<div><h4>Tailored electrocardiographic-based criteria for different pacing locations within the left bundle branch.</h4><i>Briongos-Figuero S, Paniagua ÁE, Hernández AS, Palomo DH, ... Martínez MT, Muñoz-Aguilera R</i><br /><b>Background</b><br />Electrocardiographic (ECG)-based criteria are used to confirm left bundle branch (LBB) pacing (LBBP), but current cut-off values have never been validated for different pacing locations.<br /><b>Objective</b><br />To describe diagnostic performance of V6-R wave peak time (RWPT), V6-V1 interpeak interval and aVL-RWPT for different pacing sites within the LBB and to determine 100% specific values for each criterion at each pacing location.<br /><b>Methods</b><br />Consecutive patients with confirmed LBBP were selected. Population was divided into subgroups based on the site of pacing: left bundle trunk pacing (LBTP), left septal fascicular pacing (LSFP), left posterior fascicular pacing (LPFP) and left anterior fascicular pacing (LAFP).<br /><b>Results</b><br />A total of 147 patients with unequivocal LBB capture were analyzed. Left fascicular pacing (LFP) was more frequently achieved (82.8%) than LBTP (17.2%). Diagnostic performance of V6-RWPT, V6-V1 interpeak interval and aVL-RWPT for the discrimination of LBBP was good in all subgroups. V6-RWPT cut-off values with 100% specificity (SP) for LBBP discrimination were 75 ms in LBTP, 68 ms in LPFP, 81 ms in LAFP, and 79.5 ms in LSFP. V6-V1 interpeak interval cut-off values with 100% SP for LBBP discrimination were 35.5 ms in LBTP, 53.5 ms in LPFP, 41 ms in LAFP, and 46 ms in LSFP. In LAFP, aVL-RWPT cut-off value with 100% SP for LBBP discrimination was 68 ms, while it was 74 ms in LBTP, 74.5 ms in LSFP, and 73.5 ms in LPFP.<br /><b>Conclusions</b><br />Tailored ECG-based criteria might be useful to confirm LBBP at different pacing locations within the LBB.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 21 Sep 2023; epub ahead of print</small></div>

<div><h4>Implications of Ventricular Arrhythmia After Cardiac Resynchronization Therapy.</h4><i>Ueda N, Ishibashi K, Noda T, Oka S, ... Noguchi T, Kusano K</i><br /><b>Background</b><br />Conflicting data are available on whether ventricular arrhythmia (VA) or shock therapy increases mortality. Though cardiac resynchronization therapy (CRT) reduces the risk of VA, little is known about the prognostic value of VA among patients with CRT devices.<br /><b>Objectives</b><br />This study aimed to evaluate the implications of VA as a prognostic marker for CRT.<br /><b>Methods</b><br />We investigated 330 CRT patients within one year after CRT device implantation. The primary endpoint was the composite endpoint of all-cause death or hospitalization for HF.<br /><b>Results</b><br />Forty-three patients had VA events. These patients had a significantly higher risk of the primary endpoint, even among CRT responders (p = 0.009). Fast VA compared to slow VA was associated with an increased risk of the primary endpoint (hazard ratio [HR]: 2.14; 95% confidence interval [CI]: 1.06-4.34, p = 0.035). Shock therapy was not associated with a primary endpoint (shock therapy vs. anti-tachycardia pacing, HR: 1.49; 95% CI: 0.73-3.03, p = 0.269). The patients with VA had a lower prevalence of response to CRT (23 [53%] vs. 202 [70%], p = 0.031) and longer LV-paced conduction time (174 ± 23 ms vs. 143 ± 36 ms, p = 0.003) than the patients without VA.<br /><b>Conclusion</b><br />VA occurrence within one year was related to paced electrical delay and poor response to CRT. VA could be associated with poor prognosis among CRT patients.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 20 Sep 2023; epub ahead of print</small></div>

<div><h4>Natural History of Echocardiographic Changes in Atrial Fibrillation: A Case-Controlled Study of Longitudinal Remodeling.</h4><i>Loring Z, Clare RM, Hofmann P, Chiswell K, Vemulapalli S, Piccini J</i><br /><b>Background</b><br />Atrial fibrillation (AF) can be a cause and consequence of cardiac remodeling. The natural history of remodeling associated with AF is incompletely described.<br /><b>Objectives</b><br />Describe the frequency and timing of AF-associated echocardiographic changes.<br /><b>Methods</b><br />Patients within the Duke University Health System with two or more transthoracic echocardiograms (TTEs) performed between 2005-2018 were evaluated. AF patients with normal baseline TTEs were matched to patients without AF on year of TTE, age, and CHA<sub>2</sub>DS<sub>2</sub>-VASc score. Frequency and timing of changes in chamber size, ventricular function, mitral regurgitation, and all-cause mortality were compared over five years of follow-up.<br /><b>Results</b><br />The cohort included 3,299 patients with AF at baseline and 7,613 controls without AF. Normal baseline TTEs were seen in 730 of the AF patients; 727 of these patients were matched to controls without AF. AF patients had higher rates of LA enlargement (HR 1.53 [1.27-1.85], p<0.001), LV systolic dysfunction (HR 1.80 [1.00-3.26], p=0.045), LV diastolic dysfunction (HR 1.51 [1.08-2.10], p=0.01) and moderate or greater mitral regurgitation (HR 2.09 [1.27-3.43], p=0.003) compared to controls. Atrial enlargement, systolic dysfunction, and mitral regurgitation surpassed the rates seen in the controls within 6-12 months; whereas, differences in diastolic dysfunction emerged at 24 months. There were no differences in ventricular sizes or mortality.<br /><b>Conclusions</b><br />AF is associated with higher rates of LA enlargement, LV systolic and diastolic dysfunction, and mitral regurgitation that typically manifest within 6-24 months of diagnosis. The natural history of cardiac remodeling in AF patients may inform treatment decisions and facilitate patient-tailored care.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 15 Sep 2023; epub ahead of print</small></div>

<div><h4>ECG Characteristics of \'True\' Left Bundle Branch Block: Insights from Transcatheter Aortic Valve-related LBBB and His-Purkinje Conduction System Pacing Correctable LBBB.</h4><i>Kawamura I, Batul SA, Vijayaraman P, Needelman B, ... Reddy VY, Koruth J</i><br /><b>Background</b><br />Left bundle branch block (LBBB) pattern on ECG includes patients with both complete conduction block within the His Purkinje system as well as nonspecific left ventricular conduction delay without discrete block.<br /><b>Objectives</b><br />To characterize electrocardiographic morphological features of LBBB patterns in patients with 1) LBBB after transcatheter aortic valve replacement (TAVR) and 2) LBBB correctable by conduction system pacing (CSP).<br /><b>Methods</b><br />Consecutive patients with post-TAVR (n=123) or CSP correctable LBBB (n=58) from 2 centers were included in this retrospective evaluation. QRS durations as well as detailed morphological features, including notching and slurring, of QRS complexes in leads I, aVL, V1, V2, V5, V6, and all three inferior leads were recorded.<br /><b>Results</b><br />The mean age of the entire cohort was 78.3±10.1 years with 48% of the cohort being male. In the CSP correctable group (n=58), 14 (24.1%) underwent His-bundle pacing and 44 (75.9%) left bundle branch area pacing (LBBAP). A total of 17/181 (9.4%) of the combined cohort failed to completely meet the Strauss criteria. QRS morphology in leads V1/V2 were always either rS or QS and there were no q/Q waves noted in leads V5/V6. Although dominant R waves were seen in 176/181 (97.2%) of leads I and aVL, q/Q waves were only present in 21/181 (11.6%). Importantly, notched or slurred QRS complexes were identified at least one lead of I, aVL, V5, and V6 in 181/181 (100%).<br /><b>Conclusions</b><br />Strauss criteria and QRS notching is highly prevalent in LBBB after TAVR and in those correctable by conduction system pacing.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 09 Sep 2023; epub ahead of print</small></div>

<div><h4>Association between Nighttime Heart Rate and Cardiovascular Mortality in Patients with Implantable Cardioverter Defibrillator: A Cohort Study.</h4><i>Jiang J, Sun X, Chen R, Su Y, ... Cheng C, Zhang S</i><br /><b>Background</b><br />Although studies have shown that an increased resting heart rate measured randomly at a single point of the day has been associated with adverse cardiovascular outcomes, the utility of continuous monitoring of nighttime heart rate (NTHR) has remained largely uninvestigated.<br /><b>Objective</b><br />This study aimed to explore the association between NTHR and cardiovascular mortality.<br /><b>Methods</b><br />The SUMMIT prospective cohort study enrolled patients with ICD or CRT-D between 2010 and 2015. Baseline NTHR was measured during the programmed sleep period from 30 to 60 days after implantation. The primary outcome was cardiovascular mortality, fitted by a restricted cubic spline function.<br /><b>Results</b><br />A total of 534 ICD recipients with sinus rhythm during the detection window were included in the study. The mean baseline NTHR was 59.6 ± 8.0 bpm. During the 60.4 ± 21.8 months follow-up period, 88 patients experienced cardiovascular mortality. After considering potential confounders, a linear association was observed. Each 1 bpm increase in NTHR was associated with a 7.8%, 10.1%, and 5.7% increase in the risk of cardiovascular mortality in the total population, and patients with or without heart failure, respectively.<br /><b>Conclusion</b><br />Continuous monitoring of NTHR may identify patients at high risk of cardiovascular mortality in a timely manner, with the potential for \"pre-emptive\" action.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 07 Sep 2023; epub ahead of print</small></div>

