<div><h4>Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial.</h4><i>Fontenla A, Tamargo J, Salgado R, López-Gil M, ... Bueno H, BRAKE-AF Study Investigators</i><br /><b>Background</b><br />Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting.<br /><b>Objectives</b><br />The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation.<br /><b>Methods</b><br />The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite β-blocker or calcium channel blocker treatment.<br /><b>Results</b><br />Ivabradine 1 μM inhibited \"funny\" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 μM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10).<br /><b>Conclusion</b><br />Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.<br /><br />Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 01 Jun 2023; 20:822-830</small></div>

<div><h4>MACHINE LEARNING-POWERED, DEVICE-EMBEDDED HEART SOUND MEASUREMENT CAN OPTIMIZE AV DELAY IN CRT PATIENTS.</h4><i>Westphal P, Luo H, Shahmohammadi M, Prinzen FW, Delhaas T, Cornelussen RN</i><br /><b>Background</b><br />Continuous optimization of atrioventricular (AV)-delay for CRT is mainly performed by electrical means.<br /><b>Objective</b><br />Development of an estimation model of cardiac function that uses a piezoelectric microphone embedded in a pulse generator to guide CRT optimization.<br /><b>Methods</b><br />Electrocardiogram, left ventricular pressure (LVP) and heart sounds were simultaneously collected during CRT implantation procedures. A piezoelectric alarm-transducer embedded in a modified CRT device facilitated recording of heart sounds in patients undergoing a pacing protocol with different AV-delays. Machine-learning (ML) was employed to produce a decision-tree ensemble model capable of estimating absolute maximal LVP (LVP<sub>max</sub>) and maximal rise of LVP (LVdP/dt<sub>max</sub>) using 3 heart-sound-based features. To gauge the applicability of ML in AV-delay optimization, polynomial curves were fitted to measured and estimated values.<br /><b>Results</b><br />In the dataset of ∼30,000 heartbeats, ML indicated S1-, S2-amplitude and S1-integral (S1-energy for LVdP/dt<sub>max</sub>) as most prominent features for AV-delay optimization. ML resulted in single-beat estimation precision for absolute values of LVP<sub>max</sub> and LVdP/dt<sub>max</sub> of 67% and 64%, respectively. For 20-30 beat averages, cross-correlation between measured and estimated LVP<sub>max</sub> and LVdP/dt<sub>max</sub> was 0.999 for both. The estimated optimal AV-delays were not significantly different from those measured using invasive LVP (difference: -5.6±17.1 ms for LVP<sub>max</sub> and +5.1± 6.7 ms for LVdP/dt<sub>max</sub>). The difference in function at estimated and measured optimal AV delays was not statically significant (1±3mmHg for LVP<sub>max</sub> and 9±57mmHg/s for LVdP/dt<sub>max</sub>).<br /><b>Conclusion</b><br />Heart sound sensors embedded in a CRT device, powered by a ML-algorithm provide a reliable assessment of optimal AV-delays and absolute LVP<sub>max</sub> and LVdP/dt<sub>max</sub>.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 27 May 2023; epub ahead of print</small></div>

<div><h4>Catheter ablation of ventricular premature depolarizations originating from mid interventricular septum: Significance of electrocardiographic morphology for predicting origin.</h4><i>Liang Z, Zhang T, Liu L, Qi S, ... Wang Y, Ma C</i><br /><b>Background</b><br />Ventricular premature depolarizations (VPDs) originating from the mid interventricular septum (IVS) adjacent to the atrioventricular annulus between the His bundle and coronary sinus ostium (mid IVS VPDs) have not been characterized.<br /><b>Objective</b><br />The aim of this study was to investigate the electrophysiological characteristics of mid IVS VPDs.<br /><b>Methods</b><br />Thirty-eight patients with mid IVS VPDs were enrolled. The VPDs were divided into different types according to precordial transition of the electrocardiogram (ECG) and the QRS morphology in lead V1.<br /><b>Results</b><br />4 types of VPDs were divided. The precordial transition zone appeared earlier and earlier from types 1 to 4. The notch in V1 moved gradually backwards, its amplitude gradually became higher, resulting in transition from left to right bundle branch block morphology in V1 from types 1 to 4. Based on activation and pace mapping, ablation response, and the 3830 electrode pacing morphology in the mid IVS, the 4 types of ECG morphology corresponded, respectively, to an origin in the right endocardial side, right/mid intramural region, left intramural region, and left endocardial side of the mid IVS. An intramural origin was identified for 50% of the VPDs. 89% of mid IVS VPDs could be eliminated. Bilateral ablation (waiting for delayed efficacy) or bipolar ablation was sometimes needed for intramural VPDs.<br /><b>Conclusions</b><br />Mid IVS VPDs were found to have unique electrophysiological characteristics. The ECG characteristics of mid IVS VPDs was important in terms of prediction of its exact origin, the choice of ablation method, and the likelihood of treatment being successful.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 22 May 2023; epub ahead of print</small></div>

<div><h4>Effects of Stereotactic Arrhythmia Radioablation on left ventricular ejection fraction and valve function over time.</h4><i>van der Ree MH, Luca A, Siklody CH, Le Bloa M, ... Schiappacasse L, Pruvot E</i><br /><AbstractText>Twenty patients (80% male) were included, 15 (75%) with a non-ischemic cardiomyopathy. The radiotherapy dose was 20Gy (20;25) prescribed to a planning target volume (PTV) of 25cc (18;39) resulting in a median whole-heart dose of 6.1Gy. The follow-up duration before and after STAR was 2.1 (0.6;4.5) and 1.7 (0.9;3.9) years respectively. The number of echocardiograms was 5 (3;7) before and 4 (2;7) after STAR.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 22 May 2023; epub ahead of print</small></div>

<div><h4>Optimizing diastolic filling by pacing in non-obstructive hypertrophic cardiomyopathy.</h4><i>Subramanian M, Shekar V, Krishnamurthy P, Yalagudri S, ... Chennapragada S, Narasimhan C</i><br /><b>Background</b><br />Treatment options for symptomatic patients with non-obstructive hypertrophic cardiomyopathy(nHCM) are limited.<br /><b>Objective</b><br />To determine the effect of sequential atrioventricular(AV) pacing, from different right ventricular(RV) sites with varying AV delays, on the diastolic function and functional capacity of patients with nHCM.<br /><b>Methods</b><br />Twenty-one patients with symptomatic nHCM and normal left ventricular systolic function were prospectively enrolled. Inclusion criteria included a PR interval>150ms, E/e\'>15 and an indication for ICD implantation. Doppler echocardiographic study was performed during dual chamber pacing at various AV intervals. Pacing was performed at three RV sites:RV apex(RVA),RV mid-septum(RVS),and RV outflow tract(RVO). The site and sensed AV delay(SAVD) at which optimal diastolic filling occurred was chosen based on diastolic filling period and E/e\'. During ICD implantation, the RV lead was implanted at the site identified by the pacing study. Devices were programmed in DDD mode at the optimal SAVD. During follow up, diastolic function and functional capacity were assessed.<br /><b>Results</b><br />Among the 21 patients(age 47.8+7.7yrs,males 81.0%), the baseline E/A and E/e\' were 2.4+0.6,and 17.2+2.2,respectively. There was an improvement in diastolic function (E/e\') in 18 patients(responders) when pacing from the RVA(12.9+3.4,p<0.001) compared to the RVS(16.6+2.3)and RVO(16.9+2.2). Among responders, optimal diastolic filling occurred at an SAVD of 130-160ms with RVA pacing. Non responders had longer duration of symptoms(p=0.006),lower LVEF(p=0.037),and higher LGE burden(p<0.001). During 13.5+1.5 months of follow up, there was an improvement(Δ)in diastolic function(E/e\'-4.1+0.5),functional capacity(NYHA-1.5+0.3),and reduction in NT-proBNP(-55.6+12.3pg/ml) compared to baseline.<br /><b>Conclusion</b><br />Pacing at an optimized AV delay from the RV apex improves diastolic function and functional capacity in a subset of patients with non-obstructive hypertrophic cardiomyopathy.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 18 May 2023; epub ahead of print</small></div>

