Background Recurrent atrial fibrillation (AF) occurs in up to 50 % of patients within 1 year after catheter ablation, and a clinical risk score to predict recurrence remains a critical unmet need. The aim of this study was to (1) develop a simple score for the prediction of rhythm outcome following catheter ablation; (2) compare it with the CHADS2 and CHA2DS2-VASc scores, and (3) validate it in an external cohort. Methods Rhythm outcome between 3 and 12 months after AF catheter ablation were documented. The APPLE score [one point for age>65 years, persistent AF, impaired eGFR (<60 ml/min/1.73 m2), LA diameter ≥43 mm, EF < 50 %] was associated with AF recurrence and was validated in an external cohort in 261 patients with comparable ablation and follow-up. Results In 1145 patients (60 ± 10 years, 65 % male, 62 % paroxysmal AF) the APPLE score showed better prediction of AF recurrences (AUC 0.634, 95 % CI 0.600–0.668, p < 0.001) than CHADS2 (AUC 0.538) and CHA2DS2-VASc (AUC 0.542). Compared to patients with an APPLE score of 0, the odds ratio for AF recurrences was 1.73, 2.79 and 4.70 for APPLE scores 1, 2, or ≥3, respectively (all p < 0.05). In the external validation cohort, the APPLE score showed similar results (AUC 0.624, 95 % CI 0.562–0.687, p < 0.001). Conclusions The novel APPLE score is superior to the CHADS2 and CHA2DS2-VASc scores for prediction of rhythm outcome after catheter ablation. It holds promise as a useful tool to identify patients with low, intermediate, and high risk for AF recurrence.

Background Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio, 1.3 [95% confidence intervals, 1.1–1.6]; P=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.

Background Common single nucleotide polymorphisms (SNPs) at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical AF. Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5–30% of AF cases. Objective To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases. Methods Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years, 71% male, 89% typical AF) between 2004 and 2011. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF; [AT/AF]). Results Two-hundred AT/AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76 95% confidence interval [CI] 0.6–0.95, P=0.016) compared with wild-type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio = 0.79, 95% CI 0.62–0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio = 0.61, 95% CI 0.37–1.0) (P=0.037). Conclusion Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of predominately typical AF patients. Our findings suggest the rs2200733 polymorphism may hold promise as an as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation.