1. Section III: Catheter Ablation for the Treatment of AFib

2. Section III. Catheter Ablation for the Treatment of AFib 1. Left atrial (LA) and pulmonary vein (PV) anatomy 2. Catheter ablation techniques 3. Technological issues 4. Success rates 5. Complication rates 6. Cost-effectiveness 7. Indications for catheter ablation 8. Centre experience

3. 1. Left Atrial (LA) and Pulmonary Vein (PV) Anatomy

4. Macroscopic Anatomy of the Myocardial Sleeves and the Pulmonary Veins and Sleeves Uniform PV sleeve Non-uniform PV sleeve PV

5. Macroscopic Anatomy of the Myocardial Sleeves and the Pulmonary Veins reproduced with permission, Saito T, et al. J Cardiovasc Electrophysiol (2000) 11: 888 Non-uniform sleeve Uniform sleeve Atrial-PV border

6. Microscopic Anatomy of Pulmonary Veins Myocardial sleeve Saito T, et al. J Cardiovasc Electrophysiol (2000) 11: 888 Myocardial sleeve PERMISSION TO USE PHOTO BEING REQUESTED

7. Transverse Section Perpendicular to the Axis of the Pulmonary Vein Groups of myocardial cells in different orientations Saito T, et al. J Cardiovasc Electrophysiol (2000) 11: 888 PERMISSION TO USE PHOTO BEING REQUESTED

8. Length of Myocardial Sleeves in the 4 Pulmonary Veins Saito T, et al. J Cardiovasc Electrophysiol (2000) 11: 888 Length of myocardial sleeves (mm) LSPVRSPVLIPVRIPV *p<0.01 0 2 4 8 12 16 14 10 6 ** * * *

9. Schematic Representation of Superficial Myocardial Fibres of the LA adapted from Nathan H & Eliakim M Circulation (1966) 34: 412 LSPV LLPV LA RA SVC RSPV RIPV IVC

10. Myocardial Fibre Orientation in the LA and PV – Predominant Vertical Fibre Pattern adapted from Nathan H & Eliakim M Circulation (1966) 34: 412 LIPV LSPV RSPV RIPV

11. Myocardial Fibre Orientation in the LA and PV – Predominant Horizontal Fibre Pattern adapted from Nathan H & Eliakim M Circulation (1966) 34: 412 LSPV LMPV LIPV RIPV RMPV RSPV

12. Myocardial Fibre Orientation in the LA and PV – Predominant Oblique Fibre Pattern adapted from Nathan H & Eliakim M Circulation (1966) 34: 412 LA LSPV SVC LIPV RSPV RIPV

13. Myocardial Fibre Orientation in the LA and PV – Mixed Fibre Pattern adapted from Nathan H & Eliakim M Circulation (1966) 34: 412 LIPV LSPV SVC RSPV RIPV

14. PV-Left Atrial Connections Pattern 1 – no connections Pattern 2 – partial connections Pattern 3 – good connections Tan AY, et al. J Am Coll Cardiol (2006) 48: 132 PERMISSION TO USE PHOTO BEING REQUESTED

15. Summary of Anatomical Changes in Patients with AFib Tan AY, et al. J Am Coll Cardiol (2006) 48: 132 Hassink RJ, et al. J Am Coll Cardiol (2003) 42: 1108 Atrial myocardium is more often present in the PV of patients with AFib compared with patients without AFib In the first group the atrial myocardium in the PV is characterized by more severe discontinuity, hypertrophy and fibrosis Muscular discontinuities and abrupt fibre orientation change are present in more than 50% of PV-LA segments, creating significant substrates for re-entry Adrenergic and cholinergic nerves have highest densities within 5mm of the PV-LA junction but are highly co-located

16. Typical & Atypical Branching Pattern of PV Anatomy TypicalShort Common Left TrunkLong Common Left Trunk Right Middle PVTwo Right Middle PVs Right Middle PV and Right “upper” PV DEF ABC N=16 N=18 N=7 (including 3 of D) N=5 (including 2 of D)N=2 N=4 N=3 N=1 N=0N=1 AFib Control adapted from Kato R et al. Circulation (2003) 107: 2004