<div><h4>Restoration of calcium release synchrony: A novel target for heart failure and ventricular arrhythmia.</h4><i>Chakraborty P, Aggarwal AK, Kumar Nair MK, Massé S, Riazi S, Nanthakumar K</i><br /><AbstractText>Myocardial calcium (Ca<sup>2+</sup>) signaling plays a crucial role in contractile function and membrane electrophysiology. An abnormal myocardial Ca<sup>2+</sup> transient is linked to heart failure and ventricular arrhythmias. At the subcellular level, the synchronous release of Ca<sup>2+</sup> sparks from sarcoplasmic Ca<sup>2+</sup> release units (CRUs) determines the configuration and amplitude of the global Ca<sup>2+</sup> transient. This narrative review evaluates the role of aberrant Ca<sup>2+</sup> release synchrony in the pathophysiology of cardiomyopathies and ventricular arrhythmias. The potential therapeutic benefits of restoration of Ca<sup>2+</sup> release synchrony in heart failure and ventricular arrhythmias are also discussed.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 05 Sep 2023; epub ahead of print</small></div>

<div><h4>Cryothermal Energy Demonstrates Shorter Ablation Time and Lower Complication Rates Compared with Radiofrequency in Surgical Hybrid Ablation for Recurrent Ventricular Tachycardia.</h4><i>Chung WH, Hayase J, Davies MJ, Do DH, ... Shivkumar K, Bradfield JS</i><br /><b>Background</b><br />Recurrent ventricular tachycardia (VT) following prior endocardial catheter ablation(s) presents challenges in the setting of prior cardiac surgery where percutaneous epicardial access may not be feasible.<br /><b>Objective</b><br />To compare the outcomes of cryothermal versus radiofrequency ablation in direct surgical epicardial access procedures.<br /><b>Methods</b><br />We performed a retrospective study of consecutive surgical epicardial ventricular tachycardia ablation cases. Surgical cases using cryothermal versus radiofrequency ablation were analyzed and outcomes were compared.<br /><b>Results</b><br />Between 2009 and 2022, 43 patients underwent either a cryothermal (n = 17) or radiofrequency (n = 26) hybrid epicardial ablation procedure with direct surgical access. Both groups were similarly matched for age, sex, etiology of VT, and co-morbidities with a high burden of refractory ventricular tachycardia despite previous endocardial and/or percutaneous epicardial ablations. The surgical access site was lateral thoracotomy (76.5%) in the cryothermal group compared to lateral thoracotomy (42.3%) and subxiphoid (38.5%), in the radiofrequency group, with the remainder in both groups performed via median sternotomy. The ablation time was significantly shorter in those undergoing cryothermal ablation versus radiofrequency ablation (11.54±15.5 min vs 48.48±23.6; P<0.001). There were no complications in the cryothermal group, compared to 6 patients with complications in the radiofrequency group. Recurrent VT episodes and all-cause mortality were similar in both groups.<br /><b>Conclusion</b><br />Hybrid surgical VT ablation with cryothermal or radiofrequency energy demonstrated similar efficacy outcomes. Cryothermal ablation was more efficient and safer than radiofrequency in a surgical setting and should be considered when surgical access is required.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 31 Aug 2023; epub ahead of print</small></div>

<div><h4>Diagnostic Pitfalls in Patients Referred for Arrhythmogenic Right Ventricular Cardiomyopathy.</h4><i>Sampognaro JR, Gaine SP, Sharma A, Tichnell C, ... Gasperetti A, Calkins H</i><br /><b>Background</b><br />The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging due to nonspecific clinical findings and lack of conclusive answers from genetic testing (i.e., an ARVC-related variant is neither necessary nor sufficient for diagnosis). Despite the revised 2010 Task Force criteria, patients are still misdiagnosed with ARVC.<br /><b>Objective</b><br />In patients referred for ARVC, we sought to identify the clinical characteristics and diagnostic confounders for those patients in whom ARVC was ultimately ruled out.<br /><b>Methods</b><br />Patients who were referred to our center with previously diagnosed or suspected ARVC (1/2011-9/2019, n = 726) were included in this analysis.<br /><b>Results</b><br />Among 726 patients, ARVC was ruled out in 365 (50.3%). The most common presenting symptoms in ruled-out patients were palpitations (38.1%), ventricular arrhythmias (17.0%), and chest pain (14.5%). Based on outside evaluation, 23.8% of these patients had received implantable cardioverter-defibrillators (ICDs), and device extraction was recommended in 9.0% after re-evaluation. An additional 5.5% had received ICD recommendations, all of which were reversed on re-evaluation. The most frequent final diagnoses were idiopathic premature ventricular contractions/ventricular tachycardia/ventricular fibrillation (46.6%), absence of disease (19.2%), and noncardiac presyncope/syncope (17.5%). The most common contributor to diagnostic error was cardiac magnetic resonance imaging (CMR), including mistaken right ventricular wall motion abnormalities (33.2%) and nonspecific fat (12.1%).<br /><b>Conclusion</b><br />False suspicion or misdiagnosis was found in the majority of patients referred for ARVC, resulting in inappropriate ICD implantation or recommendation in 14.5% of these patients. Misdiagnosis or false suspicion was most commonly due to misinterpretation of CMR.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 30 Aug 2023; epub ahead of print</small></div>

<div><h4>A Multicenter Retrospective Evaluation of Magnetic Resonance Imaging in Pediatric and Congenital Heart Disease Patients with Cardiac Implantable Electronic Devices.</h4><i>Gakenheimer-Smith L, Ou Z, Kuang J, Moore JP, ... Lambert LM, Pilcher TA</i><br /><b>Background</b><br />Guidelines addressing magnetic resonance imaging (MRI) in patients with cardiac implantable electronic devices (CIEDs) provide algorithms for imaging pediatric and congenital heart disease (CHD) patients. Guideline acceptance varies by institution. Guidelines also do not support routine MRI scans in patients with epicardial or abandoned leads, common in pediatric and CHD patients.<br /><b>Objective</b><br />We sought to determine the incidence of MRI-related complications in pediatric and CHD patients with CIEDs, including epicardial and/or abandoned leads.<br /><b>Methods</b><br />A multicenter retrospective review included patients with CIEDs who underwent any MRI between 2007 and 2022 at congenital cardiac centers. The primary outcome was any patient adverse event or clinically significant CIED change after MRI, defined as pacing lead capture threshold increase >0.5 V with output change, P- or R- wave amplitude decrease >50% with sensitivity change, or impedance change >50%.<br /><b>Results</b><br />Across 14 institutions, 314 patients underwent 389 MRIs; median age was 18.8 [1.3; 31.4] years. There were 288 (74%) pacemakers and 87 (22%) ICDs, with 52% containing epicardial leads; 14 (4%) were abandoned leads only. Symptoms or CIED changes occurred in 4.9% of MRI scans (6.1% of patients). On 9 (2%) occasions, warmth or pain occurred. Pacing capture threshold or lead impedance changes occurred in 1.4% and 2.0% of CIEDs post-MRI and at follow-up.<br /><b>Conclusion</b><br />Our data provide evidence that MRIs can be performed in pediatric and CHD patients with CIEDs, including non-MRI conditional CIEDs, epicardial and/or abandoned leads, with rare, minor symptoms or CIED changes but no other complications.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 28 Aug 2023; epub ahead of print</small></div>

<div><h4>Association of Epicardial and Intramyocardial Fat with Ventricular Arrhythmias.</h4><i>Sani MM, Sung E, Engels M, Trayanova N, Wu KC, Chrispin J</i><br /><b>Background</b><br />Among ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) patients, myocardial fibrosis is associated with an increased risk for VA. Growing evidence suggests that myocardial fat contributes to ventricular arrhythmogenesis. However, little is known about the volume and distribution of epicardial adipose tissue and intramyocardial fat and their relationship with VAs.<br /><b>Objective</b><br />This study aimed to assess the association of contrast-enhanced computed tomography (CE-CT) derived LV tissue heterogeneity, epicardial adipose tissue volume, and intramyocardial fat volume with the risk of VA in ICM and NICM patients.<br /><b>Methods</b><br />Patients enrolled in the PROSE-ICD registry who underwent CE-CT were included. Intramyocardial fat volume (voxels between -180 and -5 HU), epicardial adipose tissue volume (between -200 to -50 HU), and LV tissue heterogeneity were calculated. The primary endpoint was appropriate ICD shocks or sudden arrhythmic death.<br /><b>Results</b><br />Among 98 patients (47 ICM and 51 NICM), LV tissue heterogeneity was associated with VA (OR = 1.10, P = .01), particularly in the ICM cohort. In the NICM subgroup, epicardial adipose tissue and intramyocardial fat volume were associated with VA (OR = 1.11, P = .01, OR = 1.21, P = .01) but not in the ICM patients (OR = 0.92, P =.22, and OR = 0.96, P =.19).<br /><b>Conclusion</b><br />In ICM patients, increased fat distribution heterogeneity is associated with VA. In NICM patients, an increased volume of intramyocardial fat and epicardial adipose tissue is associated with a higher risk for VA. Our findings suggest that fat\'s contribution to VAs depends on the underlying substrate.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 26 Aug 2023; epub ahead of print</small></div>

<div><h4>Significance of Left Posterior Extension of Early Repolarization in Patients with J Wave Syndrome.</h4><i>Miyamoto M, Morita H, Mizuno T, Masuda T, ... Nakagawa K, Nishii N</i><br /><b>Background</b><br />J waves in the inferior or lateral leads are characteristic electrocardiographic (ECG) changes in patients with early repolarization syndrome (ERS). However, the presence of J waves in the left posterior region has not yet been evaluated.<br /><b>Objective</b><br />This study aimed to clarify the significance of J waves in the posterior left ventricle using leads V7-9 and a body surface mapping (BSM) system.<br /><b>Methods</b><br />Forty patients diagnosed with ERS were included. All patients exhibited J waves in either the contiguous inferior, lateral, or posterior leads. We evaluated the incidence of J waves in the inferolateral and posterior leads using a 15-lead ECG with synthesized V7-9, and an 87-lead BSM. Additionally, we assessed the arrhythmogenicity of the posterior regions based on the morphology of the premature ventricular complexes (PVCs) associated with ventricular fibrillation (VF).<br /><b>Results</b><br />J waves were observed in the lateral, inferior, and posterior leads of 26 (65 %), 31 (78%), and 39 (97 %) patients, respectively. J waves were found only in the posterior leads of five patients. BSM was evaluated in nine patients, all of whom exhibited a positive area on the posterior region. PVCs associated with VF were recorded in five patients. Among patients with inferolateral and posterior J waves, all except one patient who displayed left-bundle-branch-block morphology, showed PVCs originating from the posterior left ventricular region.<br /><b>Conclusions</b><br />Posterior J waves are common in ERS patients. This abnormality can be detected using leads V7-9 and the BSM system and may be associated with arrhythmogenesis.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 25 Aug 2023; epub ahead of print</small></div>

<div><h4>Selective Blockade of Interleukin-6 Trans-signaling.</h4><i>Li X, Wu X, Chen X, Peng S, ... Liu S, Xu J</i><br /><b>Background</b><br />Atrial fibrillation (AF) has been accepted as an inflammatory atrial myopathy. Interleukin 6 (IL-6)-dependent inflammatory signaling pathways take context-dependent effects on cardiovascular diseases. The IL-6 trans-signaling is predominantly pro-inflammatory. However, its effect on AF is unclear.<br /><b>Objective</b><br />The purpose of this study was to investigate the role of IL-6 trans-signaling in AF.<br /><b>Methods</b><br />Circulating levels of IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in AF patients and controls were measured to estimate the activation of IL-6 trans-signaling. A mouse model of AF was established by transverse aortic constriction (TAC) surgery. Sgp130Fc administration was used for selective blockade of IL-6 trans-signaling. Studies were conducted to evaluate the effects and underlying mechanisms of sgp130Fc on AF inducibility and atrial conduction abnormalities and structural remodeling.<br /><b>Results</b><br />In patients, the elevation of IL-6 trans-signaling level was positively associated with AF occurrence. IL-6 trans-signaling activation was recapitulated in the mouse model of AF. In TAC-challenged mice, selective blockade of IL-6 trans-signaling with sgp130Fc attenuated AF inducibility, which was attributable to the amelioration of slow conduction and conduction heterogeneity that induced by atrial dilation, fibrosis, and the reduction in connexin 40 and redistribution of connexin 43. Sgp130Fc administration also reduced immune cell infiltration and oxidative stress in the mouse atrium and abrogated IL-6 trans-signaling activation-mediated connexin dysregulation and reactive oxygen species production in atrial myocytes.<br /><b>Conclusion</b><br />IL-6 trans-signaling activation contributes to AF development, and its selective blockade may promise a novel therapeutic strategy.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 24 Aug 2023; epub ahead of print</small></div>

<div><h4>Atrioventricular node ablation is an effective management strategy for atrial fibrillation in patients with hypertrophic cardiomyopathy.</h4><i>Butcher C, Rajappan S, Wharmby AL, Ullah W, ... Hunter RJ, Honarbakhsh S</i><br /><b>Background</b><br />Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM) patients and can be challenging to manage. Atrioventricular node (AVN) ablation may be an effective management strategy for AF in these patients.<br /><b>Objective</b><br />Assess the efficacy of AVN ablation in HCM patients who have failed medical therapy and/or catheter ablation for AF.<br /><b>Methods</b><br />Multi-centre study with retrospective analysis of a prospectively collated HCM registry. AVN ablation patients were identified. Baseline characteristics, device and procedural indication were collected. Symptoms defined by NYHA and EHRA classification and echocardiographic findings during follow-up were assessed.<br /><b>Results</b><br />Fifty-nine patients were included. Indications for AVN ablation were: 6 (10.2%) inappropriate ICD shock, 35 (59.3%) ineffective rate control and 18 (30.5%) to regularize rhythm to improve symptoms. During post-AVN ablation follow-up of (79.4±61.1 months), left ventricular ejection fraction (LVEF) remained stable (pre-LVEF 48.9±12.4%, post-LVEF 49.8±10.9%, p=0.68) even in those without a CRT device (pre-LVEF 54.3±8.0% vs post-LVEF 53.8±8.0%=0.65). Forty-nine (83.1%) patients reported an improvement in symptoms regardless of AF type (17/21, 81.0% paroxysmal vs. 32/38, 84.2% persistent AF; p=1.00), presence of baseline LV 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=1.0). Symptoms improved in 16 (89%) patients who underwent AVN ablation to regularize rhythm.<br /><b>Conclusion</b><br />AVN ablation improved symptoms without impacting LV function in a majority of the patients. AVN ablation is suggestive to be an effective and safe management approach for AF in HCM and should be further evaluated in larger prospective studies.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 24 Aug 2023; epub ahead of print</small></div>

<div><h4>Chlorhexidine Gluconate Pocket Lavage to Prevent Cardiac Implantable Electronic Device Infection in High-Risk Procedures.</h4><i>Diaz JC, Braunstein ED, Cañas F, Duque M, ... Sauer WH, Romero JE</i><br /><b>Background</b><br />Infection is the most dreaded complication of cardiac implantable electronic devices (CIEDs), particularly in patients undergoing high-risk procedures (generator change, device upgrade, lead/pocket revision).<br /><b>Objective</b><br />To describe the impact of chlorhexidine gluconate (CHG) pocket lavage in high-risk procedures.<br /><b>Methods</b><br />Patients from a prospective multicenter registry undergoing high-risk procedures were included. CHG lavage was performed by irrigating the generator pocket with 20cc of 2% and normal saline (NS). Only NS irrigation was performed in the comparison group. The primary efficacy outcome was CIED-related infection at 12 months. The primary safety outcome was any CHG-associated adverse event. The secondary outcome was CIED infection during long-term follow-up. Propensity score matching analysis (PSM) was performed for the primary efficacy outcome.<br /><b>Results</b><br />A total of 1504 patients were included. At 12-month follow-up, the primary efficacy outcome occurred in 4 of 904 CHG (0.4%) and 14 of 600 NS subjects (2.3%) (Log-rank p=0.005). On multivariate analysis, the use of CHG irrigation remained associated with a lower risk of infection at one-year follow-up (Cox proportional HR 0.138, 95% CI 0.04-0.45, p=0.001). This effect persisted during long-term follow-up. PSM demonstrated a significant reduction in CIED-related infection for the CHG group (0.2% vs. 2.5%, Cox proportional HR 0.08 95% CI 0.01-0.59, p=0.014). There were no adverse events associated with the use of CHG.<br /><b>Conclusion</b><br />CHG lavage during high-risk procedures was associated with a reduction in CIED-related infections without any adverse events reported.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 18 Aug 2023; epub ahead of print</small></div>

