T waves, using the Wyatt method, as the dV/dtmax of the unipolar T wave. Entrainment or pace mapping confirmed critical sites for ablation. Results: The median global repolarization range (max-min RT per patient) was 166 ms (interquartile range [IQR] 143–181 ms) during SR mapping vs 208 ms (IQR 182–234) during SP mapping (P = .0003 vs intrinsic rhythm). Regions of late potentials (LP) had a longer RT during SP mapping compared to regions without LP (mean 394 ± 40 ms vs 342 ± 25 ms, P < .001). In paired regions of normal myocardium there was no significant spatial dispersion of repolarization (SDR)/10 mm2 during SP mapping vs SR mapping (SDR 11 ± 6 ms vs 10 ± 6 ms, P = .54). SDR/10 mm2 was greater in critical areas of the VT circuit during SP mapping 63 ± 29 ms vs SR mapping 16 ± 9 ms (P < .001). Conclusion: Ventricular repolarization is prolonged in regions of LP and increases dynamically, resulting in dynamic SDR in critical areas of the VT circuit. These dynamic substrate changes may be an important factor that facilitates VT circuits.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to conventional transvenous ICD (TV-ICD) therapy to reduce lead complications. Objective: To evaluate outcomes in channelopathy vs patients with structural heart disease in the EFFORTLESS-SICD Registry and with a previously reported TV-ICD meta-analysis in channnelopathies. Methods: The EFFORTLESS registry includes 199 patients with channelopathies (Brugada syndrome 83, long QT syndrome 24, idiopathic ventricular fibrillation 78, others 14) and 786 patients with structural heart disease. Results: Channelopathy patients were younger (39 ± 14 years vs 51 ± 17 years; P < .001) with left ventricular ejection fraction 59% ± 9% vs 41% ± 18% (P < .001). The complication rate (follow-up: 3.2 ± 1.5 years vs 3.0 ± 1.5 years) was similar: 13.6% vs 11.2% (P = .42). Appropriate shocks rates were 9.5% vs 10.8% (P = .70), with shocks for monomorphic ventricular tachycardia being 2.0% vs 6.9% (P < .02) and for polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF) 8.0% vs 5.7% (P = .30). Conversion effectiveness of VT/VF episodes was similar: 36 of 37 (97.3%) vs 151 of 155 (97.4%, P = .59). VT/VF storm event (2% vs 0.9%, P = .33) and lower inappropriate shock (IAS) (8.5% vs 12.5%, P = .12) rates were statistically similar between channelopathy and non-channelopathy patients, with 45.5% channelopathy vs 31.4% non-channelopathy patients managed with a conditional zone > 200 beats per minute (P = .0002). Annualized appropriate shock, IAS, and complication rates appear to be lower for the S-ICD vs meta-analysis TV-ICD patients, particularly lead complications. Conclusion: EFFORTLESS demonstrates similar S-ICD efficacy and a nonsignificant, lower rate of IAS in channelopathy patients as compared to structural heart disease. Comparable IAS rates were achieved with the device programmed to higher rates for channelopathy patients.

Background: We aimed to evaluate atrial fibrillation occurrence, reasons for healthcare visits, mortality, causes of death and examined patterns by relative deprivation in the UK.Methods: To study the atrial fibrillation (AF) incidence, mortality and case-fatality, we implemented a prospective cohort study with the linked electronic health records of 5.6 million population in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. A matched case-control study was used to investigate causes of hospitalisation and death comparing individuals with and without incident AF.Results: During a median follow-up of 10.3 years, 199,433(3.6%) patients developed incident AF. Increased risk of hospitalisation for heart failure, cardiovascular conditions and infection was present among patients who later developed AF. Following an AF diagnosis, patients were frequently admitted to the hospital for heart failure, lower respiratory tract infection, chronic obstructive pulmonary disease and ischemic heart disease. One in 5 AF patients died during the first year after diagnosis, and the mortality increased to 42.7% at the fifth year. The excess deaths in AF cases compared to controls may result from cardiovascular diseases, infection and metabolic disorders. Individuals from areas with higher deprivation in socioeconomic and living status had both higher AF incidence and fatality.Interpretation: We observed an elevated risk of hospitalisation for cardiovascular or respiratory diseases among incident AF patients, and the considerable disparity in AF burden by socioeconomic deprivation informs priorities for prevention and provision of patient care.Funding: The study was supported by the GlaxoSmithKline, University College London Hospital and National Institute for Health Research. The funders did not have any role in study design, data collection, data analysis, interpretation, and writing of the report.

A 64-year-old male with a high body mass index, and subcutaneous implantable cardioverter defibrillator, (S-ICD) presented with a remote transmission of inappropriately diagnosed AF episodes, due to oversensing of P and T waves. The AF monitor can be an early warning for inappropriate sensing. Oversensing, due to small amplitude signals, can be caused by the lead position not being adequately opposed to the sternum. Keywords: S-ICD, Subcutaneous implantable cardioverter defibrillator, Oversensing, ICD, Inappropriate shock, AF monitor

The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action is poorly characterised. Our aims were to identify ajmaline's mode of action in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform to test whether differences in ajmaline response could be determined between BrS patients and controls. Control hiPSCs were differentiated into spontaneously contracting cardiac clusters. It was found using multi electrode array (MEA) that ajmaline treatment significantly lengthened cluster activation-recovery interval. Patch clamping of single CMs isolated from clusters revealed that ajmaline can block both INa and IKr. Following generation of hiPSC lines from BrS patients (absent of pathogenic SCN5A sodium channel mutations), analysis of hiPSC-CMs from patients and controls revealed that differentiation and action potential parameters were similar. Comparison of cardiac clusters by MEA showed that ajmaline lengthened activation-recovery interval consistently across all lines. We conclude that ajmaline can block both depolarisation and repolarisation of hiPSC-CMs at the cellular level, but that a more refined integrated tissue model may be necessary to elicit differences in its effect between BrS patients and controls.

