Optimal Method and Outcomes of Catheter Ablation of Persistent AF: The STAR AF 2 Trial

1. Optimal Method and Outcomes of Catheter Ablation of Persistent AF: The STAR AF 2 Trial Atul Verma, Jiang Chen-yang, Tim Betts, John Radcliffe, Jian Chen, Isabel Deisenhofer, Roberto Mantovan, Laurent Macle, Carlos Morillo, Prashanthan Sanders on behalf of the STAR AF 2 Investigators ClinicalTrials.gov NCT01203748 The STAR AF 2 trial was funded by St Jude Medical Inc.

2. Disclosures • Dr Verma reports having served on advisory boards for and receiving grant support from Bayer, BoehringerIngelheim, Medtronic, Biosense Webster, and St Jude Medical. • Dr Betts reports lecture fees and grant support from St Jude Medical. • Dr Macle reports receiving consulting fees from St Jude Medical, Biosense Webster, Bristol Meyers Squibb, and Pfizer and grant support from St Jude Medical and Biosense Webster. • Dr Morillo reports receiving consulting fees from Boston Scientific, Medtronic, St Jude Medical, and BoehringerIngelheim and grant support from Boston Scientific, Biosense Webster, Pfizer, and Merck. • Dr Sanders reports having served on advisory boards for and receiving grant support and lecture fees from Biosense-Webster, Medtronic, St Jude Medical, Sanofi-Aventis, and Merck; receiving lecture fees and grant support from Biotronik; and receiving grant support from Sorin. • Drs. Jiang, Chen, Deisenhofer, and Mantovan do not have any disclosures.

3. Background • Catheter ablation is an effective treatment for symptomatic paroxysmal atrial fibrillation (AF) • Pulmonary vein isolation (PVI) is considered the cornerstone for catheter ablation of AF • Ablation of persistent AF is challenging and typically has less favorable outcomes compared to paroxysmal AF

4. Background • To improve outcomes for persistent AF, guidelines suggest that “operators should consider more extensive ablation based on linear lesions or complex fractionated electrograms” in addition to PV isolation • Whether more extensive ablation improves outcomes is unclear

5. Purpose • To compare the efficacy of three different AF ablation strategies in patients with persistent AF: (1) Pulmonary vein isolation (PVI) alone (2) PVI plus complex fractionated electrograms (PVI+CFE) (3) PVI plus linear ablation (PVI+Lines).

6. Methods - Patients • 589 patients were recruited from 48 experienced ablation centers in 12 countries • Inclusion: symptomatic persistent AF (a sustained episode > 7 days and < 3 years) refractory to at least one antiarrhythmic drug undergoing first-time ablation • Exclusion: paroxysmal AF, sustained AF episode > 3 years, left atrial diameter > 60 mm

7. Methods – Trial Design • Patients were randomized 1:4:4 to the three strategies: • PVI, PVI+CFE, PVI+Lines • Patients were blinded to the strategy (single blind) • Repeat ablation procedures allowed between 3-6 months using the same randomized strategy as the first ablation

8. Methods – Ablation Strategy • PVI = PV antral isolation with endpoint of entrance and exit block by a circular mapping catheter • PVI+CFE = PVI followed by mapping and ablation of complex fractionated electrograms during AF identified by validated software in the 3D mapping system (Ensite Velocity) • PVI+Lines = PVI followed by a left atrial roof line and a line along the mitral valve isthmus with endpoint of bidirectional block confirmed by pre-specified pacing maneuvers

9. Methods – Ablation Strategy CFE strategy Linear strategy

10. Methods – Follow-up • Patients were followed for 18 months • Visit, ECG and 24 hour Holter at 3, 6, 9, 12 and 18 months • Weekly TTM transmissions for 18 months • TTM transmissions every time symptoms felt • Tele-ECG-Card, Vitaphone, Germany

11. Outcomes • Primary Outcome • Freedom from documented AF episode > 30 seconds after one ablation procedure with or without antiarrhythmic medications* • Episodes during initial 3 month “blanking period” excluded from analysis • Secondary Outcomes • Freedom from documented AF > 30 seconds after 2 procedures with or without antiarrhythmic medications • Freedom from any atrial arrhythmia (AF/AFL/AT) after one or two procedures • Procedural time • Incidence of repeat procedures • Procedural complications** • Use of antiarrhythmic medications * TTMs and recurrences blindly adjudicated, ** blinded events committee adjudication

12. Results - Baseline Characteristics

13. Results - Ablation characteristics • 79% of patients presented to EP lab in spontaneous AF • Successful PV isolation obtained in 97% of all patients (all groups) • CFE were eliminated in 80% of patients • 11% not ablated because AF non-inducible after PVI • 9% all CFE could not be eliminated • Both lines with block achieved in 74% of patients • Roof line only 93% • Mitral line only 75%

14. Results - Procedural Characteristics

15. Results - Primary Outcome Documented AF > 30 seconds after one procedure with or without AAD p=0.15 59% 48% 44%

16. Results - Secondary Outcomes * AAD = antiarrhythmic drug

17. Results - Subgroups

18. Results - Complications

19. Conclusions • Largest randomized trial to examine outcomes of catheter ablation in persistent AF • Additional CFE or Lines ablation increased procedural time (may increase risk) • No benefit in AF reduction when additional substrate ablation (CFE or Lines) was performed in addition to PVI • PVI alone achieved freedom from recurrence in about 50% of patients – comparable to published success rates from randomized, multicenter trials in paroxysmal AF