<div><h4>Mortality and ventricular arrhythmias in patients on d,l-sotalol for rhythm control of atrial fibrillation - A nationwide cohort study.</h4><i>Lenhoff H, Jarnbert-Petersson H, Darpo B, Tornvall P, Frick M</i><br /><b>Background</b><br />The use of d,l-sotalol for rhythm control in patients with atrial fibrillation (AF) has raised safety concerns. Previous randomized studies are few and not designed for mortality outcome.<br /><b>Objective</b><br />To compare the incidence of mortality and ventricular arrhythmias in AF patients treated with d,l-sotalol for rhythm control versus matched control patients treated with cardioselective betablockers.<br /><b>Methods</b><br />This population-based cohort study included AF patients from the Swedish National Patient Registry (2006 to 2017) who underwent rhythm-control following a second cardioversion. Incidence rates (IR) and adjusted hazard ratio (aHR) for mortality and a composite endpoint of cardiac arrest/death and ventricular arrhythmias were calculated for the overall cohort and a 1:1 propensity score-matched cohort of d,l-sotalol vs. betablocker-treatment.<br /><b>Results</b><br />Among d,l-sotalol (n=4,987) and betablocker-treated (n=27,078) patients, with mean follow-up of 458 days, all-cause mortality was lower in d,l-sotalol-treated patients: IR 1.21 (95% confidence interval: 0.95-1.52) vs. 2.42 (2.26-2.60) deaths per 100 patient years, aHR 0.66 (0.52-0.83). The difference in mortality persisted in the propensity-matched comparison (n= 4,953 in each group), aHR 0.63 (0.48-0.86). No differences were observed in the composite outcome, IR in propensity cohorts: 2.13 (1.78-2.52) vs. 2.07 (1.73-2.53) events per 100 years, aHR 1.01 (0.78-1.29).<br /><b>Conclusions</b><br />There was no excess mortality with d,l-sotalol compared with cardioselective betablockers in patients with a rhythm-control strategy for AF following a second cardioversion. Our results indicate that the risk associated with d,l-sotalol treatment for AF can be mitigated by careful patient selection and strict adherence to follow-up protocols.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 18 Aug 2023; epub ahead of print</small></div>

<div><h4>Sinus rhythm QRS morphology reflects right ventricular activation and anatomical ventricular tachycardia isthmus conduction in repaired tetralogy of Fallot.</h4><i>Moore JP, Shannon KM, Khairy P, Waldmann V, ... Su J, Shivkumar K</i><br /><b>Backround</b><br />Patients with repaired tetralogy of Fallot (TOF) are at risk for ventricular tachycardia (VT) related to well-described anatomical isthmuses.<br /><b>Objectives</b><br />To explore QRS morphology as an indicator of anatomical isthmus conduction.<br /><b>Methods</b><br />Patients with repaired TOF and complete RBBB referred for transcatheter pulmonary valve replacement (PVR) or presenting with sustained VT underwent comprehensive 3D mapping in sinus rhythm. ECG characteristics were compared to RV activation and anatomical isthmus conduction properties.<br /><b>Results</b><br />Twenty-two patients (19 pre-PVR, 3 clinical VT) underwent comprehensive 3D mapping (median 39 [IQR 27, 48] years, 55% male). Septal RV activation (median 40 ms [IQR 34, 46 ms]) corresponded to the nadir in V1 and free wall activation (median 71 ms [IQR 64, 81 ms]) to the upstroke of the R\' wave. Patients with isthmus block between the pulmonary annulus and ventricular septal defect (VSD) and when present, VSD and tricuspid annulus, were more likely to demonstrate lower amplitude R\' in V1 (5.8 vs 9.4 mV, p=0.005), QRS fragmentation in V1 (15 [94%] vs 2 [13%], p<0.001) and terminal S waves in aVF (15 [94%] vs 6 [40%], p<0.001) than those with intact conduction. During catheter ablation, identical QRS changes developed with isthmus block.<br /><b>Conclusion</b><br />For patients with repaired TOF, the status of septal isthmus conduction was associated with sinus rhythm QRS morphology. Low amplitude, fragmented R\' in V1 and terminal S wave in the inferior leads were related to septal isthmus conduction abnormalities, providing a mechanistic link between RV activation and common ECG findings.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 18 Aug 2023; epub ahead of print</small></div>

<div><h4>Safety of same day discharge after lead extraction procedures.</h4><i>Dagher L, Tfaily MA, Vavuranakis M, Bhatia NK, ... Merchant FM, El-Chami MF</i><br /><b>Background</b><br />Same-day discharge (SDD) after cardiovascular procedures is rapidly gaining ground.<br /><b>Objective</b><br />We sought to evaluate the safety of same-day discharge after transvenous lead extraction (TLE).<br /><b>Methods</b><br />We performed a retrospective chart review of patients who underwent elective TLE between January 2020 to October 2021 at our institution. The primary outcome was same-day discharge, and major procedural complications and re-admissions within 30 days of the procedure were secondary outcomes.<br /><b>Results</b><br />In this analysis of 111 patients who underwent elective TLE, 80 patients (72%) were discharged on the same day (SDD group), while 31 patients (28%) stayed overnight (OG). Lead malfunction was the most common indication for TLE in both groups. Patients in the OG were more likely to have a lead dwell time of 10 years or more compared to the SDD group (38.7% vs. 20% of all leads in each group, p=0.042), have laser sheaths used for extraction and a higher number of leads extracted. No major complications were reported in both groups. In a multivariate analysis, a lower BMI and the use of laser sheath during the TLE were predictors of overnight stay. Patients who underwent a procedure using advanced extraction techniques were 3.5 times more likely to stay overnight (95% CI [1.27; 9.78], p=0.016).<br /><b>Conclusion</b><br />In appropriately selected patients undergoing elective lead extraction, same-day discharge is feasible and safe. Higher BMI, fewer extracted leads, shorter lead dwell times (<10 years) and less frequent use of laser-powered extraction sheaths were associated with an increased likelihood of SDD.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 15 Aug 2023; epub ahead of print</small></div>

<div><h4>Left Septal Fascicular Block: Evidence, causes, and diagnostic criteria.</h4><i>Pérez-Riera AR, Barbosa-Barros R, Andreou AY, Fiol-Sala M, ... Abreu LC, Nikus K</i><br /><AbstractText>The existence of a tetrafascicular intraventricular conduction system is widely accepted by researchers. In this review, we have updated the criteria for left septal fascicular block (LSFB) and the differential diagnosis of prominent anterior QRS forces. More and more evidence points to the fact that the main cause of LSFB is critical proximal stenosis of the left anterior descending coronary artery before its first septal perforator branch. The most important characteristic of LSFB that has been incorporated in the corressponding diagnostic ECG criteria is its transient/intermittent nature mostly observed in clinical scenarios of acute (i.e. acute coronary syndrome including vassospastic angina) or chronic ischemic coronary artery disease (i.e exercise-induced ichemia). In addition, the phenomenon proved to be phase 4 bradycardia rate-dependent and induced by early atrial extra stimulus. Finally, we believe that intermittent LSFB has the same clinical significance as the \"Wellens\' syndrome\" and the \"de Winter pattern\" in the acute coronary syndrome scenario.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 14 Aug 2023; epub ahead of print</small></div>

<div><h4>Acute Human Defibrillation Performance of a Subcutaneous Implantable Cardioverter-Defibrillator with an Additional Coil Electrode.</h4><i>Yap SC, Oosterwerff EFJ, Boersma LVA, van der Stuijt W, ... Hahn SJ, Knops RE</i><br /><b>Background</b><br />The subcutaneous implantable cardioverter-defibrillator delivers 80 J shocks from an 8 cm left-parasternal coil (LPC) to a 59-cc left lateral pulse generator (PG). A system that defibrillates with lower energy could significantly reduce PG size. Computer modeling and animal studies suggested a 2nd shock coil either parallel to LPC or transverse from xiphoid to PG pocket would significantly reduce defibrillation threshold (DFT).<br /><b>Objective</b><br />Acutely test defibrillation efficacy of parallel and transverse configurations in patients receiving an S-ICD.<br /><b>Methods</b><br />Testing was performed in patients receiving a conventional S-ICD system. A 65 J success was required prior to investigational testing. A second electrode was temporarily inserted from the xiphoid incision connected to the PG with an investigational Y-adapter. Phase 1 (n=11) tested the parallel configuration. Phase 2 (n=21) tested both parallel and transverse configurations in random order.<br /><b>Results</b><br />Thirty-five patients: 76% male, 52±17 years, LVEF 40±15 %, BMI 26±4, prior myocardial infarction 50%, congestive heart failure 53%, cardiomyopathy 56%. Compared to the conventional S-ICD system, mean shock impedance decreased for both parallel (69±15 vs 86±20 ohms, p<.001, n=33) and transverse (56±14 vs 81±21 ohms, p<.001, n=20). Shock success rates at 20, 30 and 40 J were 55%, 79%, 97% and 25%, 70%, 90% for parallel and transverse, respectively. DFT testing was well tolerated with no serious adverse events.<br /><b>Conclusion</b><br />Adding a 2nd shock coil, particularly in the parallel configuration, significantly reduced impedance and had a high likelihood of defibrillation success at energies ≤40J. This may enable development of a smaller S-ICD.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 12 Aug 2023; epub ahead of print</small></div>