<div><h4>Influence of Monitoring and Atrial Arrhythmia Burden on Quality of Life and Healthcare Utilization in Patients Undergoing Pulsed Field Ablation: A Secondary Analysis of the PULSED AF Trial.</h4><i>Verma A, Haines DE, Boersma LV, Sood N, ... DeLurgio DB, PULSED AF investigators</i><br /><b>Background</b><br />Freedom from atrial arrhythmia (AA) recurrence ≥30 seconds following pulsed field ablation (PFA) in patients with atrial fibrillation (AF) was reported in PULSED AF (NCT04198701). AA burden may be a more clinically meaningful endpoint.<br /><b>Objective</b><br />To determine the influence of monitoring strategies on AA detection and AA burden association with quality of life (QoL) and healthcare utilization (HCU) following PFA.<br /><b>Methods</b><br />Patients underwent 24-hour Holter at 6 and 12 months and weekly and symptomatic trans-telephonic 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.<br /><b>Results</b><br />Freedom from all AAs varied >20% when differing monitoring strategies were employed. PFA resulted in zero burden in 69.4% of paroxysmal (PAF) and 62.2% of persistent (PsAF) AF 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<0.01).<br /><b>Conclusion</b><br />The ≥30-second AA endpoint is dependent on the monitoring protocol utilized. PFA resulted in low AA burden for most patients, which was associated with clinically relevant improvement in QoL and reduced AA-related HCU.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 17 May 2023; epub ahead of print</small></div>

<div><h4>MAgnetic resonance imaging based DUal lead cardiac Resynchronization therapy: A prospectIve Left Bundle Branch Pacing Study (MADURAI LBBP study).</h4><i>Ponnusamy SS, Ganesan V, Ramalingam V, Syed T, ... Murugan M, Vijayaraman P</i><br /><b>Background</b><br />Cardiac resynchronization therapy(CRT) is a class-I indication for LVEF≤35%, and heart failure(HF). LBBB associated nonischemic-cardiomyopathy (LB-NICM) with minimal or no scar by cardiac-magnetic-resonance(CMR) imaging may be associated with excellent prognosis following CRT. Left-bundle-branch-pacing(LBBP) can achieve excellent resynchronization in LBBB patients.<br /><b>Objectives</b><br />Aim of our study was to prospectively assess feasibility and efficacy of LBBP with or without a defibrillator in patients with LB-NICM and LVEF ≤35%, risk stratified by CMR.<br /><b>Methods</b><br />Pts with LB-NICM, LVEF≤35% and HF were prospectively enrolled from 2019 to 2022. If the scar burden<10% by CMR, LBBP only (Group-I) and if ≥10%, LBBP+ICD(Group-II) was performed. Primary endpoints-1.Echocardiographic-response(ER)- ΔLVEF ≥15% at 6 months; 2.Composite of time to death, HFH or sustained VT/VF. Secondary endpoints-1.Echocardiographic-hyper-response(EHR-LVEF≥50%orΔLVEF ≥20%) at 6 and 12 months; 2.Indication for ICD-upgradation(persistent LVEF<35% at 12 months or sustained VT/VF) <br /><b>Results:</b><br/>120 patients were enrolled. CMR showed <10% scar-burden in 109 patients(90.8%). 4 patients opted for LBBP+ICD and withdrew. LBBP optimized-dual-chamber-pacemaker(LOT-DDD-P) was done in 101 patients and LOT-CRT-P in 4 patients(Group-I,n=105). Scar-burden ≥10% in 11 pts who underwent LBBP+ICD(Group-II). During mean-follow-up 21±12 months, primary endpoint of ER observed in 80%(68/85 pts) in Group-I vs 27%(3/11 pts) in Group-II(p-0.0001). Primary composite-endpoint of death,HFH or VT/VF occurred in 3.8% in group-I vs 33.3% in Group-II(p<0.0001). Secondary endpoint of EHR(LVEF≥50%) observed in 39.5%vs0%, 61.2%vs9.1% and 80%vs33.3% at 3, 6 and 12 months in group-I and group-II respectively.<br /><b>Conclusion</b><br />CMR guided CRT using LOT-DDD-P appears to be a safe and feasible approach in LB-NICM and has the potential to reduce healthcare cost.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 17 May 2023; epub ahead of print</small></div>

<div><h4>2023 HRS Expert Consensus Statement on the Management of Arrhythmias During Pregnancy.</h4><i>Joglar JA, Kapa S, Saarel EV, Dubin AM, ... Zelop CM, Zentner D</i><br /><AbstractText>This international multidisciplinary expert consensus statement is intended to provide comprehensive guidance that can be referenced at the point of care to cardiac electrophysiologists, cardiologists, and other health care professionals, on the management of cardiac arrhythmias in pregnant patients and in fetuses. This document covers general concepts related to arrhythmias, including both brady- and tachyarrhythmias, in both the patient and the fetus during pregnancy. Recommendations are provided for optimal approaches to diagnosis and evaluation of arrhythmias; selection of invasive and noninvasive options for treatment of arrhythmias; and disease- and patient-specific considerations when risk stratifying, diagnosing, and treating arrhythmias in pregnant patients and fetuses. Gaps in knowledge and new directions for future research are also identified.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 16 May 2023; epub ahead of print</small></div>

<div><h4>Improved Outcomes of Conduction System Pacing in Heart Failure with Reduced Ejection Fraction - A Systematic Review and Meta-analysis.</h4><i>Gin J, Chow CL, Voskoboinik A, Nalliah C, ... Kalman JM, Wong GR</i><br /><AbstractText>Conduction system pacing (CSP) - His bundle pacing (HBP) and Left bundle branch area pacing (LBBAP) - are emerging alternatives to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT) in heart failure. However, evidence is largely limited to small and observational studies. We conducted a meta-analysis including a total of 15 randomized control trials (RCTs) and non-RCTs that compare CSP (HBP & LBBAP) with BVP in patients with CRT indications. We assessed the mean differences in QRS duration (QRSd), pacing threshold, left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class score. CSP resulted in a pooled mean QRSd improvement of -20.3 ms (95% CI -26.1 - -14.5, p<0.05, I<sup>2</sup>=87.1%) versus BVP. For LVEF, a weighted mean increase of 5.2% (95% CI 3.5-6.9, p<0.05, I<sup>2</sup>=55.6) was observed following CSP versus BVP. The mean NYHA score was reduced by -0.40 (95% CI -0.6 - -0.2, p<0.05, I<sup>2</sup>=61.7) post-CSP versus BVP. Subgroup analysis of outcomes by LBBAP and HBP demonstrated statistically significant weighted mean improvements from both CSP modalities for QRSd and LVEF compared to BVP. LBBAP resulted in NYHA improvement compared to BVP without differences between CSP subgroups. LBBAP is associated with a significantly lowered mean pacing threshold of -0.51V (95% CI -0.68 - -0.38) whilst HBP had increased the mean threshold (0.62V, 95% CI -0.03 - 1.26) compared to BVP, however, this was associated with significant heterogeneity. Overall, both CSP techniques are feasible and effective CRT alternatives for heart failure. Further RCTs are needed to establish long-term efficacy and safety.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 10 May 2023; epub ahead of print</small></div>

<div><h4>Atrial Fibrillation in Adult Congenital Heart Disease and the General Population.</h4><i>Wu MH, Chiu SN, Tseng WC, Lu CW, Kao FY, Huang SK</i><br /><b>Background</b><br />Atrial fibrillation (AF) among adults with congenital heart disease (ACHD) may appear early, depending on individual characteristics.<br /><b>Objective</b><br />To investigate the epidemiological spectrum of AF in the entire ACHD and compare to the general population.<br /><b>Methods</b><br />A retrospective study on nationwide cohort 2000-2014 with AF onset during 2003-2014.<br /><b>Results</b><br />In ACHD cohort, 2,350 patients had AF; incidence increased with age, plateauing around age 70. In patients aged 25-29, 45-49, 65-69, 75-79, and ≥80 years, the annual incidence was 1.3, 7.9, 20.6, 23.7, and 21.4/1,000, respectively. In the non-ACHD general population, 347,979 patients had AF; the annual incidence was <1/1,000 in those aged <55 years but increased steadily with age (3.6, 8.6, and 14.2/1,000 in aged 65-69, 75-79, and ≥80, respectively). Compared to the non-ACHD, the ACHD aged <50 and both those aged 50-54 and 55-59 exhibited a 20-fold and 10-fold higher incidence of AF, respectively. Patients with complex CHD and Ebstein\'s anomaly had the highest risk of AF (cumulative risk >10% by age 50; >20% by age 60), followed by those with tetralogy of Fallot, tricuspid atresia, endocardial cushion defect, and secundum atrial septal defect (cumulative risk >5% by age 50; >10% by age 60).<br /><b>Conclusion</b><br />Compared with non-ACHD cohort, AF in ACHD likely appeared 30 years earlier, with a 10-20-fold higher incidence plateauing around age 70. Yet, incidence in non-ACHD individuals continued to rise. AF burden in ACHD is not expected to expand in a never-ending way.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 09 May 2023; epub ahead of print</small></div>

