<div><h4>Outcomes After Development of Ventricular Arrhythmias in Single Ventricular Heart Disease Patients With Fontan Palliation.</h4><i>Giacone HM, Chubb H, Dubin AM, Motonaga KS, ... Hanley FL, Chen S</i><br /><b>Background</b><br />With the advent of more intensive rhythm monitoring strategies, ventricular arrhythmias (VAs) are increasingly detected in Fontan patients. However, the prognostic implications of VA are poorly understood. We assessed the incidence of VA in Fontan patients and the implications on transplant-free survival.<br /><b>Methods</b><br />Medical records of Fontan patients seen at a single center between 2002 and 2019 were reviewed to identify post-Fontan VA (nonsustained ventricular tachycardia >4 beats or sustained >30 seconds). Patients with preFontan VA were excluded. Hemodynamically unstable VA was defined as malignant VA. The primary outcome was death or heart transplantation. Death with censoring at transplant was a secondary outcome.<br /><b>Results</b><br />Of 431 Fontan patients, transplant-free survival was 82% at 15 years post-Fontan with 64 (15%) meeting primary outcome of either death (n=16, 3.7%), at a median 4.6 (0.4-10.2) years post-Fontan, or transplant (n=48, 11%), at a median of 11.1 (5.9-16.2) years post-Fontan. Forty-eight (11%) patients were diagnosed with VA (90% nonsustained ventricular tachycardia, 10% sustained ventricular tachycardia). Malignant VA (n=9, 2.0%) was associated with younger age, worse systolic function, and valvular regurgitation. Risk for VA increased with time from Fontan, 2.4% at 10 years to 19% at 20 years. History of Stage 1 surgery with right ventricular to pulmonary artery conduit and older age at Fontan were significant risk factors for VA. VA was strongly associated with an increased risk of transplant or death (HR, 9.2 [95% CI, 4.5-18.7]; <i>P</i><0.001), with a transplant-free survival of 48% at 5-year post-VA diagnosis.<br /><b>Conclusions</b><br />Ventricular arrhythmias occurred in 11% of Fontan patients and was highly associated with transplant or death, with a transplant-free survival of <50% at 5-year post-VA diagnosis. Risk factors for VA included older age at Fontan and history of right ventricular to pulmonary artery conduit. A diagnosis of VA in Fontan patients should prompt increased clinical surveillance.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 31 May 2023:e011143; epub ahead of print</small></div>

<div><h4>Pulsed Field Versus Cryoballoon Pulmonary Vein Isolation for Atrial Fibrillation: Efficacy, Safety, and Long-Term Follow-Up in a 400-Patient Cohort.</h4><i>Urbanek L, Bordignon S, Schaack D, Chen S, ... Schmidt B, Chun KRJ</i><br /><b>Background</b><br />The cryoballoon represents the gold standard single-shot device for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Single-shot pulsed field PVI ablation (nonthermal, cardiac tissue selective) has recently entered the arena. We sought to compare procedural data and long-term outcome of both techniques.<br /><b>Methods</b><br />Consecutive AF patients who underwent pulsed field ablation (PFA) and cryoballoon-based PVI were enrolled. Cryoballoon PVI was performed using the second-generation 28-mm cryoballoon; PFA was performed using a 31/35-mm pentaspline catheter. Success was defined as no recurrence of atrial tachyarrhythmia after a 3-month blanking period.<br /><b>Results</b><br />Four hundred patients were included (56.5% men; 60.8% paroxysmal AF; age, 70 [interquartile range, 59-77] years), 200 in each group (cryoballoon and PFA), and baseline characteristics did not differ. Acute PVI was achieved in 100% of PFA and in 98% (196/200) of cryoballoon patients (<i>P</i>=0.123; 4 touch-up ablations). Median procedure time was significantly shorter in PFA (34.5 [29-40] minutes) versus cryoballoon (50 [45-60] minutes; <i>P</i><0.001), fluoroscopy time was similar. Overall procedural complications were 6.5% in cryoballoon and 3.0% in PFA (<i>P</i>=0.1), driven by a higher rate of phrenic nerve palsies using cryoballoon. The 1-year success rates in paroxysmal AF (cryoballoon, 83.1%; PFA, 80.3%; <i>P</i>=0.724) and persistent AF (cryoballoon, 71%; PFA, 66.8%; <i>P</i>=0.629) were similar for both techniques.<br /><b>Conclusions</b><br />PFA compared with cryoballoon PVI shows a similar procedural efficacy but is associated with shorter procedure time and no phrenic nerve palsies. Importantly, 12-month clinical success rates are favorable but not different between both groups.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 31 May 2023:e011920; epub ahead of print</small></div>