<div><h4>Phenotypic Variability of Filamin C-related Cardiomyopathy: Insights from a Novel Dutch Founder Variant.</h4><i>Schoonvelde SAC, Ruijmbeek CWB, Hirsch A, van Slegtenhorst MA, ... Verhagen JMA, Michels M</i><br /><b>Background</b><br />Dilated cardiomyopathy (DCM) can be caused by truncating variants in the filamin C gene (FLNC). A new pathogenic FLNC variant, c.6864_6867dup, p.(Val2290Argfs*23), was recently identified in Dutch DCM patients.<br /><b>Objective</b><br />The report aimed to evaluate the phenotype of FLNC variant carriers and to determine whether this variant is a founder variant.<br /><b>Methods</b><br />Clinical and genetic data were retrospectively collected from variant carriers. Cardiovascular magnetic resonance (CMR) studies were reassessed. Haplotypes were reconstructed to determine a founder effect. The geographical distribution and age of the variant were determined.<br /><b>Results</b><br />Thirty-three individuals (70% female) from nine families were identified. Sudden cardiac death was the first presentation in a carrier at 28 years of age. Median age at diagnosis was 41 years (range 19-67). The phenotype was heterogeneous. DCM with left ventricular (LV) dilation and reduced ejection fraction (<45%) was present in eleven individuals (33%), three (9%) of whom underwent heart transplantation. CMR showed late gadolinium enhancement (LGE) in 65% of the assessed individuals, primarily in a ring-like distribution. Non-sustained ventricular arrhythmias were detected in six (18%), and five (15%) individuals received an implantable cardioverter defibrillator. A shared haplotype spanning 2.1 Mb was found in all haplotyped individuals. The variant originated between 275-650 years ago.<br /><b>Conclusion</b><br />The pathogenic FLNC variant c.6864_6867dup, p.(Val2290Argfs*23) is a founder variant originating from the south of the Netherlands. Carriers are susceptible to developing heart failure and ventricular arrhythmias. The cardiac phenotype is characterized by ring-like LGE, even in individuals without significantly reduced LV function.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 08 Aug 2023; epub ahead of print</small></div>

<div><h4>Ischemia-Induced Ventricular Proarrhythmia and Cardiovascular Autonomic Dysreflexia After Cardioneuroablation.</h4><i>Chung WH, Masuyama K, Challita R, Hayase J, ... Shivkumar K, Ajijola O</i><br /><b>Background</b><br />Cardioneuroablation (CNA) is an attractive treatment for vasovagal syncope. Its long-term efficacy and safety remain unknown. ObjectiveTo develop a chronic porcine model of CNA to examine ventricular tachyarrhythmia (VT/VF) susceptibility and cardiac autonomic function after CNA.<br /><b>Methods</b><br />A percutaneous CNA model was developed by ablation of left- and right-sided ganglionated plexi (GP)(n=5), confirmed by histology. Reproducible bilateral vagal denervation was confirmed following CNA by extracardiac vagal nerve stimulation (ECVNS) and histology. Chronic studies included 16 pigs randomized to CNA (n=8) and sham ablation (n=8). After 6 weeks, animals underwent hemodynamic studies, assessment of cardiac sympathetic and parasympathetic function using sympathetic chain stimulation (SCS) and direct VNS respectively, and proarrhythmic potential following left anterior descending coronary artery (LAD) ligation.<br /><b>Results</b><br />After CNA, ECVNS responses remained abolished for 6 weeks despite ganglia remaining in ablated GPs. In the CNA group, direct VNS resulted in paradoxical increases in blood pressure, but not in sham animals (CNA group vs. sham: 8.36±7.0% vs. -4.83±8.7%, respectively, p=0.009). Left SCS (8Hz) induced significant QTc prolongation in the CNA group vs. sham (11.23±4.0% vs. 1.49±4.0%, respectively, p<0.001). VT/VF after LAD ligation was more prevalent and occurred earlier in the CNA group vs. control (61.44±73.7sec vs. 245.11±104.0 sec, respectively, p=0.002).<br /><b>Conclusions</b><br />Cardiac vagal denervation is maintained long-term after CNA in a porcine model. However, chronic CNA was associated with cardiovascular dysreflexia, diminished cardioprotective effects of cardiac vagal tone, and increased VT/VF susceptibility in ischemia. These potential long-term negative impacts of CNA suggest the need for rigorous clinical studies on CNA.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 08 Aug 2023; epub ahead of print</small></div>

<div><h4>Long-term Outcomes of Abandoned Leads of Cardiac Implantable Electronic Devices.</h4><i>Kwon S, Lee E, Choi EK, Lee SR, Oh S, Choi YS</i><br /><b>Background</b><br />Evidence is scarce of the long-term outcomes of abandoned leads (ALs) in patients with cardiac implantable electronic devices (CIEDs).<br /><b>Objective</b><br />This study investigated the long-term outcomes of ALs.<br /><b>Methods</b><br />This retrospective cohort study reviewed a single-center CIED registry of 2,962 procedures performed in 1984-2018 and identified 130 patients with AL (AL group). We matched two controls without AL (by age, sex, device type, and device revision/removal date) to each patient with AL (n=260) and compared CIED-related infection, venous thrombosis/stenosis, and all-cause mortality between groups using a Cox proportional hazard model analysis.<br /><b>Results</b><br />For a mean follow-up period of 11.2±8.2 years, 14 (3.6%), 7 (1.8%), and 143 (36.7%) patients had a CIED-related infection, had venous thrombosis/stenosis, or experienced all-cause mortality, respectively. The AL group had more comorbidities than the control group. Lead malfunction was the most common cause of abandonment (64.6%). After the adjustment for covariates, no significant intergroup differences were noted in the risks of infection, venous thrombosis/stenosis, or all-cause mortality (adjusted hazard ratio [aHR], 2.52; 95% confidence interval [CI], 0.77-8.25; aHR, 1.18; 95% CI, 0.25-5.64; and aHR, 1.26; 95% CI, 0.89-1.80, respectively). Patients with multiple ALs had increased risks of infection and all-cause mortality versus controls (aHR, 8.61; 95% CI, 2.13-34.84; and aHR, 2.42; 95% CI, 1.17-5.00, respectively).<br /><b>Conclusion</b><br />Patients with a single AL showed similar risks of CIED-related infections, venous thrombosis/stenosis, and all-cause mortality to those without ALs, whereas those with multiple ALs showed increased risks of infection and all-cause mortality.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 03 Aug 2023; epub ahead of print</small></div>

<div><h4>SUMOylation of the Cardiac Sodium Channel Na1.5 Modifies Inward Current and Cardiac Excitability.</h4><i>Yoon JY, Greiner AM, Jacobs JS, Kim YR, ... Irani K, London B</i><br /><b>Background</b><br />Decreased peak sodium current (I<sub>Na</sub>) and increased late sodium current (I<sub>Na,L</sub>), through the cardiac sodium channel Na<sub>V</sub>1.5 encoded by SCN5A, cause arrhythmias. Many Na<sub>V</sub>1.5 post-translational modifications have been reported. A recent report concluded that acute hypoxia increases I<sub>Na,L</sub> by increasing a Small Ubiquitin-like MOdifier (SUMOylation) at K442-Na<sub>V</sub>1.5.<br /><b>Objective</b><br />To determine whether and by what mechanisms SUMOylation alters I<sub>Na</sub>, I<sub>Na,L</sub> and cardiac electrophysiology.<br /><b>Methods</b><br />SUMOylation of Na<sub>V</sub>1.5 was detected by immunoprecipitation and immunoblotting. I<sub>Na</sub> was measured by patch clamp with/without SUMO1 overexpression in HEK293 cells expressing wild type (WT) or K442R-Na<sub>V</sub>1.5 and in neonatal rat cardiac myocytes (NRCMs). SUMOylation effects were studied in vivo by electrocardiograms and ambulatory telemetry using Scn5a heterozygous knockout (SCN5A<sup>+/-</sup>) mice and the de-SUMOylating protein SENP2 (AAV9-SENP2), AAV9-SUMO1, or the SUMOylation inhibitor anacardic acid. Na<sub>V</sub>1.5 trafficking was detected by immunofluorescence.<br /><b>Results</b><br />Na<sub>V</sub>1.5 was SUMOylated in HEK293 cells, NRCMs and human heart tissue. HyperSUMOylation at Na<sub>V</sub>1.5-K442 increased I<sub>Na</sub> in NRCMs and in HEK cells overexpressing WT but not K442R-Na<sub>v</sub>1.5. SUMOylation did not alter other channel properties including I<sub>Na,L</sub>. AAV9-SENP2 or anacardic acid decreased I<sub>Na</sub>, prolonged QRS duration, and produced heart block and arrhythmias in SCN5A<sup>+/-</sup> mice, while AAV9-SUMO1 increased I<sub>Na</sub> and shortened QRS duration . SUMO1 overexpression enhanced membrane localization of Na<sub>V</sub>1.5.<br /><b>Conclusion</b><br />SUMOylation of K442-Na<sub>v</sub>1.5 increases peak I<sub>Na without changing</sub> I<sub>Na,L</sub>, at least in part by altering membrane abundance. Our findings do not support SUMOylation as a mechanism for changes in I<sub>Na,L.</sub> Na<sub>v</sub>1.5 SUMOylation may modify arrhythmic risk in disease states and represents a potential target for pharmacological manipulation.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 03 Aug 2023; epub ahead of print</small></div>