Data presented in this article are supplementary materials to our article entitled “Catheter Ablation for Fascicular Ventricular Tachycardia: A Systematic review” (Creta et al., 2018). The current article provides additional procedural data regarding the catheter ablation for fascicular ventricular tachycardia (FVT) performed in the patients enrolled in our analysis. Furthermore, we provide data regarding the quality assessment of the studies included in our systematic review.

A young man suffered cardiac arrests with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation (VF) triggered by ventricular premature contractions (PVCs). The arrhythmia was resistant to anti-arrhythmics, so after ICD implantation he underwent successful ablation of the triggering VE beat, which was pace-mapped to the left posterior hemi-fascicle. We review the evidence for the role of the Purkinje network in the initiation and maintenance of PVT and VF, postulating a channelopathy as a possible underlying cause, and provide recommendations for PVC ablation.

Background: Areas of abnormal or heterogeneous conduction velocity (CV) are important ablation targets for ventricular tachycardias, yet precise assessment of CV in clinical contact mapping remains challenging. Numerous different CV estimation methods have been proposed., Objective: This study aimed to compare the automated local activation time (LAT)-independent omnipolar-based CV estimation method termed wave speed (WS) with 4 established LAT-based methods to formally establish the quantitative differences between them., Methods: High-density contact maps in patients with structurally normal hearts during sinus rhythm (SR) and ventricular ectopy (VE) were retrospectively analyzed. CV was assessed and compared by 5 methods: omnipolar WS, gradient method, planar wavefront fitting, circular wavefront fitting, and radial basis function. CV variations based on electrogram (EGM) type (unipolar, bipolar, and omnipolar), catheter movement, and surrogate markers for catheter contact were analyzed., Results: The study included 23 patients (47.8% male; 45.7 ± 17.3 years) with 22 SR maps (11 left ventricle, 11 right ventricle) and 16 VE maps (9 left ventricle, 7 right ventricle). The WS algorithm yielded statistically significant higher CV estimates in SR (mean, 1.41 ± 0.18 m/s) and VE (mean, 1.23 ± 0.18 m/s) maps compared with all LAT-based estimation methods, with absolute differences ranging from 0.1 m/s to 0.81 m/s. Median pointwise differences in SR and VE between WS and LAT-based methods were high, ranging from 0.55 ± 0.15 m/s (WS vs planar wavefront fitting) to 0.67 ± 0.16 m/s (WS vs radial basis function). For LAT-based methods, use of unipolar EGMs yielded significantly higher CV estimates than bipolar or omnipolar EGMs in SR., Conclusion: The CV estimation method has an important, statistically significant impact on ventricular CV measurements. Future work will focus on how these differences affect identification of pathologic conduction slowing in scar-related substrate., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Mr Monkhouse has received speaker fees from Abbott, Boston Scientific, Biotronik, Medtronic, and Phillips. He has received consulting fees from Medtronic. Prof Hunter has received speaker fees from Medtronic and Biosense Webster, educational grant from Biosense Webster, and an institutional research grant from Medtronic. Prof Lambiase has received research grants and speaker fees from Boston Scientific, Abbott, and Medtronic. He is supported by University College London Biomedicine National Institute of Health Research and Barts Biomedical Research Centre. The rest of the authors report no conflicts of interest.

Background: Obesity confers higher risks of cardiac arrhythmias. The extent to which weight loss reverses subclinical proarrhythmic adaptations in arrhythmia-free obese individuals is unknown., Objective: The purpose of this study was to study structural, electrophysiological, and autonomic remodeling in arrhythmia-free obese patients and their reversibility with bariatric surgery using electrocardiographic imaging (ECGi)., Methods: Sixteen arrhythmia-free obese patients (mean age 43 ± 12 years; 13 (81%) female participants; BMI 46.7 ± 5.5 kg/m 2 ) had ECGi pre-bariatric surgery, of whom 12 (75%) had ECGi postsurgery (BMI 36.8 ± 6.5 kg/m 2 ). Sixteen age- and sex-matched lean healthy individuals (mean age 42 ± 11 years; BMI 22.8 ± 2.6 kg/m 2 ) acted as controls and had ECGi only once., Results: Obesity was associated with structural (increased epicardial fat volumes and left ventricular mass), autonomic (blunted heart rate variability), and electrophysiological (slower atrial conduction and steeper ventricular repolarization time gradients) remodeling. After bariatric surgery, there was partial structural reverse remodeling, with a reduction in epicardial fat volumes (68.7 cm 3 vs 64.5 cm 3 ; P = .0010) and left ventricular mass (33 g/m 2.7 vs 25 g/m 2.7 ; P < .0005). There was also partial electrophysiological reverse remodeling with a reduction in mean spatial ventricular repolarization gradients (26 mm/ms vs 19 mm/ms; P = .0009), although atrial activation remained prolonged. Heart rate variability, quantified by standard deviation of successive differences in R-R intervals, was also partially improved after bariatric surgery (18.7 ms vs 25.9 ms; P = .017). Computational modeling showed that presurgical obese hearts had a larger window of vulnerability to unidirectional block and had an earlier spiral-wave breakup with more complex reentry patterns than did postsurgery counterparts., Conclusion: Obesity is associated with adverse electrophysiological, structural, and autonomic remodeling that is partially reversed after bariatric surgery. These data have important implications for bariatric surgery weight thresholds and weight loss strategies., Competing Interests: Disclosures The authors have no conflicts to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interest to declare in direct relation to this manuscript. Dr Silberbauer received speaker fees from Abbott Laboratories.

