Stepwise1864Liu Shaowen, MD. PhD.Shanghai First Peoples Hospital Shanghai Jiao Tong University

*Long-Term Follow-up for SR Maintenance Following Ablation of AF1. Ouyang F, et al. Circulation 2010;122:23682377.2. Medi C, et al. J Cardiovasc Electrophysiol 2011;22:137141.3. Weerasooriya R, et al. J Am Coll Cardiol 2011;57:160166.4. Sorgente A, et al. Am J Cardiol 2012;109:11791186.5. Tilz RR, et al. J Am Coll Cardiol 2012;60:19211929.

--Mechanisms of AFib Electrical Reconnection of PV and LA Atrial substrate modification Non-PV drivers or firing foci are important for acute termination of AFib and for long-term success. --Ouyang F, et al. Recovered PV conduction as a dominant factor for recurrent atrial tachyarrhythmias after complete circular isolation of the PVs: lessons from double Lasso technique. Circulation. Jan 18 2005;111(2):127-135.--Miyazaki S, et al. Long-term clinical outcome of extensive PVI-based catheter ablation therapy in patients with paroxysmal and persistent AF. Heart. 2011;97(8):668-673.Reasons of Recurrence After AFib AblationAfib pathophysiology

PASupRLLLIndividualized CPVA LineSongwen Chen and Shaowen Liu . Spatial torsion of the PVs. J Interv Card Electrophysiol. 2013; 37(1):35-40

Becker A et al.JCE 2001--Related to Ablation ApproachesReasons of Recurrence After AFib Ablation

Anatomic Variability

CARTOMERGE in the Ablation of AfibHuge PV AntrumPVI+Roof Line+CFAE Abl+CD

Anatomic VariabilityAblation of Afib using 3D mapping system integrated with CT image

Recovery of PV conductionDurable isolation of the PVsThe Role of Adenosine Following PVI--25%McLellan AJ, et al. A Systematic Review. JCE. 2013;24(7):742-51.The effect of waiting time--30-60 minsYamane T, et al. Circulation: Arrhythmia and Electrophysiology. 2011;4(5):601-608.LA-PV90.9%--76.8%--70.5%Songwen Chen and Shaowen Liu, et al. PACE. 2012; 35(5): 524531.Benefit of PVI Guided by Loss of Pace Capture on the Ablation Line. (83%--52%, p=0.001)Steven D, et al. J Am Coll Cardiol. 2013;62(1):44-50.Acute electrical isolation is a necessary but insufficient endpoint: The importance of closing the visual gapMiller MA, et al. Europace 2012;14(5):653-660.Prolonged ablation on critical segments of PV ostia in PAF(HR 2.6, p=0.001)Kriatselis C, et al. Pacing Clin Electrophysiol. 2014;37(5):603-9.

---16,PVI20%69%(P=0.0001)--Willems S, et al. Substrate modification combined with PVI improves outcome of catheter ablation in patients with persistent AF: a prospective randomized comparison. Eur Heart J 2006;16:16.Hocini M, et al. Techniques, evaluation, and consequences of linear block at the left atrial roof in PAF: a prospective randomized study. Circulation 2005;112:3688-96.---36% VS.74%P

CFAE ablation provided only benefit for persistent AF when combined with antral PVI (RR 0.55). Adjunctive CFAE ablation increased procedural, fluoroscopy, and RF application times, and the risk/benefit profile of adjunctive CFAE ablation deserves further evaluation.1. Kong MH, Piccini JP, Bahnson TD. Efficacy of adjunctive ablation of CFAEs and PVI for the treatment of AF: a meta-analysis of randomized controlled trials. Europace. 2011;13(2):193-204.2. Parkash R, et al. Approach to the Catheter Ablation Technique of Paroxysmal and Persistent AF: A Meta-Analysis of the Randomized Controlled Trials. JCE.. 2011;18:1540-8167.3. Li WJ, et al. Additional Ablation of CFAEs After PVAI in Patients with AF: A Meta-Analysis. Circ Arrhythm Electrophysiol. Feb 8 2011. 4. Hayward RM, et al. PVI with CFAE Ablation for Paroxysmal and Nonparoxysmal AF: A Meta-Analysis. Heart Rhythm. 2011;9. -CAFE

