INTRODUCTION:As patients with atrial fibrillation (AF) present with increasing age and comorbidities, the understanding of the safety and efficacy of catheter ablation in older patients is paramount. We sought to investigate outcomes of octogenarians undergoing catheter ablation of AF in the era of pulsed field ablation (PFA). METHODS:We retrospectively analyzed AF patients who underwent PFA with a pentaspline catheter. Patients were divided into two groups based on age: octogenarians (age ≥ 80 years) and younger group (age < 80 years). Baseline characteristics, procedural data, and recurrence of atrial arrhythmia during the follow-up course were compared between the groups. RESULTS:Among 698 AF patients (69 ± 11 years old, 64% male), 124 (18%) were octogenarians and 574 (72%) were younger than 80 years. Octogenarians had a higher prevalence of comorbidities and underwent more extensive ablation, including the posterior wall and anterior wall. However, the procedure time, ablation catheter dwell time, and the fluoroscopy time did not differ between groups. There were zero complications in the octogenarian group and 9 in the younger group (p = 0.16). Early follow-up data showed comparable recurrence rate of atrial arrhythmias after an 8 week-blanking period (log-rank p = 0.80). CONCLUSION:PFA was effective and demonstrated a highly safe profile for octogenarians despite higher baseline risks and more extensive ablation.

ABSTRACT Background Little is known about the efficacy and safety of pulsed field ablation (PFA) for repeat ablation procedures for patients with recurrent atrial fibrillation (AF) after pulmonary vein (PV) isolation. Objective The purpose of this study was to evaluate and compare the efficacy and safety of PFA using a pentaspline ablation catheter with radiofrequency ablation (RFA) in repeat ablation procedures for atrial arrhythmia. Methods We compared 320 patients (mean age 71 ± 11 years, 61% male) who underwent repeat ablation procedures with PFA and RFA. Procedural data, including lesion set‐specific acute success, safety endpoints, and recurrence of atrial arrhythmia were compared between groups. Results Overall, 200 and 120 patients were treated with PFA and RFA during repeat ablation, respectively. Although the rate of baseline PV reconnection was comparable between groups, PV, posterior wall, and superior vena cava ablation were targeted in significantly more patients in the PFA group compared to the RFA group. In the PFA group, PV, posterior wall, and superior vena cava isolation were successfully achieved by PFA alone in 100% cases. Adjunctive RFA was required in 31% of anterior wall and 50% of lateral mitral isthmus PFA cases to achieve line of block. Procedure times were significantly shorter in the PFA group. Major complication rates were comparable between the groups (PFA vs. RFA, 0% vs. 1.7%, p = 0.067). Freedom from atrial arrhythmia recurrence at 1 year was similar between PFA and RFA groups (59% vs. 56%; log‐rank p = 0.71). Conclusion Use of PFA with a pentaspline catheter for repeat AF ablation was associated with more extensive ablation compared to RFA with low complication rates but did not result in increased freedom from AF recurrence.

