Long-term outcome for patients with CTOs Thierry Lefèvre, Massy, France 10th Experts „Live“ CTO Workshop - Day2

1. EURO CTO CLUB
Toulouse 2018
Long-term outcomes of patients
with CTOs
Thierry Lefèvre, ICPS, Massy, France

2. EURO CTO CLUB
Toulouse 2018
"Study the past if you would define the future...."
Confucius

3. EURO CTO CLUB
Toulouse 2018
Nabel et al. NEJM 2012: 366; 54-63
Decline in cardiovascular death in relation with scientific advances
CTO PCI

4. EURO CTO CLUB
Toulouse 2018
Tentative Agenda
Position of the
problem
1
Natural history of
CTOs
2
High success rate
Low complications
4 5
Randomized
studies
PCI Success is
better than
failure
3
Conclusion
6

5. EURO CTO CLUB
Toulouse 2018
Position of the problem
1 2 3 4 5

6. EURO CTO CLUB
Toulouse 2018
• 13-18% of all coronary lesions in stable
coronary artery disease are chronic total
occlusions (CTO)1-3
• 95% of patients with CTO have inadequate
distal collateral supply (FFR <0.80) 4
• About 5% of PCI is performed in CTOs5
1) Fefer P et al. J Am Coll Cardiol. 2012;59:991-997
2) Råmunddal T. et Al. PLoS One. 2014;9:e103850
3) Tomasello et al. Eur heart J 2015
4) Werner et al. Eur Heart J 2006;27:2406-12
5) Brilakis E. et al. JACC Cardiovasc Intrv. 2015;8:245-53

7. EURO CTO CLUB
Toulouse 2018
You have good
collaterals

8. EURO CTO CLUB
Toulouse 2018 Benefit of Revascularization
6,7%
3,7%
1,0%
2,9%
4,8%
3,3%
1,8% 2,0%
0%
2%
4%
6%
8%
10%
Medical Rx Revasc
1.9 years after revascularization
% Total Ischemic Myocardium
1- 5% 5-10% 11-20% >20%
CardiacDeathRate
1331 56 718 109 545 243 252 267
P <.0001
Hachamovitch et al. Circulation. 2003; 107:2900-2907

9. EURO CTO CLUB
Toulouse 2018
Natural history of CTOs
1 2 3 4 5

10. EURO CTO CLUB
Toulouse 2018 Pronostic impact of CTOs
Ramundal et al. TCT 2015
16%

11. EURO CTO CLUB
Toulouse 2018 Pronostic impact of CTOs
Ramundal et al. TCT 2015
Prognostic impact of CTO

12. EURO CTO CLUB
Toulouse 2018 Pronostic impact of CTOs
Ramundal et al. TCT 2015
Prognostic impact of CTO
-Clinical subgroups-
1.34 (1.26-1.42)
1.19 (1.06-1.33)
1.18 (1.05-1.23)
1.49 (1.36-1.62)
1.66 (1.51-1.84)
HR (95%CI)
Interaction
test
p value
<0.001
n
nonCTO
5,336
12,831
36,903
19,137
1975
6,385
3,737
2,090
n
CTO
74,189 14,187

13. EURO CTO CLUB
Toulouse 2018
Success is better than failure !
1 2 3 4 5

14. EURO CTO CLUB
Toulouse 2018
 Improves angina
 Improves physical limitation
 Improves quality of life
 Improves ischemia
 Improves LF function
 Improves rhythm risk
 Decreases the need for CABG
 Improves survival
Success vs Failure

15. EURO CTO CLUB
Toulouse 2018
Forest plot for long-term all-cause mortality with successful vs.
failed CTOPCI.
Christakopoulos G, Christopoulos G, Carlino M, Jeroudi O, Roesle M, Rangan BV, Abdullah S, Grodin J, Kumbhani D, Vo
25 studies
25,486 pts
Christakopoulos et al. Am J Cardiol 2015
Success vs Failure

16. EURO CTO CLUB
Toulouse 2018
Sudakhar et al. JACC 2014:64;235-43
UK Registry, n=13443
Adj. HR 0.72; p<0.001
28%
mortality

17. EURO CTO CLUB
Toulouse 2018 UK Central Cardiac Audit Database
George et al. JACC 2014
14,439 CTO procedures

18. EURO CTO CLUB
Toulouse 2018
Can we improve success?
1 2 3 4 5
and decrease complication rates?

19. EURO CTO CLUB
Toulouse 2018 NCDR CathPCI database (n=22365)
Brilakis et al. JACC Cardiovasc 2015
17% of centres never performed CTO PCI