17. Anatomy of the Pulmonary Veins reproduced with permission, Kato R, et al. Circulation (2003) 107: 2004 RIPV RSPV LSPV LIPV LA appendage Right PV Left PV Nuclear magnetic resonance image of the ostia of the right and left superior and inferior PVs and the left atrial appendage

18. Anatomy of the Pulmonary Veins Ho YS, et al. Heart (2001) 86: 265 Note the common opening of the LPV and separate origins of the two RPV Left pulmonary veins LA longitudinal section Transverse section from above PERMISSION TO USE PHOTO BEING REQUESTED

19. Right Middle PV Kato R, et al. Circulation (2003) 107: 2004 RMPV Nuclear magnetic resonance image showing a right PV with a separate origin to the right superior and inferior PVs PERMISSION TO USE PHOTO BEING REQUESTED

20. Wittkampf FH, et al. Circulation (2003) 107: 21 Pulmonary Vein Geometry Posterior ViewInferior ViewLAO 45° Ostium of left lower PV Magnetic Resonance Angiography Fluoroangiography PERMISSION TO USE PHOTO BEING REQUESTED

21. Left superior38 18.7 ± 2.913.9 ± 3.71.4 ± 0.4 1.0-3.0 17.5 ± 2.9 Left inferior38 15.9 ± 3.111.2 ± 3.11.5 ± 0.4 1.0-2.3 15.0 ± 2.7 Both left76 1.5 ± 0.4 Right superior42 18.8 ± 2.716.0 ± 2.01.2 ± 0.1 1.0-1.5 17.5 ± 2.1 Right inferior42 17.9 ± 2.915.1 ± 3.01.2 ± 0.2 1.0-1.7 16.9 ± 3.1 Both right84 1.2 ± 0.1 Left common4 27.3 ± 6.218.7 ± 6.71.6 ± 0.5 1.0-2.2 26.5 ± 4.8 Right middle47.6 ± 3.15.6 ± 2.11.4 ± 0.41.0-2.07.0 ± 1.9 n Maximum (mm) Projected (mm) Minimum (mm) Ratio Range (mm) Dimensions of PV ostia measured with MRA. The ratio between maximal and minimal ostium diameters is a measure of the ovality of the PV ostia. * Differences in ovality were only significant between right and left PV ostia (p<0.005) Average Pulmonary Vein Ostium Diameters Wittkampf, FH et al. Circulation (2003) 107: 21

22. Parasympathetic Ganglia Fat pads

23. Distribution of Autonomic Nerves at the PV-LA Junction Anterior LA VOM LI RI LS RS PA AOSVC IVC CS Posterior LA Adrenergic Nerve Density Grade 4: 45-60 x 10 3 m 2 /mm 2 Grade 3: 30-45 x 10 3 m 2 /mm 2 Grade 2: 15-30 x 10 3 m 2 /mm 2 Grade 1: 0-15 x 10 3 m 2 /mm 2 Cholinergic Nerve Density Grade 4: 4.5-6.0 x 10 3 m 2 /mm 2 Grade 3: 3.0-4.5 x 10 3 m 2 /mm 2 Grade 2: 1.5-3.0 x 10 3 m 2 /mm 2 Grade 1: 0-1.5 x 10 3 m 2 /mm 2 Anterior junction Posterior junction S = Superior; I = Inferior; AS = Anterosuperior; PI = Postinferior; AI = Anteroinferior; PS = Postsuperior reproduced with permission, Tan AY, et al. J Am Coll Cardiol (2006) 48: 132

24. 3. Catheter Ablation Techniques From the first procedures to today

25. Maze reproduction Schwarz 1994 Right atrial linear lesions Haïssaguerre 1994 Right and left atrial linear lesions Haïssaguerre 1996 PV foci ablation Jaïs / Haïssaguerre 1997/8 Ostial PV isolation Haïssaguerre 2000 Circumferential PV ablation Pappone 2000 Ablation of non-PV foci Lin 2003 Antral PV ablation Maroucche / Natale 2004 Double Lasso technique Ouyang / Kuck 2004 CFAE sites ablation Nademanee 2004 Ostial or circumferential or antral PV ablation plus extra lines (mitral isthmus, posterior wall, roof) Jaïs / Hocini 2004/5 Circumferential PV ablation with vagal denervation Pappone 2004 TechniquePublication date Landmarks in Catheter Ablation Techniques and Success Rates

