The document summarizes the results of the CABANA Pilot Study, which compared catheter ablation to antiarrhythmic drug therapy for atrial fibrillation. The study found that ablation was more effective than drugs at preventing recurrent symptomatic atrial fibrillation over 12 months of follow-up. However, the pilot study had some limitations due to its small sample size and short follow-up duration. It established the feasibility of conducting a larger pivotal trial to determine long-term outcomes of ablation versus drug therapy for atrial fibrillation.

1. Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation: Results of the CABANA Pilot Study Douglas L. Packer, Kerry L. Lee, Daniel B. Mark, Kristi H. Monahan, Kathleen L. Hoffmann, Gail E. Hafley, Jeanne E. Poole, Tristram D. Bahnson, David J. Bradley, Richard Robb, Maryam Rettmann, David R. Holmes III, William Stevenson, John D. Hummel, Steven J. Bailin, John D. Day, Anil K. Bhandari, Francis Marchlinski, Neil Kay, Hugh Calkins, David J. Wilber ACC Atlanta March 15, 2010

2. Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation: Results of the CABANA Pilot Study Research Relationships (DLP) with Biosense, Acuson, Siemens, Cryocath, EPT, St. Jude, Cardiofocus, Symphony, Prorhythm, NIH Royalties from IP licensed by St. Jude Medical Unpaid consulting relationships: Medtronic, Boston Scientific, St. Jude, Biosense, Siemens, Cryocath Other information available from Mayo Communications Funded by St. Jude Medical Foundation, St. Paul, Minnesota

3. Disclosures The CABANA Pilot study was funded by St. Jude Medical Foundation. Dr. D. Packer in the past 12 months has provided consulting services for Biosense Webster, Inc., Boston Scientific, CyberHeart, Medtronic, Inc., nContact, Sanofi-Aventis, St. Jude Medical, and Toray Industries. Dr. Packer received no personal compensation for these consulting activities. Dr. Packer receives research funding from the NIH, Medtronic, Inc., CryoCath, Siemens AG, EP Limited, Minnesota Partnership for Biotechnology and Medical Genomics/ University of Minnesota, Biosense Webster, Inc. and Boston Scientific. Mayo Clinic and Drs. D. Packer and R. Robb have a financial interest in mapping technology that may have been used at some of the 10 centers participating in this pilot research. In accordance with the Bayh-Dole Act, this technology has been licensed to St. Jude Medical, and Mayo Clinic and Drs. Packer and Robb have received annual royalties greater than $10,000, the federal threshold for significant financial interest. Mayo Clinic and Dr. R. Robb have a financial interest in Analyze-AVW technology that was used to analyze some of the heart images in this research. In accordance with the Bayh-Dole Act, this technology has been licensed to commercial entities, and both Mayo Clinic and Dr. Robb have received royalties greater than $10,000, the federal threshold for significant financial interest. In addition, Mayo Clinic holds an equity position in the company to which the AVW technology has been licensed.

6. CABANA Pilot Study Baseline Characteristics in 60 Patients Age (yrs) 61±10 Age <65 yrs old with  2 risk factors 25 66% Gender Male / Female (%) 77% 23% Hypertension (%) 48 80% Diabetes (%) 11 18% CAD (%) 21 35% Prior MI (%) 6 10% Prior CABG/PTCA (%) 13 22% Dilated cardiomyopathy (%) 10 17% Congestive heart failure 13 22% Ejection fraction (%) 55 ± 10 LA size (mm) 4.4±1.0 Left atrial enlargement None (%) 8 16% Mild–moderate (%) 27 54% Severe (%) 15 30% CHADS2 score  1 36 61%  2 23 39% CABANA Pilot Study; ACC 2010

7. CABANA Pilot Study Arrhythmia History Type of AF Paroxysmal 19 32% Persistent 22 37% Long standing persistent 19 32% Years since first AF episode (yrs) 3.3±4.6 CCS AF severity Class 1-2 18 32% Class 3-4 35 61% Prior anti-arrhythmic drugs (no.) 0 42 70% 1 15 25% 2 3 5% Hospitalized for AF 28 47% Direct current cardio-version 32 53% History of atrial flutter 14 23% CABANA Pilot Study; ACC 2010