<div><h4>Left bundle branch area pacing reduces epicardial dispersion of repolarization compared to biventricular cardiac resynchronization therapy.</h4><i>Elliott MK, Strocchi M, Sieniewicz BJ, Mehta V, ... Niederer S, Rinaldi CA</i><br /><b>Background</b><br />Biventricular endocardial pacing (BiV-endo) and left bundle branch area pacing (LBBAP) are novel methods of delivering cardiac resynchronization therapy (CRT). These techniques are associated with improved activation times and acute hemodynamic response compared to conventional biventricular epicardial pacing (BiV-epi), however the effects on repolarization and arrhythmic risk are unknown.<br /><b>Objective</b><br />To compare the effects of temporary BiV-epi, BiV-endo and LBBAP on epicardial left ventricular repolarization using electrocardiographic imaging (ECGi).<br /><b>Methods</b><br />11 patients indicated for CRT underwent a temporary pacing protocol and ECGi. BiV-endo was delivered via endocardial stimulation of the left ventricular (LV) lateral wall. LBBAP was delivered by pacing the LV septum. Epicardial LV repolarization time (LVRT-95), LVRT dispersion, mean LV activation recovery interval (ARI), LV ARI dispersion and RT gradients were calculated.<br /><b>Results</b><br />The protocol was completed in 10 patients. During LBBAP there were significant reductions in LVRT-95 (94.9 ± 17.4 vs 125.0 ± 29.4 ms; P=0.03) and LV RT dispersion (29.4 ± 6.3 vs 40.8 ± 11.4 ms; P=0.015) compared to BiV-epi. In contrast, there were no significant differences between baseline, BiV-epi or BiV-endo. There was a non-significant reduction in mean RT gradients between LBBAP and baseline rhythm (0.74 ± 0.22 vs 1.01 ± 0.31 ms/mm; P=0.07). There were no significant differences between groups in mean LV ARI or LV ARI dispersion.<br /><b>Conclusion</b><br />Temporary LBBAP reduces epicardial dispersion of repolarization compared to conventional BiV-epi. Further study is required to determine if these repolarization changes on ECGi translate into reduced risk of ventricular arrhythmia in clinical practice.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 27 Jul 2023; epub ahead of print</small></div>

<div><h4>Worsening Tricuspid Regurgitation Associated with Permanent Pacemaker and Implantable Cardioverter-Defibrillator Implantation: A Systematic Review and Meta-Analysis of over 66,000 Subjects.</h4><i>Alnaimat S, Doyle M, Krishnan K, Biederman RWW</i><br /><b>Background</b><br />Worsening TR following either PPM or ICD implantation is an emerging clinical challenge. Early recognition of this entity is essential in guiding treatment.<br /><b>Objective</b><br />This meta-analysis was designed to identify overall incidence and patient-specific predictors of TR post-implantation.<br /><b>Methods</b><br />We searched electronic databases from inception to January 2023 for published studies that reported incidence of TR worsening post-device implantation. Log odds ratio was used to summarize group differences.<br /><b>Results</b><br />Our analysis included 29 studies with 66,590 participants. Patients with device implantation (n=1,008) were significantly more likely to develop worsening TR when compared with controls (n=58,605) (OR: 3.18, p<0.01). Amongst a total of 7,777 patients, pooled incidence of at least one-degree worsening of TR post-implantation was 23%. Worsening TR post-implantation significantly increases mortality (HR 1.42, p=0.02). Larger right atrial area (OR 1.11, p<0.01) is significantly associated with an increased risk of worsening TR post-implantation, while males are less likely to develop this complication when compared to females (OR 0.74, p<0.01). Importantly, there is no statistically significant difference between the type of implanted device (ICD vs PPM) and post-device TR. Further, RV dysfunction, pulmonary artery pressure, baseline mitral regurgitation, LVEF, baseline atrial fibrillation, and age have no association with worsening TR post-implantation.<br /><b>Conclusion</b><br />A substantial number of patients undergoing PPM or ICD implantation are at an increased risk of worsening TR. Importantly, in this largest review to date incorporating over 66,000 subjects, this significantly increases mortality by greater than 140%, accordingly deserving more recognition and clinical attention in the current era.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 26 Jul 2023; epub ahead of print</small></div>

<div><h4>Early Left Bundle Branch Pacing in Heart Failure with Mildly-Reduced Ejection Fraction and Left Bundle Branch Block.</h4><i>Zeng J, He C, Zou F, Qin C, ... Fan X, Zou J</i><br /><b>Background</b><br />Left bundle branch pacing (LBBP) achieves resynchrony and improves cardiac function in heart failure (HF) patients with reduced ejection fraction (EF) by correcting left bundle branch block (LBBB). Few data studied the efficacy of early LBBP in HF with mildly-reduced EF (HFmrEF) and LBBB.<br /><b>Objective</b><br />To explore the efficacy of early LBBP in patients with HFmrEF and LBBB.<br /><b>Methods</b><br />Consecutive patients with HFmrEF (LVEF 35%-50%) and LBBB were prospectively enrolled to receive LBBP (Early-LBBP group) plus guideline-directed medical therapy (GDMT) or GDMT alone (GDMT group). Study outcomes included changes in LVEF, LV end diastolic diameter (LVEDD), NYHA classification and NT-ProBNP, and clinical events (HF rehospitalization or syncope). A subgroup analysis compared efficacy of LBBP between patients with LBBB only without comorbidities or late gadolinium enhancement (LGE)(LBBB-Only group) and patients with either comorbidities or LGE (LBBB-Combined group).<br /><b>Results</b><br />Fifty-four patients were enrolled and analysis included 37 in Early-LBBP and 15 in GDMT group. LBBP achieved greater improvement in LVEF (+14.75±7.37% vs. -2.42±2.84%, p<0.001), reduction of LVEDD (-7.51±5.40 vs. -0.87±4.36mm, p<0.001) and NYHA classification (-0.84±0.76 vs. -0.13±0.74, p=0.004), and similar reduction of NT-proBNP (-408.83±920.29pg/ml vs. -229.05±1579.17pg/ml, p=0.610) at 6-month. Early LBBP showed significantly reduced clinical events (0.0% vs. 40.0%, p<0.001) after 20.68±13.55 month follow-up. Subgroup analysis showed patients in LBBB-Only group benefited more from LBBP in LVEF improvement and LVEDD reduction compared with LBBB-Combined group.<br /><b>Conclusion</b><br />Early LBBP with GDMT demonstrated greater improvement of cardiac function and reduced clinical events compared to GDMT alone in patients with HFmrEF and LBBB.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 24 Jul 2023; epub ahead of print</small></div>

<div><h4>Provocation Testing in Congenital Long QT Syndrome: A Practical Guide.</h4><i>Abrahams T, Davies B, Laksman Z, Sy RW, ... Krahn AD, Han HC</i><br /><AbstractText>Congenital long QT syndrome (LQTS) is a hereditary cardiac channelopathy with an estimated prevalence of 1 in 2500. A prolonged resting QT-interval corrected for heart rate (QTc) remains a key diagnostic component; however, the QTc value may be normal in up to 40% of genotype positive LQTS patients and borderline in a further 30%. Provocation of QTc prolongation and T-wave changes may be pivotal to unmasking the diagnosis and useful in predicting genotype. LQTS provocation testing involves assessment of repolarization during and following exercise, in response to changes in heart rate or autonomic tone, with LQTS patients exhibiting a maladaptive repolarization response. We review the utility and strengths and limitations of four forms of provocation testing - stand-up test, exercise stress test, epinephrine challenge and mental stress test - in diagnosing LQTS and provide some practical guidance for performing provocation testing. Ultimately, exercise testing when feasible, is the most useful form of provocation testing when considering diagnostic sensitivity and specificity.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 20 Jul 2023; epub ahead of print</small></div>