The majority of CFAEs reflect far-field signals, AF acceleration, or disorganization.Narayan SM, et al. Classifying fractionated electrograms in human AF using MAP and activation mapping. Heart Rhythm. 2011;8(2):244-253.CS CFAEs are common in controls with induced AF. No difference in the DF during AF was seen. Teh AW, et al. Prevalence of CFAE in the CS: comparison between patients with PsAF or PAF and a control population. Heart Rhythm. 2010;7(9):1200-1204.Functional nature of electrogram fractionation demonstrated by LA high-density mapping.Jadidi AS, et al. Circ Arrhythm Electrophysiol. 2012;5(1):32-42.CFAEs!Mechanisms of CFAE

Mechanisms of CFAEPVAI plus EAT-based ablation efficiently eliminates high-frequency sources/ CFE and yields relatively high success (During 16-month follow-up, freedom from AF on AADs: 78% vs 60%, P

Lin YJ, et al. J Cardiovasc Electrophysiol. 2014 Mar 13.Limited Versus Extensive Atrial Substrate Modification After CPVI in Nonparoxysmal Atrial Fibrillation--A Prospective and Randomized study(continuous complex fractionated atrial electrogram, CFAE:

Katritsis DG, et al. J Am Coll Cardiol.2013;62(24):2318-25. Autonomic denervation added to PVI for PAF---a randomized clinical trial3(74%)

(56%)

(48%)

Individualized Circumferential PV Ablation LinePAPARLRLRAORAO

O'Neill MD, et al. Long-term follow-up of persistent AF ablation using termination as a procedural endpoint. Eur Heart J. 2009;30(9):1105-1112. PATIENT FLOW CHART----49%69%95%52%85%15%--70.6%14.4%

Elayi CS, et al. Atrial fibrillation termination as a procedural endpoint during ablation in long-standing persistent atrial fibrillation. Heart Rhythm, 2010,7:1261.

Shanghai First People Hospital, Jiao Tong Universityp < 0.0018(3-241//Genqing Zhou, and Shaowen Liu. JCE. 2013;24(10):1192.

75%67.7%48%29%Shanghai First People Hospital, Jiao Tong UniversityAF>SRAF>AT>SRAF>AT>XAF>XGenqing Zhou, and Shaowen Liu. JCE. 2013;24(10):1192.

Reasons of Recurrence After AFib Ablation --Impact of Ablation procedure end-pointFaustino M, et al. Heart Rhythm. 2014 May 23.

N=3966 (PAF 36%, PsAF 20%, LSP 44%)Redo N=987(PAF 29%, PsAF 20%, LSP 51%)LAA firing: 266 (27%) (PAF 18%, PsAF 23%, LSP 58%)Freedom from AF/ATMonthsDi Biase and Natale. LAA: an underrecognized trigger site of AF. Circulation. 2010;122(2):109-118Reasons of Recurrence After AFib AblationMechanisms of AFib

*Focal impulse and rotor modulation (FIRM) in AF AblNarayan SM, et al. JACC 2012;60(7): 628-636.

Ablation of FIRM reduces late recurrence of AF compared with trigger ablation alone1.20.4 procedures70.4%36.9%Narayan SM, et al. J Am Coll Cardiol. 2014 May 6;63(17):1761-8.

Focal impulse and rotor modulation (FIRM) in AF AblRavelli F, Mas M. Europace. 2014;16(5):714-23.

Body Surface Localization of Left and Right Atrial High Frequency Rotors in AF PtsRodrigo M, et al. Heart Rhythm. 2014 May 17.A Clinical-Computational StudyPhase analysis of surface potential signals after HDF-filtering during AF shows reentrant drivers localized to either the LA or RA, helping in localizing ablation targets

*Pokushalov E, et al. J Am Coll Cardiol 2012; 60(13): 1163-1170.n=13, 29%n=14, 69%RSD reduces SBP and DBP in pts with drug-resistant hypertension and reduces AF recurrences when combined with PVIRSD in addition to PVI in Pts with Refractory Symptomatic AF and Resistant HypertensionRestoring NSR in pts with AF and HTN resulted in a sustained decrease in DBP and MBP Ramirez A, et al. The effects of radio-frequency ablation on blood pressure control in pts with AF and hypertension. J Interv Card Electrophysiol. 2012;35(3):285-291.Sanders NA, et al. Restoring sinus rhythm results in blood pressure reduction in pts with PsAF and a history of hypertension. J Cardiovasc Electrophysiol. 2012;23(7):722-726.In pts with sleep apnea syndrome and AF, restoring SR by RFCA leaded to a decrease in apnea-hypopnea index Naruse Y, et al. Radiofrequency catheter ablation of PsAF decreases a sleep-disordered breathing parameter during a short follow-up period. Circ J. 2012;76(9):2096-2103.Maintenance of sinus rhythm after DCC may have a favorable effect on the SQ of patients with AF. Kayrak M, et al. Self-Reported Sleep Quality of Pts with AF and the Effects of Cardioversion on Sleep Quality. Pacing Clin Electrophysiol. 2013 Feb 25.