<div><h4>Mild elevation of extracellular potassium greatly potentiates the effect of sodium channel block to cardiovert atrial fibrillation: The Lankenau approach.</h4><i>Burashnikov A, Antzelevitch C</i><br /><b>Background</b><br />Cardioversion of atrial fibrillation (AF) is a common clinical necessity and there is a need for more effective and safe options for acute cardioversion of AF.<br /><b>Objective</b><br />To test the hypothesis that the efficacy and time course of AF cardioversion by sodium channel current (I<sub>Na</sub>) block can be improved by mild elevation of extracellular potassium ([K<sup>+</sup>]<sub>0</sub>).<br /><b>Methods</b><br />Using a canine acetylcholine (ACh)-mediated AF model (isolated coronary-perfused right atrial preparations with a rim of right ventricle), we evaluated the ability of flecainide to suppress AF in the presence of [K<sup>+</sup>]<sub>0</sub> ranging from 3 to 8 mM.<br /><b>Results</b><br />At [K<sup>+</sup>]<sub>0</sub> of 4 mM (baseline), persistent AF (>1 hour) was induced in 5/5 atria in the presence of 0.5 μM ACh. Flecainide alone (1.5 μM) cardioverted 3/6 atria at 4 mM [K<sup>+</sup>]<sub>0</sub>, 1/6 atria at 3 mM [K<sup>+</sup>]<sub>0</sub>, 5/5 atria at 5 mM and 6 mM [K<sup>+</sup>]<sub>0</sub>, and 4/4 atria at 8 mM [K<sup>+</sup>]<sub>0</sub>. In the absence of flecainide, an increase in [K<sup>+</sup>]<sub>0</sub> from 4 to 5, 6 and 8 mM terminated AF in 0/5, 2/6, and 4/4 atria. The time to conversion was also abbreviated by elevation of [K<sup>+</sup>]<sub>0</sub>. Following AF termination with flecainide plus elevated [K<sup>+</sup>]<sub>0</sub>, AF was either not inducible or brief (< 100 sec). Combined flecainide and elevated [K<sup>+</sup>]<sub>0</sub> (6 mM) caused an atrial preferential depression of excitability.<br /><b>Conclusion</b><br />Our findings suggest that a combination of I<sub>Na</sub> block accompanied by mild elevation of serum potassium may be a novel approach to more effectively, rapidly, and safely cardiovert AF and prevent its recurrence in the short term.<br /><br />Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 09 May 2023; epub ahead of print</small></div>

<div><h4>Multicenter Clinical and Functional Evidence Reclassifies a Recurrent Non-canonical Filamin C Splice-altering Variant.</h4><i>O\'Neill MJ, Chen SN, Rumping L, Johnson R, ... Mestroni L, Shoemaker MB</i><br /><b>Background</b><br />Truncating variants in Filamin C (FLNC) can cause arrhythmogenic cardiomyopathy (ACM) through haploinsufficiency. Non-canonical splice-altering variants may contribute to this phenotype.<br /><b>Objective</b><br />To investigate the clinical and functional consequences of a recurrent FLNC intronic variant of uncertain significance (VUS), c.970-4A>G.<br /><b>Methods</b><br />Clinical data in 9 variant heterozygotes from 4 kindreds were obtained from 5 tertiary healthcare centers. We used in silico predictors and functional studies with peripheral blood and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Isolated RNA was studied by reverse transcription polymerase chain reaction (RT-PCR). iPSC-CMs were further characterized at baseline and following nonsense-mediated decay (NMD) inhibition, using quantitative PCR (qPCR), RNA-seq, and cellular electrophysiology. American College of Medical Genetics and Genomics (ACMG) criteria were used to adjudicate variant pathogenicity.<br /><b>Results</b><br />Variant heterozygotes displayed a spectrum of disease phenotypes, spanning mild ventricular dysfunction with palpitations, to severe ventricular arrhythmias requiring device shocks or progressive cardiomyopathy requiring heart transplantation. Consistent with in silico predictors, the c.970-4A>G FLNC variant activated a cryptic splice acceptor site, introducing a 3-bp insertion containing a premature termination codon. NMD inhibition upregulated aberrantly spliced transcripts by qPCR and RNA-seq. Patch clamp studies revealed irregular spontaneous action potentials, increased action potential duration, and increased sodium late current in proband-derived iPSC-CMs. These findings fulfilled multiple ACMG criteria for pathogenicity.<br /><b>Conclusion</b><br />Clinical, in silico, and functional evidence support the prediction that the intronic c.970-4A>G VUS disrupts splicing and drives ACM, enabling reclassification from VUS to pathogenic.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 08 May 2023; epub ahead of print</small></div>

<div><h4>Stereotactic arrhythmia radioablation: a novel therapy for cardiac arrhythmia.</h4><i>Wang S, Luo H, Mao T, Xiang C, ... Yu L, Jiang H</i><br /><AbstractText>Cardiac arrhythmia is a global health problem, and catheter ablation has been one of its main treatments for decades. However, catheter ablation is an invasive method that cannot reach the deep myocardium, and it carries a considerable risk of side effects and recurrence. Therefore, it is necessary to explore a novel approach is necessary. Stereotactic body radiotherapy(SBRT), which has been widely used in the field of radiation oncology, has recently expanded in the treatment of cardiac arrhythmia; when used in this context, it is known as stereotactic arrhythmia radioablation(STAR). As a non-invasive, effective and well-tolerated treatment, STAR may be a suitable alternative method for patients with cardiac arrhythmia who are resistant or intolerant to catheter ablation. The main particles used to deliver energy in STAR are photons, protons and carbon ions. Most studies have shown the short-term effectiveness of STAR, but problems such as a high long-term recurrence rate with a cumulative VT-free survival from the published literature of 38.6%, and related complications have also emerged. Therefore, in this article, we review the application of SBRT in cardiac arrhythmia, analyze its potential problems and explore methods for improvement.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 05 May 2023; epub ahead of print</small></div>

<div><h4>Safety evaluation of smart scales, smart watches, and smart rings with bioimpedance technology shows evidence of potential interference in cardiac implantable electronic devices.</h4><i>Ha GB, Steinberg BA, Freedman R, Bayés-Genís A, Sanchez B</i><br /><b>Background</b><br />Smart scales, smart watches, and smart rings with bioimpedance technology may create interference in patients with cardiac implantable electronic devices (CIEDs).<br /><b>Objectives</b><br />The purpose of this study was to determine interference at CIEDs with simulations and benchtop testing, and to compare the results with maximum values defined in the ISO 14117 electromagnetic interference standard for these devices.<br /><b>Methods</b><br />The interference at pacing electrodes was determined by simulations on a male and a female computable model. A benchtop evaluation of representative CIEDs from 3 different manufacturers as specified in the ISO 14117 standard also was performed.<br /><b>Results</b><br />Simulations showed evidence of interference with voltage values exceeding threshold values defined in the ISO 14117 standard. The level of interference varied with the frequency and amplitude of the bioimpedance signal, and between male and female models. The level of interference generated with smart scale and smart rings simulations was lower than with smart watches. Across device manufacturers, generators demonstrated susceptibility to oversensing and pacing inhibition at different signal amplitudes and frequencies.<br /><b>Conclusions</b><br />This study evaluated the safety of smart scales, smart watches, and smart rings with bioimpedance technology via simulation and testing. Our results indicate that these consumer electronic devices could interfere in patients with CIEDs. The present findings do not recommend the use of these devices in this population due to potential interference.<br /><br />Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 01 May 2023; 20:561-571</small></div>