26. 1994: Reproduction of Cox Procedure using Catheter Ablation by Schwarz Traditional Cox-Maze surgical procedure adapted from Cox JL, et al. J Thor Cardivasc Surg (1991) 101: 569 RAA LAA LA IVC

27. 1994: Right Atrium Linear Lesions adapted from Haïssaguerre M, et al. J Cardiovasc Electrophysiol (1994) 5: 1045 In the same year, Haïssaguerre placed three linear lesions in the right atrium using radiofrequency energy 46-year old patient: AF-free with no AADs after 3- months Right atrium SVC IVC 1 2 3 T

28. 1996: Technique Extended to Right and Left Atrial Ablation adapted from Haïssaguerre M, et al. J Cardiovasc Electrophysiol (1996) 7: 1132 In 1996 Haïssaguerre modified the procedure extending linear lesions to the left atrium Aim was to isolate compartments of atrial tissue as in the Cox procedure 1234 1234

29. 1998: Ablation of PV Foci Using multi-electrode catheter mapping Haïssaguerre identified atrial foci triggering AFib in 45 patients refractory to drug treatment – Single focus in 29 patients (64%) – 2 foci in 9 patients (20%) – 3 to 4 foci in 7 patients (16%) Spontaneous Initiation of Atrial Fibrillation by Ectopic Beats Originating in the Pulmonary Veins Haïssaguerre, M, Jaïs, P, Shah, DC, et al. N Engl J Med (1998) 339: 659

30. PV Foci Triggering Afib reproduced with permission, Haïssaguerre M, et al. N Engl J Med (1998) 339: 659 Superior vena cava Inferior vena cava Fossa ovalis Septum Coronary sinus 94% 25%45% 9%16% Pulmonary Veins Right AtriumLeft Atrium 94% of foci located inside PV (2-4 cm from ostium) – 45% in LSPV, 25% in RSPV, 16% in LIPV, 9% in RIPV

31. Ectopic Beats Initiating AFib from Foci in the RI and LS PVs reproduced with permission, Haïssaguerre M, et al. N Engl J Med (1998) 339: 659 Ectopic beats (arrowed) RIPV LSPV

32. PV Foci Ablation: Results and Conclusions Radiofrequency ablation of ectopic foci was associated with a 62% success rate (absence of recurrence at 8  6m follow-up) Haïssaguerre M, et al. N Engl J Med (1998) 339: 659

33. 2000: Ostial PV Isolation Key study in 90 patients to investigate whether complete isolation of PV ectopic foci correlates with improved success End point was elimination of ectopy, spontaneous or induced, and elimination of PV muscle conduction Electrophysiological End Point for Catheter Ablation of Atrial Fibrillation Initiated from Multiple Venous Foci Haïssaguerre, M, Jaïs, P, Shah, DC, et al. Circulation (2000) 101: 1409--177

34. Ostial PV Isolation reproduced with permission, Haïssaguerre M, et al. Circulation (2000) 101: 1409 Atrial activation preceding PVP Discharges from PV Local PV activity dissociated distally at a slow rate

35. Ostial PV Isolation: Results and Conclusions Haïssaguerre M, et al. Circulation (2000) 101: 1409 Success, defined by elimination of AFib without drugs, was correlated with the procedural end point of abolition of distal PV potentials – After a mean follow-up of 8+5 months, AFib was completely eliminated in 64 patients (71%) without AADs – Anticoagulants were interrupted in 52 cases – The other 26 patients were prescribed a drug that was ineffective before ablation, resulting in total elimination of AFib in 12 of 26 Recovery of local PV potential and the inability to abolish it were significantly associated with AF recurrences (90% success rate with versus 55% without PV potential abolition)

36. 2000: Circumferential PV ablation Anatomical approach guided by a non-fluoroscopic mapping system to generate 3D electroanatomic maps in 26 patients and to perform circular linear lesions around the ostium of the PV Circumferential Radiofrequency Ablation of Pulmonary Vein Ostia A New Anatomic Approach for Curing Atrial Fibrillation Pappone, C, Rosanio, S, Oreto, G, et al. Circulation (2000) 102: 2619-28