Improving the Outcome of Catheter Ablation in AF Afib pathophysiology*Within or out of the PVsGP or RSDLines, CFAE or FIRM

AP M541LA 33mmEF 58%Failed 3 Shocks: 300J-360J-360J

Mapping of AT

Periodogram of AF recorded in the CS at baseline (A), 3 minutes prior to conversion (B), and the frequency of AT (C). At baseline, the dominant frequency (DF) of AF is 6.60 Hz (A). Ablation of CFAEs results in a decrease in DF of AF; however, there is no change in the frequency of the spectral component (B, arrow). After termination of AF to AT, the frequency of AT (4.84 Hz) is similar to the frequency of the spectral component identified in the periodogram of AF (C). The mechanism of AT was mitral isthmus dependent flutter in this example. Yoshida K, et al. Relationship between the spectral characteristics of AF and AT that occur after catheter ablation of AF. Heart Rhythm. 2009;6(1):11-17.

Elimination of spectral components of AF by targeted linear ablation suggests that spectral components may indicate site-specific ATs that coexist with AF despite a lower frequency than the DF of AF Yokokawa M, et al. Effect of linear ablation on spectral components of AF. Heart Rhythm. 2010;7(12):1732-1737.BaselineAntral PVILinear ablationEffect of antral PVI and linear ablation on the prevalence of spectral components in the left atrium, coronary sinus, and right atrium.

Distinctive patterns of dominant frequency trajectory behavior in drug-refractory persistent AFSalinet JL, et al. J Cardiovasc Electrophysiol. 2014;25(4):371-9.Characterization of spatiotemporal instabilityIdentification and tracking of the center of gravity (CG) of the highest DF cloud for a specific time (A). Three types of behavior: localized (B), cyclical (C), and chaotic (D).

SmartTouch

STn=53n=50P/30/2330/200.72758.411.460.89.70.26978.0104.249.976.00.123mm39.67.837.19.70.15924/539/410.0030.921.032.081.37

Wide area durable CPVILinear ablation Limited CFAE Ablation Ablation end-pointsOut of procedure...Characteristics of patients with AFibStepwise

Shanghai Evening

***Recovered PV connection was the major cause of the AF recurrences despite undergoing multiple catheter ablation procedures. It is advisable to inspect all PVs during the AF recurrence. Repeated PV isolation plus left atrial linear ablations could effectively eliminate the AF with satisfactory outcomes(Lo LW, Tai CT, Lin YJ, et al. Characteristics and outcome in patients receiving multiple (more than two) catheter ablation procedures for paroxysmal AF. J Cardiovasc Electrophysiol. 2008;19(2):150-156.)The SVC harbors the majority of non-PV triggers of AF. SVCI is feasible, safe, and may be considered as an adjunctive strategy to PVAI for ablation of AF. The long-term favorable outcome of this hybrid approach remains to be evaluated in a larger series of patients.(Arruda M, Mlcochova H, Prasad SK, et al. Electrical Isolation of the Superior Vena Cava: An Adjunctive Strategy to Pulmonary Vein Antrum Isolation Improving the Outcome of AF Ablation. J Cardiovasc Electrophysiol. 2007;11:11.)In our series of paroxysmal AF patients, empirically adding SVCI to CPVI did not significantly reduce the AF recurrence after ablation. Superior vena cava isolation may be useful, however, in selected patients in whom the SVC is identified as a trigger for AF. However, because of the preliminary property of the study and its relatively small sample size, the impact of SVCI on clinical results should be evaluated in a large series of patients (Wang XH, Liu X, Sun YM, et al. Pulmonary vein isolation combined with superior vena cava isolation for atrial fibrillation ablation: a prospective randomized study. Europace. 2008;10(5):600-605.)*Eliminate more fociMore part of substrate involved in the aiffb have been modified *Incidence of PV conduction recovery in pts without clinical recurrence after ablation of PAF: Mechanistic implicationsJiang RH, et al. Heart Rhythm. 2014;11(6):969-76.