<div><h4>Breathless Nights and Heart Flutters: Understanding the Relationship Between Obstructive Sleep Apnea and Atrial Fibrillation.</h4><i>Mills EW, Antman EM, Javaheri S</i><br /><AbstractText>There is an extraordinary and increasing global burden of atrial fibrillation (AF) and obstructive sleep apnea (OSA), two conditions which frequently accompany one another and which share underlying risk factors. Whether a causal pathophysiologic relationship connects OSA to the development and/or progression of AF, or whether shared risk factors promote both conditions, is unproven. With increasing recognition of the importance of controlling AF-related risk factors, numerous observational studies now highlight the potential benefits of OSA treatment on AF-related outcomes. Physicians are regularly faced with caring for this important and increasing population of patients despite a paucity of clinical guidance on the topic. Here, we review the clinical epidemiology and pathophysiology of AF and OSA with a focus on key clinical studies and major outstanding questions that should be addressed in future studies.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 29 Apr 2023; epub ahead of print</small></div>

<div><h4>Deciphering hERG Mutation in Long QT Syndrome Type 2 Using Antisense Oligonucleotide-Mediated Techniques: Lessons from Cystic Fibrosis.</h4><i>Zheng Z, Song Y, Tan X</i><br /><AbstractText>Long QT syndrome type 2 (LQT2) is a genetic disorder caused by mutations in the KCNH2 gene, also known as the human ether-a-go-go-related gene (hERG). Over 30% of hERG mutations result in a premature termination codon (PTC) that triggers a process called nonsense-mediated mRNA decay (NMD), where the mRNA transcript is degraded. NMD is a quality control mechanism that removes faulty mRNA to prevent the translation of truncated proteins. Recent advances in antisense oligonucleotide (ASO) technology in the field of cystic fibrosis (CF) have yielded significant progress, including the ASO-mediated comprehensive characterization of key NMD factors and exon-skipping therapy. These advances have contributed to our understanding of the role of PTC-containing mutations in disease phenotypes and have also led to the development of potentially useful therapeutic strategies. Historically, studies of CF have provided valuable insights for the research on LQT2, particularly concerning increasing the expression of hERG. In this article, we outline the current state of knowledge regarding ASO, NMD, and hERG and discuss the introduction of ASO technology in the CF to elucidate the pathogenic mechanisms through targeting NMD. We also discuss the potential clinical therapeutic benefits and limitations of ASO for the management of LQT2. By drawing on lessons learned from CF research, we explore the potential translational values of these advances into LQT2 studies.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 28 Apr 2023; epub ahead of print</small></div>

<div><h4>Quality improvement and the Rumsfeld Matrix.</h4><i>Sandhu RK, Andrade JG</i><br /><AbstractText>In this issue of the Journal, Chui and colleagues<sup>3</sup> report on the results of a large retrospective observational study evaluating CRT-D utilization rates across hospitals, and the impact of this variation on mortality and readmission rates. The population included 30,134 guideline-eligible adult patients treated at 1,377 hospitals. Patients were identified using the National Cardiovascular Data Registry (NCDR) ICD registry with outcomes evaluated by linkage with Medicare claims data. The key findings include: (i) a wide variation in hospital rates of CRT-D utilization (range 0-100%), (ii) after adjustment of patient- and hospital-level characteristics, most of the variation in CRT-D utilization rates was attributable to the hospital in which the patient was receiving care (interclass correlation, 0.74), and (iii) a significant proportion of mortality and readmission were attributable to hospital variation in CRT utilization. Based on their findings, the authors suggest hospital rates of appropriate CRT-D implantation should be a be considered as a performance measure suitable for quality improvement, value-based care, and potentially public reporting.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 22 Apr 2023; epub ahead of print</small></div>

<div><h4>Author\'s reply to Dynamic Exposure: Good Practices in Survival Analysis.</h4><i>D\'Onofrio A, Gargaro A</i><br /><AbstractText>Hence, our original results are conservative. Two caveats may be worth considering regarding results of time-dependent covariate analyses. First, they should not be used for long-term risk assessment. Second, they are increasingly dependent on temporal variations of other uncontrolled variables (e.g., therapy changes) with shorter analysis intervals.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 18 Apr 2023; epub ahead of print</small></div>

<div><h4>Safety of Magnetic Resonance Imaging in Patients with Surgically Implanted Permanent Epicardial Leads.</h4><i>Ma YD, Watson RE, Olson NE, Birgersdotter-Green U, ... Friedman PA, Cha YM</i><br /><b>Background</b><br />Magnetic resonance imaging (MRI) safety in patients with an epicardial cardiac implantable electronic device (CIED) is uncertain.<br /><b>Objective</b><br />To assess the safety and adverse effects of MRI in patients who had surgically implanted epicardial CIED.<br /><b>Methods</b><br />Patients with surgically implanted CIEDs who underwent MRI with an appropriate Cardiology-Radiology collaborative protocol between January 2008 and January 2021 were prospectively studied in two clinical centers. All patients underwent close cardiac monitoring through MRI procedures. Outcomes were compared between the epicardial CIED group and matched the non-MRI-conditional transvenous CIED group.<br /><b>Results</b><br />Twenty-nine consecutive patients with epicardial CIED (male 41.4%, mean age of 43 years) underwent 52 MRIs in the 57 anatomic regions. Sixteen patients had pacemakers, 9 had cardiac defibrillators or cardiac resynchronization therapy defibrillators, and 4 had no device generators. There were no significant adverse events in epicardial or transvenous CIED groups. The battery life, pacing, sensing thresholds, lead impedance and cardiac biomarkers were not significantly changed, except one patient had a transient decrease in atrial lead sensing function.<br /><b>Conclusion</b><br />MRI of CIEDs with epicardially implanted leads does not represent a greater risk than the transvenous CIEDs when performed with a multidisciplinary collaborative protocol centered on patient safety.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 17 Apr 2023; epub ahead of print</small></div>

<div><h4>Dual-Chamber Leadless Pacing: Atrioventricular Synchrony in Preclinical Models of Normal or Blocked Atrioventricular Conduction.</h4><i>Reddy VY, Neuzil P, Booth DF, Knops RE, ... Ligon D, Ip JE</i><br /><b>Background</b><br />Dual-chamber leadless pacemakers (LP) require robust communication between distinct right atrial (RA) and right ventricular (RV) LPs to achieve atrioventricular (AV) synchrony.<br /><b>Objective</b><br />This preclinical study evaluated a novel, continuous implant-to-implant (i2i™) communication methodology for maintaining AV-synchronous, dual-chamber DDD(R) pacing by the 2 LPs.<br /><b>Methods</b><br />RA and RV LPs were implanted and paired in 7 ovine subjects, 4 of 7 with induced complete heart block. AV synchrony (% AV intervals <300 ms) and i2i communication success (% successful i2i transmissions between LPs) were evaluated acutely and chronically. During acute testing, 12-lead ECG and LP diagnostic data were collected from 5-minute recordings, in 4 postures and 2 rhythms (AP-VP and AS-VP or AP-VS and AS-VS) per subject. Chronic i2i performance was evaluated through 23 weeks post-implant (final i2i evaluation period: week 16-23).<br /><b>Results</b><br />Acute AV synchrony and i2i communication success across multiple postures and rhythms were 100.0% [100.0-100.0] (median [interquartile range]) and 99.9% [99.9-99.9], respectively. AV synchrony and i2i success rates did not differ across postures (P=0.59, P=0.11) or rhythms (P=1.00, P=0.82). During the final i2i evaluation period, the overall i2i success was 98.9% [98.1-99.0].<br /><b>Conclusion</b><br />Successful AV-synchronous, dual-chamber DDD(R) leadless pacing using a novel, continuous, wireless communication modality was demonstrated across variations in posture and rhythm in a preclinical model.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 17 Apr 2023; epub ahead of print</small></div>

