Ablation ou traitement pharmacologique pour la FA : quelles stratégie à suivre ? Par le Pr L. Jordaens

1. Ablation ou traitement
pharmacologique pour la FA:
quelle stratégie a suivre ?
Luc Jordaens
Nouvelles frontières pour la prise en charge
de la fibrillation auriculaire
Brussels 29-11-2014

2. Usual care: Current AF management
ESC guidelines for the management of AF
Camm AJ, Kirchhof P, et al. European Heart Journal 31: 2369-2429. (2010)

3. Maintenance of sinus rhythm
in atrial fibrillation
received a bad reputation in the
early years 2000

4. AFFIRM
NEJM 2002;347:1825
• 4060 patients
• No survival benefit (23.8% vs 21.3%)
• 23 % Prior HF

5. Atriale fibrillatie en hartfalen (HF):
overleving (cardiale sterfte) i.f.v. behandeling
Naar Flaker, SPAF studie 1992
0 90 180 270 360 450 540 630 720
Tijd in SPAF (dagen)
0
20
40
60
80
100
%
HF, wel AAD
HF, geen AAD

6. Class Ic anti-arrhythmics
AF + RBBB + LBBB
VT ?
Sinus

7. RACE : Sub-study HF
Hagens et al. Am Heart J 2005;149:1106
If sinus rhythm is maintained,
prognosis may
improve (less CV
death, HF
hospitalizations
and bleeding)

8. DIAMOND : sinus rhythm and mortality
Pedersen et al. Circulation 2001;104:292
• 506 pts with LV dysfunction
• Randomized to Dofetilide or Placebo
• No effect on mortality
• Effect of SR on mortality RR 0.44 (0.30-0.64)
Survival according to Rx
Survival according to rhythm

9. Atrial fibrillation:
rate or rhythm control ?
Rate control can be acceptable
Rhythm control has some
advantages , when wisely used

10. SINUS RHYTHM IS BETTER !
Catheter / surgical ablation
is aimed to
achieve sinus rhythm

11. First diagnosed episode of AF
Persistent
(> 7 days or requires CV)
Long standing
Persistent (> 1 year)
Permanent
(accepted)
Paroxysmal
(usually ≤ 48 h)
Silent AF

12. 12
AF Duration
AF is a Progressive Disease
Paroxysmal
Trigger
dependent
(Initiation)
Permanent
Substrate
dependent
(Maintenance)
Relative
Importance
Khan IA. Int J Card. 2003;87:301-302

13. PAROXYSMAL PERSISTENT
maintain sinus
rhythm !
maintain sinus
rhythm !
cardioversion
DRUGS
DRUGS
ABLATION

14. ANTIARRHYTHMIC DRUGS AND AF

15. Sopher and Camm, 1996

16. ?
ANTIARRHYTHMIC DRUGS AND AF Rhythm control

17. ANTIARRHYTHMIC DRUGS AND AF Rhythm control

18. 2 late +
INCLUSION
N = 39
DIGOXIN
9 / 19
PLACEBO
8 / 20
Digoxin in high IV
dose for PAF
Jordaens et al, 1997
HEART RATE ACCORDING TO TREATMENT GROUP
0 10 20 30
0
50
100
150
200
beats / min
18
17
16
17
min
: p < 0.02
*
*
NS
< 0.002
CONVERTERS AND TREATMENT
0 10 20 30
0
50
100
150
200
beats / min
< 0.02
NS
7
9
6
8
Placebo
Digoxin

19. New class III
drugs

20. Vos et al, 1998

21. Duytschaever et al, PACE 1998

22. Roy et al, 2000
Patients without
recurrence (%)
Prophylactic antiarrhythmic therapy
in ’’ paroxysmal” atrial fibrillation

23. Torp-Pedersen et al, 2000
Antiarrhythmic therapy
for paroxysmal atrial fibrillation in CHF

24. Meta analysis of drugs: mortality
11 new studies comprising 20.771 patients.
Compared with controls, class IA drugs quinidine
and disopyramide (OR 2.39, 95% confidence
interval (95%CI) 1.03 to 5.59, number needed to
harm (NNH) 109, 95%CI 34 to 4985) and sotalol (OR
2.47, 95%CI 1.2 to 5.05, NNH 166, 95%CI 61 to
1159) were associated with increased all-cause
mortality. Other antiarrhythmics did not seem to
modify mortality.
Cochrane review, 2012

25. • Several class IA (disopyramide, quinidine), IC
(flecainide, propafenone) and III (amiodarone,
dofetilide, dronedarone, sotalol) drugs
significantly reduced recurrence of AF (OR
0.19 to 0.70, number needed to treat (NNT) 3
to 16).
• Beta-blockers (metoprolol) also reduced
significantly AF recurrence (OR 0.62, 95% CI
0.44 to 0.88, NNT 9).
Meta analysis of drugs: efficacy
Cochrane review, 2012

26. • All analysed drugs increased withdrawals due
to adverse affects and all but amiodarone,
dronedarone and propafenone increased pro-
arrhythmia.
• Possible benefits on clinically relevant
outcomes (stroke, embolisms, heart failure)
remain to be established.
Meta analysis of drugs: adverse effects
Cochrane review, 2012