<div><h4>Sex differences in leadless pacemaker implantation: a propensity matched analysis from i-LEAPER registry.</h4><i>Mitacchione G, Schiavone M, Gasperetti A, Arabia G, ... Curnis A, Forleo GB</i><br /><b>Background</b><br />The impact of sex in clinical and procedural outcomes in leadless pacemakers (LPMs) patients has not been investigated yet.<br /><b>Objective</b><br />To investigate sex-related differences in patients undergoing LPMs implantation.<br /><b>Methods</b><br />Consecutive patients enrolled in the i-LEAPER registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity-matching for age and comorbidities. The primary outcome was the comparison of major complication rates; sex-related differences regarding electrical performance and all-cause mortality during follow-up were deemed secondary outcomes.<br /><b>Results</b><br />In the overall population (n=1179 patients; median age 80 years), 64.3% were men. After propensity-matching, 738 patients with no significant baseline differences among groups were identified. During a median follow-up of 25 (interquartile range [IQR] 24-39) months, female sex was not associated with LPM-related major complications (hazard ratio [HR] 2.03, 95% confidence interval [CI] 0.70-5.84, p=0.190) and with all-cause mortality (HR 0.98, 95% CI 0.40-2.42, p=0.960). LPM electrical performance resulting comparable between groups, excepting for a higher pacing impedance in women at implant and during follow-up (24-month: 670 [550-800] vs 616 [530-770] ohms, p=0.014), however remaining within normal limits.<br /><b>Conclusions</b><br />In a real-world setting, we found differences in sex-related referral patterns for LPM implantation with an under-representation of women, although major complication rate, and LPM performances were comparable between sexes. Female patients showed higher impedance values, not showing any impact on the overall device performance. Electrical parameters remained within normal limits in both groups during the entirety of follow-up.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 20 Jul 2023; epub ahead of print</small></div>

<div><h4>Guided implantation of a leadless LV endocardial electrode and acoustic transmitter using computed tomography anatomy, dynamic perfusion and mechanics, and predicted activation pattern.</h4><i>Sidhu BS, Lee AWC, Gould J, Porter B, ... Rinaldi CA, Niederer SA</i><br /><b>Background</b><br />The WiSE-CRT system permits leadless left ventricular (LV) pacing. Currently no intra-procedural guidance is used to target optimal electrode placement whilst simultaneously guiding acoustic transmitter placement in close proximity to the electrode to ensure adequate power delivery.<br /><b>Objectives</b><br />Assess the use of computed tomography (CT) anatomy, dynamic perfusion, and mechanics, and predicted activation pattern to identify both the optimal electrode and transmitter locations.<br /><b>Method</b><br />A novel CT protocol whereby images and simulations were used pre-procedurally to identify target segments (TS) for electrode implantation with late electrical and mechanical activation with ≥5mm wall thickness without perfusion defects. Modeling of the acoustic intensity from different transmitter implant sites to the TS was used to identify the optimal transmitter location. During implantation, TS were overlaid onto fluoroscopy to guide optimal electrode location that were evaluated by acute hemodynamic response (AHR).<br /><b>Results</b><br />Ten patients underwent the implantation procedure. The transmitter could be implanted within the recommended site based on pre-procedural analysis in all patients. CT identified a mean of 4.8±3.5 segments per patient with wall thickness <5mm. During electrode implantation, biventricular pacing within TS resulted in a significant improvement in AHR versus non-TS (25.5±8.8 vs.12.9±8.6%;P<0.001). Pacing in CT identified scar resulted in either failure to capture or minimal AHR improvement. The electrode was targeted to the TS in all patients and was implanted in the TS in 80%.<br /><b>Conclusion</b><br />Pre-procedural imaging and modeling data with intra-procedural guidance can successfully guide WiSE-CRT electrode and transmitter implantation to allow optimal AHR and adequate power delivery.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 13 Jul 2023; epub ahead of print</small></div>

<div><h4>Differences among young unwitnessed sudden cardiac death, according to time from last seen alive: insights from a 15-year nationwide study.</h4><i>Hansen CJ, Svane J, Lynge TH, Stampe NK, ... Tfelt-Hansen J, Winkel BG</i><br /><b>Background</b><br />More than half of all sudden cardiac deaths (SCD) are unwitnessed, but the composition of the unwitnessed SCD population is poorly described.<br /><b>Objective</b><br />This study aimed to compare clinical and autopsy characteristics of young unwitnessed SCD, depending on the time from last contact to being found dead.<br /><b>Method</b><br />All unwitnessed SCD aged 1-35 years in Denmark from 2000-2014 identified through a multi-source approach were included. Time from last seen alive to being found dead was dichotomized in <1 hour or 1-24 hours. Clinical characteristics and autopsy results were compared, and predictors of autopsy were assessed by logistic regression.<br /><b>Results</b><br />Of 440 unwitnessed SCD, 366 (83%) had not been seen alive within one hour of being found dead. Comorbidities differed between the groups with more epilepsy (17% vs 5%) and psychiatric diseases (13% vs 7%) in the 24-hour group. The 24-hour group died more frequently during sleep (64% vs 23%), the autopsy rate was higher (75% vs 61%), and deaths were more often unexplained after autopsy (69% vs 53%). Having been seen within one hour of death independently decreased the chance of being autopsied with OR 0.51 [95% CI 0.27-1.00, p = 0.0497].<br /><b>Conclusions</b><br />The majority of unwitnessed SCD had not been seen alive within one hour of being found dead. Clinical- and autopsy-related characteristics differed among the two groups. Differences were mainly attributable to death-related circumstances and comorbidities. Excluding SCD cases not seen alive within one hour of being found dead would severely underestimate the burden of SCD.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 13 Jul 2023; epub ahead of print</small></div>

<div><h4>Towards Advanced Diagnosis and Management of Inherited Arrhythmia Syndromes: Harnessing the Capabilities of Artificial Intelligence and Machine Learning.</h4><i>Asatryan B, Bleijendaal H, Wilde AAM</i><br /><AbstractText>The use of advanced computational technologies, such as artificial intelligence (AI), is now exerting a significant influence on various aspects of life, including healthcare and science. AI has garnered remarkable public notice with the release of deep-learning models that can model anything from artwork to academic papers with minimal human intervention. Machine learning (ML), a method that uses algorithms to extract information from raw data and represent it in a model, and deep learning, a method that uses multiple layers to progressively extract higher-level features from the raw input with minimal human intervention, are increasingly leveraged to tackle problems in the health sector including utilization for clinical decision-support in cardiovascular medicine. Inherited arrhythmia syndromes (IAS) are a clinical domain where multiple unanswered questions remain despite unprecedented progress over the past two decades with the introduction of large panel genetic testing and the first steps in precision medicine. In particular, AI tools can help address gaps in clinical diagnosis by identifying individuals with concealed or transient phenotypes; enhance risk stratification by elevating recognition of underlying risk burden beyond widely recognized risk factors; improve prediction of response to therapy, and further prognostication. In this contemporary review, we provide a summary of the AI models developed to solve challenges in IAS and also outline gaps that can be filled with the development of intelligent AI models.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 11 Jul 2023; epub ahead of print</small></div>

<div><h4>Omnipolar versus bipolar mapping to guide ventricular tachycardia ablation.</h4><i>Ascione C, Kowalewski C, Bergonti M, Yokoyama M, ... Jaïs P, Sacher F</i><br /><b>Background</b><br />Omnipolar technology (OT) was recently proposed to generate electroanatomical voltage maps with orientation-independent electrograms. We describe the first cohort of patients undergoing ventricular tachycardia (VT) ablation guided by OT.<br /><b>Objectives</b><br />The purpose of this study was to compare omnipolar and bipolar high-density maps regarding voltage amplitude, late potentials (LP) annotation, and isochronal late activation maps (ILAM) distribution.<br /><b>Methods</b><br />A total of 24 patients (16 ischemic cardiomyopathy, 12 redo cases) underwent VT ablation under OT guidance. Twenty-seven sinus rhythm substrate maps and 10 VT activation maps were analyzed. Omnipolar and bipolar (HD Wave solution) voltages were compared. Areas of late potentials were correlated to the VT isthmuses areas and late electrograms misannotation was evaluated. Deceleration zones based on ILAM were analysed by 2 blinded operators and compared to the VT isthmuses.<br /><b>Results</b><br />Omnipolar maps had higher points density (13.8 vs 8.0 points/cm2). Omnipolar points had 7.1% higher voltages than bipolar points within areas of dense scar and border zone. The number of misannotated points was significantly lower in omnipolar maps (6.8% vs 21.9%, p=0.01), showing comparable sensitivity (53% vs 59%) but higher specificity (79% vs 63%). The sensitivity and specificity of deceleration zones detection of the VT critical isthmus were respectively 75% and 65% for OT, and 35% and 55% for bipolar. At 8.4 months, 71% freedom from VT recurrence was achieved.<br /><b>Conclusions</b><br />OT is a valuable tool for guiding VT ablation, providing more accurate identification of late potentials and isochronal crowding due to slightly higher voltages.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 04 Jul 2023; epub ahead of print</small></div>