<div><h4>Combination of Slow Pathway Late Activation Maps and Voltage Gradient Maps in Guidance of Atrioventricular Nodal Reentry Tachycardia Cryoablation.</h4><i>Tseng WC, Wu MH, Lu CW, Wu KL, ... Chen CA, Chiu SN</i><br /><b>Background</b><br />The optimal strategy for electroanatomic mapping-guided cryoablation of atrioventricular nodal reentry tachycardia (AVNRT) remains unclear.<br /><b>Objective</b><br />To investigate the effectiveness of slow pathway late activation mapping (SPLAM) and voltage gradient mapping for AVNRT cryoablation.<br /><b>Methods</b><br />From June 2020 to February 2022, all consecutive patients with AVNRT underwent SPLAM to define the wave collision point and voltage gradient mapping to define the low voltage bridge (LVB). Conventional procedures performed from August 2018 to May 2020 served as control.<br /><b>Results</b><br />The study and control groups comprised 36 (aged 16.5±8.2 years) and 37 patients (aged 15.5±7.3 years), respectively. Total procedural times were comparable, and acute success rates were 100% in both groups. Compared to controls, number of cryomapping attempts (median 3 vs. 5, p=0.012) and cryoablation applications (median 1 vs. 2, p<0.001) were significantly lower in the study group. At a median follow-up of 14.6 and 18.3 months, recurrence rates were 5.6% (2 patients) and 10.8% (4 patients) in the study and control groups (p=0.402), respectively. Mapping of Koch\'s triangle took 11.8±3.6 min, in which 1562±581 points were collected. In SPLAM, wave collision points were defined and compatible with the final successful lesion sites in all patients, including those with multiple slow pathways. LVB could not be defined in 6 patients (16.7%), and LVB was not compatible with the final successful lesion in another 6 (16.7%).<br /><b>Conclusions</b><br />For AVNRT cryoablation, SPLAM could effectively guide the localization of slow pathway ablation sites and was particularly beneficial in patients with multiple slow pathways.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 17 Apr 2023; epub ahead of print</small></div>

<div><h4>Causes and Clinical Consequences of Inappropriate Shocks Experienced by Patients Wearing a Cardioverter-Defibrillator.</h4><i>Berger JM, Sengupta JD, Bank AJ, Casey SA, ... Stanberry LI, Hauser RG</i><br /><b>Background</b><br />The LifeVest® wearable cardioverter-defibrillator (WCD) prevents sudden cardiac death in at-risk patients who are not candidates for an implantable defibrillator. The WCD\'s safety and efficacy may be impacted by inappropriate shocks (IAS).<br /><b>Objective</b><br />Assess causes and clinical consequences of WCD inappropriate shocks in survivors of IAS events.<br /><b>Methods</b><br />The FDA Manufacturers and User Facility Device Experience (MAUDE) database was searched for IAS adverse events (AE) that were reported during 2021 and 2022.<br /><b>Results</b><br />A total of 2,568 IAS-AE were found (average # IAS/event: 1.5±1.9; range: 1-48). IAS were caused by tachycardias (1,255, 48.9%), motion artifacts (840, 32.7%), and oversensing (OS) of low-level electrical signals (473, 18.4%) (p<0.001). Tachycardias included atrial fibrillation (AF; 828,32.2%), supraventricular tachycardia (SVT; 333,13.0%), and non-sustained ventricular tachycardia/fibrillation (NSVT/VF; 87, 3.4%). Activities responsible for motion-induced IAS included riding a motorcycle, lawnmower, or tractor (n=128). IAS induced sustained VT or VF in 19 patients that were subsequently terminated by appropriate WCD shocks.Thirty patients fell and suffered physical injuries. Conscious patients (n=1905) did not use the response buttons to abort shocks (47.9%) or used them improperly (20.2%). IAS resulted in 1,190 emergency room visits or hospitalizations, and 17.3% (421/2440) of patients discontinued the WCD after experiencing IAS, especially multiple IAS.<br /><b>Conclusions</b><br />The LifeVest WCD may deliver IAS caused by AF, SVT, NSVT/VF, motion artifacts and oversensing of electrical signals. These shocks may be arrhythmogenic, result in injuries, precipitate WCD discontinuation, and they consume medical resources. Improved WCD sensing, rhythm discrimination, and methods to abort IAS are needed.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 13 Apr 2023; epub ahead of print</small></div>

<div><h4>High-density electro-anatomical activation mapping to guide slow pathway modification in patients with persistent left superior vena cava.</h4><i>Gerontitis D, Pope MT, Elmowafy M, Sadagopan S, Yue AM</i><br /><b>Background</b><br />Slow pathway (SP) mapping and modification can be challenging in patients with persistent left superior vena cava (PLSVC) due to anatomical variance of Koch\'s triangle (KT) and coronary sinus (CS) dilatation. There is a lack of studies using detailed 3-dimensional (3D) electro-anatomical mapping (EAM) to investigate conduction characteristics and guide ablation targets in this condition.<br /><b>Objectives</b><br />To describe a novel technique of slow pathway mapping and ablation in sinus rhythm using 3D EAM in patients with PLSVC after validation in a cohort with normal coronary sinus anatomy.<br /><b>Methods</b><br />Seven patients with PLSVC and dual AV node physiology who underwent slow pathway modification with the use of 3D EAM were included. Twenty-one normal heart patients with AV nodal re-entrant tachycardias formed the validation group. High-resolution, ultra-high-density local activation timing (LAT) mapping of the right atrial septum and proximal coronary sinus in sinus rhythm was performed.<br /><b>Results</b><br />SP ablation targets were consistently identified by an area in the right atrial septum with the latest activation time and multi-component atrial electrogram (EGM) adjacent to a region with isochronal crowding (deceleration zone). In PLSVC patients, these targets were located at or within 1 cm of the mid anterior CS ostium. Ablation in this area led to successful SP modification reaching standard clinical endpoints with a median of 43 sec of radio frequency energy or 14 mins of cryoablation without complications.<br /><b>Conclusion</b><br />High-resolution activation mapping of Koch\'s triangle in sinus rhythm can facilitate localisation and safe slow pathway ablation in patients with PLSVC.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 03 Apr 2023; epub ahead of print</small></div>

<div><h4>2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.</h4><i>Ferrick AM, Raj SR, Deneke T, Kojodjojo P, ... Stühlinger M, Varosy PD</i><br /><AbstractText>Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 30 Mar 2023; epub ahead of print</small></div>

<div><h4>Utility of a multi-purpose catheter for transvenous extraction of old broken leads: A novel technique for fragile leads.</h4><i>Okada A, Higuchi S, Shoda M, Tabata H, ... Motoki H, Kuwahara K</i><br /><b>Background</b><br />Transvenous lead extraction has been possible since the 1980s. However, complications during lead extraction, such as the distal end fragment of the lead remaining in the myocardium or venous system and injury to the veins or heart, have been reported.<br /><b>Objective</b><br />Extraction of long-term implanted devices is difficult using standard methods and may require additional procedures. Therefore,. the removal of leads with inner conductor coil and lead tip separated from outer insulation, conductor coil and proximal ring electrode using a multi-purpose catheter is reported.<br /><b>Methods</b><br />In total, 345 consecutive patients who underwent transvenous lead extraction (TLE) from April 2014 to March 2021 were retrospectively analyzed. Lead characteristics, device type, and indications for extraction were further analyzed in 20 patients who developed separation of the proximal ring electrode and outer conductor coil from the inner conductor and distal tip at the time of extraction.<br /><b>Results</b><br />Extractions were performed using an excimer laser sheath laser and a Byrd polypropylene telescoping sheath (n=15), a laser, a Byrd polypropylene telescoping sheath, and an Evolution RL (n=2), a laser and an Evolution RL (n=3), a Byrd polypropylene telescoping sheath and an Evolution RL (n=1), a Byrd polypropylene telescoping sheath only (n=4), and an Evolution RL only (n=2). Twenty-seven leads had been implanted >10 years ago, which resulted in lead separation. A multi-purpose catheter was used to protect the fragile leads from further damage. All leads were completely extracted.<br /><b>Conclusion</b><br />All distal tip-to-proximal ring electrode separated leads were successfully removed using laser and other sheaths with the assistance of a multi-purpose catheter, without any part of the leads remaining in the heart.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 29 Mar 2023; epub ahead of print</small></div>