20. EURO CTO CLUB
Toulouse 2018
Brilakis et al. JACC Cardiovasc 2015
NCDR CathPCI database (n=22365)

21. EURO CTO CLUB
Toulouse 2018
Riley et al. Eurointerv 2018; published online
Periprocedural Complications in open CTO
a public service to our readership, this article -- peer reviewed by the Editors of EuroIntervention - has been pub
on acceptance as it was received. The content of this article is the sole responsibility of the authors, and not th
Epicardial 5 (62.5%)
b. Comparison of 12 Month Mortality between those with and without Comp
during CTO PCI
Months
All-Cause Mortality
Complication No Complication
0 4.1 ± 2.0% 0.0 ± 0.0%
1 11.3 ± 3.2% 0.2 ± 0.2%
6 11.3 ± 3.2% 2.0 ± 0.5%
12 12.4 ± 3.3% 3.1 ± 0.6%
p-value <0.001
Reported as percentages ± standard error

22. EURO CTO CLUB
Toulouse 2018 Role of Proctoring
Sharma et al. Openheart 2015

23. EURO CTO CLUB
Toulouse 2018
Sharma et al. Openheart 2015
Role of Proctoring

24. EURO CTO CLUB
Toulouse 2018
Randomized studies
1 2 3 4 5

25. EURO CTO CLUB
Toulouse 2018
• Prospective, multicenter, randomized trial.
• 1284 Pts
• OMT vs OMT+PCI
• Silent ischemia, stable angina or ACS.
• De novo CTO proximal to mid epicardial coronary
artery with a reference diameter of ≥2.5 mm.
• Primary endpoint: Composite of death, MI,
stroke and revascularization at 3 years.
Decision CTO Trial
SJ Park TCT 2017

26. EURO CTO CLUB
Toulouse 2018 Decision CTO Trial
Study Flow
834 patients randomized
from 2010.3.22 to 2016.10.10
417 allocated to PCI398 allocated to OMT
310 treated with OMT
72 treated with PCI
5 treated with OMT after failed PCI
11 had incomplete data
346 treated with PCI
(success rate: 90.6%)
29 treated with OMT
36 treated with OMT after failed PCI
6 had incomplete data
1-year FU
348/357 (97.5%)
1-year FU
344/354 (97.2%)
3-year FU
215/231 (93.1%)
3-year FU
218/238 (91.6%)
19 withdrew consents
SJ Park TCT 2017
18%
8%

27. EURO CTO CLUB
Toulouse 2018 Decision CTO Trial
SJ Park TCT 2017
Primary End Point
(Death, MI, Stroke, Any Repeat Revascularization)
ITT Population
No. at Risk
OMT 398 305 246 178 129 72
PCI 417 293 241 175 117 65
Y e a rs S in c e R a n d o m iz a tio n
Probability(%)
0 1 2 3 4 5
0
1 0
2 0
3 0
4 0
5 0
6 0
Crude HR 0.95 (95% CI, 0.74-1.22), P=0.67
Adjusted HR 0.91 (95% CI, 0.68-1.23), P=0.54
20.6%
19.6%
25.1%
26.3%
PCI
OMT
Death, MI, Stroke, any revascularization

28. EURO CTO CLUB
Toulouse 2018 Decision CTO Trial
SJ Park TCT 2017
0 1 2 3 4 5
0
1 0
2 0
3 0
4 0
5 0
6 0
Y e a r s s i n c e R a n d o m i z a t i o n
Probability(%)
Death from any cause
ITT Population
No. at Risk
OMT 398 344 285 207 140 81
PCI 417 337 285 202 142 74
Crude HR 1.50 (95% CI, 0.75-3.03), P=0.25
4.4%
3.0%
4.5%
7.9%
PCI
OMT
Any death

29. EURO CTO CLUB
Toulouse 2018 Decision CTO Trial
SJ Park TCT 2017
Intent to treat analysis:
OMT non-inferior to PCI
Per protocol and as treated analysis:
OMT not non-inferior.