<div><h4>Atrial Fibrillation Ablation in Young Adults: Measuring Quality of Life Using Patient-Reported Outcomes Over 5 Years.</h4><i>Johnson BM, Wazni OM, Farwati M, Saliba WI, ... Nakagawa H, Hussein AA</i><br /><b>Background</b><br />Ablation is used for both rhythm control and improved quality of life (QoL) in atrial fibrillation (AF). It has been suggested that young adults may experience high recurrence rates after ablation and data remain lacking regarding QoL benefits. We aimed to investigate AF ablation outcomes and QoL benefits in young adults undergoing AF ablation using a large prospectively maintained registry and automated patient-reported outcomes (PRO).<br /><b>Methods</b><br />All patients undergoing AF ablation (2013-2016) at our center were prospectively enrolled. Patients aged 50 years or younger were included. For PROs, QoL measures and symptoms were assessed at baseline, 3 months after ablation, and every 6 months thereafter. The AF severity score served as the main assessment of QoL.<br /><b>Results</b><br />A total of 241 young adults (age, 16-50 years) were included (17% female, 40.3% persistent AF). In all, 77.2% of patients remained arrhythmia-free during the first year of follow-up (80% in nonstructural AF and 66% in structural AF). Using PROs, 90% of patients reported improvement in QoL throughout all survey time points up to 5 years postablation (<i>P</i><0.0001). The baseline median AF severity score was 14 and improved to between 2 and 4 on all follow-up after ablation (<i>P</i><0.0001). Patients also reported fewer and shorter AF episodes, fewer emergency room visits secondary to AF, and fewer hospitalizations (<i>P</i><0.0001).<br /><b>Conclusions</b><br />Ablation remains an effective rhythm-control strategy in young adults with AF. Young adults also experience significant improvement in QoL with reduction of the frequency and duration of AF episodes and AF-related healthcare utilization.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 15 May 2023:e011565; epub ahead of print</small></div>

<div><h4>Early Impact of Proton Beam Therapy on Electrophysiological Characteristics in a Porcine Model.</h4><i>Imamura K, Deisher AJ, Dickow J, Rettmann ME, ... Foote RL, Packer DL</i><br /><b>Background</b><br />Particle therapy is a noninvasive, catheter-free modality for cardiac ablation. We previously demonstrated the efficacy for creating ablation lesions in the porcine heart. Despite several earlier studies, the exact mechanism of early biophysical effects of proton and photon beam delivery on the myocardium remain incompletely resolved.<br /><b>Methods</b><br />Ten normal and 9 infarcted in situ porcine hearts received proton beam irradiation (40 Gy) delivered to the left ventricular myocardium with follow-up for 8 weeks. High-resolution electroanatomical mapping of the left ventricular was performed at baseline and follow-up. Bipolar voltage amplitude, conduction velocity, and connexin-43 were determined within the irradiated and nonirradiated areas.<br /><b>Results</b><br />The irradiated area in normal hearts showed a significant reduction of bipolar voltage amplitude (10.1±4.9 mV versus 5.7±3.2, <i>P</i><0.0001) and conduction velocity (85±26 versus 55±13 cm/s, <i>P</i>=0.03) beginning at 4 weeks after irradiation. In infarcted myocardium after irradiation, bipolar voltage amplitude of the infarct scar (2.0±2.9 versus 0.8±0.7 mV, <i>P</i>=0.008) was significantly reduced as well as the conduction velocity in the infarcted heart (43.7±15.7 versus 26.3±11.4 cm/s, <i>P</i>=0.02). There were no significant changes in bipolar voltage amplitude and conduction velocity in nonirradiated myocardium. Myocytolysis, capillary hyperplasia, and dilation were seen in the irradiated myocardium 8 weeks after irradiation. Active caspase-3 and reduction of connexin-43 expression began in irradiated myocardium 1 week after irradiation and decreased over 8 weeks.<br /><b>Conclusions</b><br />Irradiation of the myocardium with proton beams reduce connexin-43 expression, conduction velocity, and bipolar conducted electrogram amplitude in a large porcine model. The changes in biomarkers preceded electrophysiological changes after proton beam therapy.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 15 May 2023:e011179; epub ahead of print</small></div>