Background: The PRAETORIAN score estimates the risk of failure of subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy by using generator and lead positioning on bidirectional chest radiographs. The PRospective randomized compArative trial of subcutanEous implanTable cardiOverter-defibrillatoR ImplANtation with and without DeFibrillation Testing (PRAETORIAN-DFT) investigates whether PRAETORIAN score calculation is noninferior to defibrillation testing (DFT) with regard to first shock efficacy in spontaneous events., Objective: This prespecified subanalysis assessed the predictive value of the PRAETORIAN score for defibrillation success in induced ventricular arrhythmias., Methods: This multicenter investigator-initiated trial randomized 965 patients between DFT and PRAETORIAN score calculation after de novo S-ICD implantation. Successful DFT was defined as conversion of induced ventricular arrhythmia in <5 seconds from shock delivery within 2 attempts. Bidirectional chest radiographs were obtained after implantation. The predictive value of the PRAETORIAN score for DFT success was calculated for patients in the DFT arm., Results: In total, 482 patients were randomized to undergo DFT. Of these patients, 457 (95%) underwent DFT according to protocol, of whom 445 (97%) had successful DFT and 12 (3%) had failed DFT. A PRAETORIAN score of ≥90 had a positive predictive value of 25% for failed DFT, and a PRAETORIAN score of <90 had a negative predictive value of 99% for successful DFT. A PRAETORIAN score of ≥90 was the strongest independent predictor for failed DFT (odds ratio 33.77; confidence interval 6.13-279.95; P < .001)., Conclusion: A PRAETORIAN score of <90 serves as a reliable indicator for DFT success in patients with S-ICD, and a PRAETORIAN score of ≥90 is a strong predictor for DFT failure., Competing Interests: Disclosures Dr Knops reports consultancy fees and research grants from Abbott, Boston Scientific, Medtronic, and Cardiac and has stock options from AtaCor Medical Inc. Dr El-Chami reports consultancy fees from Medtronic and Boston Scientific. Dr Marquie reports consultancy fees from Boston Scientific.Dr Tilz reports consultancy fees from Boston Scientific, Biotronik, Biosense Webster, and Abbott Medical; speaker’s honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and LifeTech; and research grants from Abbott, Biosense Webster, and LifeTech. Dr Lambiase reports research contracts with Boston Scientific and is a member of the advisory board of Boston Scientific. Dr Manyam reports consultancy fees from Janssen and Abbott. Dr Betts received honoraria for speaking and proctoring from Boston Scientific. Dr Bijsterveld presented at a conference of Abbott and gave a presentation sponsored by AstraZeneca. Dr Field reports being a speaker and proctor for Boston Scientific. Dr Golovchiner reports being a proctor for Boston Scientific. Dr de Jong reports consultancy fees from Medtronic. Dr Lewis reported to receive travel grants and honoraria from Abbott, Boston Scientific, and Medtronic. Dr Martin reported to receive research grants, honoraria, and speaker’s fees from Boston Scientific and honoraria and speaker’s fees from Medtronic and Biosense Webster. Dr Miller reported to receive consultancy fees from Boston Scientific. Dr Shaik reported to receive consultancy fees from Boston Scientific, Medtronic, and Biotronik. Dr Kuschyk reported to receive consultancy fees and honoraria from Boston Scientific, consultancy fees from Impulse Dynamics, and honoraria fees from Medtronic. Dr Boveda reported to receive consultancy fees from Medtronic, Boston Scientific, MicroPort, and Zoll. Dr Kaiser is a proctor for Boston Scientific. Dr Maass reported to receive consultancy fees from Boston Scientific and Medtronic, with all fees going to the department of Cardiology of the University Medical Center Groningen. Dr Wilde is a consultant for ARMGO and Thyrvv Therapeutics. The rest of the authors report no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification., Objective: The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management., Methods: Genetic testing reports for patients referred to our clinic from 2004-2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management., Results: We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options., Conclusion: In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo., Methods: CMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests., Results: 77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [r s ] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high (r s between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively)., Conclusion: Our high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insights into arrhythmogenesis and potentially pave the way for more personalised risk stratification., Clinical Trial Registration: Title: Multimorbidity Life-Course Approach to Myocardial Health-A Cardiac Sub-Study of the MRC National Survey of Health and Development (NSHD) (MyoFit46). National Clinical Trials (NCT) number: NCT05455125. URL: https://clinicaltrials.gov/ct2/show/NCT05455125?term=MyoFit&draw=2&rank=1., (© 2023. The Author(s).)

