1. more than mortality benefit Klinikum Coburg, Germany
The CASTLE AF trial:
more than mortality benefit
Johannes Brachmann
Klinikum Coburg, Germany
Klinikum Coburg

2. Disclosure
J. Brachmann: Study honoraria, advisory board, speaker´s bureau:
Biotronik, Medtronic, SJM, BSC, Sorin, Boehringer Ingelheim, Bayer, Pfizer/Bristol Myers Squibb, Daiichi Sankyo, Siemens
CASTLE-AF was supported by BIOTRONIK

3. CASTLE-AF Primary Endpoint
Marrouche NF and Brachmann J et al, NEJM 2018

4. CASTLE AF AF Burden Derived from Memory of Implanted Devices

5. Background and Rationale
Post-hoc analysis:
Is there an association between AF recurrence and clinical outcome ?
Can we predict long-term clinical outcome based on AF burden early after ablation ?
Which role plays the relative reduction of AF burden clinical outcome ?

6. Analysis of AF Burden on Clinical Outcome in CASTLE-AF
ITT population
As-treated population
179 pts
148 pts
150 pts*
Randomized to Ablation
Ablated within 12 weeks after Baseline
Enrollment
& Randomization
Baseline
Run-in
5 weeks
31 pts
5 pts
Randomized to Medical Therapy
Not ablated within 12 weeks after Baseline
398 pts
363 pts
184 pts
179 pts
210 pts

7. CASTLE-AF: Time to first 30 sec recurrence
P < (log-rank test)
AF burden cut-off sind 5%. Blanking in der Ablationsgruppe von 90 Tagen
Log-rank <
Gruppen heißen “ablated” und “non-ablated”

8. AF recurrence (30 sec) was not associated with primary outcomeHR
95% CI
P-value
Ablated patients
2.13
0.87 – 5.18
0.097
Non-ablated patients
0.96
0.44 – 2.09
0.914
AF burden cut-off sind 5%. Blanking in der Ablationsgruppe von 90 Tagen, Primärer Endpunkt

9. Short-term burden predictive values
Ablation patients
<=5%
>5% AND <=80%
>80%
19/86 (22.1)
7/24 (29.2)
1.26 ( )
0.599
5/10 (50.0)
2.73 ( )
0.047
20/84 (23.8)
8/33 (24.2)
0.91 ( )
0.822
7/18 (38.9)
1.48 ( )
0.373
17/81 (21.0)
7/34 (20.6)
0.91 ( )
0.829
8/19 (42.1)
2.04 ( )
0.096
18/84 (21.4)
5/34 (14.7)
0.60 ( )
0.317
8/16 (50.0)
2.49 ( )
0.032
20/97 (20.6)
2/18 (11.1)
0.53 ( )
0.391
6/15 (40.0)
1.98 ( )
0.144
10 days
30 days
90 days
180 days
90 days blanking
180 days
Ist jetzt 25% Transmission, nur ablated;
Time period for AF burden calculation [days]

10. Short-term burden predictive values Non-Ablation patients
<=5%
>5% AND <=80%
>80%
30/76 (39.5)
5/15 (33.3)
0.90 ( )
0.823
39/89 (43.8)
1.15 ( )
0.576
29/73 (39.7)
11/23 (47.8)
1.22 ( )
0.569
37/87 (42.5)
1.09 ( )
0.729
25/67 (37.3)
12/24 (50.0)
1.50 ( )
0.250
31/81 (38.3)
1.06 ( )
0.841
17/56 (30.4)
15/30 (50.0)
2.13 ( )
0.034
27/73 (37.0)
1.31 ( )
0.388
No blanking applied in non-ablated patients
10 days
30 days
90 days
180 days
90 days blanking
180 days
Ist jetzt 25% Transmission, nur non-ablated;
Time period for AF burden calculation [days]

11. CASTLE AF-Primary Endpoint AF Burden-Ablation group
Sensitivity
AUC=0.66 [ ];
p=0.012
ROC Kurven nur für Ablationsgruppe (die rechte Abb. ist noch von allen Patienten !). Daten sind von 730 Tagen ohne Blanking

12. Results-Primary Endpoint AF Burden-Non Ablation group
Sensitivity
ROC Kurven für nicht-abladierte kommen hier Ablationsgruppe. Daten sind von 730 Tagen ohne Blanking

13. Effect of Absolute AF Burden Reduction on Primary Endpoint and Mortality
Composite Endpoint
Mortality
HR, 3.36 (95% CI, );
P=0.030
HR, 2.33 (95% CI, );
P=0.028

14. Effect of Absolute AF Burden Reduction (<50%) on Primary Endpoint and Mortality

15. Effect of Relative AF Burden Reduction on Primary Endpoint and Mortality (blanking period)
Composite Endpoint
Mortality
HR, 3.39 (95% CI, );
P=0.037
HR, 2.52 (95% CI, );
P=0.021
In die unteren Grafiken bitte noch die p-Werte einfügen – sind in den exportierten Rohdaten enthalten.
Achsenbeschriftung für KM Kurven:
x-Achse: "Months of Follow-up"
Y-Achse: "Probability of Survival free from Primary Composite Endpoint“ (links) bzw. “Probability of Survival” (rechts)
Überschrift löschen; Kasten mit “Any ablation…” löschen; Kasten mit “Censored” löschen

16. Effect of Relative AF Burden Reduction (<30%) on Primary Endpoint and Mortality
(blanking period)
Mortality
Composite Endpoint *
p<0.05 *
p<0.05 * *
Cut-off: -30% *
Cut-off: -30% *

17. Is there an effect of AF ablation on VT/VF in CASTLE-AF

18. Sinus rhythm and VT/VF/SCD in CASTLE-AF
Ablation better
Pharmacological treatment better

19. Sinus rhythm and VF in CASTLE-AF
Ablation better
Pharmacological treatment better

20. Sinus rhythm and VF in CASTLE-AF
Ablation better
Pharmacological treatment better

21. Hazard Ratio for VF in CASTLE-AF
Ablation better
Pharmacological treatment better

22. Conclusions
In patients suffering from atrial fibrillation and heart failure:
AF ablation improved AF burden and time-to first recurrence
High AF burden was assicated with increased risk of composite endpoint of mortality and heart failure admissions. Reduction of relative AF burden was associated with a favorable outcome.
Time to first recurrence did not predict composite endpoint and mortality
AF ablation reduced risk of VT and VF
Das fehlt noch komplett !!!