1. Substrate Ablation (CAFE) A Promising or Vanishing Technique
Walid I. Saliba, M.D.
Director, Atrial Fibrillation Center
Section of Pacing and Electrophysiology, Department of Cardiovascular Medicine
THE CLEVELAND CLINIC FOUNDATION
Cleveland, Ohio 1

2. Goal
To confuse you

3. Natural History of AF Dual Substrate Model
Ablation of Triggers
Modification of Substrate
Persistent
Sinus can be restored electrically or chemically
Paroxysmal
Self terminating AF episodes
Permanent
Sinus cannot be maintained
Atrial remodeling:
↓Refractory Period ↓ Conduction velocity
Favors Arrhythmia
“AF begets AF”
Trigger initiation
Substrate maintenance

4. Alternative Strategies
More Ablation
Where?
Why?
How much more?
CAFE
Dominant Frequency
Ganglionic Plexi
Stepwise/Tailored
AF Nest
SVC / CS / Septum / Crista
LAA, LoM
Flutter? CTI
Lines, circles …
Primary therapy
Adjunctive therapy to PVI

5. What are CAFÉ’s EGMs with CL < 120 ms
EGMs with continuous electrical activity
EGMs with low amplitude and more than 2 deflections
EGMs with CL shorter than in the CS or LAA

6. Mechanisms Underlying CAFE
Pathological anisotropic conduction
Slow conduction , Pivot and anchor points or Collision of the wavelets (Alessie 1996)
Focal microreentry (Gardner/Alessie 1985)
Wave break and fibrillatory conduction at the Borderzone of the mother rotors and areas of dominant frequencies. (Kalifa et al Circ 2006)
Calcium transient triggering activities from hyperactive autonomic ganglionic plexi with shortening of the RP (Scherlag et al. 2004)

7. CAFÉ’s in Atrial Fibrillation Ablation
Stand Alone Targets ( Nademaneee)
Hybrid approach with PVI

8. Substrate-Guided Ablation: CAFÉ’s
Nademanee et al, JACC 2004
Rationale
Target key atrial regions responsible for perpetuating AF rather than targeting the triggers in the PV’s
End Points
Complete elimination of areas with CFAE’s
Conversion of AF to SR

9. Substrate-Guided Ablation: CFAE
Fractionated electrograms composed of 2 deflections or more and continuous deflection of baseline
Atrial EGMs with very short CL <120 msec
Nademanee et al, JACC 2004

10. Substrate-Guided Ablation: CFAE’s
Median RF lesions: 64
60% patients had CFAEs clustered around PV’s
87% patients had CFAEs clustered around septum and roof, close to PVs.
Nademanee et al, JACC 2004

11. Substrate-Guided Ablation: CFAE’s Only
121 pts
(51 PAF, 64 Chronic AF)
91% of pts free of arrhythmia
23% required a 2nd. Ablation
13% on AAD
Nademanee et al, JACC 2004

12. Stepwise Ablation Approach
Haissaguerre et al. JCE 2005
Ablation of CAFÉ’s as part of a stepwise approach to achieve conversion to SR
Rationale:
Structures contributing to initiation and maintenance of AF are sequentially targeted
With increasing ablation of left atrial structures, there is a cumulative increase in AFCL resulting in “AF termination” with each ablation step performed.

13. The Stepwise Ablation Approach
Lasso Guided PV Isolation
Roof Line Ablation
Ablation of CS & Complex LA activities
Mitral Isthmus Ablation
Right Atrial / SVC Ablation
Cardioversion

14. EGM Based Ablation
Haissaguerre et al. J CardiovascElectrophysiol2005;16:

15. Stepwise Ablation Approach
60 pts with Non-PAF
87% (52) had AF termination during ablation (SR:7 ; AT:45)
60% success rate with a single procedure
(40% required repeat ablation)
95% success rate with multiple procedures
Sinus rhythm at 11±6 months f/u ,without AAD’s
Good atrial transport function
Haissaguerre et al., J C E, Vol. 16, pp Nov 2005

16. Some Observations
The greatest magnitude of prolongation of fibrillatory cycle length occurred during ablation at the
PV-LA junction (Antrum)
Coronary sinus
Anterior LA
Almost half of the residual atrial tahycardias originated these same sites.