<div><h4>Predicting all-cause mortality by means of multisensor implantable defibrillator algorithm for HF monitoring.</h4><i>D\'Onofrio A, Vitulano G, Calò L, Bertini M, ... Valsecchi S, Boriani G</i><br /><b>Background</b><br />The HeartLogic algorithm has proved to be a sensitive and timely predictor of impending heart failure (HF) decompensation.<br /><b>Objective</b><br />To determine whether remotely monitored data from this algorithm could be used to identify patients at high risk of mortality.<br /><b>Methods</b><br />The algorithm combines implantable defibrillator (ICD)-measured accelerometer-based heart sounds, intrathoracic impedance, respiration rate, the ratio of respiration rate to tidal volume, night heart rate, and patient activity into a single index. An alert is issued when the index crosses a programmable threshold. The feature was activated in 568 ICD patients from 26 centers.<br /><b>Results</b><br />During a median follow-up of 26 months [25th-75th percentile: 16-37], 1200 alerts were recorded in 370 (65%) patients. Overall, the time IN-alert state was 13% of the total observation period (151 out of 1159 years) and 20% of the follow-up period of the 370 patients with alerts. During follow-up, 55 patients died (46 in the group with alerts). The rate of death was 0.25/patient-year (95% CI: 0.17-0.34) IN-alert state and 0.02/patient-year (95% CI: 0.01-0.03) OUT of the alert state, with an incidence rate ratio of 13.72 (95% CI: 7.62-25.60, p<0.001). After multivariate correction for baseline confounders (age, ischemic cardiomyopathy, kidney disease, atrial fibrillation), the IN-alert state remained significantly associated with the occurrence of death (hazard ratio: 9.18, 95% CI: 5.27-15.99, p<0.001).<br /><b>Conclusion</b><br />The HeartLogic algorithm provides an index that can be used to identify patients at higher risk of all-cause mortality. The index state identifies periods of significantly increased risk of death.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 24 Mar 2023; epub ahead of print</small></div>

<div><h4>Sudden Cardiac Arrest During the COVID-19 Pandemic: A Two-Year Prospective Evaluation in a North American Community.</h4><i>Chugh HS, Sargsyan A, Nakamura K, Uy-Evanado A, ... Chugh SS, Reinier K</i><br /><b>Background</b><br />Early in the COVID-19 pandemic, higher SCA incidence and lower survival rates were reported. However, ongoing effects on SCA during the evolving pandemic have not been evaluated.<br /><b>Objective</b><br />We assessed the impact of COVID-19 on SCA during two years of the pandemic.<br /><b>Methods</b><br />In a prospective study of Ventura County, CA (2020 Pop. 843,843; 44.1% Hispanic), we compared SCA incidence and outcomes during the first two years of the COVID-19 pandemic to the prior four years.<br /><b>Results</b><br />Of 2,222 OHCA cases identified, 907 occurred during the pandemic (March 2020 - Feb 2022) and 1315 occurred pre-pandemic (March 2016 - Feb 2020). Overall age-standardized annual SCA incidence increased from 39/100,000 [95% CI 37-41] pre-pandemic to 54/100,00 [95% CI 50 - 57, p<0.001] during the pandemic. Among Hispanics, incidence increased by 77%, from 38/100,00 [95% CI 34-43] to 68/100,00 [95% CI 60-76, p<0.001]. Among non-Hispanics, incidence increased by 26% from 39/100,000 [95% CI 37-42, p<0.001] to 50/100,00 [95% CI 46-54]. SCA incidence rates closely tracked COVID-19 infection rates. During the pandemic, SCA survival was significantly reduced (15% to 10%, p<0.001) and Hispanics were less likely than non-Hispanics to receive bystander CPR (45% vs. 55%, p=0.005) and present with shockable rhythm (15% vs. 24%, p=0.003).<br /><b>Conclusion</b><br />Overall SCA rates remained consistently higher and survival outcomes consistently lower, with exaggerated effects during COVID infection peaks. This longer evaluation uncovered higher increases in SCA incidence among Hispanics, with worse resuscitation profiles. Potential ethnicity-specific barriers to acute SCA care warrant urgent evaluation and intervention.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 23 Mar 2023; epub ahead of print</small></div>

<div><h4>Long-term risk of cardiovascular implantable electronic device re-interventions following external cardioversion of atrial fibrillation and flutter - a nationwide cohort study.</h4><i>Elgaard AF, Dinesen PT, Riahi S, Hansen J, ... Lip GYH, Larsen JM</i><br /><b>Background</b><br />External cardioversion (ECV) is an essential part of rhythm control of atrial fibrillation and flutter in patients with and without cardiovascular implantable electronic devices (CIED). Long-term follow-up data on ECV-related CIED dysfunctions are limited.<br /><b>Objective</b><br />This study aims to investigate the risk of CIED re-intervention following ECV in a nationwide cohort.<br /><b>Methods</b><br />We identified CIED implants and surgical re-interventions from 2005 to 2021 in the Danish Pacemaker and ICD Register. We included CIED patients undergoing ECV from 2010 to 2019 from the Danish National Patient Registry. For each ECV-exposed generator, five matched generators without ECV were identified, and for each ECV-exposed lead, three matched leads. The primary endpoints were generator replacement and lead re-intervention.<br /><b>Results</b><br />We compared 2,582 ECV-exposed patients with 12,910 matched patients with pacemakers (47%), ICDs (29%), CRT-pacemakers (6%), or CRT-defibrillators (18%). During 2 years of follow-up, 210 (8.1%) ECV-exposed generators vs. 670 (5.2%) matched generators underwent replacements, and 247 (5.6) ECV-exposed leads vs. 306 (2.3%) matched leads underwent re-intervention. The unadjusted hazard ratios were 1.61 (95%CI:1.37;1.91, p<0.001) for generator replacement and 2.39 (95%CI:2.01;2.85, p<0.001) for lead re-intervention. The 1-year relative risks were 1.73 (95%CI:1.41;2.12, p<0.001) for generator replacement and 2.85 (95%CI:2.32;3.51, p<0.001) for lead re-intervention, and the 2-years relative risks were 1.39 (95%CI:1.19;1.63, p<0.001) and 2.18 (95%CI:1.84;2.57, p<0.001), respectively.<br /><b>Conclusion</b><br />External cardioversion in patients with cardiovascular implantable electronic devices is associated with a higher risk of generator replacement and lead re-intervention. The risks of re-interventions were more pronounced within the first year after cardioversion.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 23 Mar 2023; epub ahead of print</small></div>

<div><h4>Variation in hospital use of cardiac resynchronization therapy-defibrillator among eligible patients and association with clinical outcomes.</h4><i>Chui PW, Lan Z, Freeman JV, Enriquez AD, ... Ong EL, Curtis JP</i><br /><b>Background</b><br />Despite strong guideline recommendations for cardiac resynchronization therapy-defibrillator (CRT-D) In select patients, this therapy is underutilized with substantial variation among hospitals, and the association of this variation with outcomes is unknown.<br /><b>Objective</b><br />To assess if facility variation in CRT-D utilization is associated with differences in hospital-level outcomes <br /><b>Methods:</b><br/>We linked Medicare claims data with the NCDR ICD Registry from 2010 to 2015. We assessed the intraclass correlation coefficient to quantify the degree of variation in patient-level CRT usage that can be explained by interfacility variation on a hospital level. To quantify the degree of hospital variation in patient-level outcomes (all-cause mortality, readmissions, and cardiac readmissions) that can be attributed to variations in CRT-D usage, we utilized multi-level modeling.<br /><b>Results</b><br />The study included 30,134 patients across 1,377 hospitals. The median rate of CRT-D implantation among those meeting guideline indications was 89%, but there was a wide variation across hospitals. After adjustment, most of the variation (74%) in hospital rates of CRT-D utilization was attributable to the hospital in which the patient was treated. Differences in hospital CRT-D utilization was associated with 8.76%, 5.26%, and 4.71% of differences in hospital mortality, readmissions, and cardiac readmission rates, respectively (p<0.001 for all outcomes).<br /><b>Conclusions</b><br />There is wide variation in the use of CRT-D across hospitals that was not explained by case mix. Hospital-level variation in CRT-D utilization was associated with clinically significant differences in outcomes. A measure of CRT-D utilization in eligible patients may serve as a useful metric for quality improvement efforts.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 22 Mar 2023; epub ahead of print</small></div>

