Data_Sheet_1_Impact of frailty on early rhythm control outcomes in older adults with atrial fibrillation: A nationwide cohort study.docx

PurposeRhythm-control therapy administered early following the initial diagnosis of atrial fibrillation (AF) has superior cardiovascular outcomes compared to rate-control therapy. Frailty is a key factor in identifying older patients’ potential for improvement after rhythm-control therapy. This study evaluated whether frailty affects the outcome of early rhythm-control therapy in older patients with AF.MethodsFrom the Korean National Health Insurance Service database (2005–2015), we collected 20,611 populations aged ≥65 years undergoing rhythm- or rate-control therapy initiated within 1 year of AF diagnosis. Participants were emulated by the EAST-AFNET4 trial, and stratified into non-frail, moderately frail, and highly frail groups based on the hospital frailty risk score (HFRS). A composite outcome of cardiovascular-related mortality, myocardial infarction, hospitalization for heart failure, and ischemic stroke was compared between rhythm- and rate-control.ResultsEarly rhythm-control strategy showed a 14% lower risk of the primary composite outcome in the non-frail group [weighted incidence 7.3 vs. 8.6 per 100 person-years; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.79–0.93, p ConclusionAlthough the degree attenuated with increasing frailty, the superiority of cardiovascular outcomes of early rhythm-control in AF treatment was maintained without increased risk for safety outcomes. An individualized approach is required on the benefits of early rhythm-control therapy in older patients with AF, regardless of their frailty status.</p

Data_Sheet_1_Association of ZFHX3 Genetic Polymorphisms and Extra-Pulmonary Vein Triggers in Patients With Atrial Fibrillation Who Underwent Catheter Ablation.docx

Background: The ZFHX3 gene (16q22) is the second most highly associated gene with atrial fibrillation (AF) and is related to inflammation and fibrosis. We hypothesized that ZFHX3 is associated with extra-pulmonary vein (PV) triggers, left atrial (LA) structural remodeling, and poor rhythm outcomes of AF catheter ablation (AFCA).Methods: We included 1,782 patients who underwent a de novo AFCA (73.5% male, 59.4 ± 10.8 years old, 65.9% paroxysmal AF) and genome-wide association study and divided them into discovery (n = 891) and replication cohorts (n = 891). All included patients underwent isoproterenol provocation tests and LA voltage mapping. We analyzed the ZFHX3, extra-PV trigger-related factors, and rhythm outcomes.Result: Among 14 single-nucleotide polymorphisms (SNPs) of ZFHX3, rs13336412, rs61208973, rs2106259, rs12927436, and rs1858801 were associated with extra-PV triggers. In the overall patient group, extra-PV triggers were independently associated with the ZFHX3 polygenic risk score (PRS) (OR 1.65 [1.22–2.22], p = 0.001, model 1) and a low LA voltage (OR 0.74 [0.56–0.97], p = 0.029, model 2). During 49.9 ± 40.3 months of follow-up, clinical recurrence of AF was significantly higher in patients with extra-PV triggers (Log-rank p Conclusion: The extra-PV triggers had significant associations with both ZFHX3 genetic polymorphisms and acquired LA remodeling. Although extra-PV triggers were an independent predictor of AF recurrence after AFCA, the studied AF risk SNPs intronic in ZFHX3 were not associated with AF recurrence.</p

Image_1_Association of ZFHX3 Genetic Polymorphisms and Extra-Pulmonary Vein Triggers in Patients With Atrial Fibrillation Who Underwent Catheter Ablation.TIF

Background: The ZFHX3 gene (16q22) is the second most highly associated gene with atrial fibrillation (AF) and is related to inflammation and fibrosis. We hypothesized that ZFHX3 is associated with extra-pulmonary vein (PV) triggers, left atrial (LA) structural remodeling, and poor rhythm outcomes of AF catheter ablation (AFCA).Methods: We included 1,782 patients who underwent a de novo AFCA (73.5% male, 59.4 ± 10.8 years old, 65.9% paroxysmal AF) and genome-wide association study and divided them into discovery (n = 891) and replication cohorts (n = 891). All included patients underwent isoproterenol provocation tests and LA voltage mapping. We analyzed the ZFHX3, extra-PV trigger-related factors, and rhythm outcomes.Result: Among 14 single-nucleotide polymorphisms (SNPs) of ZFHX3, rs13336412, rs61208973, rs2106259, rs12927436, and rs1858801 were associated with extra-PV triggers. In the overall patient group, extra-PV triggers were independently associated with the ZFHX3 polygenic risk score (PRS) (OR 1.65 [1.22–2.22], p = 0.001, model 1) and a low LA voltage (OR 0.74 [0.56–0.97], p = 0.029, model 2). During 49.9 ± 40.3 months of follow-up, clinical recurrence of AF was significantly higher in patients with extra-PV triggers (Log-rank p Conclusion: The extra-PV triggers had significant associations with both ZFHX3 genetic polymorphisms and acquired LA remodeling. Although extra-PV triggers were an independent predictor of AF recurrence after AFCA, the studied AF risk SNPs intronic in ZFHX3 were not associated with AF recurrence.</p

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Inclusion criteria.

Inclusion criteria.</p