1. Contemporary Outcomes with Chronic Total Occlusion Revascularization
David E. Kandzari, MD, FACC, FSCAI
Chief Scientific Officer
Director, Interventional Cardiology
Piedmont Heart Institute
Atlanta, Georgia

2. Disclosure
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below
Affiliation/Financial Relationship Company
Grant/Research Support Abbott Vascular, Boston Scientific, Medtronic CardioVascular, Biotronik, St. Jude Medical/Thoratec
Consulting Fees/Honoraria Boston Scientific Corporation, Medtronic CardioVascular, Micell, St. Jude Medical
Major Stock Shareholder/Equity None
Royalty Income None
Ownership/Founder None
Intellectual Property Rights None
Other Financial Benefit None

3. CTO Revascularization: Clinical Outcomes
What is the procedural success and safety following CTO PCI with contemporary CTO PCI?
What are the clinical and health status outcomes following CTO PCI with contemporary technique and advanced generation DES?
Are the clinical outcomes following CTO PCI similar to non- CTO PCI?
In what clinical settings might CTO PCI influence the risk of major adverse events?

4. 0.9% pericardiocentesis, 0.2% stroke
Appleton Cardiology, WI
Baylor Heart and Vascular Hospital, TX
Columbia University, NY
Central Arkansas VAMC, AR
Dallas VAMC/UTSW, TX
Henry Ford Hospital, MI
Massachusetts General Hospital, MA
Medical Center of the Rockies, CO
Minneapolis VAMC, MN
PeaceHealth St. Joseph MC, WA
Piedmont Heart Institute, GA
San Diego VAMC and UCSD, CA
St Luke’s Mid America Heart Institute, MO
Torrance Medical Center, CA
UPMC Medical Center, PA
1/2012 to 9/2016
15 centers, 1,974 lesions
Technical success: 88%
Major complications: 2.6%
0.6% mortality, 0.9% MI
0.9% pericardiocentesis, 0.2% stroke
0.1% CABG, 0.3% re-PCI
Successful technique

5. Temporal Trends in CTO PCI Success
Michael, Karmpaliotis, Brilakis, Kandzari et al. CCI 2015

6. Temporal Trends in Contrast/Fluoroscopy Utilization
Michael, Karmpaliotis, Brilakis, Kandzari et al. CCI 2015

7. Outcomes Following CTO PCI Evidence of Quality of Life Benefit
No CTO
n=1833
Baseline Health Status
     SAQ Physical Limitation Score
72.1 ± 26.9
77.9 ± 23.4
0.016
     SAQ Angina Frequency Score
70.1 ± 28.1
72.9 ± 23.6
0.212
     SAQ Quality of Life Score
54.3 ± 25.5
56.0 ± 25.4
0.487
     Rose Dyspnea Score
1.9 ± 1.5
1.7 ± 1.5
0.209
6-Month Health Status
96.2 ± 12.8
95.7 ± 12.9
0.742
91.0 ± 19.0
93.2 ± 15.1
0.126
80.6 ± 21.4
80.5 ± 19.9
0.951
1.0 ± 1.4
0.9 ± 1.3
0.497
Safley D, Grantham JA, Jones P, and Spertus JA , ACC 2012

8. PERSPECTIVE Trial 500 CTO Patients
Percutaneous Revascularization at Piedmont for Chronic Total Occlusions Survey
500 CTO Patients
Primary Endpoints:
CTO Procedural Success (<50% residual stenosis and > TIMI 2 Flow)
1 Year Death/MI/TLR (MACE)
Secondary Endpoints:
Change in angina frequency and quality of life (SAQ, EQ5D) from baseline to 1 year
Adherence to and classification of AUC
Pre/post PCI SYNTAX score for assessment of completeness of revascularization
Procedural resource utilization and medication adherence
Clinicaltrials.gov Identifier NCT

9. CTO Percutaneous Revascularization Need for Randomized Trial
Is mortality appropriate as singular endpoint?
Failed CTO PCI part of ITT or OMT?
Management of
Variable operator experience
Selection bias
Treatment bias
Crossover to revascularization

10. CTO Percutaneous Revascularization Need for (Feasibility of) Randomized Trials?

11. CTO Percutaneous Revascularization Need for (Feasibility of) Randomized Trials?

12. Successful vs Failed CTO Revascularization ‘Open Artery Hypothesis’
Study
Year N
Follow-Up Yrs
Mortality Difference (%)
P Value
Suero
2001
2,007 10
27 vs 35
0.001
Hoye
2003
854 5
6.5 vs 12.0
0.02
Buller
1,458 1
10.0 vs 19.0
Olivari
376
1.1 vs 7.2
0.005
Aziz
2007
543
1.7
2.5 vs 7.3
0.004
Prasad
2008
1,267
22 vs 28
0.025
Valenti
486 2
8.4 vs 12.6
Thompson
487 7
13 vs 26
0.09
DeLabroille
172
4.9 vs 5.3
0.30
Mehran
2011
1,791
2.9
6.0 vs 8.6
0.01
Jones
2012
836
4.5 vs 17.2
<0.0001
George
2014
13,443
2.7
7.0 vs 10.0
Jaguszewski
2015
1,110 3
2.2 vs 4.2
0.056
Ramunddal
2016
6,442 6
15% ARR
0.034
Lee
1,173
4.6
8.0 vs 7.1
0.83
N=32,445
Absolute Risk Difference +0.9% to -15.0%