37. Circumferential PV ablation reproduced with permission, Pappone C, et al. Circulation (2000) 102: 2619 Color coding represents activation times. In all maps, earliest activation (red) is located at pacing site. After ablation, conduction delay is characterized by abrupt color change from shades of yellow or green to blue or purple (latest activation) Pre-ablation Post-ablation Voltage maps

38. Circumferential PV ablation : Results and conclusions Pappone C, et al. Circulation (2000) 102: 2619 Among 14 patients with AFib at the beginning of the procedure, 64% had sinus rhythm restoration during ablation PV isolation was demonstrated in 76% of 104 PVs treated After 9+3 months, 22 patients (85%) were free of AFib (62% not on AADs), with no difference between paroxysmal and permanent AFib

39. 2003: Non-Pulmonary Vein Foci Most of the ectopic beats initiating paroxysmal AFib (PAF) originate from the PV. Lin et al. investigated PAF originating from non-PV areas Catheter Ablation of Paroxysmal Atrial Fibrillation Initiated by Non-Pulmonary Vein Ectopy Lin, W-S, Tai, C-T, Hsieh, M-H, et al. Circulation (2003) 107: 3176

40. LPFW27 (37%) 63 ± 145.2 ± 4.0 50 39.5 ± 5.9 10056 SVC27 (37%) 57 ± 124.7 ± 4.8 22 36.8 ± 5.1 4426 CT10 (14%) 63 ± 124.1 ± 3.2 0 29.7 ± 5.0 4020 LOM6 (8%) 66 ± 133.1 ± 2.5 50 41.3 ± 1.5 8350 CSO1 (1.4%)6710- 00 IAS1 (1.4%)442100- 100 Patients (n) Age (y) Late Recurrence (%) History (y) LA size (mm) Multiple AF Foci (%) Group SHD indicates structural heart disease Other SHD (%) Non-Pulmonary Vein Foci Lin W, et al. Circulation (2003) 107: 3176 Non-PV foci identified in 28% of patients: – left atrial posterior free wall (LPFW), superior vena cava (SVC), crista terminalis (CT) ligament of Marshall (LOM) coronary sinus ostium (CSO), interatrial septum (IAS)

41. Ablation of non-PV Ectopy reproduced with permission, Lin W, et al. Circulation (2003) 107: 3176 Ablation of ectopic triggers from the ligament of Marshall BeforeAfter

42. Ablation of non-PV Ectopy: Results and conclusions Catheter ablation eliminated AFib with acute success rates of 63%, 96%, 100%, 50%, 100%, and 0% in left atrial posterior free wall, superior vena cava, crista terminalis, ligament of Marshall, coronary sinus ostium, and interatrial septum, respectively During a follow-up period of 22+11 months, 43 patients (63.2%) were off AADs without AFib recurrence Lin W, et al. Circulation (2003) 107: 3176

43. 2004: PV Antrum Isolation Isolation of PVs guided by ICE and circular mapping catheter in order to more precisely identify border of the PV antrum and reduce risk of PV stenosis Pulmonary Vein Antrum Isolation: Intracardiac Echocardiography-Guided Technique Verma, A, Marrouche, NF, and Natale, A J Cardiovasc Electrophys (2004) 15: 1335-40

44. PV Antrum Isolation 3D multi-slice images of PVs reproduced with permission, Verma A, et al. J Cardiovasc Electrophys (2004) 15: 1335 Tubular ostium defined by PV angiography Actual PV antrum extends more posteriorly Antral borders defined by ICE

45. PV Antrum Ablation 315 patients undergoing ostial isolation of all PVs using either: – Circular-mapping (CM) alone (group 1, n=56) – CM and intracardiac echocardiography (ICE) (group 2, n=107) – CM and ICE with titration of RF energy based on visualization of microbubbles (group 3, n=152) Phased-Array Intracardiac Echocardiography Monitoring During Pulmonary Vein Isolation in Patients with Atrial Fibrillation Impact on Outcome and Complications Marrouche, NF, Martin, DO, Wazni, O, et al. Circulation (2003) 107: 2710

