1. Tecniche alternative dell' ablazione trans catetere della Fibrillazione Atriale Laboratorio di Elettrofisiologia e Cardiostimolazione Cattedra e Divisione di Cardiologia Università degli Studi e Spedali Dr. M. Cerini Prof. A. Curnis Francavilla al Mare, 10 Ottobre 2014 LIVE ATRIAL FIBRILLATION

2. Types of Atrial Fibrillation European Heart Journal (2010) 31, 2369-2429 “Natural time course of AF”

3. PATHOGENETIC MECHANISMS Trigger VS Substrate Increasing importance Persistent AF ParoxysmalPermanent Trigger Substrato “Atrial fibrillation begets atrial fibrillation”

4. Hwang Circulation 2000 Critical Fibers Critical Fibers Sueda Ann Thorac Surg 1997 Microcircuits Microcircuits Haissaguerre NEJM 1998 Focal Triggers TRIGGERS in POLMONARY VEINS

5. Ganglionated Plexi Activation of G-plexi maintains AF by reducing local refractory period. Yellow regions = fat pads

6. Choice of rate and rhythm control strategies European Heart Journal (2010) 31, 2369-2429

7. Devices available Surgical Ablation Endocardial Approach Target PVIs HD Mesh PVAC LaserCryobaloon Irrigated RF

8. European Heart Journal (2010) 31, 2369-2429 Surgical ablation of AF a Class of recommendation. b Level of evidence. AF = atrial fibrillation.

9. Cox-Maze IV

10. Atrial Fibrillation Catheter Ablation Versus Surgical Ablation Treatment (FAST) Boersma L V et al. Circulation 2012;125:23-30  This study describes the first randomized clinical trial comparing their efficacy and safety during a 12-month follow-up.  124 patients with drug-refractory AF with left atrial dilatation and hypertension or failed prior catheter ablation  Randomized to catheter ablation or surgical ablation  The catheter-ablation procedure consisted of pulmonary vein isolation with optional lesions (operator’s discretion);  The surgical approach consisted of radiofrequency isolation of the pulmonary veins, ganglionated plexi ablation and left atrial appendage excision, with additionallesions as needed.

11. FAST: Results Boersma L V et al. Circulation 2012;125:23-30 Surgical approach shown superior in achieving freedom from arrhytmias at one year Surgical approach shown superior in achieving freedom from arrhytmias at one year Safety: 34.4% of patients with surgical ablation had an adverse event, driven largely by procedural events such as pneumothorax and major bleeding Safety: 34.4% of patients with surgical ablation had an adverse event, driven largely by procedural events such as pneumothorax and major bleeding …important for physitians and patients deciding which type of invasive therapy they need…

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

13. MANTRA-PAF Aim: To compare radiofrequency ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment in patients with paroxysmal atrial fibrillation (AF). Europace (2009) 11, 917-923

14. Results (after 24 months) Number of patients P=0.012 P=0.004 At 24 months AF-burden and occurrence of any and symptomatic AF were significantly lower in the RFA group than in the AAD group. At 24 months AF-burden and occurrence of any and symptomatic AF were significantly lower in the RFA group than in the AAD group. No significant difference was observed in the cumulative burden of AF between AAD and RFA. No significant difference was observed in the cumulative burden of AF between AAD and RFA. QOL (PCS) better in the RFA group after 12 and 24 months. QOL (PCS) better in the RFA group after 12 and 24 months. These data support RFA as a first- line treatment in patients with paroxysmal AF. These data support RFA as a first- line treatment in patients with paroxysmal AF. The results of the MANTRA-PAF trial support the idea of early ablation for AF to avoid progression of AF on the long term.

15. RAAFT-2 (The Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Therapy of Atrial Fibrillation ) C. Morillo. Heart Rhytm Society 2012 Scientific Session A Study to determinate whether catheter-based pulmonary vein isolation is superior to antiarrhythmic drugs (AAD) as first-line therapy in patients with symptomatic paroxysmal recurrent AF not previously treted with therapeutic doses of AADs. Primary outcomes: Time to first episode of symptomatic atrial fibrillation

16. RAAFT-2 (The Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Therapy of Atrial Fibrillation ) C. Morillo. Heart Rhytm Society 2012 Scientific Session Radiofrequency PVI is safe and significantly superior to AAD (46%RRR) in extending time to first recurrence of symptomatic and asymptomatic AF, AFL and AT in patients with paroxysmal AF. These findings support the indication of radiofrequency PVI as first line therapy in patients with paroxysmal AF.arrhythmic drugs. « To be able to claim victory with ablation, you really need to monitor these patients very judiciosly… These findings support the indication of radiofrequency pulmonary vein isolation as first-line therapy in patients with paroxysmal atrial fibrillation » Dr. Carlos Morillo

