1. ©2012 MFMER | slide-1 New methods and techniques in catheter ablation of atrial fibrillation Yong-Mei Cha, MD Mayo Clinic NCF Shenyang, 2014

2. ©2012 MFMER | slide-2 Patient selection for cryoablation Patients with symptomatic AF FDA has approved cryoballoon catheter for patients with paroxysmal AF Off-label use cryoballoon for patients with persistent AF

3. ©2012 MFMER | slide-3 Cryoballoon ablation Ablates at the point of balloon contact Ice formation and thawing Apoptosis Necrosis Hypothermic Zone Ablation Zone (sub-zero)

4. ©2012 MFMER | slide-4 How Arctic Front ® Balloon Catheter and Achieve TM Work 1. Access targeted vein 2. Inflate and position 3. Occlude and ablate (4min) 4. Assess PV isolation 4

5. ©2012 MFMER | slide-5 LIPV cryo-balloon isolation

6. ©2012 MFMER | slide-6 Before balloon inflation

7. ©2012 MFMER | slide-7 Pre-cryo Post-cryo Adenosine

8. ©2012 MFMER | slide-8 European Clinical Study Results NeumannVan BelleKojodjojo Prospective study PAF, n=293 Persistent, n=53 PAF: 74% off AAD at 1y, Persistent, 43% 7.5% Phrenic nerve palsy; all recovered at < 1 year No PV stenosis Prospective study PAF, n=141 73% off AAD at 1 year 2.8% phrenic nerve palsy; all resolved within 6 months No PV stenosis Prospective study PAF, n=90 Persistent, n=34 77% off AAD at 13m 1.8% transient phrenic nerve palsy 0.8% pericardial effusion Neumann T, et al. J Am Coll Cardiol. 2008;52:273-278. Van Belle Y, et al. Europace. 2008;10:1271-1276. Kojodjojo P, et al. Heart. 2010;96:1379-1384.

9. ©2012 MFMER | slide-9 Months Free from AF (%) Koiodioio Heart 2010 Months after ablation061218 Cryoablation90796926 Radiofrequency ablation53423312 ConventionalCryo KM free from AF

10. ©2012 MFMER | slide-10 CARTO® SMARTTOUCH™ 3D Technology Catheter ‐ tissue contact is critical for effective lesion creation Ablating with consistent power, increase in contact force: Increases lesion size, Increases incidence of steam pop/perforations LOCATION SENSOR* Detects micro-movement of transmitter coil TRANSMITTER COIL Sends location reference signal PRECISION SPRING* Provides consistent movement in response to contact force

11. ©2012 MFMER | slide-11 Below Threshold Within Threshold Above Threshold 30g

12. ©2012 MFMER | slide-12 Allows to monitor the stability, consistency, and amount of contact force on the tissue Based on user defined parameters, display ablation data including: Total Time Impedance Temperature Power Force Over Time (NEW) Average Force (NEW) Force Time Integral: is a calculation of force and time, in gram seconds CARTO®SMARTTOUCH™ Technology

13. ©2012 MFMER | slide-13 Minimal contact and time Maximal contact and time Increased contact and time

14. ©2012 MFMER | slide-14 Contact Force Sensing for Pulmonary Vein Isolation in Paroxysmal AF Marijon: JCE, 2014 Randomized study SmartTouch Thermocool n=30 Thermocool n=30 Complete PVI in all patients Fluoro time 20 min vs 27 min RF time 45 min vs 65 min AF recurrence Contact force 10.5% Noncontact force 35.9% Days At risk (no.)03-mo6-mo9-mo12-mo CF3030292827 Control3030252221 P=0.04 CF group Control group

15. ©2012 MFMER | slide-15 nMARQ™ Multi-Ablation Technology Combining multi-ablation capability with irrigation technology Uniform irrigation at the site of tissue contact. Each nMARQ™ Catheter boasts 10 irrigation holes per electrode completely surrounding the electrodes for more efficient cooling Multi-electrode Mapping (MEM) allows you to acquire multiple mapping points simultaneously Ablate with any or all of the 10 catheter electrodes The nMARQ™ Technology enables full visualization of the catheter loop and electrodes

16. ©2012 MFMER | slide-16 Comparison of different ablation technologies used for PVI in treatment of paroxysmal AF Technology Acute success (%) Procedure time (min) Fluoroscopy time (min) n Conventional RF ablation 97.6165242870 Cryoballoon ablation 97.516034905 Visually guided laser ablation 98.820031200 PVAC1001333089 nMARQ catheter 1001102325 Shin DI, Heart Rhythm. 2014