46. PV Antrum Ablation: Results Freedom from recurrent AF (%) 30 Follow-up (days) 150270390510750630870 0 100 90 70 50 80 60 40 Group 1 (n=56) Group 2 (n=107) Group 3 (n=152) Group 1 vs Group 3; p=0.009 Group 1 vs Group 2; p=0.08 Group 2 vs Group 3; p=0.08 Marrouche NF, et al. Circulation (2003) 107: 2710

47. PV Antrum Ablation: Results Intracardiac echocardiography improves the outcome of cooled-tip PV isolation Freedom from recurrent AF (%) 30 Follow-up (days) 150270390510750630870 0 100 90 70 50 80 60 40 ICE (n=259) No ICE (n=56) p=0.01 Marrouche NF, et al. Circulation (2003) 107: 2710

48. 2004: Double L ASSO ® Catheter Ablation Isolates pairs of pulmonary veins using two L ASSO ® catheters Continuous circular lesions (CCLs) around PVs guided by 3D mapping Complete Isolation of Left Atrium Surrounding the Pulmonary Veins New Insights from the Double-Lasso Technique in Paroxysmal Atrial Fibrillation Ouyang, F, Bänsch, D, Ernst, S, et al. Circulation (2004) 110: 2090

49. 2004: Double L ASSO ® Catheter Ablation reproduced with permission, Ouyang F, et al. Circulation (2004) 110: 2090

50. Double L ASSO ® Catheter Ablation Automatic activity and PV tachycardia provide an arrhythmogenic substrate for AFib This activity could be eliminated in the majority of patients by isolating all PVs with closed circular lesions reproduced with permission, Ouyang F, et al. Circulation (2004) 110: 2090

51. Double L ASSO ® Catheter Ablation: Results and Conclusions During a mean follow-up of 6 months, recurrence occurred in 10 patients. Nine patients underwent a repeat procedure Conduction gaps in the left CCL in 9 patients and in the right CCL in 2 patients were closed during the second procedure No AFib recurred in 39 patients after PV isolation during follow-up These results strongly support the hypothesis that it is necessary to isolate all PVs to prevent recurrence and stress the importance of the PV-LA junction in the initiation and perpetuation of PAF Ouyang F, et al. Circulation (2004) 110: 2090

52. 2004: Complex Fractionated Electrograms (CFAEs) Site Ablation Complex fractionated electrograms (CFAEs) recorded during AFib used as target sites for ablation Based on C ARTO ™ System mapping, the biatrial replica could be divided into distinct areas where RF energy was delivered according to CFAE detection A New Approach for Catheter Ablation of Atrial Fibrillation: Mapping of the Electrophysiologic Substrate Nademanee, K, McKenzie, J, Kosar, E, et al. J Am Coll Cardiol (2004) 43: 2044

53. 2004: Complex Fractionated Electrograms (CFAEs) Site Ablation reproduced with permission, Nademanee K, et al. J Am Coll Cardiol (2004) 43: 2044 Fractionated electrograms with continuous prolonged activation complex over posterior septal areas

54. CFAEs Site Ablation reproduced with permission, Nademanee K, et al. J Am Coll Cardiol (2004) 43: 2044

55. CFAEs Site Ablation reproduced with permission, Nademanee K, et al. J Am Coll Cardiol (2004) 43: 2044

56. CFAEs Site Ablation: Results and Conclusions Nademanee K, et al. J Am Coll Cardiol (2004) 43: 2044 Ablations of areas associated with CFAEs terminated AFib in 115 of 121 patients (95%) After one-year, 110 (91%) patients were free of AFib Areas with CFAEs are ideal target sites for ablation of AFib

57. 2004: Spectral Analysis to Guide Catheter RF Ablation A new method for treating paroxysmal AFib by targeting AFib “nests” of “fibrillar” myocardium – areas of atrial substrate that can be identified by spectral analysis through fast Fourier transforms (FFTs) A New Treatment for Atrial Fibrillation Based on Spectral Analysis to Guide the Catheter RF-Ablation Pachon, JC, Pachon, EI, Pachon, JC, et al. Europace (2004) 6: 590