Background: Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and can be challenging to manage. Atrioventricular nodal (AVN) ablation may be an effective management strategy for AF in these patients., Objective: The purpose of this study was to assess the efficacy of AVN ablation in HCM patients who have failed medical therapy and/or catheter ablation for AF., Methods: A multicenter study with retrospective analysis of a prospectively collated HCM registry was performed. AVN ablation patients were identified. Baseline characteristics and device and procedural indications were collected. Symptoms defined by New York Heart Association and European Heart Rhythm Association classification and echocardiographic findings during follow-up were assessed., Results: Fifty-nine patients were included in the study. Indications for AVN ablation were 6 (10.2%) inappropriate implantable cardioverter-defibrillator shock, 35 (59.3%) ineffective rate control, and 18 (30.5%) to regularize rhythm for symptom improvement. During post-AVN ablation follow-up of 79.4 ± 61.1 months, left ventricular ejection fraction (LVEF) remained stable (pre-LVEF 48.9% ± 12.6% vs post-LVEF 50.1% ± 10.1%; P = .29), even in those without a cardiac resynchronization therapy (CRT) device (pre-LVEF 54.3% ± 8.0% vs post-LVEF 53.8% ± 8.0%; P = .65). Forty-nine patients (83.1%) reported an improvement in symptoms regardless of AF type (17/21 [81.0%] paroxysmal vs 32/38 [84.2%] persistent; P = 1.00), presence of baseline left ventricular impairment (22/26 [84.6%] LVEF ≤50% vs 27/33 [81.8%] LVEF ≥50%; P = 1.00) or CRT device (27/32 [84.4%] CRT vs 22/27 [81.5%] no CRT; P = 1.00). Symptoms improved in 16 patients (89.0%) who underwent AVN ablation to regularize rhythm., Conclusion: AVN ablation improved symptoms without impacting left ventricular function in the majority of patients. The data suggest that AVN ablation is an effective and safe management approach for AF in HCM and should be further evaluated in larger prospective studies., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

This international multidisciplinary document is intended to guide electrophysiologists, cardiologists, other clinicians, and health care professionals in caring for patients with arrhythmic complications of neuromuscular disorders (NMDs). The document presents an overview of arrhythmias in NMDs followed by detailed sections on specific disorders: Duchenne muscular dystrophy, Becker muscular dystrophy, and limb-girdle muscular dystrophy type 2; myotonic dystrophy type 1 and type 2; Emery-Dreifuss muscular dystrophy and limb-girdle muscular dystrophy type 1B; facioscapulohumeral muscular dystrophy; and mitochondrial myopathies, including Friedreich ataxia and Kearns-Sayre syndrome, with an emphasis on managing arrhythmic cardiac manifestations. End-of-life management of arrhythmias in patients with NMDs is also covered. The document sections were drafted by the writing committee members according to their area of expertise. The recommendations represent the consensus opinion of the expert writing group, graded by class of recommendation and level of evidence utilizing defined criteria. The recommendations were made available for public comment; the document underwent review by the Heart Rhythm Society Scientific and Clinical Documents Committee and external review and endorsement by the partner and collaborating societies. Changes were incorporated based on these reviews. By using a breadth of accumulated available evidence, the document is designed to provide practical and actionable clinical information and recommendations for the diagnosis and management of arrhythmias and thus improve the care of patients with NMDs., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Mechanisms sustaining persistent atrial fibrillation (AF) remain uncertain., Objectives: The purpose of this study was to use electrocardiographic imaging (ECGI) mapping to guide localized driver ablation in patients with persistent AF., Methods: Patients undergoing catheter ablation for persistent AF <2 years were included. Patients were enrolled consecutively between 2018 and 2020. ECGI mapping was used to identify focal and rotational potential drivers (PDs). PDs were ablated after pulmonary vein isolation (PVI). The ablation response and freedom from AF/atrial tachycardia (AT) at 1 year were assessed., Results: Forty patients were enrolled. AF terminated with PVI in 8 patients, and 32 underwent ECGI-guided driver ablation. Average procedural duration was 228.8 ± 66.7 minutes, with a total radiofrequency delivery time of 38.9 ± 14.1 minutes. During 1 year of follow-up, the primary endpoint of freedom from AF/AT was achieved in 26 patients (65%). The secondary endpoint of freedom from AF was achieved in 30 patients (75%). AF termination was achieved in 20 of 40 patients (50%). The composite endpoint of an ablation response (AF termination or cycle length slowing ≥10%) occurred in 37 of 40 patients (92.5%). In total, 181 drivers (48 focal and 133 rotational) were ablated, with an ablation response achieved in 59 (32.6%). Focal drivers and drivers with a higher recurrence rate and greater temporal stability were more likely to be associated with an ablation response including AF termination (P <.001)., Conclusion: ECGI-guided ablation plus PVI results in high freedom from AF during follow-up and an ablation response in a large proportion of patients. Using driver type and characteristics may facilitate a hierarchical ablation approach., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection., Objective: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population., Methods: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted., Results: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus., Conclusion: The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear., Objective: The purpose of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology., Methods: In 10 patients undergoing open heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transesophageal echocardiography. Parameters were matched to 6 American Heart Association LV model segments. The association between changes in regional myocardial segment length and activation-recovery interval (ARI; a conventional surrogate for action potential duration) was studied using mixed-effect models., Results: Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01-0.38] ms/%; P = .04) and increased local ARI dispersion (effect size -0.13 [-0.23 to -0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01)., Conclusion: Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Identification of targets for ablation of post-infarction ventricular tachycardias (VTs) remains challenging, often requiring arrhythmia induction to delineate the reentrant circuit. This carries a risk for the patient and may not be