<div><h4>Effects of Atrioventricular Optimization on Left Ventricular Reverse Remodeling With Cardiac Resynchronization Therapy: Results of the SMART-CRT Trial.</h4><i>Gold MR, Ellenbogen K, Leclercq C, Lowy J, ... Stein KM, Auricchio A</i><br /><b>Background</b><br />The role of atrioventricular optimization (AVO) to improve cardiac resynchronization therapy outcomes remains controversial. Previous post hoc analyses of a multicenter trial showed that measures of electrical dyssynchrony (right ventricular-left ventricular [LV] or QLV durations) are associated with patients who benefit from AVO.<br /><b>Methods</b><br />This was a global, multicenter, prospective, randomized trial of de novo cardiac resynchronization therapy implant patients with an right ventricular-LV duration ≥70 ms to determine whether AVO results in greater reverse remodeling. Patients were randomized 1:1 for either an AVO algorithm (SmartDelay) that determines atrioventricular delay and pacing chamber, biventricular or LV only, or a fixed atrioventricular delay of 120 ms with biventricular pacing. Paired echocardiograms performed at baseline and 6 months were evaluated. The primary end point was echocardiographic cardiac resynchronization therapy response, defined dichotomously as a >15% reduction in LV end-systolic volume.<br /><b>Results</b><br />A total of 310 patients (n=120 women) were randomized and had completed 6 months of follow-up. The echocardiographic cardiac resynchronization therapy response rate did not statistically differ between the groups (SmartDelay, 74.8%; fixed, 67.7%; <i>P</i>=0.17). Analyses of prespecified secondary end points demonstrated significant improvements in the absolute (median: SmartDelay, -41.0 mL; fixed, -33.0 mL; <i>P</i>=0.01) and relative change in LV end-systolic volume (SmartDelay, -38.3%; fixed, -27.8%; <i>P</i>=0.03) for patients with SmartDelay optimization. Similar results were observed for the relative improvement in LV ejection fraction (SmartDelay, 46.7%; fixed, 32.1%; <i>P</i>=0.050); absolute improvement in LV ejection fraction trended to be higher with SmartDelay (<i>P</i>=0.06).<br /><b>Conclusions</b><br />Analysis of reverse remodeling parameters demonstrated that AVO via SmartDelay, relative to the nonoptimized fixed atrioventricular delay comparator group, improved absolute and relative changes in LV function in patients with longer right ventricular-LV duration.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT03089281.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 15 May 2023:e011714; epub ahead of print</small></div>

<div><h4>Systematic Electrophysiological Study Prior to Pulmonary Valve Replacement in Tetralogy of Fallot: A Prospective Multicenter Study.</h4><i>Waldmann V, Bessière F, Gardey K, Bakloul M, ... Khairy P, Combes N</i><br /><b>Background</b><br />Ventricular arrhythmias and sudden death are recognized complications in tetralogy of Fallot. Electrophysiological studies (EPS) before pulmonary valve replacement (PVR), the most common reintervention in tetralogy of Fallot, could potentially inform therapy to improve arrhythmic outcomes.<br /><b>Methods</b><br />A prospective multicenter study was conducted to systematically assess EPS with programmed ventricular stimulation in patients with tetralogy of Fallot referred for PVR from January 2020 to December 2021. A standardized stimulation protocol was used across all centers.<br /><b>Results</b><br />A total of 120 patients were enrolled, mean age 39.2±14.5 years, 53.3% males. Sustained ventricular tachycardia was induced in 27 (22.5%) patients. When identifiable, the critical isthmus most commonly implicated (ie, in 90.0%) was between the ventricular septal defect patch and pulmonary annulus. Factors independently associated with inducible ventricular tachycardia were history of atrial arrhythmia (OR, 8.56 [95% CI, 2.43-34.73]) and pulmonary annulus diameter >26 mm (OR, 5.05 [95% CI, 1.47-21.69]). The EPS led to a substantial change in management in 23 (19.2%) cases: 18 (15.0%) had catheter ablation, 3 (2.5%) surgical cryoablation during PVR, and 9 (7.5%) defibrillator implantation. Repeat EPS 5.1 (4.8-6.2) months after PVR was negative in 8 of 9 (88.9%) patients. No patient experienced a sustained ventricular arrhythmia during 13 (6.1-20.1) months of follow-up.<br /><b>Conclusions</b><br />Systematically performing programmed ventricular stimulation in patients with tetralogy of Fallot referred for PVR yields a high rate of inducible ventricular tachycardia and carries the potential to alter management. It remains to be determined whether a standardized treatment approach based on the results of EPS will translate into improved outcomes.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT04205461.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 12 May 2023:e011745; epub ahead of print</small></div>