30. EURO CTO CLUB
Toulouse 2018 Decision CTO Trial
SJ Park TCT 2017
Quality of Life Measures Over Time
0.0 1.0 6.0 12.0
30
40
50
60
70
80
90
100
6 Mon
303 309
P=0.29P=0.94 P=0.74
Baseline 12 Mon
244 242 231 222
1 Mon
P=0.58
264 277
(A) EQ-5D Visual Analogue Scale
MeanScore
0.0 1.0 6.0 12.0
30
40
50
60
70
80
90
100
305 312
P=0.80P=0.52 P=0.75
243 242 231 221
P=0.05
265 276
(B) SAQ, Physical Limitation
MeanScore
6 MonBaseline 12 Mon1 Mon
6.0 12.0
30
40
50
60
70
80
90
100
304 312
P=0.15P=0.24 P=0.35
244 244 231 222
P=0.17
265 276
(C) SAQ, Angina Stability
MeanScore
6 MonBaseline 12 Mon1 Mon
30
40
50
60
70
80
90
100
304 313
P=0.62P=0.26 P=0.86
244 244 231 222
P=0.001
265 278
(D) SAQ, Angina Frequency
MeanScore
6 MonBaseline 12 Mon1 Mon
30
40
50
60
70
80
90
100
304 313
P=0.96P=0.06 P=0.89
244 244 231 222
P=0.25
265 278
(E) SAQ, Treatment Satisfaction
MeanScore
6 MonBaseline 12 Mon1 Mon
30
40
50
60
70
80
90
100
304 313
P=0.06P=0.28 P=0.90
244 244 231 222
P=0.81
265 278
(F) SAQ, Quality of Life
MeanScore
6 MonBaseline 12 Mon1 Mon
ITT Population

31. EURO CTO CLUB
Toulouse 2018
• Prospective, multi-center randomized trial
• Stable angina with symptoms/ischemia/viability
• OMT vs OMT+PCI
• CTO in a major artery ≥2.5mm
• Other lesions treated before randomization
• Primary efficacy endpoint: health status at 12
months’ follow-up as assessed by the Seattle
Angina Questionnaire (SAQ)
• Primary safety endpoint: 3 years of follow-up.
Euro CTO Trial
Werner et al. Eur Heart J. 2018;39(26):2484-2493

32. EURO CTO CLUB
Toulouse 2018 Euro CTO Trial
• 1200 patients were planned to be enrolled to
achieve a 90 % power for the safety endpoint
at 36 months’ follow-up
• 600 patients were calculated as required for
the primary efficacy endpoint
• The study concluded enrolment with 407 Pts
Werner et al. Eur Heart J. 2018;39(26):2484-2493

33. EURO CTO CLUB
Toulouse 2018 Euro CTO Trial
OMT
(N=137)
PCI
(N=259)
Target vessel
RCA (%) 57.4 63.7
LAD (%) 27.0 25.5
LCX (%) 15.6 10.8
Reference diameter (mm) 3.0 ± 0.41 2.9 ± 0.44
Length of occlusion (mm) 26.5 ± 16.0 31.4 ± 20.5
Lesion calcifications (%) 36.1 37.3
Lesion tortuosity (%) 12.8 21.3
J-CTO score 1.67 ± 0.91 1.82 ± 1.07
Werner et al. Eur Heart J. 2018;39(26):2484-2493

34. EURO CTO CLUB
Toulouse 2018 Euro CTO Trial
OMT
(N=137)
PCI
(N=259)
P-value
Successful revascularization (%) - 86.3 -
Patients with any adverse event (%) 6.7 5.2 0.52
All cause death 0 0.8 0.55
Cardiac death 0 0.8
Myocardial infarction 0 1.9 0.17
Non-Q-wave 0 1.6
Q-wave 0 0.4
Ischemia-driven revascularization 6.7 2.9 0.10
Cerebrovascular event 0.7 0.8 0.99
Stent thrombosis 0 0.4 0.99
Werner et al. Eur Heart J. 2018;39(26):2484-2493

35. EURO CTO CLUB
Toulouse 2018 Euro CTO Trial
Werner et al. Eur Heart J. 2018;39(26):2484-2493
0
10
20
30
40
50
60
70
80
90
100
OMT PCI
Physical
limitation
Anginal
frequency
Anginal
stability
Treatment
satisfaction
Quality of
life
Primary endpoint: SAQ health status
BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU BL FU
P=0.022
P=0.009
P=0.049
P=0.89
P=0.47

36. EURO CTO CLUB
Toulouse 2018
Conclusion
1 2 3 4 5 6

37. EURO CTO CLUB
Toulouse 2018
If the muscle subtended by the CTO is
–Alive (> 50%)
–Ischemic (10-20%)
Then the patient would be better off if
that artery were magically reopened
The HDS aphorism

38. EURO CTO CLUB
Toulouse 2018
 Treat patients with ischemia and viability
 Assess the benefit/risk balance
 Maximize success rate
 Minimize complication rate
 Create strong networks between CTO centers
and non CTO centers everywere in the world
in order to treat more patients
A bright future of CTO PCI

39. EURO CTO CLUB
Toulouse 2018

40. EURO CTO CLUB
Toulouse 2018
To maximize potential benefit
 Treat ischemic CTO lesions
 Assess the risk of the procedure
 Concentrate expertise
 Minimize contrast use and radiation exposure
 Adjust the difficulty to your level of expertise
 Know when to stop and ask an expert