feasible. Substrate mapping has emerged as a safer strategy to uncover arrhythmogenic regions. However, VT recurrence remains common., Goal: To use computer simulations to assess the ability of different substrate mapping approaches to identify VT exit sites., Methods: A 3D computational model of the porcine post-infarction heart was constructed to simulate VT and paced rhythm. Electroanatomical maps were constructed based on endocardial electrogram features and the reentry vulnerability index (RVI - a metric combining activation (AT) and repolarization timings to identify tissue susceptibility to reentry). Since scar transmurality in our model was not homogeneous, parameters derived from all signals (including dense scar regions) were used in the analysis. Potential ablation targets obtained from each electroanatomical map during pacing were compared to the exit site detected during VT mapping., Results: Simulation data showed that voltage cut-offs applied to bipolar electrograms could delineate the scar, but not the VT circuit. Electrogram fractionation had the highest correlation with scar transmurality. The RVI identified regions closest to VT exit site but was outperformed by AT gradients combined with voltage cut-offs. The performance of all metrics was affected by pacing location., Conclusions: Substrate mapping could provide information about the infarct, but the directional dependency on activation should be considered. Activation-repolarization metrics have utility in safely identifying VT targets, even with non-transmural scars., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The spatial QRS-T angle (QRS-Ta) derived from the vectorcardiogram (VCG) is a strong risk predictor for ventricular arrhythmia and sudden cardiac death with potential use for mass screening. Accurate QRS-Ta estimation in the presence of ECG delineation errors is crucial for its deployment as a prognostic test. Our study assessed the effect of inaccurate QRS and T-wave marker placement on QRS-Ta estimation and proposes a robust method for its calculation. Reference QRS-Ta measurements were derived from 1,512 VCGs manually annotated by three expert reviewers. We systematically changed onset and offset timings of QRS and T-wave markers to simulate inaccurate placement. The QRS-Ta was recalculated using a standard approach and our proposed algorithm, which limits the impact of VCG marker inaccuracies by defining the vector origin as an interval preceding QRS-onset and redefines the beginning and end of QRS and T-wave loops. Using the standard approach, mean absolute errors (MAE) in peak QRS-Ta were >40% and sensitivity and precision in the detection of abnormality (>105°) were <80% and <65% respectively, when QRS-onset was delayed or QRS-offset anticipated >15 ms. Using our proposed algorithm, MAE for peak QRS-Ta were reduced to <4% and sensitivity and precision of abnormality were >94% for inaccuracies up to ±15 ms. Similar results were obtained for mean QRS-Ta. In conclusion, inaccuracies of QRS and T-wave markers can significantly influence the QRS-Ta. Our proposed algorithm provides robust QRS-Ta measurements in the presence of inaccurate VCG annotation, enabling its use in large datasets., (© 2020 The Author(s).)

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate., Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants., Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10 -18 ) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10 -13 ). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency., Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

Background: The long-term effect of tricuspid regurgitation (TR) after device implantation on long-term mortality remains unknown. In the present study, we sought to examine whether patients undergoing an implantable cardiac device procedure (pacemaker, cardiac defibrillator or cardiac resynchronisation therapy) have an increased risk of TR and to determine the effect of this on long-term survival., Methods: A total of 304 patients who underwent device implant and had pre- and post-implant transthoracic echocardiogram were included in the analysis. All-cause mortality was the study endpoint over a follow-up period of median 11.6 years., Results: New ≥ moderate tricuspid regurgitation post-device implantation developed in 66/304 (21.7%) patients. New right ventricular dysfunction post-device implantation occurred in 59/304 (19.4%) patients. Independent predictors of new RV dysfunction were ischaemic heart disease (OR 4.23, 95% CI 1.58 - 11.33, p = 0.004), left ventricular impairment (OR 2.74, 95% CI 5.41 - 30.00, p < 0.0001) and new ≥ moderate TR (OR 7.72, 95% CI 3.27 - 18.23, p < 0.001). Independent predictors of mortality were new ≥ moderate TR [HR: 3.14 (95% CI 1.29 - 7.63) p = 0.01] and new RV impairment [HR: 2.82 (95% CI 1.33 - 5.98) p = 0.01., Conclusions: Worsening TR and RV dysfunction post-device implantation is common. New post-implant ≥ moderate TR is associated with increased risk of new RV impairment and poor long term (>10 years) survival., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT., Objective: The purpose of this study was to provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate., Methods: Eighteen VT ablation patients (16 male; 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analyzed offline. Activation time (AT), activation-recovery interval (ARI), and repolarization time (RT) were measured. Vulnerability to reentry was mapped based on RVI and spatial distribution of AT, ARI, and RT. The distance from sites identified as vulnerable to reentry to the VT site of origin was measured, with distances <10 mm and >20 mm indicating accurate and inaccurate localization, respectively., Results: The origins of 18 VTs (6 entrainment, 12 pace-mapping) were identified. RVI maps included 1012 (408-2098) (median, 1st-3rd quartiles) points per patient. RVI accurately localized 72.2% VT sites of origin, with median distance of 5.1 (3.2-10.1) mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%; odds ratio 0.12; P = .035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI and were nonsignificantly larger for sites showing highest AT and ARI gradients., Conclusion: RVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has shown favorable outcomes in large registries with broad inclusion criteria. The cohorts reported had less heart disease and fewer comorbidities than standard ICD populations., Objective: The purpose of this study is to characterize acute performance for primary prevention patients with a left ventricular ejection fraction (LVEF) ≤35% (primary prevention ≤35%)., Methods: Primary prevention ≤35% patients with no prior documented sustained ventricular tachycardia (VT), pacing indication, end-stage heart failure, or advanced renal failure were prospectively enrolled. Analyses included descriptive