<div><h4>Heterogeneity of Repolarization and Cell-Cell Variability of Cardiomyocyte Remodeling Within the Myocardial Infarction Border Zone Contribute to Arrhythmia Susceptibility.</h4><i>Amoni M, Vermoortele D, Ekhteraei-Tousi S, Doñate Puertas R, ... Claus P, Sipido KR</i><br /><b>Background</b><br />After myocardial infarction, the infarct border zone (BZ) is the dominant source of life-threatening arrhythmias, where fibrosis and abnormal repolarization create a substrate for reentry. We examined whether repolarization abnormalities are heterogeneous within the BZ in vivo and could be related to heterogeneous cardiomyocyte remodeling.<br /><b>Methods</b><br />Myocardial infarction was induced in domestic pigs by 120-minute ischemia-reperfusion injury. After 1 month, remodeling was assessed by magnetic resonance imaging, and electroanatomical mapping was performed to determine the spatial distribution of activation-recovery intervals. Cardiomyocytes were isolated and tissue samples collected from the BZ and remote regions. Optical recording allowed assessment of action potential duration (di-8-Anepps, stimulation at 1 Hz, 37 °C) of large cardiomyocyte populations while gene expression in cardiomyocytes was determined by single nuclear RNA sequencing.<br /><b>Results</b><br />In vivo, activation-recovery intervals in the BZ tended to be longer than in remote with increased spatial heterogeneity evidenced by a greater local SD (3.5±1.3 ms versus remote: 2.0±0.5 ms, <i>P</i>=0.036, n<sub>pigs</sub>=5). Increased activation-recovery interval heterogeneity correlated with enhanced arrhythmia susceptibility. Cellular population studies (n<sub>cells</sub>=635-862 cells per region) demonstrated greater heterogeneity of action potential duration in the BZ (SD, 105.9±17.0 ms versus remote: 73.9±8.6 ms; <i>P</i>=0.001; n<sub>pigs</sub>=6), which correlated with heterogeneity of activation-recovery interval in vivo. Cell-cell gene expression heterogeneity in the BZ was evidenced by increased Euclidean distances between nuclei of the BZ (12.1 [9.2-15.0] versus 10.6 [7.5-11.6] in remote; <i>P</i><0.0001). Differentially expressed genes characterizing BZ cardiomyocyte remodeling included hypertrophy-related and ion channel-related genes with high cell-cell variability of expression. These gene expression changes were driven by stress-responsive TFs (transcription factors). In addition, heterogeneity of left ventricular wall thickness was greater in the BZ than in remote.<br /><b>Conclusions</b><br />Heterogeneous cardiomyocyte remodeling in the BZ is driven by uniquely altered gene expression, related to heterogeneity in the local microenvironment, and translates to heterogeneous repolarization and arrhythmia vulnerability in vivo.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 02 May 2023:e011677; epub ahead of print</small></div>

<div><h4>Causes of Early Mortality After Catheter Ablation of Atrial Fibrillation.</h4><i>Tan MC, Rattanawong P, Karikalan S, Deshmukh AJ, ... Munger TM, Lee JZ</i><br /><b>Background</b><br />Recognition of the causes of early mortality after atrial fibrillation (AF) catheter ablation is essential for the improvement of patient safety. This study sought to determine the causes of early mortality (≤90 days) after AF ablation.<br /><b>Methods</b><br />We performed a retrospective analysis of AF ablation from January 1, 2013, to December 1, 2021 at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a comprehensive chart review of the electronic health record from within the Mayo Clinic system and outside records when available.<br /><b>Results</b><br />A total of 6723 patients were included in the study. The 90-day all-cause mortality rate was 0.22% (n=15). Among all 90-day deaths, majority of the deaths (73.3%) did not have a direct relationship with the procedure. Sudden death was the most common cause of early death (20%), followed by peri-procedural stroke (13%), respiratory failure (13%), atrioesophageal fistula (13%), infection (7%), heart failure (7%), and traumatic brain injury (7%). The 90-day mortality rate directly due to AF ablation procedural complications was 0.06% (n=4).<br /><b>Conclusions</b><br />AF ablation procedure has a 90-day mortality of 0.22%, and the most common cause of early mortality was sudden death. The majority (73.3%) of early mortality was not directly associated with a procedural complication, and the mortality rate due to complications associated with the AF ablation procedure was low at 0.06%. Further studies are required to investigate causes and risk factors associated with sudden death in this patient population.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 21 Apr 2023:e011365; epub ahead of print</small></div>

