Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): a randomized, multicentre, international trial

Abstract

Aims: This multicentre, randomized trial compared three strategies of AF ablation: ablation of complex fractionated electrograms (CFE) alone, pulmonary vein isolation (PVI) alone, and combined PVI + CFE ablation, using standardized automated mapping software.

Methods and results: Patients with drug-refractory, high-burden paroxysmal (episodes >6 h, >4 in 6 months) or persistent atrial fibrillation (AF) were enrolled at eight centres. Patients (n = 100) were randomized to one of three arms. For CFE alone (n = 34), spontaneous/induced AF was mapped using validated, automated CFE software and all sites <120 ms were ablated until AF termination/non-inducibility. For PVI (n = 32), all four PV antra were isolated and confirmed using a circular catheter. For PVI + CFE (n = 34), all four PV antra were isolated, followed by AF induction and ablation of all CFE sites until AF termination/non-inducibility. Patients were followed at 3, 6, and 12 months with a visit, ECG, 48 h Holter. Atrial fibrillation symptoms were confirmed by loop recording. Repeat procedures were allowed within the first 6 months. The primary endpoint was freedom from AF >30 s at 1 year. Patients (age 57 +/- 10 years, LA size 42 +/- 6 mm) were 35% persistent AF. In CFE, ablation terminated AF in 68%. Only 0.4 PVs per patient were isolated as a result of CFE. In PVI, 94% had all four PVs successfully isolated. In PVI + CFE, 94% had all four PVs isolated, 76% had inducible AF with additional CFE ablation, with 73% termination of AF. There were significantly more repeat procedures in the CFE arm (47%) vs. PVI (31%) or PVI + CFE (15%) (P = 0.01). After one procedure, PVI + CFE had a significantly higher freedom from AF (74%) compared with PVI (48%) and CFE (29%) (P = 0.004). After two procedures, PVI + CFE still had the highest success (88%) compared with PVI (68%) and CFE (38%) (P = 0.001). Ninety-six percent of these patients were off anti-arrhythmics. Complications were two tamponades, no PV stenosis, and no mortality.

Conclusion: In high-burden paroxysmal/persistent AF, PVI + CFE has the highest freedom from AF vs. PVI or CFE alone after one or two procedures. Complex fractionated electrogram alone has the lowest one and two procedure success rates with a higher incidence of repeat procedures. ClinicalTrials.gov identifier number NCT00367757.

Figure 1

Study patient randomization flowchart. A total of 101 patients were enrolled in the study. Only 100 underwent ablation, with one patient in the PVI arm not undergoing the ablation procedure.

Figure 2

(A–C) Representative left atrial (LA) electroanatomical maps illustrating the three ablation strategies used in the study. On the left side are panels showing posterior or modified posterior views of the LA and on the right side are panels showing the anterior view of the LA. (A) Pulmonary vein isolation (PVI) strategy. Brown points represent points of radiofrequency (RF) energy application around the four pulmonary venous (PV) antra with the endpoint of electrical isolation of all four PV antra. (B) Complex fractionated electrogram (CFE) strategy. The colour-coded map shows regions of highly fractionated atrial electrograms during AF (shown in red and white colours, equivalent to a local cycle length <120 ms). The brown points represent applications of RF energy over CFE regions with the endpoint of AF termination/non-inducibility. (C) Combined procedure of PVI followed by CFE ablation. The brown points illustrate ablation points applied around all four PV antra with the endpoint of electrical isolation. The colour-coded map shows regions of highly fractionated electrograms (red and white) that were mapped during AF post-PVI. The green points represent RF energy applications to CFE regions after PVI with the endpoint of AF termination/non-inducibility.

Figure 3

(A and B) Kaplan–Meier curves depicting time to first atrial fibrillation (AF) recurrence (A) and time to first AF, atrial flutter (AFL), or atrial tachycardia (AT) recurrence (B) after one procedure in the pulmonary vein isolation (PVI) strategy, the complex fractionated electrogram (CFE) strategy, and the combined strategy of PVI followed by CFE ablation (PVI + CFE). PVI + CFE had a significantly higher freedom from AF after one procedure (74%) compared with either PVI (48%) or CFE (29%) alone (log-rank P = 0.004). PVI + CFE also had a significantly higher freedom from AF/AFL/AT after one procedure (74%) compared with either PVI (45%) or CFE (24%) alone (log-rank P = 0.003). Post hoc analysis comparing individual groups is detailed in text. Ninety-six percent of patients who were considered successful were off anti-arrhythmic medications and were evenly distributed among groups (also detailed in text). Numbers at risk for each group are indicated below the x-axis.

Figure 4

(A and B) Kaplan–Meier curves depicting time to first atrial fibrillation (AF) recurrence (A) and time to first AF, atrial flutter (AFL), or atrial tachycardia (AT) recurrence (B) after two procedures in the pulmonary vein isolation (PVI) strategy, the complex fractionated electrogram (CFE) strategy, and the combined strategy of PVI followed by CFE ablation (PVI + CFE). For the endpoint of AF (A), the combined strategy of pulmonary vein isolation followed by complex fractionated electrogram ablation (PVI + CFE) had a significantly higher freedom from AF (88%) compared with either pulmonary vein isolation (PVI) (68%) or complex fractionated electrogram ablation (CFE) (38%) alone (P = 0.001). For the endpoint of AF/AFL/AT, PVI + CFE still had the highest freedom from arrhythmia (88%) compared with PVI (68%) or CFE (32%) alone (P = 0.001). Post hoc analysis comparing individual groups is detailed in text. Numbers at risk for each group are indicated below the x-axis.

Figure 5

Percentage of patients free from either atrial fibrillation (AF) or AF, atrial flutter (AFL) or atrial tachycardia (AT) in the high-burden paroxysmal and persistent subgroups after one procedure. The freedom from arrhythmia was highest in the combined pulmonary vein isolation followed by complex fractionated electrogram ablation arm (PVI + CFE) in both the high-burden paroxysmal and persistent subgroups. However, the difference between PVI + CFE and pulmonary vein isolation alone (PVI) was not statistically significant in the high-burden paroxysmal subgroup (P = 0.14), whereas it was statistically significant in the persistent subgroup (P = 0.03). PVI + CFE had a significantly higher success rate compared with CFE in both subgroups for both endpoints.

Figure 6

Percentage of patients undergoing repeat ablation procedures in each of the three arms of the study. The combined arm of pulmonary vein isolation followed by complex fractionated electrogram ablation (PVI + CFE) had the lowest percentage of patients undergoing repeat procedures (15%). This difference was statistically significant compared with the complex fractionated electrogram (CFE) arm alone (P = 0.008) which had 47% of patients undergoing repeat ablation. There was only a trend towards significance compared with the pulmonary vein isolation (PVI) arm alone (P = 0.07), which had 31% of patient undergoing repeat ablation. There was no statistical difference between the percentage of repeat procedures in the PVI and CFE arms alone (P = 0.21).