<div><h4>Sinus Rhythm Electrocardiographic Abnormalities, Sites of Origin, and Ablation Outcomes of Ventricular Premature Depolarizations Initiating Ventricular Fibrillation.</h4><i>Arceluz MR, Thind M, Garcia FC, Guandalini GS, ... Zado ES, Marchlinski FE</i><br /><b>Background</b><br />Ventricular fibrillation (VF) can be initiated by ventricular premature depolarizations (VPDs) in the absence of obvious structural abnormalities.<br /><b>Objective</b><br />To determine the prevalence of 12-lead ECG sinus rhythm reduced QRS amplitude, QRS fractionation (QRSf) and early repolarization (ER) pattern, and the outcome of catheter ablation and VPD anatomic distribution in patients with VPDs initiating VF.<br /><b>Methods</b><br />We compared a cohort with no apparent structural heart disease and VPDs initiating VF (Group 1, n=42) to a reference cohort (Group 2, n=61) of patients with no structural heart disease and symptomatic unifocal VPDs.<br /><b>Results</b><br />A reduced QRS amplitude (<.55 mV) in aVF (59 % vs 10%, p<0.001), QRSf in ≥2 contiguous leads (50% vs 16%, p<0.001) and early repolarization pattern (21.4% vs 1.6%, p=0.01) were more common in Group 1 vs Group 2. At least one abnormal ECG finding was present in 34 (81%) Group 1 vs 17 (28%) Group 2 patients, (p<0.001). VPD origin included RV and LV distal Purkinje system and moderator band/ papillary muscles, in 83% Group 1 vs 18% Group 2 patients, p<0.001. VF was eliminated with single ablation procedure in 77% of Group 1 patients with at least 2 years of follow-up.<br /><b>Conclusions</b><br />A reduced QRS amplitude (<.55 mV) in aVF, QRS fractionation in ≥2 contiguous leads and/or an early repolarization pattern are frequently observed in patients with VPDs initiating VF. VPDs initiating VF typically originate from the distal Purkinje system and papillary muscles and can be successfully eliminated with catheter ablation.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 21 Mar 2023; epub ahead of print</small></div>

<div><h4>SCAI/HRS expert consensus statement on transcatheter left atrial appendage closure.</h4><i>Saw J, Holmes DR, Cavalcante JL, Freeman JV, ... Wang DD, Whisenant BK</i><br /><AbstractText>Exclusion of the left atrial appendage to reduce thromboembolic risk related to atrial fibrillation was first performed surgically in 1949. Over the past 2 decades, the field of transcatheter endovascular left atrial appendage closure (LAAC) has rapidly expanded, with a myriad of devices approved or in clinical development. The number of LAAC procedures performed in the United States and worldwide has increased exponentially since the Food and Drug Administration approval of the WATCHMAN (Boston Scientific) device in 2015. The Society for Cardiovascular Angiography & Interventions (SCAI) has previously published statements in 2015 and 2016 providing societal overview of the technology and institutional and operator requirements for LAAC. Since then, results from several important clinical trials and registries have been published, technical expertise and clinical practice have matured over time, and the device and imaging technologies have evolved. Therefore, SCAI prioritized the development of an updated consensus statement to provide recommendations on contemporary, evidence-based best practices for transcatheter LAAC focusing on endovascular devices.</AbstractText><br /><br />Copyright © 2023 [Author/Employing Institution]. Published by Elsevier Inc. All rights reserved.<br /><br /><small>Heart Rhythm: 20 Mar 2023; epub ahead of print</small></div>

<div><h4>Bilateral Cardiac Sympathetic Denervation in Patients with Congenital Long QT Syndrome.</h4><i>Tobert KE, Bos JM, Moir C, Polites SF, Ackerman MJ</i><br /><b>Background</b><br />Long QT syndrome (LQTS) is a potentially lethal, yet treatable genetic heart disease for which left cardiac sympathetic denervation (LCSD) is a class I recommendation. Recent reports have suggested bilateral CSD (BiCSD) as the initial surgical denervation therapy in LQTS.<br /><b>Objective</b><br />To determine the frequency and settings in which BiCSD was used in a tertiary referral center with expertise in LCSD.<br /><b>Methods</b><br />We performed retrospective review of 234 LCSD patients/1,638 (14%) LQTS patients who underwent sympathetic denervation at our institution to identify the subset with BiCSD. Cardiac events (CEs) before LCSD, after LCSD, and after completion of BiCSD were recorded and defined as being an appropriate ICD shock, arrhythmic syncope or sudden cardiac arrest.<br /><b>Results</b><br />Only 11 patients (4.7%, 6[55%] females) had BiCSD at our institution. Patients who received BiCSD trended towards being younger at diagnosis (6±15 vs. 14±13 years, p=0.06) and being more likely to be symptomatic (73% vs. 53%, p=0.07) than the larger LCSD-only cohort. Continued CEs post-LCSD (3.8 CEs per patient on average) was the predominant determinant to return for BiCSD. Over 60 combined years of follow-up, 4 patients have not had a post-BiCSD CE, while the other 7 patients average 3.6 non-lethal CEs.<br /><b>Conclusions</b><br />Less than 5% of all patients receiving denervation therapy underwent BiCSD. When BiCSD was chosen, it was almost always done in a staged sequential manner starting with LCSD first and when driven by the arrhythmogenicity of the LQTS substrate, despite otherwise optimized guideline-directed therapies.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 17 Mar 2023; epub ahead of print</small></div>

<div><h4>Clinical Predictors of Incomplete CS Lead Removal during Transvenous Lead Extraction in the Patients with Cardiac Resynchronization Therapy.</h4><i>Hayashi K, Younis A, Callahan T, Baranowski B, ... Nakhla S, Wilkoff BL</i><br /><b>Background</b><br />Reports of coronary sinus (CS) lead removal include small studies with short implant durations. Procedural outcomes for mature CS leads removed with long duration implantation are unavailable.<br /><b>Objective</b><br />To examine the safety, efficacy, and clinical predictors for incomplete CS lead removal by Transvenous Lead Extraction (TLE) in a large, long implant duration cardiac resynchronization therapy (CRT) patient cohort.<br /><b>Methods</b><br />Consecutive patients with CRT devices in the Cleveland Clinic Prospective TLE Registry who had TLE between 2013 and 2022.<br /><b>Results</b><br />CS leads, n=231, implant duration = 6.1±4.0 years, removed from 226 patients were included, employing powered sheaths for 137 leads (59.3%). Complete CS lead success was achieved in 95.2% of leads (n=220) and in 95.6% of patients (n=216). Major complications occurred in 5 patients (2.2%). Patients who had the CS lead extracted 1st had significantly higher incomplete removal rates than when the other leads were 1st removed. Multivariable analysis showed that older CS lead age (OR 1.35, 95% CI 1.01-1.82; P = 0.03), and removing the CS lead 1st (OR 7.48, 95% CI 1.02-54.95; P = 0.045) were independent predictors of incomplete CS lead removal.<br /><b>Conclusion</b><br />Complete and safe lead removal rate of long implant duration CS leads by TLE was 95%. However, CS lead age and the order that leads were extracted were the independent predictors of incomplete CS lead removal. Therefore, before the CS lead is extracted, physicians should first extract the leads from the other chambers and employ powered sheaths.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 16 Mar 2023; epub ahead of print</small></div>

<div><h4>Imaging Modality for Left Ventricular Ejection Fraction Estimation and Effect of Implantable Cardioverter Defibrillator on Mortality in Patients with Heart Failure.</h4><i>Smith A, Kumar S, Moore HJ, Iskandrian AE, ... Ahmed A, Lam PH</i><br /><b>Background</b><br />Implantable cardioverter-defibrillators (ICD) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known whether outcomes varied between the two non-invasive imaging modalities used to estimate LVEF, the 2-dimensional echocardiography (2DE) and multi-gated acquisition radionuclide ventriculography (MUGA), which use different principles (geometric vs. count-based, respectively).<br /><b>Objectives</b><br />To examine if the effect of ICD on mortality in patients with HF and LVEF ≤35% varied based on LVEF measured by 2DE or MUGA.<br /><b>Methods</b><br />Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), 1676 were randomized to either placebo or ICD, of whom 1386 had LVEF measured by 2DE (n=971) or MUGA (n=415). Hazard ratios (HRs) and 97.5% CIs for mortality associated with ICD use were estimated overall, checking for interaction, and within the two imaging subgroups.<br /><b>Results</b><br />Among the 1386 patients in the current analysis, all-cause mortality occurred in 23.1% (160/692) and 29.7% (206/694) of patients randomized to ICD or placebo, respectively (HR, 0.77; 97.5% CI, 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.46-1.11), respectively (p for interaction, 0.693). Similar associations were observed for cardiac and arrhythmic mortalities.<br /><b>Conclusions</b><br />We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the non-invasive imaging method used to measure LVEF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 10 Mar 2023; epub ahead of print</small></div>

<div><h4>Rate and nature of complications of conduction system pacing compared with right ventricular pacing: results of a propensity-matched analysis from a multicentre registry.</h4><i>Palmisano P, Ziacchi M, Dell\'Era G, Donateo P, ... Biffi M, Accogli M</i><br /><b>Background</b><br />Conduction system pacing (CSP) using His-bundle pacing (HBP) or left bundle branch area pacing (LBBAP) has emerged as an alternative to right ventricular pacing (RVP). Comparative data on the risk of complications between CSP and RVP are lacking.<br /><b>Objective</b><br />Prospective, multicenter, observational study aimed to compare the long-term risk of device-related complications between CSP and RVP.<br /><b>Methods</b><br />A total of 1,029 consecutive patients undergoing pacemaker implantation with CSP (including HBP and LBBAP) or RVP were enrolled. Propensity matching for baseline characteristics yielded 201 matched pairs. Rate and nature of device-related complications occurring during follow-up were prospectively collected and compared between the two groups.<br /><b>Results</b><br />During a mean follow-up of 18 months, device-related complications were observed in 19 patients: 7 in RVP (3.5%), and in 12 in CSP (6.0%) (p=0.240). Dividing the matched cohort in three groups with similar baseline characteristics according to the pacing modality (RVP, n=201; HBP, n=128; LBBAP, n=73), HBP patients showed a rate of device-related complications significantly higher compared to RVP patients (8.6 vs. 3.5%; p=0.047), and to LBBAP patients (8.6 vs. 1.3%; p=0.034). LBBAP patients showed a rate of device-related complications similar to that of RVP patients (1.3 vs. 3.5%, p=0.358). Most of the complications observed in HBP patients (63.6%) were lead-related.<br /><b>Conclusions</b><br />Globally, CSP was associated with a risk of complications similar to that of RVP. Considering separately HBP and LBBAP, HBP showed a significantly higher risk of complications than both RVP and LBBAP, whereas LBBAP showed a risk of complications similar to RVP.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 09 Mar 2023; epub ahead of print</small></div>

<div><h4>Catheter Ablation of Coronary Sinus Accessory Pathways in the Young.</h4><i>Müller MJ, Fischer O, Dieks J, Schneider HE, Paul T, Krause U</i><br /><b>Background</b><br />Accessory atrioventricular pathways (AP) are the most common tachycardia substrate for supraventricular tachycardia (SVT) in the young. Endocardial catheter ablation of AP may be unsuccessful in up to 5% due to a coronary sinus location.<br /><b>Objective</b><br />Data on ablation of accessory pathways within the coronary venous system (CVS) in the young is sparse.<br /><b>Methods</b><br />Analysis of feasibility, outcome, and safety in patients ≤18 years with coronary sinus accessory pathways (CS-AP) and catheter ablation via CVS in a tertiary pediatric electrophysiological referral center (05/2003-12/2021). Control group adjusted for age, weight, and pathway location was established from patients of the prospective European Multicenter Pediatric Ablation Registry who all had endocardial AP ablation.<br /><b>Results</b><br />24 individuals had mapping and intended AP ablation within the CVS (age: 2.7-17.3 years, body weight: 15.0-72.0 kg). Due to proximity to coronary artery, ablation was withheld in 2/24. Overall procedural success was achieved in 20/22 (90.9%) study patients and in 46/48 (95.8%) controls. Coronary artery injury after RF ablation was noted in 2/22 (9%) study patients and in 1/48 (2%) controls. In CVS patients repeat SVT occurred in 5/22 (23%) during a median follow-up of 8.5 years, 4/5 underwent reablation resulting in 94.4% overall success. Controls were free from SVT during follow-up of 12 months as defined by registry protocol.<br /><b>Conclusions</b><br />Success of CS-AP ablation in the young was comparable to endocardial AP-ablation. Substantial risk of coronary artery injury should be considered when CS-AP ablation is performed in the young.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 08 Mar 2023; epub ahead of print</small></div>

<div><h4>Clinical risk prediction score for post-operative accelerated junctional rhythm and junctional ectopic tachycardia in children with congenital heart disease.</h4><i>Dasgupta S, Shalhoub K, El-Assaad I, O\'Leary E, ... Kheir JN, Dionne A</i><br /><b>Background</b><br />Accelerated junctional rhythm (AJR) and Junctional ectopic tachycardia (JET) are common post-operative arrhythmias associated with morbidity/mortality. Studies suggest that pre- or intra-operative treatment may improve outcomes, but patient selection remains a challenge.<br /><b>Objectives</b><br />Our objective was to describe contemporary outcomes of post-operative AJR/JET and develop a risk-prediction score to identify patients at highest risk.<br /><b>Methods</b><br />Retrospective cohort study of children 0-18 years undergoing cardiac surgery (2011-2018). AJR was defined as usual complex tachycardia with ≥1:1 ventricular-atrial association and junctional rate >25<sup>th</sup> percentile of sinus rate for age but < 170 bpm while JET was defined as a rate >170 bpm. A risk prediction score was developed using random forest analysis and logistic regression.<br /><b>Results</b><br />From 6364 surgeries, AJR occurred in 215 (3.4%) and JET in 59 (0.9%). Age, heterotaxy syndrome, aortic cross-clamp time, ventricular septal defect closure and atrio-ventricular canal repair were independent predictors of AJR/JET on multivariate analysis and included in the risk prediction score. The model accurately predicted the risk of AJR/JET with a C-index of 0.72 [95% CI 0.70, 0.75]. Post-operative AJR and JET was associated with prolonged ICU and hospital length of stay, but not with early mortality.<br /><b>Conclusion</b><br />We describe a novel risk prediction score to estimate the risk of post-operative AJR/JET permitting early identification of at-risk patients who may benefit from prophylactic treatment.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 08 Mar 2023; epub ahead of print</small></div>

<div><h4>Injectable Contraceptive, Depo-Provera, Produces Erratic Beating Patterns in Patient-Specific Induced Pluripotent Stem Cell-derived Cardiomyocytes with Type 2 Long QT Syndrome.</h4><i>Pinsky AM, Gao X, Bains S, Kim CJ, ... Giudicessi JR, Ackerman MJ</i><br /><b>Background</b><br />Long QT syndrome type 2 (LQT2) is caused by pathogenic variants in KCNH2. LQT2 may manifest as QT prolongation on an ECG and present with arrhythmic syncope/seizures, sudden cardiac arrest/death. Oral progestin-based contraceptives may increase the risk of LQT2-triggered cardiac events in women. We previously reported on a LQT2 woman with recurrent cardiac events temporally related and attributed to the progestin-based contraceptive, medroxyprogesterone acetate (\"Depo-Provera\", Depo).<br /><b>Objective</b><br />To evaluate the arrhythmic-risk of Depo in a patient-specific induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of LQT2.<br /><b>Methods</b><br />An iPSC-CM line was generated from a 40-year-old female with p.G1006Afs*49-KCNH2. A CRISPR/Cas9 gene-edited/variant-corrected, isogenic control (IC) iPSC-CM line was generated. FluoVolt was used to measure the action potential duration (APD) following treatment with 10 μM Depo. Erratic beating patterns characterized as alternating spike amplitudes, alternans, or early after depolarization-like phenomena were assessed using multi-electrode array (MEA) following 10 μM Depo, 1 μM isoproterenol (ISO), or combined Depo + ISO treatment.<br /><b>Results</b><br />Depo treatment shortened the APD-90 of the G1006Afs*49 iPSC-CMs from 394±10 ms to 303±10 ms (p<0.0001). Combined Depo and ISO treatment increased the percent of electrodes displaying erratic beating in G1006Afs*49 iPSC-CMs [baseline 18±5% vs. Depo + ISO 54±5% (p<0.0001)] but not in IC iPSC-CMs [baseline 0±0% vs. Depo + ISO 10±3% (p=0.9659)].<br /><b>Conclusion</b><br />This cell study provides a potential mechanism for the patient\'s clinically documented Depo-associated episodes of recurrent ventricular fibrillation. This in-vitro data should prompt a large-scale clinical assessment of Depo\'s potential pro-arrhythmic effect in women with LQT2.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 06 Mar 2023; epub ahead of print</small></div>