1. Donghui Yang, Lianjun Gao Department of Cardiology First affiliated hospital of Dalian Medical University Will the endpoint of AF ablation be unified? 房颤的消融终点需要统一吗？

2. 1. Mechanisms of AF 1. Mechanisms of AF 2. Ablation procedures 2. Ablation procedures 3. Results of ablation 3. Results of ablation

3. Mechanisms

4. Mechanisms

5. COX-Maze procedure COX, The surgical treatment of atrial fibrillation. III. Development of a definitive surgical procedure. J Thorac Cardiovasc Surg. 1991 Apr;101 (4):569-83. Modified maze procedure. Sandoval N, Concomitant mitral valve or atrial septal defect surgery and the modified Cox- maze procedure. Am J Cardiol. 1996 Mar 15;77(8):591-6 Success rate 90% /8 months Musci M, COX-Maze III Musci M, Z Kardiol. 1998 Mar;87(3):202-8.Success rate 94% /14 months Different Maze procedures could cure AF successfully, which strengthened the reentry mechanism of AF Kim. Modifications of the Cox-Maze III procedure. Ann Thorac Surg. 2001 Mar;71(3):816-22 Mechanisms—Reentry

6. Mechanisms—Trigger Not only reentry but also trigger play crucial roles in AF. Muscle sleeves of intra-cardiac veins, including pulmonary veins and superior and inferior vena cava may are an important source of focal firing that may trigger or maintain AF

7. Mechanisms—Nerve Heart rate variability implied that both vagal and sympathetic nerves play crucial roles in AF From direct recording of left stellate ganglion nerve activity in dogs, Tan found that simultaneous vagosympathetic activation was the most common trigger of paroxysmal atrial tachycardia and paroxysmal AF Patterson Patterson showed that simultaneous infusion of norepinephrine and acetylcholine during RAP shortened action potential duration and increased Cai simultaneously. Elevated Cai activated the forward mode of the sodium/calcium exchanger, resulting in early afterdepolarizations and triggered activity Autonomic nerve denervation could improve the success rate of AF ablation

8. Mechanisms—CFAEs CFAEs during AF represent either continuous reentry of the fibrillation waves into the same area or overlap of different wavelets entering the same area at different times Katritsis reported that CFAEs at presumed anatomic sites of GP were identified in 68.8% patients with paroxysmal AF Infusion of Ach could generate CFAEs and AF CFAEs increase with duration of AF In our canine experiment, pathology examination manifested that areas of CFAEs full of autonomic nerves and myocardial arranged in disorder

9. Is the endpoint of AF ablation uniformity ? 1. Mechnisms 1. Mechnisms 2. Ablation procedures 2. Ablation procedures 3. Results of ablation 3. Results of ablation

10. Different ablation procedures for AF 10 Focal ablation -- Pierre Jais, France Segmental PV isolation -- Haissaguerre, France Segmental + linear ablation -- Haissaguerre, France Circumferential LA ablation -- Pappone ， Italy Circumferential PV isolation -- Ouyang ， Germany Antrum PV isolation -- Natale, USA Ganglion plexus ablation -- Nakagawa, USA CFAE ablation -- Nademanee, Thailand AF nests ablation --Pachon, Brazil Stepwise ablation -- Haissaguerre, France

11. 11 AF Ablation

12. AF ablation Pappone, Circulation,2000;102; 2619- 2628. 9 months success rate 85% Haïssaguerre, foci ablation. N Engl J Med. 1998;339(10):659-66 8 month, success rate 62% Nademanee, JACC, 2004,43,2044-53 CAFs ablation 1 year success rate 91% Haïssaguerre, segmental ablation Circulation 2000;102;2463-2465 Pachon. A new treatment for atrial fibrillation based on spectral analysis to guide the catheter RF-ablation. PAF 94% Haïssaguerre M, Catheter ablation of long- lasting persistent atrial fibrillation: critical structures for termination. J Cardiovasc Electrophysiol. 2005 Nov;16(11):1125-37 Feifan Ouyang, Circulation. 2004 Oct 12;110(15):2090-6. Success rate 95.1%

13. Is the endpoint of AF ablation uniformity ? 1. Mechnisms 1. Mechnisms 2. Ablation procedures 2. Ablation procedures 3. Results of ablation 3. Results of ablation

14. 14 Focal Ablation 45 patients of PAF End point: elimination of PV ectopy Follow up 8±6months 28 patients (62 %) had no recurrence of AF Haïssaguerre, foci ablation. N Engl J Med. 1998;339(10):659-66 8 month, success rate 62%

15. 15 Segmental Ablation 70 PAF involved End point: elimination of PV-LA conduction Follow-up 4±5 months 51 (73%) free of AF Segment by segment linear ablation with an articulated bilimb catheter: initial experimental results. Pacing Clin Electrophysiol. 1998;21(11 Pt 2):2539-46 Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation. 2000;102(20):2463-5

16. 16 Pappone C,et al. Circulation. 2000 21;102(21):2619-28. Pappone C,et al. Circulation. 2001 20;104(21):2539-44. Pappone C,et al. Circulation. 2004 27;109(3):327-34. Pappone C.et al. N Engl J Med. 2006 2;354(9):934-41. Ablation—CPVA 26 AF (paroxysmal 14, permanent 12) circumferential lines of conduction block around each PV at a distance of 5 mm from the PV ostia. End point: 1. Low peak-to-peak bipolar potentials (≤0.1 mV) inside the lesion 2. local endocardial activation times (LAT) delay>30 ms between contiguous points lying in the same axial plane on the external and internal sides of the line Follow up 9±3 months, 22 (85%) free of AF