BACKGROUND:Atrial fibrillation (AF) is associated with substantial morbidity and mortality. We sought to investigate the predictive value of serum metabolomics for 5-year incident AF in the context of clinical and polygenic risk score (PRS) stratification tools. METHODS:We studied a cohort of 240 628 patients UK Biobank participants with proton nuclear magnetic resonance spectroscopy measurements of 170 serum metabolites at enrollment. Five-year incidence of AF was assessed using Cox proportional hazards models. Cohorts for Heart and Aging Research in Genomic Epidemiology-AF (CHARGE-AF) and AF polygenic risk score (AF-PRS) scores were used as benchmark risk models for comparison. Models were trained on 80% of the cohort, and performances were validated on the remaining 20% cohort. Performance of clinical, AF-PRS, and combined metabolomics models was evaluated using time-dependent area under the receiver operating characteristic curve, net reclassification improvement, and relative integrated discrimination improvement analysis. RESULTS:During follow-up, 4174 (1.7%) participants developed AF. After training a model on the full metabolomics panel in addition to Cohorts for Heart and Aging Research in Genomic Epidemiology-AF and AF-PRS, the final model retained 8 metabolites. Creatinine level was associated with increased risk (hazard ratio, 1.01 per 1 SD log-transformed value [95% CI, 1.00-1.03]) while linoleic acid level (hazard ratio, 0.985 [0.979-0.994]) was associated with decreased risk of AF. The addition of metabolomics to the CHARGE-AF+AF-PRS model improved risk prediction (5-year time-dependent area under the receiver operating characteristic curve, 0.789 [0.776-0.802] versus 0.755 [0.738-0.772]; P<0.05) and stratification on the validation set (NRIcases: 11.1%, NRIcontrols: 3.1%, IDIrelative: 11.6%). A model using only age, sex, metabolomics, and AF-PRS had fair risk prediction on the validation set (5-year time-dependent area under the receiver operating characteristic curve, 0.787 [0.773-0.801]). CONCLUSIONS:The addition of metabolomics to clinical and genomic risk scores improves the prediction of 5-year incident AF. A risk stratification tool using age, sex, and serum metabolomics and AF-PRS provides excellent AF risk prediction. Mechanisms by which specific metabolites reflect AF risk require further exploration.

BACKGROUND:Transvenous lead extraction/removal (TLE) is recommended for management of cardiac implantable electronic device (CIED)-associated infective endocarditis (IE). The effect of inter-hospital transfer on management and outcomes of CIED-associated IE has not been studied. OBJECTIVE:To analyze the impact of inter-hospital transfer on management and outcome of CIED-associated IE. METHODS:We analyzed 22,682 admissions from the Nationwide Readmissions Database 2016-2019 of patients with CIEDs with a diagnosis of IE. Centers receiving any transfers in a given year for CIED-associated IE were classified as hubs, and others as spokes. Admissions were categorized into direct admissions to spokes, direct admissions to hubs, and transfers to hubs. RESULTS:Among admissions, 64% were direct to spokes, 22% were direct to hubs, and 15% were transfers to hubs. Transfers were associated with male sex, Staphylococcus aureus infection, and heart failure. TLE rates among direct admissions to spokes, direct admissions to hubs, and transfers to hubs were 4.0%, 12.9%, and 38.1%, respectively (P < .001). Compared with direct admissions to spokes, direct admissions to hubs (adjusted odds ratio [aOR] 3.12, 95% confidence interval [CI] 2.55-3.81) and transfers to hubs (aOR 11.51, 95% CI 9.28-14.25) were independently associated with TLE. After adjustment for age and comorbidities, index and early mortality were similar among direct admissions to spokes, direct admissions to hubs, and transfers to hubs. Among patients who underwent TLE, TLE-associated complications and mortality were similar across groups. CONCLUSION:Direct admissions to hubs and transfers to hubs are associated with higher utilization of TLE. Mortality and complication rates among patients undergoing TLE at hubs and spokes were comparable.

AIMS:Utilization of transvenous lead extraction/removal (TLE) for the management of cardiac implantable electronic device (CIED)-associated infective endocarditis (IE) remains low. The aim of this study was to examine the impact of hospital TLE procedural volume on TLE utilization and outcomes for patients with CIED-associated IE. METHODS AND RESULTS:Using the Nationwide Readmissions Database, we evaluated 21 545 admissions for patients (mean age 70 years, 39% female) with CIEDs hospitalized with IE at TLE centres. Hospitals were categorized based on annual volume tertiles: (i) low-volume (1-17 TLEs/year), (ii) medium-volume (18-45 TLEs/year), and (iii) high-volume centres (>45 TLEs/year). Between 2016 and 2019, 57% of admissions in the study were to low-volume TLE centres. Transvenous lead extraction/removal was performed during 6.9, 19.3, and 26% of admissions for CIED-associated IE at low-, medium-, and high-volume TLE centres, respectively (P < 0.001). After adjustment for age and comorbidities, hospitalization for IE at high-volume centres was independently associated with TLE when compared with low-volume centres (adjusted odds ratio 4.26; 95% confidence interval 3.53-5.15). Transvenous lead extraction/removal-associated complication rates were similar at 2.5, 2.3, and 3.4% at low-, medium-, and high-volume centres, respectively (P = 0.493). Overall inpatient mortality during admissions to low-, medium-, and high-volume centres was also similar. CONCLUSION:Admissions to high-volume TLE centres were associated with higher utilization of TLE for management of CIED-associated IE. Transvenous lead extraction/removal-associated complications and mortality among patients hospitalized with CIED-associated IE were similar when stratified by hospital TLE volume, but this needs to be considered in context of significant differences in patient comorbidity burden between centres.