statistics, Kaplan-Meier time to event, and multivariable linear and logistic regression., Results: In 1112 of 1116 patients, an S-ICD was successfully implanted (99.6%). Predictors for longer procedure time included 3-incision technique, higher body mass index (BMI), performing defibrillation testing (DFT), imaging, younger age, black race, and European vs North American centers. Patients undergoing DFT (82%) were successfully converted (99.2%; 93.5% converting at ≤65 J). Higher BMI was predictive of failing DFT at ≤65 J. The rate of 30-day freedom from complications was 95.8%. Most complications involved postoperative healing (45%) or interventions after DFT or impedance check (19%)., Conclusion: The procedural outcome data of UNTOUCHED reinforce that S-ICD therapy has low perioperative complication rates and high conversion efficacy of induced ventricular fibrillation, even in a higher-risk cohort with low LVEF and more comorbidities than previous S-ICD studies. Higher BMI warrants more careful attention to implant technique., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The relationship between the surface electrocardiogram (ECG) T wave to intracardiac repolarization is poorly understood., Objective: The purpose of this study was to examine the association between intracardiac ventricular repolarization and the T wave on the body surface ECG (SECG TW )., Methods: Ten patients with a normal heart (age 35 ± 15 years; 6 men) were studied. Decapolar electrophysiological catheters were placed in the right ventricle (RV) and lateral left ventricle (LV) to record in an apicobasal orientation and in the lateral LV branch of the coronary sinus (CS) for transmural recording. Each catheter (CS, LV, RV) was sequentially paced using an S1-S2 restitution protocol. Intracardiac repolarization time and apicobasal, RV-LV, and transmural repolarization dispersion were correlated with the SECG TW , and a total of 23,946 T waves analyzed., Results: RV endocardial repolarization occurred on the upslope of lead V 1 , V 2 , and V 3 SECG TW , with sensitivity of 0.89, 0.91, and 0.84 and specificity of 0.67, 0.68, and 0.65, respectively. LV basal endocardial, epicardial, and mid-endocardial repolarization occurred on the upslope of leads V 6 and I, with sensitivity of 0.79 and 0.8 and specificity of 0.66 and 0.67, respectively. Differences between the end of the upslope in V 1 , V 2 , and V 3 vs V 6 strongly correlated with right to left dispersion of repolarization (intraclass correlation coefficient 0.81, 0.83, and 0.85, respectively; P <.001). Poor association between the T wave and apicobasal and transmural dispersion of repolarization was seen., Conclusion: The precordial SECG TW reflects regional repolarization differences between right and left heart. These findings have important implications for accurately identifying biomarkers of arrhythmogenic risk in disease., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Identification of targets for catheter ablation of ventricular tachycardias (VTs) remains a significant challenge. VTs are often driven by re-entrant circuits resulting from a complex interaction between the front (activation) and tail (repolarization) of the electrical wavefront. Most mapping techniques do not take into account the tissue repolarization which may hinder the detection of ablation targets. The re-entry vulnerability index (RVI), a recently proposed mapping procedure, incorporates both activation and repolarization times to uncover VT circuits. The method showed potential in a series of experiments, but it still requires further development to enable its incorporation into a clinical protocol. Here, in-silico experiments were conducted to thoroughly assess RVI maps constructed under clinically-relevant mapping conditions. Within idealized as well as anatomically realistic infarct models, we show that parameters of the algorithm such as the search radius can significantly alter the specificity and sensitivity of the RVI maps. When constructed on sparse grids obtained following various placements of clinical recording catheters, RVI maps can identify vulnerable regions as long as two electrodes were placed on both sides of the line of block. Moreover, maps computed during pacing without inducing VT can reveal areas of abnormal repolarization and slow conduction but not directly vulnerability. In conclusion, the RVI algorithm can detect re-entrant circuits during VT from low resolution mapping grids resembling the clinical setting. Furthermore, RVI maps may provide information about the underlying tissue electrophysiology to guide catheter ablation without the need of inducing potentially harmful VT during the clinical procedure. Finally, the ability of the RVI maps to identify vulnerable regions with specificity in high resolution computer models could potentially improve the prediction of optimal ablation targets of simulation-based strategies., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The comparative efficacy of antiarrhythmic drug (AAD) therapy vs ventricular tachycardia (VT) ablation in arrhythmogenic right ventricular cardiomyopathy (ARVC) is unknown., Objective: We compared outcomes of AAD and/or β-blocker (BB) therapy with those of VT ablation (with AAD/BB) in patients with ARVC who had recurrent VT., Methods: In a multicenter retrospective study, 110 patients with ARVC (mean age 38 ± 17 years; 91[83%] men) with a minimum of 3 VT episodes were included; 77 (70%) were initially treated with AAD/BB and 32 (29%) underwent ablation. Subsequently, 43 of the 77 patients treated with AAD/BB alone also underwent ablation. Overall, 75 patients underwent ablation., Results: When comparing initial AAD/BB therapy (n = 77) and VT ablation (n = 32) after ≥3 VT episodes, a single ablation procedure rendered 35% of patients free of VT at 3 years compared with 28% of AAD/BB-only-treated patients (P = .46). Of the 77 AAD/BB-only-treated patients, 43 subsequently underwent ablation. For all 75 patients who underwent ablation, 56% were VT-free at 3 years after the last ablation procedure. Epicardial ablation was used in 40/75 (53%) and was associated with lower VT recurrence after the last ablation procedure (endocardial/epicardial vs endocardial-only; 71% vs 47% 3-year VT-free survival; P = .05). Importantly, there was no difference in survival free of death or transplantation between the ablation- and AAD/BB-only-treated patients (P = .61)., Conclusion: In patients with ARVC and a high VT burden, mortality and transplantation-free survival are not significantly different between drug- and ablation-treated patients. These patients have a high risk of recurrent VT despite drug therapy. Combined endocardial/epicardial ablation is associated with reduced VT recurrence as compared with endocardial-only ablation., (Copyright © 2018. Published by Elsevier Inc.)