17. ©2012 MFMER | slide-17 Highly accurate hybrid electroanatomical mapping system provides an optimal blend of magnetic and impedance technologies, accuracy ≤ 1-2mm Continuous mapping – No point-by-point acquisition collecting thousands of points Eliminate need for time consuming manual annotations Superior resolution & signal quality Clearly assess gaps and lesions The Rhythmia™ Mapping System

18. ©2012 MFMER | slide-18 Open basket 64 low-noise electrodes 2.5 mm inter-electrode spacing 192 intracardiac channels + Surface ECG 8.5F, bi-directional steerability 8 smooth, flexible splines, variable diameter (3-22mm) for use in various anatomical structures Flushing port designed to prevent clot formation Potential lasso alternative during PVI IntellaMap Orion™ High-Resolution Mapping Catheter

19. ©2012 MFMER | slide-19 Carto System Physician accepts each point in manual process 30 minutes: 276 usable points Rhythmia Medical System Proprietary algorithm sorts inputs from 64-pole basket in real time 10 minutes: 3,689 usable points

20. ©2012 MFMER | slide-20 Find the gap Source: Nakagawa H, Rapid high resolution electroanatomical mapping: evaluation of a new system in a canine atrial linear lesion model. Circulation Arrhythmia Electrophysiology. 2012 Apr;5(2):417-24

21. ©2012 MFMER | slide-21 V3 CS Bip1-2 Uni 1 Uni 2 Double potential Left Atrial Activation Map During AT 59M, Prior Ablation of AFx4 Channel/gap Fractionated

22. ©2012 MFMER | slide-22 Topera’s RhythmView™ 3D Electrophysiological Mapping System Multi-polar FIRMap™ catheter Single beat mapping of the whole heart chamber all at once Advanced signal processing algorithms Self referenced map Rapidly analyze of the arrhythmia 64 evenly-spaced electrodes

23. ©2012 MFMER | slide-23 Treatment of Atrial Fibrillation by the Ablation of Localized Sources: CONFIRM Trial Narayan et al: JACC 60:628, 2012 Right Atrial Rotor, Left Atrial Focal Beat in AF FIRM: Sinus Rhythm in 5.5 minutes

24. ©2012 MFMER | slide-24 Treatment of Atrial Fibrillation by the Ablation of Localized Sources: CONFIRM Trial Narayan et al: JACC 60:628, 2012 92 patients with paroxysmal or persistent AF Randomized to FIRM guided + conventional Conventional only AF termination 86% vs 20% After single procedure AF free 82% vs 45% Mean follow-up 9 months Days P=0.016 1 st ablation Freedom from Atrial Fibrillation Event-free survival Entire Population Population Off Anti-Arrhythmic Meds FIRM-blind FIRM-guided FIRM-blind, 1 st ablation FIRM-guided, 1 st ablation P=0.006 all cases P=0.015 1 st ablation P=0.003 all cases

25. ©2012 MFMER | slide-25 Summary Both cryoballoon and RF ablation are effective technology for pulmonary vein isolation in patients with symptomatic AF RF ablation with contact force sensing and multi- electrodes ablation may improve RF ablation outcome, shorten procedure time and reduce complications Newer 3D mapping system will increase mapping efficiency (more accuracy, higher resolution/quality, shorter time…) to facilitate ablative therapy

26. ©2012 MFMER | slide-26 Mayo Clinic

27. ©2012 MFMER | slide-27 CARTOU NIVU ™ Module Concept Integration of Fluoroscopy images into the C ARTO ® 3 System Reducing fluoroscopy exposure Serve as virtual biplane fluoro monitor track vessel course during Complex EP procedures (AO root, congenital, CS) Assist in delineating PV Ostia

28. ©2012 MFMER | slide-28 Pace Mapping Software (PASO) 1.Objectively and efficiently compares the 12 lead PVC/VT ECG morphology and the Pace Map 2.Calculates the correlation value 3.Displays appropriate tag and color to the map Clinical VT Pace Map (PM)VT-PM Matching

29. ©2012 MFMER | slide-29 RVOT Pace Mapping (PaSo) QRS match 64%

30. ©2012 MFMER | slide-30 LVOT Left Aortic Cusp Pace Mapping (PaSo) QRS match 98%

31. ©2012 MFMER | slide-31 Acute Termination of Human AF by Identification and Catheter Ablation of Localized Rotors and Sources: 1 st Multicenter Experience of Focal Impulse and Rotor Modulation Ablation Shivkumar et al: JCE 23(12):1277, 2012 2 Rotors and 1 Focal Source in AF FIRM at Rotors, Focal Beat (<10 min) Terminates AF