8. CABANA Pilot Study Treatment % Drug Therapy n=31 Rate Rhythm Rate & rhythm Ablation n=29 PV isolation WACA/ antral isolation Linear Abl CFAE GP % n=13 46% n=25 89% n=11 38% n=6 21% n=1 4% 4 13% 5 16% 22 71% 29 (100) CABANA Pilot Study; ACC 2010 100 80 60 40 20 0 100 80 60 40 20 0

9. CABANA Pilot Study First Post-Blanking AF Event Over Follow-up 1 st AF episode (%) Months 3-6 6-9 9-12 n=16 52% n=7 24% n=3 10% n=3 10% n=1 3% n=4 14% Drug (n=31) Ablation (n=29) CABANA Pilot Study; ACC 2010

10. Freedom from Recurrence of Symptomatic Atrial Fibrillation Post Blanking Period Freedom from AF recurrence Time (months) Ablation Drug Rx HR 0.42 (0.19-0.95) P=0.033 Blanking period*  24% 1 28 27 23 20 7 2 31 30 16 13 7 65% 41%

11. Freedom from Recurrence of Any Symptomatic AF, AFL, or AT 1 28 27 22 19 7 2 31 30 16 12 6 Freedom from AF/AFL/ AT recurrence Months since treatment start Ablation Drug Rx HR 0.46 (0.21-0.99) P=0.042 Blanking period* 61% 38%  23%

12. CABANA Pilot Study Cross-Overs and Redo Therapy CABANA Pilot Study; ACC 2010 *2 failed Ic; 2 failed IIIs Crossover to Abl AA Rx n=6 21% Drug Rx n=31 n=4 13%* n=8 28% Ablation Rx n=29 Pt (%) Re-ablation

13. Maintenance of Sinus Rhythm in CABANA Pilot at 12 Months No AF on Rx AAD Rx n=18 No AF No drug No AF Late off drug No AF on drug Non AF with redo n=5 Ablation Rx n=29 n=13 n=15 n=17 n=17 +2 pt +2 pt +0 pt CABANA Pilot Study; ACC 2010

14. CABANA Pilot Study Recurrence of Any AF, AFL, or AT AF/AFL/AT recurrence (%) Time (months) Ablation Rx 29 26 18 14 4 Drug Rx 31 30 12 8 5 CABANA Pilot Study; ACC 2010 Drug Ablation HR 0.69 (0.37-1.32) P=0.264 (36) (72) (50) 72% 66% (59) Blanking period

15. CABANA Pilot Study Recurrence of Any Atrial Fibrillation Probability of recurrence Time (months) Drug HR 0.56 (0.28-1.11) P=0.089 Ablation Abla Rx 28 26 21 18 5 Drug Rx 31 30 13 10 6 (55) (25) (66) (36) 69% 55% Blanking period CABANA Pilot Study; ACC 2010  14%

16. CABANA Pilot Study Perception of Atrial Fibrillation 61 8 29 64 4 13 0 20 40 60 80 100 Baseline 3 mo 12 mo Patients (%) Drug (n=31) Ablation (n=29) CABANA Pilot Study; ACC 2010

17. Adverse Events in the CABANA Pilot Study Ablation Drug Rx n=29 n=31 DVT (%) 1 (3.4) AV fistula/pseudo aneurysm (%) 2 (6.8) CVA/TIA (%) 1 (3.4) PV stenosis Moderate (50-75%) 1 (3.4) Severe (75-95%) 0 (0) Atrial esophageal fistula (%) 0 (0) Tamponade (%) 1 (3.4) Congestive heart failure (%) 3 (10.2) 1 (3.2) Volume overload (%) 2 (6.8) 0 (0) Myocardial infarction (%) 1 (3.4) 0 (0) Bradycardia (%) 1 (3.4) 0 (0) Ventricular tachycardia (%) 0 (0) 1 (3.2) Atrial flutter (%) 0 (0) 1 (3.2) LFT increase (%) 0 (0) 1 (3.2) UTI (%) 1 (3.4) 0 (0) Death, Cardiac Arrest, CVA 0 (0) 0 (0) CABANA Pilot Study; ACC 2010

22. CABANA Pilot Study Time to Treatment Initiation Drug n=31 Ablation n=28 Randomization To ablation To Rx 5 (1,15) Blanking 90 days Blanking 90 days 23 (17,42) CABANA Pilot Study; ACC 2010 Time

23. CABANA Pilot Study Change in LA Size in Ablated Patients Baseline 3 mo Change Volume Baseline 3 mo Change Volume index CABANA Pilot Study; ACC 2010