Background: Myocardial scar assessment using late gadolinium enhancement Cardiovascular Magnetic Resonance (LGE CMR) is commonly indicated for patients with cardiac implantable electronic devices (CIEDs), however metal artifact can degrade images. We evaluated the clinical impact of LGE CMR incorporating a device-dependent metal artifact reduction strategy in patients with CIEDs., Methods: 136 CMR studies were performed in 133 consecutive patients (age 56 ± 19 years, 69% male) with CIEDs (22% implantable loop recorders [ILRs], 40% permanent pacemakers [PPMs], 38% implantable cardioverter defibrillators [ICDs]; 42% non-MRI conditional) over 2 years, without complication. LGE imaging was tailored to the CIED, using a wideband sequence for left-sided PPMs and ICDs and conventional sequences for ILRs and right-sided PPMs, scoring segmental artifact. Diagnostic utility and impact on clinical management were scored by consensus of experts., Results: CMR provided unexpected diagnoses in 22 (16%) and changed management in 113 (83%) patients. Myocardial scar was present in 92 (68%), with other abnormalities detected in another 13%. Using conventional LGE, 43 (32%) studies were non-diagnostic (79% of defibrillators) compared to 0% using wideband LGE imaging. Wideband LGE results changed clinical management in an additional 39 (75%) defibrillator patients and 10 (19%) pacemaker patients when compared to imaging with conventional LGE sequences., Conclusion: The clinical yield from CMR using optimized LGE sequences in patients with CIEDs is high with no demonstrated clinical risk. A device-dependent LGE imaging strategy using wideband LGE is needed to achieve clinical utility especially in ICD recipients., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Catheter ablation has been evaluated as treatment for fascicular ventricular tachycardia (FVT) in several single-centre cohort studies, with variable results regarding efficacy and outcomes., Methods: A systematic search was performed on PubMed, EMBASE and Cochrane database (from inception to November 2017) that included studies on FVT catheter ablation., Results: Thirty-eight observational non-controlled case series comprising 953 patients with FVT undergoing catheter ablation were identified. Three studies were prospective and only 5 were multi-centre. Eight-hundred and eighty-four patients (94.2%) had left posterior FVT, 25 (3.4%) left anterior FVT and 30 (2.4%) other forms. In 331 patients (41%), ablation was performed in sinus rhythm (SR). The mean follow-up period was 41.4 ± 10.7 months. Relapse of FVT occurred in 100 patients (10.7%). Among the 79 patients (8.3%) requiring a further procedure after the index ablation, 19 (2%) had further FVT relapses. Studies in which ablation was performed in FVT had similar success rate after multiple procedures compared to ablation in SR only (95.1%, CI 95% 92.2-97%, I 2  = 0% versus 94.8%, CI 95% 87.6-97.9%, I 2  = 0%, respectively). Success rate was numerically lower in paediatric-only series compared to non-paediatric cases (90.0%, CI 95% 82.1-94.6%, I 2  = 0% versus 94.3%, CI 95% 92.2-95.9%, I 2  = 0%, respectively)., Conclusion: Data derived from observational non-controlled case series, with low-methodological quality, suggest that catheter ablation is a safe and effective treatment for FVT, with a 93.5% success rate after multiple procedures. Ablation during FVT represents the first-line and most commonly used approach; however, a strategy of mapping and ablation during SR displayed comparable procedural results to actively mapping patients in FVT and should therefore be considered in selected cases where FVT is not inducible., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Rate-dependent conduction velocity (CV) slowing is associated with atrial fibrillation (AF) initiation and reentrant mechanisms., Objective: The purpose of this study was to assess the relationship between bipolar voltage, CV dynamics, and AF drivers., Methods: Patients undergoing catheter ablation for persistent AF (<24 months) were enrolled. Unipolar electrograms were recorded with a 64-pole basket catheter during atrial pacing at 4 pacing intervals (PIs) during sinus rhythm. CVs were measured between pole pairs along the wavefront path and correlated with underlying bipolar voltage. CV dynamics within low-voltage zones (LVZs <0.5 mV) were compared to those of non-LVZs (≥0.5 mV) and were correlated to driver sites mapped using CARTOFINDER (Biosense Webster)., Results: Eighteen patients were included (age 62 ± 10 years). Mean CV at 600 ms was 1.59 ± 0.13 m/s in non-LVZs vs 0.98 ± 0.23 m/s in LVZs (P <.001). CV decreased incrementally over all 4 PIs in LVZs, whereas in non-LVZs a substantial decrease in CV was only seen between PIs 300-250 ms (0.59 ± 0.09 m/s; P <.001). Rate-dependent CV slowing sites measurements, defined as exhibiting CV reduction ≥20% more than the mean CV reduction seen between PIs 600-250 ms for that voltage zone, were predominantly in LVZs (0.2-0.5 mV; 75.6% ± 15.5%; P <.001). Confirmed rotational drivers were mapped to these sites in 94.1% of cases (sensitivity 94.1%, 95% CI 71.3%-99.9%; specificity 77.9%, 95% CI 74.9%-80.7%)., Conclusion: CV dynamics are determined largely by the extent of remodeling. Rate-dependent CV slowing sites are predominantly confined to LVZs (0.2-0.5 mV), and the resultant CV heterogeneity may promote driver formation in AF., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Background: Better characterization