<div><h4>Novel Approaches for the Diagnosis of Concealed Nodo-Ventricular and His-Ventricular Pathways.</h4><i>Higuchi S, Gerstenfeld EP, Hsia HH, Wong CX, ... Belhassen B, Scheinman MM</i><br /><b>Background</b><br />Confirming the presence and participation of concealed nodo-ventricular (cNV) or His-ventricular (cHV) pathways in tachyarrhythmias is challenging. We describe novel observations to aid in diagnosing cNV or cHV pathways.<br /><b>Methods</b><br />We present 7 cases of cNV and cHV pathway-mediated arrhythmias and focus on several laboratory observations: (1) differential ventricular overdrive pacing (VOD) from the base versus apex, (2) response to His refractory premature ventricular complexes, (3) paradoxical atriohisian response (shorter atriohisian interval during tachycardia than that during sinus rhythm) in long RP tachycardia, and (4) the role of adenosine to aid in the diagnosis.<br /><b>Results</b><br />Three cases underwent differential VOD during tachycardia. All demonstrated a shorter postpacing interval minus tachycardia cycle length during basal pacing than apical pacing with one case exhibiting apical VOD results compatible with atrioventricular nodal reentrant tachycardia. Basal VOD was useful for localizing the ventricular connection in a case with cHV pathway. In 3 cases, His refractory premature ventricular complexes reset the tachycardia without conduction to the atrium, which excluded the involvement of an atrioventricular pathway or atrial tachycardia, or atrioventricular nodal reentrant tachycardia alone. One case had His refractory premature ventricular complexes followed by subsequent constant AA interval and then tachycardia termination, suggesting a bystander cNV pathway involvement. Two cNV pathway cases presented with long RP tachycardia had paradoxical atriohisian shortening of >15 ms, suggesting parallel activation of the atrium and the atrioventricular node. Adenosine terminated the tachycardia with retrograde block in 2 cases with cNV pathways but had no response on a cHV pathway.<br /><b>Conclusions</b><br />cNV and cHV pathways mediated tachyarrhythmias can present with variable clinical presentations. We emphasize the important role of differential VOD sites, His refractory premature ventricular complexes that reset or terminate the tachycardia without conduction to the atrium, paradoxical atriohisian response in long RP tachycardia, and the use of adenosine for diagnosing cNV and cHV pathways.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 21 Apr 2023:e011771; epub ahead of print</small></div>

<div><h4>Transcatheter Leadless Pacing in Children: A PACES Collaborative Study in the Real-World Setting.</h4><i>Shah M, Borquez AA, Cortez D, McCanta A, ... Ramesh Iyer V, Williams MR</i><br /><b>Background</b><br />Transcatheter Leadless Pacemakers (TLP) are a safe and effective option for adults with pacing indications. These devices may be an alternative in pediatric patients and patients with congenital heart disease for whom repeated sternotomies, thoracotomies, or transvenous systems are unfavorable. However, exemption of children from clinical trials has created uncertainty over the indications, efficacy, and safety of TLP in the pediatric population. The objectives of this study are to evaluate clinical indications, procedural characteristics, electrical performance, and outcomes of TLP implantation in children.<br /><b>Methods</b><br />Retrospective data were collected from patients enrolled in the Pediatric and Congenital Electrophysiology Society TLP registry involving 15 centers. Patients ≤21 years of age who underwent Micra (Medtronic Inc, Minneapolis, MN) TLP implantation and had follow-up of ≥1 week were included in the study.<br /><b>Results</b><br />The device was successfully implanted in 62 of 63 registry patients (98%) at a mean age of 15±4.1 years and included 20 (32%) patients with congenital heart disease. The mean body weight at TLP implantation was 55±19 kg and included 8 patients ≤8 years of age and ≤30 kg in weight. TLP was implanted by femoral (n=55, 87%) and internal jugular (n=8, 12.6%) venous approaches. During a mean follow-up period of 9.5±5.3 months, there were 10 (16%) complications including one cardiac perforation/pericardial effusion, one nonocclusive femoral venous thrombus, and one retrieval and replacement of TLP due to high thresholds. There were no deaths, TLP infections, or device embolizations. Electrical parameters, including capture thresholds, R wave sensing, and pacing impedances, remained stable.<br /><b>Conclusions</b><br />Initial results from the Pediatric and Congenital Electrophysiology Society TLP registry demonstrated a high level of successful Micra device implants via femoral and internal venous jugular approaches with stable electrical parameters and infrequent major complications. Long-term prospective data are needed to confirm the reproducibility of these initial findings.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 11 Apr 2023:e011447; epub ahead of print</small></div>

<div><h4>Randomized Trial of Stand-Alone Use of the Antimicrobial Envelope in High-Risk Cardiac Device Patients.</h4><i>Ellis CR, Greenspon AJ, Andriulli JA, Gould PA, ... Amaral AP, Mittal S</i><br /><b>Background</b><br />Cardiac implantable electronic device (CIED) infection has a high mortality. Previous investigations showed reduced postoperative infections using skin preparation with chlorhexidine, preoperative intravenous antibiotics, and a TYRX-a antibacterial envelope. The additional benefit of antibiotic pocket wash and postoperative antibiotics has not been systematically studied.<br /><b>Methods</b><br />ENVELOPE was a prospective, multicenter, randomized, controlled trial enrolling patients undergoing CIED procedures with ≥2 risk factors for infection. The control arm received standard chlorhexidine skin preparation, intravenous antibiotics, and the TYRX-a antibiotic envelope. The study arm received pocket wash (500 mL antibiotic solution) and postoperative antibiotics for 3 days along with the prophylactic control measures. The primary end point was CIED infection and system removal at 6 months.<br /><b>Results</b><br />One thousand ten subjects (505 per arm) were enrolled and randomized. Patients were seen in person for a wound check with digital photo 2 weeks postimplant and at 3 and 6 months. CIED infection rate was low in both groups (1.0% control arm and 1.2% study arm, <i>P</i>=0.74). In the 11 subjects with infection and system removal, the time to study end point was 107±92 days with a PADIT (Prevention of Arrhythmia Device Infection Trial) score of 7.4 and a 64% 1-year mortality. Prior history of CIED infection independently predicted CIED system removal at 6 months in all subjects (odds ratio, 9.77, <i>P</i>=0.004). Of 11 infections requiring system removal, 5 were in the setting of pocket hematoma.<br /><b>Conclusions</b><br />The use of antibiotic pocket irrigation and postoperative oral antibiotics provides no additional benefit to the prophylactic measures of chlorhexidine skin preparation, preoperative intravenous antibiotics, and an antibiotic envelope in reducing CIED infection. Postoperative hematoma is a major risk factor for infection, driven by the use of antiplatelet and anticoagulant medications. The strongest predictor of CIED removal at 6 months, regardless of intervention, was prior CIED infection.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifier: NCT02809131.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 24 Mar 2023:e011740; epub ahead of print</small></div>

<div><h4>Outcomes of Early Rhythm Control Therapy in Patients With Atrial Fibrillation and a High Comorbidity Burden in Large Real-World Cohorts.</h4><i>Dickow J, Kany S, Roth Cardoso V, Ellinor PT, ... Yao X, Rillig A</i><br /><b>Background</b><br />A recent subanalysis of the EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) suggests a stronger benefit of early rhythm control (ERC) in patients with atrial fibrillation and a high comorbidity burden when compared to patients with a lower comorbidity burden.<br /><b>Methods</b><br />We identified 109 739 patients with newly diagnosed atrial fibrillation in a large United States deidentified administrative claims database (OptumLabs) and 11 625 patients in the population-based UKB (UK Biobank). ERC was defined as atrial fibrillation ablation or antiarrhythmic drug therapy within the first year after atrial fibrillation diagnosis. Patients were classified as (1) ERC and high comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4); (2) ERC and lower comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 2-3); (3) no ERC and high comorbidity burden; and (4) no ERC and lower comorbidity burden. Patients without an elevated comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score 0-1) were excluded. Propensity score overlap weighting and cox proportional hazards regression were used to balance patients and compare groups for the primary composite outcome of all-cause mortality, stroke, or hospitalization with the diagnoses heart failure or myocardial infarction as well as for a primary composite safety outcome of death, stroke, and serious adverse events related to ERC.<br /><b>Results</b><br />In both cohorts, ERC was associated with a reduced risk for the primary composite outcome in patients with a high comorbidity burden (OptumLabs: hazard ratio, 0.83 [95% CI 0.72-0.95]; <i>P</i>=0.006; UKB: hazard ratio, 0.77 [95% CI, 0.63-0.94]; <i>P</i>=0.009). In patients with a lower comorbidity burden, the difference in outcomes was not significant (OptumLabs: hazard ratio, 0.92 [95% CI, 0.54-1.57]; <i>P</i>=0.767; UKB: hazard ratio, 0.94 [95% CI, 0.83-1.06]; <i>P</i>=0.310). The comorbidity burden interacted with ERC in the UKB (interaction- <i>P</i>=0.027) but not in OptumLabs (interaction-<i>P</i>=0.720). ERC was not associated with an increased risk for the primary safety outcome.<br /><b>Conclusions</b><br />ERC is safe and may be more favorable in a population-based sample of patients with high a comorbidity burden (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥4).<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 21 Mar 2023:e011585; epub ahead of print</small></div>

<div><h4>Intracardiac Echocardiography-Guided Implantation for Proximal Left Bundle Branch Pacing.</h4><i>Kuang X, Zhang X, Cui Y, Wei F, ... Huang W, Fan J</i><br /><b>Background</b><br />Multiple screw-in attempts under fluoroscopy are often needed to place the pacing lead tip near or at the left bundle branch (LBB). This study was conducted to evaluate the feasibility of implanting an LBB pacing lead in the proximal LBB (PLBB) guided by intracardiac echocardiography (ICE).<br /><b>Methods</b><br />The distribution of the LBB was initially determined by ICE anatomic imaging and 3-dimensional electrical mapping of His and LBB potentials in 20 patients in the first parts of the study. In the second part, 101 consecutive pacemaker-indicated patients were randomized into the ICE-guided and non-ICE groups for LBB pacing implantation. The procedural details and electrophysiological characteristics of the 2 groups were compared.<br /><b>Results</b><br />In the first part of the study, PLBB was identified at 10 to 20 mm from the tricuspid annulus toward the apex with an area of 4.5±1.1 cm<sup>2</sup>. In the second part, the number of lead screw-in attempts in the septum was fewer in the ICE group than in the non-ICE group (1.43±0.62 versus 1.98±0.75, <i>P</i>=0.0002). The duration of the procedure (26±8 versus 43±9 minutes, <i>P</i><0.001) and fluoroscopy for LBB pacing implantation (7.4±1.8 versus 10.7±2.4 minutes, <i>P</i><0.001) in the ICE group was significantly shorter than those in the non-ICE group. LBB pacing in the ICE group generated a lesser QRS duration with more cases of LBB trunk pacing (46.8% versus 25%, <i>P</i>=0.031) and PLBB (91.5% versus 72.7%, <i>P</i>=0.0267) pacing compared with that in the non-ICE group.<br /><b>Conclusions</b><br />The basal left ventricular septum can be better visualized using ICE. ICE-guided PLBB pacing is feasible and safe, with a shorter duration required for the procedure and fluoroscopy, and generates greater LBB trunk pacing and PLBB pacing.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 16 Mar 2023:e011408; epub ahead of print</small></div>