17. RF ablation of CAFÉ’s in PV’s, LA and CS
100 pts with Chronic AF
RF ablation of CAFÉ’s in PV’s, LA and CS
End point: All CAFÉ’s eliminated or AF termination
Circulation.2007;115:2606

18. CAFÉ’s 1 PV 46% CS 55% Septum/roof All CFAEs EGM: CL< 120 msec
CL < CL n CS
Fractionated and/or continuous electric activity
1 PV 46%
CS 55%
Septum/roof All

19. Results 33% in SR after a single ablation procedure
Repeat ablation in 44%
CAFÉ’s in antrum, PV tachycardia, Macroreentrant flutter and circuits……
57% in SR at ~1 year follow up.

20. “The modest efficacy attained in this study despite extensive ablation of left atrial and coronary sinus CFAEs suggests either that CFAEs do not accurately identify sites that are critical to the maintenance of chronic AF or that ablation of CFAEs is not sufficient to eliminate the driving mechanisms of chronic AF in a large proportion of patients.”

21. Oral et al. J Am Coll Cardiol 2009;53:782–9)
A Randomized Assessment of the Incremental Role of Ablation of Complex Fractionated Atrial Electrograms After Antral PV Isolation for Long-Lasting Persistent AF
n=119
Group A:
Termination with PVAI (n=19)
Group B:
No Termination→Cardioversion (n=50)
Group C:
No termination →CFAE* (n=50)
*LA and CS for up to 2 hrs additional ablation
Oral et al. J Am Coll Cardiol 2009;53:782–9)

22. CAFÉ: LA sites

23. A Randomized Assessment of the Incremental Role of Ablation of Complex Fractionated Atrial Electrograms After Antral PV Isolation for Long-Lasting Persistent AF
After a single Ablation
SR at 10 months
Group A:
Termination with PVAI (n=19)
Group B:
No Termination→Cardioversion (n=50)
Group C:
No termination →CFAE (n=50)
79%
36%
P=0.84
34%
Up to 2 h of additional ablation of CFAEs after PVAI
does NOT appear to improve clinical outcomes in patients with long-lasting persistent AF.
Oral et al. J Am Coll Cardiol 2009;53:782–9)

24. Repeat Ablation in 34 randomized patients.
SR at 9 months
Group B:
No Termination→Cardioversion (n=50)
Group C:
No termination →CFAE (n=50)
68%
P=0. 4
60%
No Difference even with repeat ablation
Oral et al. J Am Coll Cardiol 2009;53:782–9)

25. Methods Elayi et al. ;Heart Rhythm. 2008 5(12):1665
144 patients with permanent AF randomized to:
Group I: Pulmonary Vein Antrum Isolation .(PVAI) n=48
Group II: Hybrid approach. (CFAE’s + PVAI) n=49
Initial defragmentation: targeting bi-atrial and CS CFAE, and started randomly in the right or left atrium followed by PVAI
Group III: Large area circumferential ablation. (LACA) n=47
Targeting voltage reduction using electroanatomic mapping. (CARTO)

26. Defragmentation +PVAI
Acute Results
Group I
Group II
PVAI
N=48
Defragmentation ONLY
N=49
Defragmentation +PVAI
P value SR 3
(6%)
(0%) 2
(4%) NS AT 18
(38%) 1
(2%) 34
(70%)
P<0.001 AF 27
(56%) 48
(98%) 13
(26%)
P=0.01
Defragmentation alone did not have a significant effect on AF organization.
Defragmentation as an adjunctive strategy to PVAI increases the rate of conversion from AF to organized arrhythmias.