of drivers in atrial fibrillation (AF) may facilitate their identification., Objective: The purpose of this study was to demonstrate that certain driver characteristics are associated with greater mechanistic importance in maintaining AF., Methods: Persistent AF was mapped in patients using the CARTOFINDER system with a 64-pole basket catheter to identify and ablate drivers with rotational or focal activity after pulmonary vein isolation. An ablation response was defined as cycle length (CL) slowing ≥30 ms or AF termination. Driver sites with an ablation response were correlated to sites of fastest CL, highest dominant frequency (DF), and greatest organization (lowest cycle length variability [CLV] and highest regularity index [RI]). Parameters predicting AF termination with driver ablation were evaluated., Results: All 29 patients had ≥1 driver identified. Forty-four potential drivers were identified. The predefined ablation response occurred with 39 drivers (89%): 23 rotational and 16 focal. During a 30-second recording, each driver occurred 8.7 ± 5.4 times and completed 3.1 ± 0.9 consecutive repetitions per occurrence. Driver sites correlated best with markers of organization, corresponding to the site of lowest CLV (29/39 [74%]) and highest RI (26/39 [67%]). Correlation with sites of fastest CL and highest DF was poor (17/39 and 15/39, respectively) and depended on driver temporal stability. Greater temporal stability (3.4 ± 0.9 vs 2.7 ± 0.6; P = .001) and driver correlation with sites of lowest CLV and highest RI (both P <.001) predicted AF termination with ablation., Conclusion: Intermittent focal or rotational drivers were identified in all patients. Drivers consistently correlated to organization markers. Greater temporal stability and organization predicted AF termination with driver ablation., (Copyright © 2018. Published by Elsevier Inc.)

Background: Almost 1/3 of heart failure patients fail to respond to cardiac resynchronization therapy (CRT). A simple clinical score to predict who these patients are at the moment of referral or at time of implant may be of importance for early optimization of their management., Methods: Observational study. A risk score was derived from factors associated to CRT response. The derivation cohort was composed of 1301 patients implanted with a CRT defibrillator in a multi-center French cohort-study. External validation of this score and assessment of its association with CRT response and all-cause mortality and/or heart transplant was performed in 1959 CRT patients implanted in 4 high-volume European centers., Results: Independent predictors of CRT response in the derivation cohort were: female gender (OR = 2.08, 95% CI 1.26-3.45), NYHA class ≤ III (OR = 2.71, 95% CI 1.63-4.52), left ventricular ejection fraction ≥ 25% (OR = 1.75, 95% CI 1.27-2.41), QRS duration ≥ 150 ms (OR = 1.70, 95% CI 1.25-2.30) and estimated glomerular filtration rate ≥ 60 mL/min (OR = 2.01, 95% CI 1.48-2.72). Each was assigned 1 point. External validation showed good calibration (Hosmer-Lemeshow test-P = 0.95), accuracy (Brier score = 0.19) and discrimination (c-statistic = 0.67), with CRT response increasing progressively from 37.5% in patients with a score of 0 to 91.9% among those with score of 5 (Gamma for trend = 0.44, P < 0.001). Similar results were observed regarding all-cause mortality or heart transplant., Conclusion: The ScREEN score (Sex category, Renal function, ECG/QRS width, Ejection fraction and NYHA class) is composed of widely validated, easy to obtain predictors of CRT response, and predicts CRT response and overall mortality. It should be helpful in facilitating early consideration of alternative therapies for predicted non-responders to CRT therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Up to a third of patients undergoing cardiac resynchronization therapy (CRT) do not have a clinical or echocardiographic response. It is also unclear, whether contractile reserve (CR) could predict CRT response. This meta-analysis examines whether the presence of CR improves response to CRT and whether this is modulated by other clinical factors., Methods: Search of PubMed/EMBASE/Cochrane databases for articles examining response to CRT stratified by the presence or not of CR. End-point classified as clinical or echocardiographic response. The analysis compared response to CRT (echocardiographic or clinical) between patients with or without CR., Results: 824 patients in 12 studies were included. The presence of left ventricular CR was associated with a significant reduction in echocardiographic non-responders to CRT compared to patients without CR (OR: 0.16, 95% CI 0.08-0.33, p<0.00001). The presence of left ventricular CR was associated with a significant reduction in clinical non-responders to CRT compared to patients without CR (OR: 0.23, 95% CI 0.14-0.37, p<0.00001). Sensitivity analysis showed no difference in response when pooling studies using left ventricular ejection fraction (LVEF) or non-LVEF markers of CR. Meta-regression showed that CR was associated with lower rates of non-responders and this was more pronounced in patients with a narrower mean QRS complex., Conclusions: Identification of CR is associated with improved response to CRT. Importantly, QRS width is a potential moderator variable which can explain part of the heterogeneity in echo response. The combination of CR and QRS width may modulate the response to CRT., (Copyright © 2017 Elsevier B.V. All rights reserved.)