<div><h4>Bronchial Safety After Pulsed-Field Ablation for Paroxysmal Atrial Fibrillation.</h4><i>Füting A, Reinsch N, Brokkaar L, Hartl S, ... Rausch E, Neven K</i><br /><b>Background</b><br />Thermal left atrial ablation can cause bronchial damage. Pulsed-field ablation (PFA) is a novel, nonthermal ablation modality for paroxysmal atrial fibrillation. We report on bronchial effects after pulmonary vein isolation using PFA for paroxysmal atrial fibrillation.<br /><b>Methods</b><br />A computed tomography scan showing the respiratory tract adjacent to the left atrial was obtained. Oral anticoagulation was interrupted on procedure day. Peri-procedurally, patients received heparin with an activated clotting time goal of >350 seconds. All pulmonary veins were individually isolated with a 13F steerable sheath and a pentaspline PFA catheter using either a straight-tip or J-tip guide wire. The J-tip guide wire patients were added to test the hypothesis that the straight-tip guidewire was associated with bleeding complications. One day afterward, bronchoscopy was performed. Serial hemoglobin levels were measured during 30-day follow-up.<br /><b>Results</b><br />In 2 series of 30 patients, PFA was performed, with all pulmonary veins acutely isolated. Clinical course was uneventful, no patient had chest discomfort, coughing, or hemoptysis. All patients underwent uncomplicated bronchoscopy, without thermal lesions or ulcers. In 12 out of 30 (40%) straight-tip guide wire patients, small amounts of old blood without active bleeding were seen in multiple segments. All hemoglobin levels remained clinically stable. At 30-day follow-up, all patients were asymptomatic.<br /><b>Conclusions</b><br />Pulmonary vein isolation using PFA for paroxysmal atrial fibrillation does not cause thermal lesions in the bronchial system. Use of a straight-tip, extrastiff guide wire for the over-the-wire PFA catheter can lead to asymptomatic bleeding in the bronchial system without clinical relevance at 30-day follow-up, opposite to use of a J-tip guide wire.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 13 Mar 2023:e011547; epub ahead of print</small></div>

<div><h4>Ablation of Ventricular Preexcitation to Cure Preexcitation-Induced Dilated Cardiomyopathy in Infants: Diagnosis and Outcome.</h4><i>Zhang Y, Jiang H, Cui J, Li MT, Zhou HM, Li XM</i><br /><b>Background</b><br />To investigate the clinical features of preexcitation-induced dilated cardiomyopathy in infants and evaluate safety and efficacy of radiofrequency ablation (RFCA) in these patients.<br /><b>Methods</b><br />This study included 10 infants (4 males and 6 females) with mean age of 6.78±3.14 months, mean weight of 8.11±1.71 kg, and mean left ventricular ejection fraction (LVEF) was 32.6±10.34%. Tachycardiomyopathy has been excluded and all patients were refractory to the drugs. All of these 10 patients underwent RFCA. All 10 patients underwent RFCA.<br /><b>Results</b><br />All the accessory pathways in these patients were located on right free wall and the acute success rate was 100%. No complication associated with the procedure occurred. In one case preexcitation recurred and was ablated successfully during the second attempt. There were 3 patients with mild cardiac dysfunction (LVEF, 40≤LVEF<50%), 3 with moderate (30≤LVEF<40%), and 4 with severe cardiac dysfunction (LVEF<30%, the ages were 3, 6, 7, and 10 months, respectively). The time for LVEF normalization was 1 week, 1 to 3 months, and ≥3 months, respectively. In 3 of the 4 severe cardiac dysfunction patients, the LVEF normalized at 3, 6, and 12 months after ablation, the LVEF of the remaining case did not recover at 3 months and is still being followed.<br /><b>Conclusions</b><br />Ventricular preexcitation could lead to severe cardiac dysfunction during infancy. RFCA may be a safe and effective treatment option in right free wall accessory pathways, even in infants with cardiac dysfunction. Cases of more severe cardiac dysfunction might require a longer time for LVEF recovery after RFCA.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 09 Mar 2023:e011569; epub ahead of print</small></div>