Background Institutional characteristics can affect atrial fibrillation (AF) catheter ablation procedural outcomes. Although hospital teaching status may affect patient care in other settings, its effect on AF ablation is unknown. We sought to determine variations in procedural characteristics and complications according to hospital teaching status. Methods We included all adult patients in the prospective National Cardiovascular Data Registry AFib Ablation Registry. Hospitals were categorized as university hospitals, nonuniversity teaching hospitals, and nonteaching hospitals. Associations were analyzed using adjusted logistic regression models. Results A total of 212 327 AF ablations (mean age of patients, 67.0±10.3 years, 35.5% female) were performed between January 2016 and June 2024. University hospitals performed the fewest cryoablations (unadjusted proportions: 14.4% versus 29.9% at nonuniversity teaching hospitals and 16.9% at nonteaching hospitals, P<0.001), adjunctive lesions (59.0% versus 63.3% versus 66.9%, P<0.001), and empiric linear lesions (27.4% versus 30.2% versus 38.1%, P<0.001). Single transseptal punctures were most common at nonuniversity teaching hospitals and least common at nonteaching hospitals (68.9% versus 47.9%, P<0.001). Procedural differences persisted after adjusting for patient characteristics and procedural volume. Same‐day discharge rates were lower at university hospitals compared with nonuniversity teaching hospitals and nonteaching hospitals (34.1% versus 44.5% versus 44.0%, P<0.001). Overall complication rates (2.3% versus 2.2% versus 2.1%, P=0.179) and major complication rates (0.8% versus 0.7% versus 0.7%, P=0.064) were similar based on teaching status. Conclusions After adjustment for patient characteristics and procedural data, AF ablation procedural approaches differ by hospital teaching status. Overall complication rates are low with no differences between hospitals by teaching status.

PURPOSE:Hardikar syndrome (HS, MIM #301068) is a female-specific multiple congenital anomaly syndrome characterized by retinopathy, orofacial clefting, aortic coarctation, biliary dysgenesis, genitourinary malformations, and intestinal malrotation. We previously showed that heterozygous nonsense and frameshift variants in MED12 cause HS. The phenotypic spectrum of disease and the mechanism by which MED12 variants cause disease is unknown. We aim to expand the phenotypic and molecular landscape of HS and elucidate the mechanism by which MED12 variants cause disease. METHODS:We clinically assembled and molecularly characterized a cohort of 11 previously unreported individuals with HS. Additionally, we studied the effect of MED12 deficiency on ciliary biology, hedgehog, and yes-associated protein (YAP) signaling; pathways implicated in diseases with phenotypic overlap with HS. RESULTS:We report novel phenotypes associated with HS, including cardiomyopathy, arrhythmia, and vascular anomalies, and expand the molecular landscape of HS to include splice site variants. We additionally demonstrate that MED12 deficiency causes decreased cell ciliation, and impairs hedgehog and YAP signaling. CONCLUSION:Our data support updating HS standard-of-care to include regular cardiac imaging, arrhythmia screening, and vascular imaging. We further propose that dysregulation of ciliogenesis and YAP and hedgehog signaling contributes to the pathogenesis of HS.