27. ESC guidelines 2012
Drugs or ablation ?

28. Wilber et al, 2012

29. Morillo et al, 2014
Paroxysmal AF vs drugs – RAAFT 2

30. KCE, 2012

31. KCE, 2012

32. Catheter ablation for AF
• A total of 32 RCTs (3.560 patients) were included.
RCTs were small in size and of poor quality.
• CA compared with medical therapies: 7 RCTs
indicated that CA was better in inhibiting AF
recurrence [RR 0.27; 95% CI 0.18, 0.41)] (with
significant heterogeneity).
• There was limited evidence to suggest that sinus
rhythm was restored during CA (RR 0.28, 95% CI
0.20-0.40), and at the end of follow-up (RR 1.87,
95% CI 1.31-2.67; I2=83%).
Cochrane library, Chen et al, 2012

33. Catheter ablation for AF
• There were no differences in mortality (RR,
0.50, 95% CI 0.04 to 5.65), fatal and non-fatal
embolic complication (RR 1.01, 95% CI 0.18 to
5.68) or death from thrombo-embolic events
(RR 3.04, 95% CI 0.13 to 73.43).
Cochrane library, Chen et al, 2012:

34. Catheter ablation for AF
Comparisons of different CAs; 25 RCTs
compared CA of various kinds.
Circumferential pulmonary vein ablation was
better than segmental pulmonary vein
ablation in improving symptoms of AF
(p<=0.01) and in reducing the recurrence of
AF (p<0.01).
There is limited evidence to suggest which
ablation method was the best.
Cochrane library, Chen et al, 2012:

35. ESC guidelines 2012: paroxysmal AF

36. Incidence of new ischemic events (ACT >300)
No clinical events
2/27 (7.4%) 1/23 (4.3%) 9/24 (37.5%)
P=0.003
Herrera C et al. J Am Coll Cardiol 2011;58:681-88

39. Antral isolation
Ostial isolation
before & after
ANTRAL ABLATION
Van Belle et al, 2008

40. Early and late recurrence : event-free rates
after one procedure with blanking
AF
ICE
Months
24120
Actuarialevent-freerate(%)
100
0
80
60
40
20
N at
risk 1137
135 1563
73%
AF (only after
3 months)
N = 141
(any AF)
135
Van Belle et al, Europace 2008

41. Early and late recurrence : event-free rates
after one procedure with blanking
AF
ICE
Months
24120
Actuarialevent-freerate(%)
0
40
20
100
80
60
73%
N = 141
(any AF)
Van Belle et al, Europace 2008
This will be better
with the new balloon

42. AF
ICE
Months
24120
Actuarialevent-freerate(%)
100
0
80
60
40
20
All AF
N at
risk 1137
135 1563
73%
Early and late recurrence : event-free rates after one
procedure with and without blanking
AF (only after
3 months)
N = 141
(any AF)
135
Van Belle et al, Europace 2008

43. • No PV narrowing (30% criterion;
repeated MRI)
• Phrenic Nerve Palsy: 26/346
patients, usual with the small balloon
• No fistula, death, stroke…
Cryoablation with the ICE balloon:
results of a multicentre study
Neumann et al, JACC 2008

44. Cryoballoon efficacy – Meta analysis
Andrade JG, et al. Heart Rhythm 2011

45. Comparable efficacy to conventional RF
1 Andrade JG, et al. Heart Rhythm. Published online March 30, 2011.
4 Calkins H, et al. Circ Arrhythm Electrophysiol. August 2009;2(4):349-361.

46. Better than conventional RF ?

47. Onset VTAF

51. Wat zijn onze resultaten ?
blijven de zelfde na 550 procedures
( > 100 in BHC)
Geen CVA / TIA
Geen PV stenose
Geen overlijden

52. Persistent Atrial fibrillation:
suitable for catheter ablation?

53. Paroxysmal Persistent Permanent
*

54. 0
10
20
30
40
50
60
70
80
Mild Moderate Extensive
Paroxysmal AF
Persistent AF
Marrouche et al, JAMA 2014

55. KCE, 2012

56. Survival curves for the primary endpoint in persistent AF
Mont L et al. Eur Heart J 2014;35:501-507

57. 0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 3 6 9 12 15 18
Arhhythmiafreesurvival
Follow up (months)
346 250 38120128215
n pts
paroxysmal = 293
persistent = 53
Event Free Probability in Pts Without AAD After 3 Month
Neumann et al
Only 41 with
FU > 3 months
Neumann et al, JACC 2008

58. METACSA
Expected to recruit jan. 2015
Persistent “Light”
Atrial fibrillation:
suitable for catheter ablation ?
Exclusion of valvular pathology

59. METACSA (PROSPECTIVE STUDY OF MEDICAL
THERAPY AGAINST CRYOBALLOON ABLATION IN
PATIENTS WITH SYMPTOMATIC RECENT ONSET
PERSISTENT ATRIAL FIBRILLATION)
Expected to recruit jan. 2015
Persistent “Light”
Atrial fibrillation:
suitable for catheter
ablation ?
Exclusion of valvular
pathology
Normal atrial size
More info or a
candidate ?
luc@jordaens.be
BHC
St Luc
ULg
UZ Gent
R’dam

60. 1. Catheter ablation seems to be better
than drug therapy for paroxysmal AF (wide
circumferential ablation)
2. Persistent atrial fibrillation without
valvular pathology and normal anatomy
seems to be treatable with catheter
ablation
3. There are not enough good
antiarrhythmic drugs on the market in
Belgium

61. PAROXYSMAL PERSISTENT
maintain sinus
rhythm !
maintain sinus
rhythm !
cardioversion
DRUGS
DRUGS
ABLATION