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 Sanderson behalf of the STAR AF 2 Investigators

ClinicalTrials.gov NCT01203748

The STAR AF 2 trial was funded by St Jude Medical Inc.

Disclosures

• Dr Verma reports having served on advisory boards for and receiving grant support from Bayer, Boehringer Ingelheim, 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 Boehringer Ingelheim 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.

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

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

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).

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

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

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

Methods – Ablation Strategy

Linear strategy

CFE strategy

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

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

Results - Baseline CharacteristicsCharacteristic PVI PVI+CFE PVI+Lines

Age - year 58 ± 10 60 ± 9 61 ± 9Male sex – n (%) 52 (78) 213 (82) 196 (76)Ejection fraction (%) 55 ± 11 57 ± 10 57 ± 10Left atrial diameter (mm) 44 ± 6 44 ± 6 46 ± 6

Time from first AF diagnosis (yrs) 4.3 ± 6.3 4.2 ± 5.0 3.6 ± 4.2

AF burden at Baseline* (hr/month) 83 ± 36 85 ± 33 80 ± 37

Constantly in AF >6 months – n (%) 52 (78) 207 (80) 186 (72)

Medical history – n (%)Hypertension 32 (48) 143 (55) 158 (62)Diabetes 6 (9) 31 (12) 26 (10)Coronary disease 2 (3) 21 (8) 29 (11)Stroke/TIA 6 (9) 14 (5) 19 (7)Heart failure 3 (4) 10 (4) 15 (6)

CHADS2 score - n (%)0 31 (46) 93 (36) 81 (32)1 25 (37) 126 (48) 127 (50)2 6 (9) 31 (12) 29 (11)>2 5 (7) 10 (4) 19 (7)

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%

PVI PVI+CFE PVI+LINES p value

Procedure time (min) 166.95 ± 54.83 229.16 ± 83.20 222.56 ± 89.37 <0.0001

Mapping time (min) 13.89 ± 6.64 18.75 ± 14.01 14.38 ± 7.68 <0.0001

Fluoroscopy time (min) 29.35 ± 16.21 42.11 ± 21.70 40.91 ± 24.97 0.0003

Results - Procedural Characteristics

Results - Primary Outcome

p=0.15

Documented AF > 30 seconds after one procedure with or without AAD

59%

48%

44%

PVI PVI+CFE PVI+LINES p value

Freedom from AF/AFL/AT after 1 procedure 49 % 41 % 37 % 0.15

Freedom from AF after 2 procedures 72 % 60 % 58 % 0.18

Freedom from AF/AFL/AT after 2 procedures 60 % 50 % 48 % 0.24

Percentage of patients still on AAD at 18 mo 11 % 12 % 12 % 0.35

Results - Secondary Outcomes

* AAD = antiarrhythmic drug

Results - Subgroups

Results - Complications

CategoryPVI

(n=64)PVI+CFE(n=254)

PVI+Lines(n=250)

Total(n=568)

Access site hematoma 2 0 3 5Access site arteriovenous fistula or pseudoaneurysm 0 3 3 6

Pericarditis 0 1 2 3

Fluid overload 0 1 3 4Sedation related complication 0 3 5 8

Skin burn 1 0 0 1

Cardiac tamponade 1 0 2 3

Transient ischemic attack or Stroke 0 2 1 3

Atrial esophageal fistula - procedural death 0 1 0 1

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