58. Spectral Analysis to Guide Catheter RF Ablation reproduced with permission, Pachon JC, et al. Europace (2004) 6: 590

59. Spectral Analysis to Guide Catheter RF Ablation Pachon JC, et al. Europace (2004) 6: 590 Six control and 34 drug-refractory paroxysmal or persistent AFib patients were studied and treated RF was applied to all sites outside the pulmonary veins presenting right-FFT-shift (AFib nests) RF-ablation of AF nests, decreasing the fibrillar/compact myocardium ratio, eliminated 94% of the paroxysmal AFib in patients at 9.9+5 months of follow-up Paroxysmal AFib may be cured or controlled by applying RF in several places outside the PV, thus avoiding PV stenosis

60. Identification of an Atrial Frequency Gradient using Dominant Frequencies Investigated whether patients with AFib manifest a left-to-right atrial frequency gradient Presence of Left-to-Right Atrial Frequency Gradient in Paroxysmal but Not Persistent Atrial Fibrillation in Humans Lazar, S, Dixit, S, Marchlinski, FE, et al. Circulation (2004) 110: 3181

61. DF Atrial Gradients: Results and Conclusions In patients with paroxysmal AFib there is a significant left-to-right atrial DF gradient, with DF highest at the PV/LA junction, intermediate at the coronary sinus and lowest in the RA In patients with persistent AFib there are no significant differences between DF recorded from the LA/PV junction, CS, and RA These findings suggest that in induced paroxysmal AFib, the posterior LA may serve an important role in maintaining AFib Lazar S, et al. Circulation (2004) 110: 3181

62. Ablation of Sites of Dominant Frequency Activation using Spectral Analysis Electroanatomic mapping performed in 32 patients with 5-second electrograms obtained at each point to determine the highest-amplitude frequency on spectral analysis and to construct 3D dominant frequency (DF) maps Ablation was performed with the operator blinded to the DF maps to determine the effect of ablation at sites with or without high-frequency DF sites Spectral Analysis Identifies Sites of High- Frequency Activity Maintaining Atrial Fibrillation in Humans Sanders, P, Berenfeld, O, Hocini, M, et al. Circulation (2005) 112: 789

63. Ablation of Sites of Dominant Frequency Activation using Spectral Analysis reproduced with permission, Sanders P, et al. Circulation (2005) 112: 789 A: DF map in patient with paroxysmal AFib (6 hours). Note DF sites in each PV. B: DF map in patient with permanent AFib (24 months). Maximal DF and atrial frequency are higher than in patient in A. In addition, many DF sites are located outside PVs.

64. Ablation of Sites of Dominant Frequency Activation using Spectral Analysis Paroxysmal AFPermanent AF Anterior Posterior IVC CS LAA MV TV RAA SVC adapted with permission, Sanders P, et al. Circulation (2005) 112: 789 Greater clustering of DF sites seen in paroxysmal AFib

65. Ablation of DF Sites using Spectral Analysis: Results and Conclusions The spatial distribution of the DF sites was different in patients with paroxysmal and permanent AFib – In patients with paroxysmal AFib, the DF sources of activity are often localized to the PVs. In contrast, patients with permanent AFib demonstrate DF sites that are more often localized to the atria, including RA sites Ablation at these DF sites resulted in a significant slowing of the fibrillatory process and termination of sustained AFib in 87% of patients with paroxysmal AFib, confirming the role of localized sites of high frequency in the maintenance of AF All patients with persisting AFib had additional DF sites outside the ablated zones Sanders P, et al. Circulation (2005) 112: 789

66. 2004: Ostial or Circumferential or Antral PV Ablation plus Extra Lines Jaïs P, et al. Circulation (2004) 110: 2996 In addition to PV isolation, other investigators have shown that extra ablation lines may further improve results - Mitral isthmus (Jaïs 2004) - LA roof (Hocini 2005) - Posterior wall

67. 2004: Ostial or Circumferential or Antral PV Ablation plus Extra Lines Prospective, randomised study of mitral isthmus ablation vs PV isolation alone Technique and Results of Linear Ablation at the Mitral Isthmus Jaïs, P, Hocini, M, Hsu, L-F, et al. Circulation (2004) 110: 2996

68. reproduced with permission, Jaïs P, et al. Circulation (2004) 110: 2996 Incomplete block Complete block during CS pacing Completely blocked mitral isthmus Linear Ablation at the Mitral Isthmus