17. 17 Pappone C,et al. Circulation. 2001 20;104(21):2539-44. Ablation—CPVA 251 AF (paroxysmal 179, permanent 72) underwent CPVA End point: 1. Low peak-to-peak bipolar potentials (≤0.1 mV) inside the lesion 2. local endocardial activation times (LAT) delay>30 ms between contiguous points lying in the same axial plane on the external and internal sides of the line Follow up 10.4±4.5 months, paroxysmal 152 (85%) and permanent 49 (68%) free of AF

18. 18 Pappone C,et al. Circulation. 2004 27;109(3):327-34 Pappone C.et al. N Engl J Med. 2006 2;354(9):934-41. Ablation—CPVA 146 chronic AF. 77 CPVA+amiodarone; 69 amiodarone CPVA with additional lines in the posterior left atrium or roof and along the mitral isthmus. Additional ablation was performed within the circles, outside the pulmonary veins, where the local electrogram amplitude exceeded 0.2 mV End point: 80 percent reduction in the amplitude of the electrogram or a total of 40 seconds of energy application. Following up 12 months, 74% of CPVA free of AF

19. 19 Ablation—Circumferential PV isolation 41 PAF. CPVA+isolation guided by 2 Lasso catheters placed within the ipsilateral superior and inferior PVs End point: 1. Absence of all PV spikes documented with the 2 Lasso catheters within the ipsilateral PVs at least 30 minutes after isolation 2. No recurrence of the PV spikes within all PVs after intravenous administration of 9 to 12 mg of adenosine during sinus rhythm or coronary sinus pacing. Following up 6 months, 39 (95%)free of AF Feifan Ouyang. Circulation 2004;110;2090-2096

20. 20 Ablation—Antrum isolation guided by Doppler 315 AF [160 PAF. circular mapping (CM) (56), CM and ICE (107) patients), CM +ICE with titration of radiofrequency energy based on visualization of microbubbles by ICE (152)] PV antrum ablation gudied by ICE+Lasso End point: electrical isolation of the PVs Following up 417±145 days, 137/152 (91.2%) free of AF Nassir. Circulation 2003;107;2710-2716

21. 21 Nademanne,et al. J Am Coll Cardiol. 2004;43:2044–53 Ablation—CFAEs 121 AF (PAF 57) CFAEs ablation Endpoint: eliminate CFAE and/or convert to sinus rhythm Following-up 1 year, 110 (91%) free of AF

22. Ablation—Nerve 60 AF. 27 PVI, 33 PVI+GP ablation GP identification guided by high frequency stimulation Endpoint: Pulmonary antrum isolation. The endpoint of GP ablation was elimination of the vagal response at these sites Following up 12 months, 74% PVI and 91% PVI+GP free of AF 19 PAF GP alone ablation: Following up 1 year, 26% free of AF Scherlag BJ, Nakagawa H, Interv Card Electrophysiol. 2005 Aug;13 Suppl 1:37-42 Demosthenes, The American Journal of Cardiology. 330-334

23. 23 Pachon. Europace (2004) 6, 590e601 Ablation—AF nests 34 AF (paroxysmal 20, persistent 14) AF nests ablation guided by dominant frequency Endpoint: eliminating AF nests Following-up 9.9±5 months, 31 (91%) free of AF

24. 24 HaïssaguerreHaïssaguerre J Am Coll Cardiol. 2007 Mar 27;49(12):1306-14. Epub 2007 Mar Ablation—stepwise ablation 153 persistent AF AF nests ablation guided by dominant frequency Endpoint: AF termination Following-up 32±11 months, sinus rhythm was maintained in 95% in whom AF was terminated compared with 52% in those in whom AF could not be terminated

25. ablation Endpoint AF type Follow-up Success Segmental PVI PAF 4±5 mons 53% CPVA PAF+CAF 9±3 mons 85% CPVA PAF 10.4±4.5 mons 85% CPVA CAF 10.4-12 mons 68-74% CFAEs PAF+CAF 1 year 91% Step-wise AF termi CAF 32±11mons 95% PVI+GP VR elimination PAF 1 year 91% GP alone VR elimination PAF 1 year 26% AF nests eliminating AF nests PAF+CAF 9.9±5 mos 91% 25 Different Endpoints Low potential LAT>30ms CFAEs disap AF to SR

26. Different Endpoints AF ablation is getting better and better, than ADD Many reports have demonstrated GP ablation alone for AF may be not enough GP identification is still a question Benefit of termination of persistent AF during the procedure is not clear Efficiency of CFAEs ablation couldn’t be duplicated in most center AF nests ablation in debate

27. Complex mechanisms of AF Different AF type and diseases Different ablation Different endpoints Different results Is the endpoint of AF ablation uniformity ? So, the endpoint of AF ablation could not be unified.

28. 28 Is the endpoint of AF ablation uniformity ?

29. Different Endpoints  However, in past 10 years, we have gradually reached consensus  PVI is very important for both PAF and chronic AF (cornerstone)  CPVA could eliminate focal firing and improve substrate  CFAEs ablation may be an important and adjunctive procedure for chronic AF  Autonomic nerve denervation could improve success rate  Current ablation procedures for AF include  PAF: CPVA with endpoint of PVI  Chronic AF: CPVA with endpoint of PVI with necessary line ablation and CFAEs ablation

30. Is the endpoint of AF ablation uniformity ? Advice A EP doctor should stick to the way he is good at. Same strategy, same endpoint. Do not follow the new strategy reported with the highest success rate. Setup the ablation endpoint before RF discharge. Modify if needed, but not often, not much. 师出有门，武当？少林？

31. Is the endpoint of AF ablation uniformity ? Challenge Investigation AF mechanism New tech, new strategy needs further clinical trials Optimize the procedure and individualize patients

32. Welcome to Dalian 8th China Atrial Fibrillation Symposium, July 2010