3.1 Baseline characteristics

There were 279 patients in the Direct-to-catheter group and 536 in the Second-line ablation group. The average age was similar between the groups, with Group 1 averaging 62.1 years and Group 2, 62.0 years (p = 0.92). Sex distribution was also comparable, with females making up 21.1% of the Direct-to-catheter group and 20.5% of the Second-line ablation group. There was no significant difference within the groups in terms of treatment arms (In the direct-to-catheter group, 130 patients [46%] underwent pulmonary vein isolation; in the second-line ablation group, 278 patients [52%] underwent pulmonary vein isolation, p = 0.15). There were no significant differences between the groups in terms of the presence of comorbidities such as congestive heart failure (CHF), hypertension (HTN), diabetes mellitus (DM), previous stroke, vascular disease VascularDx, tobacco use, coronary artery disease (CAD), coronary artery bypass grafting (CABG), mitral valve disease. Hyperlipidemia was more prevalent in the second-line ablation group (36.5% vs 28.8%, p = 0.03) (Table 1).

Table 1 Baseline Characteristics3.2 Compliance rates and primary outcome

Within the 3-month blanking period, the compliance rates are 33 ± 30% and 32 ± 30% (p = 0.24) for the Direct-to-catheter group and Second-line ablation respectively. Within the post blanking period, the compliance rates are 30 ± 28% and 26 ± 26% (p = 0.054) for the Direct-to-catheter group and Second-line ablation groups respectively. The rates of the primary outcome were identical in both groups, with 44.8% in the direct-to-catheter group and 44.4% in the Second-line ablation group, showing no statistical difference (p = 0.91; Fig. 1). Similarly, there was no difference in the time to primary outcome between both groups (285 days for direct-to-catheter group versus 288 days for Second-line ablation group, p = 0.79). The post-ablation arrhythmia burden at 12 months was also similar between the two cohorts (20% for direct-to-catheter vs 16% for second-line ablation, p = 0.08).

Fig. 1

Time-to-primary outcome analysis

3.3 Multivariate analysis

In the assessment of factors contributing to AF recurrence, a Cox proportional hazards regression analysis was conducted. The analysis included the following covariates: medication status (History of AADs), patient age (AgeYrs), sex, CHF, HTN, DM, history of stroke, VascularDx, tobacco use, CAD and hyperlipidemia. Age, LA volume and sex were found to be a significant predictor of the outcome. In contrast, the history of AADs use was not a significant predictor of outcome (p > 0.05). The analysis of the other covariates in the model did not reach statistical significance, suggesting no evidence to indicate that these factors independently affected the outcome in this cohort (Table 2).

Table 2 Multivariate analysis of the primary outcome of interest3.4 Secondary outcomes3.4.1 Quality of life and early remodeling

In this post-hoc analysis, the Quality-of-Life outcomes measured by SF-36 and AFSS scores were compared between the two groups before and after ablation. The SF-36 scores pre-ablation were 67.0 (49.3—79.4) for the second-line ablation group and 67.3 (53.0 – 81.0) for the direct-to-catheter group, with no significant difference (p = 0.28). Post-ablation, the scores increased to 83.7 (69.1—91.8) and 85.4 (72.3—92.0) respectively, still showing no significant difference (p = 0.18). AFSS scores pre-ablation were 11.0 (5.0—18.0) for the second-line ablation group and 13.0 (6.0—19.0) for the direct-to-catheter group (p = 0.09), and post-ablation, the two groups reported respectively the scores of 2.0 (0.0—8.0) and 3.0 (0.0—7.0), again with no significant difference (p = 0.21; Fig. 2). Additionally, the change in SF-36 and AFSS scores from baseline to post-ablation was statistically significant in both groups. More specifically, median SF-36 increase in the “second-line ablation” group is 12.1 (3.4—26.3; p < 0.001) and in the “direct-to-catheter” group is 12.7 (2.4—24.9; p < 0.001) but no difference among the two groups (p = 0.86). The median AFSS decrease in the “second-line ablation” group is 6.0 (1.0—12.0; p < 0.001) and 6.0 (1.0—12.0; p < 0.001) in the “direct-to-catheter” group with no significant differences among the two groups as well (p = 0.79).

Fig. 2

Quality of Life using the SF-36 and AFSS score compared between the 2 groups before and after ablation. No Statistical Difference Was Achieved

The Left Atrial Volume Index (LAVI) reduction indicated early remodeling with reductions of 9.1 (1.6, 18.0)in the second-line ablation group and 9.5 (2.5, 19.7) in the direct-to-catheter group, without a significant difference (p = 0.11; Table 3).

Table 3 Early Remodeling reflected by the LA volume indexed to Body Surface Area as assessed by LGE-MRI and compared between the 2 groups3.4.2 Impact of individual antiarrhythmic drugs on AF recurrence rates

We examined the relationship of amiodarone (n = 144), dofetilide (n = 23), dronedarone (n = 14), flecainide (n = 90), sotalol (n = 70) with the primary outcome. On multivariate analysis, each individual AAD used was not predictive of AF recurrence. (Table 4).

Table 4 Multi-variate analysis of the primary outcome. No statistical difference in each of the individual anti-arrhythmic medications