69. Jaïs P, et al. Circulation (2004) 110: 2996 Linear Ablation at the Mitral Isthmus Bidirectional isthmus block was confirmed by demonstrating (1) a parallel corridor of double potentials during CS pacing (2) an activation detour by pacing either side of the line, and (3) differential pacing techniques At 1 year after the last procedure, 87/100 patients with mitral isthmus ablation and 69/100 without were arrhythmia free without AADs Cardiac tamponade was noted in 4% of patients

70. Prospective, randomised study of roofline ablation vs PV isolation alone in 90 patients with paroxysmal AFib Roofline ablation joining the 2 superior PVs Linear Block at the Left Atrial Roof Techniques, Evaluation, and Consequences of Linear Block at the Left Atrial Roof in Paroxysmal Atrial Fibrillation: A Prospective Randomized Study Hocini, M, Jaïs, P, Sanders, P, et al. Circulation (2005) 112: 3688

71. Linear Block at the Left Atrial Roof I II III V1 1 2 3 4 Map LSPV LIPV RSPV RIPV 1 2 3 4 adapted with permission, Hocini M, et al. Circulation (2005) 112: 3688

72. Hocini M, et al. Circulation (2005) 112: 3688 Roofline ablation resulted in a significant increase in the fibrillatory cycle length and non-inducibility of AFib At 15+4 months, 87% of the roofline group and 69% with PV isolation alone were AFib-free without AADs Linear block of the LA roof may prolong the fibrillatory cycle and terminate AFib, and may be associated with better clinical outcome compared to PV isolation alone Linear Block at the Left Atrial Roof

73. 2004: Adjunctive PV Denervation during Circumferential PV Ablation Ablation of all evoked vagal reflexes around all PV ostia (complete vagal denervation) Pulmonary Vein Denervation Enhances Long-Term Benefit After Circumferential Ablation for Paroxysmal Atrial Fibrillation Pappone, C, Santinelli, V, Manguso, F, et al. Circulation (2004) 109: 327

74. 2004: Adjunctive PV Denervation during Circumferential PV Ablation reproduced with permission, Pappone C, et al. Circulation (2004) 109: 327 Vagal reflexes evoked (blue dots)

75. Adjunctive PV denervation During Circumferential PV Ablation reproduced with permission, Pappone C, et al. Circulation (2004) 109: 327 Pre- and post-ablation voltage maps vagal reflexes abolished after ablation

76. Pappone C, et al. Circulation (2004) 109: 327 0.8 0.6 0.4 0.2 0 Cumulative proportion of patients AFib Recurrence (months) 024681012 1.0 Vagal reflexes No vagal reflexes 101 102101 166 195166 # at risk 101 166 Vagal reflexes No vagal reflexes Log-rank p=0.0002 Adjunctive PV Denervation During Circumferential PV Ablation

77. Pappone C, et al. Circulation (2004) 109: 327 In 297 patients undergoing circumferential PV ablation for paroxysmal AFib complete vagal denervation was achieved in 34.3% of cases Patients undergoing complete vagal denervation were less likely to have recurrence of AFib Only the percentage area of left atrial isolation and complete vagal denervation were predictors of AFib recurrence Adjunctive PV Denervation: Results and Conclusions

78. Trigger - Ectopic Foci PV & non-PV Foci Ablation, PV Isolation Autonomic Nervous System AFib CFAEs Ablation Linear Lesions (e.g. mitral isthmus, roof) Substrate - Atrial tissue A Combination of Techniques may be used Depending on the Type of AFib Vagal Denervation (parasympathetic ganglia ablation)

79. Tailored Approach to Catheter Ablation This study determined the feasibility of a tailored catheter ablation strategy guided by the electrophysiological characteristics of AFib, without the use of a standardized lesion set (PV isolation and/or encirclement with or without additional ablation lines) Primary end point was absence of frequent atrial ectopy and spontaneous AFib during isoproterenol infusion and non-inducibility of AFib A Tailored Approach to Catheter Ablation of Paroxysmal Atrial Fibrillation Oral, H, Chugh, A, Good, E, et al. Circulation (2006) 113: 1824