<div><h4>Economic and Health Value of Delaying Atrial Fibrillation Progression Using Radiofrequency Catheter Ablation.</h4><i>Berman AE, Kabiri M, Wei T, Galvain T, Sha Q, Kuck KH</i><br /><b>Background</b><br />Radiofrequency catheter ablation (RFCA) is an established treatment for atrial fibrillation (AF) refractory to antiarrhythmic drugs. The economic value of RFCA in delaying disease progression has not been quantified.<br /><b>Methods</b><br />An individual-level, state-transition health economic model estimated the impact of delayed AF progression using RFCA versus antiarrhythmic drug treatment for a hypothetical sample of patients with paroxysmal AF. The model incorporated the lifetime risk of progression from paroxysmal AF to persistent AF, informed by data from the ATTEST (Atrial Fibrillation Progression Trial). The incremental effect of RFCA on disease progression was modeled over a 5-year duration. Annual crossover rates were also included for patients in the antiarrhythmic drug group to mirror clinical practice. Estimates of discounted costs and quality-adjusted life years asssociated with health care utilization, clinical outcomes, and complications were projected over patients\' lifetimes.<br /><b>Results</b><br />From the payer\'s perspective, RFCA was superior to antiarrhythmic drug treatment with an estimated mean net monetary benefit per patient of $8516 ($148-$16 681), driven by reduced health care utilization, cost, and improved quality-adjusted life years. RFCA reduced mean (95% CI) per-patient costs by $73 (-$2700 to $2200), increased mean quality-adjusted life years by 0.084 (0.0-0.17) and decreased the mean number of cardiovascular-related health care encounters by 24%.<br /><b>Conclusions</b><br />RFCA is a dominant (less costly and more effective) treatment strategy for patients with AF, especially those with early AF for whom RFCA could delay progression to advanced AF. Increased utilization of RFCA-particularly among patients earlier in their disease progression-may provide clinical and economic benefits.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 09 Mar 2023:e011237; epub ahead of print</small></div>

<div><h4>Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.</h4><i>Gao J, Makiyama T, Yamamoto Y, Kobayashi T, ... Horie M, Kimura T</i><br /><b>Background</b><br />CaM (calmodulin) is a ubiquitously expressed, multifunctional Ca<sup>2+</sup> sensor protein that regulates numerous proteins. Recently, CaM missense variants have been identified in patients with malignant inherited arrhythmias, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the exact mechanism of CaM-related CPVT in human cardiomyocytes remains unclear. In this study, we sought to investigate the arrhythmogenic mechanism of CPVT caused by a novel variant using human induced pluripotent stem cell (iPSC) models and biochemical assays.<br /><b>Methods</b><br />We generated iPSCs from a patient with CPVT bearing <i>CALM2</i> p.E46K. As comparisons, we used 2 control lines including an isogenic line, and another iPSC line from an patient with long QT syndrome bearing <i>CALM2</i> p.N98S (also reported in CPVT). Electrophysiological properties were investigated using iPSC-cardiomyocytes. We further examined the cardiac RyR2 (ryanodine receptor) and Ca<sup>2+</sup> affinities of CaM using recombinant proteins.<br /><b>Results</b><br />We identified a novel de novo heterozygous variant, <i>CALM2</i> p.E46K, in 2 unrelated patients with CPVT accompanied by neurodevelopmental disorders. The E46K-cardiomyocytes exhibited more frequent abnormal electrical excitations and Ca<sup>2+</sup> waves than the other lines in association with increased Ca<sup>2+</sup> leakage from the sarcoplasmic reticulum via RyR2. Furthermore, the [<sup>3</sup>H]ryanodine binding assay revealed that E46K-CaM facilitated RyR2 function especially by activating at low [Ca<sup>2+</sup>] levels. The real-time CaM-RyR2 binding analysis demonstrated that E46K-CaM had a 10-fold increased RyR2 binding affinity compared with wild-type CaM which may account for the dominant effect of the mutant CaM. Additionally, the E46K-CaM did not affect CaM-Ca<sup>2+</sup> binding or L-type calcium channel function. Finally, antiarrhythmic agents, nadolol and flecainide, suppressed abnormal Ca<sup>2+</sup> waves in E46K-cardiomyocytes.<br /><b>Conclusions</b><br />We, for the first time, established a CaM-related CPVT iPSC-CM model which recapitulated severe arrhythmogenic features resulting from E46K-CaM dominantly binding and facilitating RyR2. In addition, the findings in iPSC-based drug testing will contribute to precision medicine.<br /><br /><br /><br /><small>Circ Arrhythm Electrophysiol: 03 Mar 2023:e011387; epub ahead of print</small></div>