17. Antiarrhythmic drugs and/or left atrial ablation for rhythm control in AF. European Heart Journal (2012) 33, 2919-2747

18. Recommendations for left atrial ablation European Heart Journal (2012) 33, 2919-2747

19. Outcome (Ablation)

20. Single procedure success at 5-years F.U. Multiple Procedure Success at 5-years F.U.

21. Hybrid ablation in persistent AF: why? Medical therapy inadequate Medical therapy inadequate Limited success of isolated catheter-based ablations (50-55%) Limited success of isolated catheter-based ablations (50-55%) Isolated open-chest surgical procedures with conventional Isolated open-chest surgical procedures with conventional devices not accepted by cardiologists and patients devices not accepted by cardiologists and patients Hybrid treatment of AF by endoscopic PV isolation (Box-lesion) + transcatheter ablation

22. “BOX LESION” as the master lesion Single continuous line Single continuous line (without interceptions) One plane line One plane line Significant reduction of LA area Significant reduction of LA area (up to 40%) Macro-reentry circuits Macro-reentry circuits LA heterogenicity LA heterogenicity Fragmented potentials Fragmented potentials Advantages Advantages

23. Goals of Hybrid-AF surgery Success rates higher than isolated catheter-based procedures with less complications Success rates higher than isolated catheter-based procedures with less complications Lower rate of recurrences Lower rate of recurrences Procedure duration less than isoalted cath. ablation Procedure duration less than isoalted cath. ablation Avoidance of any chest opening (fully endoscopic) Avoidance of any chest opening (fully endoscopic)

24. Hybrid approach: procedural algorithm SURGERY before EP - Faster procedure - The BOX lesion - Target ablation of the ganglionated plexi - EP procedure targeted to gaps or additional areas - 2 separate procedures required  

25. Hybrid approach: procedural algorithm EP before SURGERY - Definition of AF mechanisms - Tailored approach ?? - Surgery in case of recurrences   - PV isolation longer than surgery - Efficacy of lesions lower - Connecting lesions - Ganglionated plexi untreated - 2 separate procedures required

26. CONCOMITANT   - Complete treatment in 1 step - Immediate assessment of lesions - Long duration of general anesthesia - Hybrid suite !!! -Pitfalls in evaluation of lesions - Esophageal complications ? Hybrid approach: procedural algorithm

27. HYBRID APPROACH MANAGEMENT OF ATRIAL FIBRILLATION: THE BRESCIA EXPERIENCE

28. 75 patients refractory to medical treatment & CVE 75 patients refractory to medical treatment & CVE Mean age: 63,3 ± 9,2 yrs Mean age: 63,3 ± 9,2 yrs Mean LA dimensions: 49,2 ± 5,6 mm Mean LA dimensions: 49,2 ± 5,6 mm Mean AF duration: 48 months Mean AF duration: 48 months Mean EF 57 ± 7,9 % Mean EF 57 ± 7,9 % AF type: - persistent: 10 (13,3%) AF type: - persistent: 10 (13,3%) - long term persistent: 65 (86,7%) - long term persistent: 65 (86,7%) Hybrid Approch – the Brescia Experience

29. Surgery first (endoscopic BOX lesion) Surgery first (endoscopic BOX lesion) - before surgical procedure, Catheter in coronary sinus - before surgical procedure, Catheter in coronary sinus 3-4 weeks later EP ablation EP ablation - Completeness PV isolation (if needed) - Completeness PV isolation (if needed) - Istumus cavo-tricuspidalis - Istumus cavo-tricuspidalis - Firing foci ablation - Firing foci ablation - Fragmented potentials (killing / lowering)… - Fragmented potentials (killing / lowering)… HYBRID APPROACH: TIMING

30. Division of Cardiac Surgery, University of Brescia Medical School

31. Surgical ablation probe - Epicardial device - Suction-based - RF unipolar - Internal irrigation (cooling) - Settings: 150 W, 90 sec, 80 °C - Temperature feedback Division of Cardiac Surgery, University of Brescia Medical School

32. Surgical Time Division of Cardiac Surgery, University of Brescia Medical School

33. 1 ST EPICARDIAL BIPOLAR CLAMPING SUCTION CATHETER Draws tissue out of cooling blood flow path Overcomes the last obstacles of epicardial ablation to achieve bipolar clamping with a linear suction probe BIPOLAR ENERGY ESTECH NEXT GENERATION DEVICE

34. …before surgical procedure… Catheter in coronary sinus !!!