80. Tailored Approach to Catheter Ablation Tailored ablation - after encircling of the right-sided pulmonary veins, left atrial ablation was performed to target high-frequency and/or complex electrograms. reproduced with permission, Oral H, et al. Circulation (2006) 113: 1824

81. Tailored Approach to Catheter Ablation: Results and Conclusions Oral H, et al. Circulation (2006) 113: 1824 During follow-up, left atrial flutter developed in 19% of patients and was still present in 10% at 12 weeks of follow-up A repeat ablation procedure was performed in 18% of patients During a mean follow-up of 11+4 months, 77% of patients were free from AFib and/or atrial flutter without AADs Acute non-inducibility of AFib after ablation was associated with a better clinical outcome than in patients left with inducible AFib

82. Tailored Approach to Catheter Ablation Evaluated a step-wise approach to achieve non- inducibility of AFib 74 patients with paroxysmal AFib underwent PV isolation, if still inducible one or two additional linear lesions were placed at the mitral isthmus or LA roof Long-term Evaluation of Atrial Fibrillation Guided by Noninducibility Jaïs, P, Hocini, M, Sanders, P, et al. Heart Rhythm (2006) 3: 140

83. Tailored Approach to Catheter Ablation No: stop Inducible or persisting arrhythmia after step 1 ? Yes Step 1 No: stop Inducible or persisting arrhythmia after step 2 ? Yes Step 2 Step 3 or adapted from Jaïs P, et al. Heart Rhythm (2006) 3: 140

84. Ja ï s P, et al. Heart Rhythm (2006) 3: 140 Tailored Approach to Catheter Ablation: Results and Conclusions In 42 patients (57%), PV isolation restored SR and AFib was non-inducible In the remaining 32 patients, a single linear lesion achieved non-inducibility in 20 patients An additional linear lesion was required in 12 patients, with 10 remaining non-inducible At 18+4 months follow-up, 91% of patients were free from AFib without AADs

85. 3. Technological Aspects

86. Technological Aspects of Catheter Ablation Ablation catheters Energy sources Mapping catheters Electrophysiological mapping systems Cardiac imaging technologies

87. 3. Technological Aspects Ablation catheters and energy sources

88. Ablation Catheters Non-irrigated tip catheters – 4mm and 8mm Irrigated tip catheters – open shower, chilled Balloon catheters – ultrasound, laser

89. Ablation Catheters Irrigated RF catheters – Permit use of higher radiofrequency energy – Ablation temperatures reduced – Char formation minimized

90. Light Ring Inflatable Balloon Catheter

91. Energy Sources Radiofrequency – Most common source Cryoablation Ultrasound Laser Microwave

92. 3. Technological Aspects Mapping catheters

93. Special Mapping Catheters Circular multi-electrode mapping catheter (L ASSO ® Catheter) Other multi-electrode mapping catheters – BASKET, MESH, P ENTARAY ™ Catheter

94. Circular Mapping Catheter (L ASSO ® Catheter) 1 2 3 4 5 6 7 8 9 10 RSPV mapping Fully Expanded 25 mm Precise mapping of potentials and exit sites at PVs Fully Contracted 15 mm LSPV mapping 1 2 3 4 5 6 7 8 9 10

95. 5 radiating spines (markers on spine A and B) 20 localized electrodes Central irrigation lumen High Density Multi-Electrode Mapping Catheter (P ENTARAY ™ Catheter) A B C D E B A

96. 3. Technological Aspects Electrophysiological mapping systems

97. Electrophysiological Mapping Systems 3D-electroanatomic mapping – C ARTO ™ System / C ARTO M ERGE ™ Image Integration Software Module Robotic magnetic navigation – Stereotaxis

98. C ARTO ™ System – Localization of catheter to within 1 mm – Increase safety margin during ablation

99. Anatomic Maps Using C ARTO ™ System 3D-electroanatomic maps (C ARTO ™ System) showing ablation points encircling PVs

100. Circumferential Electroanatomical Ablation around PV Ostia reproduced with permission, Pappone C, et al. Circulation (2001) 104: 2539 Pre-ablationPost-ablation Delayed activation Point by point RF lesions 3D-electroanatomic maps (C ARTO ™ System) showing pre- and post-ablation electrical activity Endpoint is complete electrical isolation of left atrium