27. Long Term Results
Group I
PVAI
n=48
Group II CFAE+PVAI
n=49
Mean follow-up (months)
11.4 ± 1.1
11.2 ± 1.2
Patients in sinus rhythm after a single procedure
42%
61%
Patients in sinus rhythm after two procedures and with AAD if needed
83%
94%
Better success rate when defragmentation was performed in conjunction with PVAI

28. LAA
Cristal Terminalis
CS Pre RF
CS Post RF

29. Presenting for Ablation
LSPV
Post Antral Isolation
Post CS & LA-CAFE
AT Ablation

30. In high-burden paroxysmal/persistent AF,
Substrate vs. Trigger Ablation for Reduction of AF: An International, Multicenter, Randomized Trial (STAR-AF)
In high-burden paroxysmal/persistent AF,
PVI+CAFE has the highest freedom from AF
versus PVI or CAFE alone after one procedure.
CAFE alone has the lowest procedure success rates with a higher incidence of repeat procedures
Comparison of 3 strategies of AF ablation:
(n=100 pts, 35% persistent)
CFE ablation alone
PVI ablation alone
PVI+CFE hybrid ablation
74%
47%
Freedom from AF
29%
Verma et al, HRS LBT 2009

31. Outcomes of Different Ablation Approaches That Incorporated CFAE Ablation in Patients With Persistent AF N AF
CAFÉ only
PVI only
PVI + CAFÉ
Nademanee et al (2004)
121
P+C
91%
Oketani et al (2008)
410
81%
Verma et al (2007) 40 C
82%
Star AF (2009)
100
29%
47%
74%
Haissaguerre (2005) 60
95% *
Orale at al.(2009) 50
60%
Orale et al.(2006)
57%
Meulet et al.(2007) 96
67%
66%
Elayi et al. (2008) 97
83%
94%
60%
66%
83%
After 1-2 ablations
F/U ~1 year

32. Does CAFÉ substrate modification offer additional success?
Conclusion
Does CAFÉ substrate modification offer additional success?
Different techniques, Different Operators, Different Skills, Different interpretations, Different endpoints, different experiences, different follow up’s:
Can we generalize the information
Can we trust the data: Is this Science?
Significance of CAFÉ: Active vs Passive role?
Is it just more Controlled Debulking? (CEDCA)
I will let you draw your own conclusion

33. PV Antrum Isolation

34. Overlap of CFAE and PVI?
Majority of ablated CFAE in tailored approach were in the LA
Extensive “fixed” PV antral isolation includes most areas of CAFÉ.

35. Is More ablation better?
More Ablation: Potential for More atrial Flutter
More ablation: Compromise LA mechanical function
More ablation: Interatrial / intraatrial dyssynchrony
More ablation: More fluoro / More potential complications

36. OK, but
what else
can we ablate?…
ﺒﻜﻔﻱ
CAFE

37. END

38. “AF-Nests” Spectral Mapping Guided AF Nests Ablation in Sinus Rhythm
An Adjunctive Approach to PVAI and SVCI
Well connected cells
Loose cells, anisotropic conduction
40 Hz
50 Hz
120 Hz
200 Hz
Segmented Spectrum
Continuous Spectrum
“AF-Nests”

39. AF NEST AF NEST Typical Sites Fibrillar Myocardium Pre RF CS
AF NEST CS
Post RF CS

40. 157 Pts Prospectively Studied 91Pts > 2mo F/U Randomized
AFN+PVAI+SVCI
45Pts
PVAI+SVCI
Recurrences
PAF 11%
Pers/Perm 20%
Recurrences
PAF 20%
Pers/Perm 30%

41. Stepwise Ablation Approach
Number of Patients Terminating with each Step of Ablation
Cumulative benefit
Progressive decrease in incremental benefit per stage after five stages of ablation beyond which further LA ablation is probably of no clinical benefit
up to a limit