35. If the capture is possible Not isolated (no conduction block) = If the capture is not possible Isolated (conduction block) = Lesion Test: Exit/Entrance Block (Pacing) PVs -Pacing Cs- Pacing

36. Mean ablation time: 32 + 7 minutes Mean overall procedural time: 90 + 16 mins Procedure performed with: General Anesthesia: 70 pts Epidural Anesthesia: 5 pts Post-procedural Validation: Entrance Block 75/75 pz Exit Block 70/75 pz (93,3%) 77% Sinusal Rhythm Before SurgeryPost Surgery HYBRID APPROACH Endoscopic Surgery 58 75 17

37. Endo - Surgery Full functional recovery on 1st post-op day No intraoperative complications occurred Minor post-operative Complications in 2 pts: 1 Pleural Effusion 1 bleeding chest HYBRID APPROACH OUTCOMES

38. Spot ECGs are not acceptable !!! Spot ECGs are not acceptable !!! 24-Holter ECG monitoring still inaccurate 24-Holter ECG monitoring still inaccurate Trans-telephonic monitoring still inaccurate Trans-telephonic monitoring still inaccurate Many episodes of paroxysmal AF can be asymptomatic !! Many episodes of paroxysmal AF can be asymptomatic !! Sinus rhythm monitoring

39. Post-operative Sinus rhythm monitoring Implantable loop recorder (continuous monitoring)

40. Electroanatomical Mapping by CARTO 3 / NavX EP Time trans-septal puncture

41. - To evaluate the maintenance of conduction block following surgical ablation - To identify gaps in the surgical box lesion set - To perform additional ablations Hybrid procedure

42. Electroanatomical Mapping by CARTO / NavX EP Time ENTRY BLOCK IN UPPER LEFT VEIN EXIT BLOCK IN UPPER LEFT VEIN ENTRY BLOCK IN UPPER LEFT VEIN EXIT BLOCK IN UPPER LEFT VEIN EXIT BLOCK IN UPPER RIGHT VEIN ENTRY BLOCK IN UPPER RIGHT VEIN EXIT BLOCK IN LOWER RIGHT VEIN ENTRY BLOCK IN LOWER RIGHT VEIN

43. ELECTROPHYSIOLOGICAL PROCEDURE HYBRID APPROACH OUTCOMES 62,5% 77% RITMO POST EPI FA RS Fl A Before Surgery Post SurgeryBefore EP 75 58 17 47 27

44. HYBRID APPROACH OUTCOMES ELECTROPHYSIOLOGICAL PROCEDURE 62,5% 77% Absent Block Complete Block Exit Block Entrance Block

45. 42% 29% 23% 6% GAPs HYBRID APPROACH OUTCOMES ELECTROPHYSIOLOGICAL PROCEDURE

46. HYBRID APPROACH OUTCOMES 62,5% 77% 100% ELECTROPHYSIOLOGICAL PROCEDURE 75 58 17 47 27 75

47. 36 Months: -SR : 62/75 (82,2%) -AF : 13/75 (17,8%) of which: - 3 pts: persistent AF - 10 pts: paroxysmal AF FOLLOW UP: 75 pts HYBRID APPROACH Long-term Outcomes

48. FOLLOW UP: 75 pts reduction of symptoms in the 13 pts with AF Pre Ablation Post-Ablation HYBRID APPROACH OUTCOMES

49. FOLLOW UP : 75 pts Reduction AADs & OAC Reduction 47% AADs Reduction 20% TAO Stop between 3°- 6°month HYBRID APPROACH OUTCOMES 80 72 64 56 48 40 32 24 16 8 0

50. SURGICAL SCARS AFTER 20 DAYS

51. Conclusions The Hybrid approach is a feasible and effective strategy, especially in persistent and long-standing persistent AF The Hybrid approach is a feasible and effective strategy, especially in persistent and long-standing persistent AF Intra-op and post-op ( Carto 3 / NavX at 1 month) EP study is mandatory to provide a clear evaluation of the endoscopic ablation and to refine the surgical procedure Intra-op and post-op ( Carto 3 / NavX at 1 month) EP study is mandatory to provide a clear evaluation of the endoscopic ablation and to refine the surgical procedure

52. Conclusions Continuous monitoring device (Medtronic Reveal XT) is also mandatory to evaluate results and to discontinue anticoagulation and AAD’s Continuous monitoring device (Medtronic Reveal XT) is also mandatory to evaluate results and to discontinue anticoagulation and AAD’s It combines advantages and reduces risks and limitations of both the surgical and EP procedures It combines advantages and reduces risks and limitations of both the surgical and EP procedures Further studies are warranted in order to confirm optimal timing and potential improvements of the technique Further studies are warranted in order to confirm optimal timing and potential improvements of the technique

53. Tecniche alternative dell' ablazione trans catetere della Fibrillazione Atriale Laboratorio di Elettrofisiologia e Cardiostimolazione Cattedra e Divisione di Cardiologia Università degli Studi e Spedali Dr. M. Cerini Prof. A. Curnis Francavilla al Mare, 10 Ottobre 2014 LIVE ATRIAL FIBRILLATION