<div><h4>Left Ventricular Lead Implantation Failure in an Unselected Nationwide Cohort.</h4><i>Friedman DJ, Qin L, Freeman JV, Singh JP, ... Al-Khatib SM, Jackson KP</i><br /><b>Background</b><br />Left ventricular(LV) lead implantation is often the most challenging aspect of cardiac resynchronization therapy(CRT) procedures; early studies reported implant failure rates in approximately 10% of cases.<br /><b>Objective</b><br />To define rates, reasons for, and factors independently associated with, LV lead implant failure.<br /><b>Methods</b><br />We studied patients with left bundle branch block(LBBB) and ejection fraction ≤35% who underwent planned de novo transvenous CRT implantation(2010-2016) and were reported to the NCDR ICD Registry. Independent predictors of LV lead implant failure were determined using logistic regression; age, sex, and variables with a univariate p<0.15 were considered for inclusion in the model.<br /><b>Results</b><br />Of the 111,802 patients who underwent a planned CRT procedure, LV lead implant failed in 3.6%(n=3,979) of patients. Reasons for implant failure included venous access(7.5%), coronary sinus access(64.3%), tributary vein access(13.5%), coronary sinus dissection(7.6%), unacceptable threshold(4.4%), and diaphragmatic stimulation(1.7%). Significant independent predictors of LV lead implant failure included younger age(OR 1.01, CI 0.1.01-1.02), female sex(OR 1.38, CI 1.29-1.47), Black race(vs. white, OR 1.44 CI 1.32-1.57), Hispanic ethnicity(OR 1.23, CI 1.08-1.40), QRS duration(OR 1.055 per 10 ms, CI 1.038 - 1.072), obstructive sleep apnea(OR 1.14 CI 1.04-1.24), and implant by a physician without specialized training (vs. electrophysiology trained(OR 1.53, CI 1.34-1.76).<br /><b>Conclusion</b><br />LV lead implant failure is uncommon in the current era and is most commonly due to coronary sinus access failure. Predictors of LV lead implant failure included younger age, female sex, Black race, Hispanic ethnicity, increased QRS duration, sleep apnea, and absence of electrophysiology training.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 03 Jul 2023; epub ahead of print</small></div>

<div><h4>Artificial Intelligence for Detection of Ventricular Oversensing Machine Learning Approaches for Noise Detection Within Non-Sustained Ventricular Tachycardia Episodes Remotely Transmitted by Pacemakers and Implantable Cardioverter Defibrillators.</h4><i>Strik M, Sacristan B, Bordachar P, Duchateau J, ... Dubois R, Ploux S</i><br /><b>Background</b><br />Pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) increasingly automatically record and remotely transmit non-sustained ventricular tachycardia (NSVT) episodes which may reveal ventricular oversensing.<br /><b>Objectives</b><br />We aimed to develop and validate a machine learning algorithm which accurately classifies NSVT episodes transmitted by PMs and ICDs in order to lighten healthcare workload burden and improve patient safety.<br /><b>Methods</b><br />PMs or ICDs (Boston Scientific) from four French hospitals with ≥1 transmitted NSVT episode were split into three subgroups: training set, validation set, and test set. Each NSVT episode was labelled as either physiological or non-physiological. Four machine learning algorithms (2DTF-CNN, 2D-DenseNet, 2DTF-VGG, and 1D-AgResNet) were developed using a training and validation dataset. Accuracies of the classifiers were compared with an analysis of the remote monitoring team of the Bordeaux University Hospital using F2 scores (favoring sensitivity over predictive positive value) using an independent test set.<br /><b>Results</b><br />807 devices transmitted 10.471 NSVT recordings (82% ICD, 18% PM), of which 87 devices (10.8%) transmitted 544 NSVT recordings with non-physiological signals. The classification by the remote monitoring team resulted in an F2 score of 0,932 (sensitivity of 95%, specificity of 99%) The four machine learning algorithms showed high and comparable F2 scores (2DTF-CNN: 0,914, 2D-DenseNet: 0,906, 2DTF-VGG: 0,863, 1D-AgResNet: 0,791) and only 1D-AgResNet had significantly different labeling as compared with the remote monitoring team.<br /><b>Conclusion</b><br />Machine learning algorithms were accurate in detecting non-physiological signals within EGMs transmitted by pacemaker and ICDs. An artificial intelligence approach may render remote monitoring less resourceful and improve patient safety.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 03 Jul 2023; epub ahead of print</small></div>

<div><h4>Pacemaker lead insertion sites contribute to abnormalities of myocardial function and histopathology.</h4><i>Castellanos DA, Carreon CK, Prakash A, Sanders SP, ... Ghelani SJ, Mah DY</i><br /><b>Background</b><br />Ventricular pacing can cause myocardial dysfunction but how lead anchoring to myocardium affects function has not been studied.<br /><b>Objective</b><br />Evaluate patterns of regional and global ventricular function in patients with a ventricular lead using cine cardiac computed tomography (CCT) and histology.<br /><b>Methods</b><br />This was a single center retrospective study with two groups of patients with a ventricular lead: (1) those who underwent a cine CCT from September 2020 to June 2021 and (2) those whose cardiac specimen was analyzed histologically. Regional wall motion abnormalities by CCT were assessed in relation to lead characteristics.<br /><b>Results</b><br />For the CCT group, 122 ventricular lead insertion sites were analyzed in 43 patients (47% female, median age 19 years, range 3-57 years). Regional wall motion abnormalities were present at 51/122 (42%) lead insertion sites among 23/43 (53%) patients. The prevalence of a lead insertion associated regional wall motion abnormality was higher with active pacing (55% vs 18%; p < 0.001). Patients with lead insertion associated regional wall motion abnormalities had a lower systemic ventricular ejection fraction (median 38% vs 53%, p < 0.001) compared to those without regional wall motion abnormalities. For the histology group, three patients with 10 epicardial lead insertion sites were studied. Myocardial compression, fibrosis, and calcifications were commonly present directly under active leads.<br /><b>Conclusion</b><br />Lead insertion site regional wall motion abnormalities are common and associated with systemic ventricular dysfunction. Histopathologic alterations including myocardial compression, fibrosis, and calcifications beneath active leads may explain this finding.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 28 Jun 2023; epub ahead of print</small></div>

<div><h4>Ventricular arrhythmias in hypertrophic cardiomyopathy patients: prevalence, distribution, predictors and outcome.</h4><i>Segev A, Wasserstrum Y, Arad M, Larrañaga-Moreira JM, ... Barriales-Villa R, Sabbag A</i><br /><b>Background</b><br />Hypertrophic cardiomyopathy (HCM) carries an increased risk of sudden cardiac death (SCD). Ventricular fibrillation (VF) is thought to be the common culprit arrhythmia.<br /><b>Objective</b><br />To describe the incidence and predictors of sustained ventricular arrhythmias (VTA) in HCM patients.<br /><b>Methods</b><br />We retrospectively analyzed all patients with HCM and an ICD from a prospectively-derived registry in 2 tertiary medical centers. Clinical, electrocardiographic, echocardiographic, ICD interrogation and genetic data were collected and compared, first between patients with or without VTA and then between patients with only VF and those with VT with or without VF.<br /><b>Results</b><br />Out of 1328 HCM patients, 207 (70% male, 33±16 years old) were implanted with ICDs. Over a mean follow-up of 10±6 years, 37 (18%) patients with ICDs developed sustained VTA. These were associated with a family history of SCD and personal history of VTA (P=0.036 and P=0.001, respectively). Sustained monomorphic ventricular tachycardia was the most common arrhythmia (70%) and was linked to decreased left ventricular ejection fraction (LVEF) and increased LV end-systolic and end-diastolic diameters. Anti-tachycardia pacing (ATP) successfully terminated 79% of the 326 VT events. Mortality rates were comparable between patients with and without VTA (17% vs. 15%; P=0.27) and in those with and without ICDs (16% vs. 20%; P=0.367).<br /><b>Conclusions</b><br />VT rather than VF is the most common arrhythmia in patients with HCM, it is amenable to ATP and is associated with lower LVEF and higher LV diameters. Therefore, ATP-capable devices may be considered in HCM patients with these LV features.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 27 Jun 2023; epub ahead of print</small></div>