*CPVI alone is sufficient to restore SR in 43.2% of patients with long-standing PsAF. Multiple procedures and additional ablation strategies are often required to maintain stable SRTilz RR, et al. Catheter ablation of long-standing persistent atrial fibrillation: a lesson from circumferentia PVI. J Cardiovasc Electrophysiol. 2010;21(10):1085-1093.Additional lesions in the interpulmonary isthmus following PVAI do not have incremental value in preventing AF recurrenceThe Impact of Catheter Ablation in the Interpulmonary Isthmus on Atrial Fibrillation Ablation Outcomes: A Randomized Study.Letsas KP, et al. J Cardiovasc Electrophysiol. 2014 Mar 5.

**CFAE distribution was highly variable, depending on direction and rate of activation (SR versus CSp versus AF). Fractionation in SR and CSp occurred at sites of wave collision in 71% and at sites of slow conduction in 24%. All sites with continuous fractionation in AF displayed normal voltage (1.0 mV) in SR, suggesting absence of structural scar; however, during AF, the electrogram voltage was higher at continuous CFAE sites than at non-CFAE sites (0.53 versus 0.30 mV, P0.0001). These findings indicate that electrogram fractionation and voltage are predominantly functional in nature, and most CFAE sites occur at regions of wave collision. Jadidi AS, et al. Circ Arrhythm Electrophysiol. 2012;5(1):32-42.

*Increased epicardial adipose tissue (EAT) volume is associated with atrial fibrillation (AF). However, the efficacy of EAT-based left atrial (LA) ablation for persistent AF (PsAF) is unclearIn 60 PsAF patients (group I), 3-dimensional reconstructed CT images depicting EAT were merged with NavX-based dominant-frequency (DF) and complex fractionated electrogram (CFE) maps obtained during AF. PVAI was followed by map-guided EAT-based ablation. Results were compared to those in a historical control group (group II, case-matched patients who underwent generalized stepwise ablation including linear plus CFE-targeted ablation).

*The optimal substrate ablation approach in pts with persistent AF (Per AF) remains unclear. This was a prospective randomized study comparing the efficacy of limited (continuous complex fractionated atrial electrogram, CFAE: 160 mm Hg despite triple drug therapy) were eligible for enrolment. Consenting patients were randomized to PVI only or PVI with renal artery denervation. All patients were followed >/=1 year to assess maintenance of sinus rhythm and to monitor changes in blood pressure. RESULTS: Twenty-seven patients were enrolled, and 14 were randomized to PVI only, and 13 were randomized to PVI with renal artery denervation. At the end of the follow-up, significant reductions in systolic (from 181 +/- 7 to 156 +/- 5, p < 0.001) and diastolic blood pressure (from 97 +/- 6 to 87 +/- 4, p < 0.001) were observed in patients treated with PVI with renal denervation without significant change in the PVI only group. Nine of the 13 patients (69%) treated with PVI with renal denervation were AF-free at the 12-month post-ablation follow-up examination versus 4 (29%) of the 14 patients in the PVI-only group (p = 0.033). Renal artery denervation reduces systolic and diastolic blood pressure in patients with drug-resistant hypertension and reduces AF recurrences when combined with PVI.

**The initiation and perpetuation of a tachyarrhythmia requires both triggers for its onset and a substrate for its maintenance. Increased data also suggested that the autonomic nervous system play an important role in the process of initiation as well as perpetuation of AFib.These mechanisms are not mutually exclusive and are likely to co-exist at various times in patients with AF.

*Time- and frequency-domain characteristics of atrial fibrillation (AF) recorded in the coronary sinus (CS). A: At baseline, the dominant frequency (DF) ofAF was 5.81 Hz, and there was a spectral component with a frequency of 3.05 Hz (arrow). B: Antral pulmonary vein isolation (APVI) did not have an effect on thespectral component. C: After linear ablation, however, the spectral component was no longer present. Shown are ECG leads II, V1, and V5 and bipolar intracardiacelectrograms recorded from the CS. Linear ablation was performed along the LA roof and mitral isthmus in 25 patients and along the cavotricuspid isthmus in 5 patients who remained in AF after APVI.****