13. Repeat Revascularization Relative to Successful CTO PCI
CABG 100%
22.1%
11.5%
CABG 3%
Jones et al. JACC Intv 2012

14. Successful CTO PCI 802/1,035 (77%) 66% 1st Generation DES
Clinical and Angiographic Outcomes Following CTO PCI Florence CTO PCI Registry, 2003 to 2010
1 Year Events
N=802
Successful CTO PCI 802/1,035 (77%)
66% 1st Generation DES
Mean stent length 52 mm
82% Angiographic Follow-up
Retrograde 3.1% (25/802)
1st Generation PES and SES (N=508)
TLR
14.1
Reocclusion
10.1
Everolimus Eluting Stents (N=294)
10.5
3.0
STAR (N=34)
32.3
57.0
RE SciComm SYNTAX Stat requests_15SEP08_v2.xls.doc
Data Expressed As Percent

15. EXPERT CTO XIENCE EES 1 Year Clinical Outcomes
Hierarchical Composite (%)
MACE
ARC MI definition
18.5
Protocol MI definition
10.0
TLF
15.8
9.1
TVF
16.7
Non-Hierarchical Components (%)
Death
1.9
Myocardial Infarction
ARC definition
13.9
Protocol definition
3.4
Clinically-Driven TLR
6.3
TLR - CABG
0.5
TLR - PCI
5.8
RE SciComm SYNTAX Stat requests_15SEP08_v2.xls.doc
Kandzari et al. JACC Intv 2015

16. EXPERT CTO Myocardial Infarction According to CK MB Elevation
5.4%
12/220
3.6%
8/220
1.8%
4/220
RE SciComm SYNTAX Stat requests_15SEP08_v2.xls.doc
Kandzari et al. JACC Intv 2015

17. Prognostic Significance of Periprocedural MI in CTO PCI
RE SciComm SYNTAX Stat requests_15SEP08_v2.xls.doc
Predictors of PPMI:
Renal Failure OR 4.25, 95% CI , P=0.004
Retrograde OR 2.27, 95% CI , P=0.002
Non CTO target lesion PCI OR 1.74, 95% CI , P=0.006
Stent Number OR 1.38, 95% CI , P=0.011
Lee et al. JACC Intv 2016

18. DES in CTO Revascularization
Era
Trials
Comparison
Reocclusion
%, RR
Restenosis,
Repeat Revascularization,%, RR
GISSOC, TOSCA, STOP, SPACTO, SICCO
PTCA vs BMS, Randomized
22 vs 9, 59%
67 vs 37, 45%
35 vs 19, 46%
ACROSS, ASIAN, RESEARCH, etc.
DES, Observational 2 8
2006
PRISON II, GISSOC II
BMS vs DES, Randomized
15 vs 2, 87%
52 vs 9, 83%
33 vs 7, 79%
ASIAN, RESEARCH, etc.
PES vs SES, Observational ─
18 vs 7, 61%
6 vs 4, 33%
2010
Metanalyses
BMS vs DES
10 vs 5, 50%
37 vs 10, 73%
30 vs 5, 83%
2011--
PRISON III, CIBELES
SES vs ZES/EES, Randomized
3.2 SES vs 1 EES
10.5 SES vs 9.1 EES
11.6 SES vs 7.9 EES
EXPERT CTO, ACE CTO, Florence Registry,
PRISON IV
EES, BP-SES
Observational and Randomized
2.2 BP-SES vs 1.4 EES
Florence 3.0%
PRISON IV:
BP-SES 8.0%, EES 2.1%
Florence 10.5% (MACE)
EXPERT CTO 6.3% (TLR)
PRISON IV 10.5% BP-SES, 4.0% EES

19. Survival According to CTO PCI Success Comparisons with Non-CTO PCI and PCI Failure
5 Year Survival
sCTO PCI 4.5% vs non-CTO PCI 6.7%, P=0.10
17.2%
6.7%
4.5%
Jones et al. JACC Intv 2012

20. CTO PCI Outcome Comparisons with Non-CTO PCI 2 Year Outcomes with R-ZES
P Value
Total Stent Length (mm)
48.7 ± 30.1
30.1 ± 19.8
<0.001
TLF
9.1
10.4
0.55
Cardiac Death
2.8
2.7
0.84
TVMI
4.2
0.40
TLR
4.8
5.2
0.88
Def/prob ST
1.2
1.1
0.76
Kelbaek et al. Eurointervention 2014

21. An Interventional Risk Treatment Paradox Negative Impact of CTO Treatment on Clinical Outcomes in SYNTAX Trial
CTO Prevalence
PCI 26.3%, CABG 36.4%
CTO Location
68.1% in proximal/mid vasculature
PCI success rate 49.4%
Presence of CTO strongest independent predictor of incomplete revascularization (HR 2.70)
4-Year MACCE
Farooq et al. J Am Coll Cardiol 2013

22. Survival According to Completeness of Revascularization in CTO Patients
George et al. JACC 2014

23. Impact of CTO in Patients with ACS and LV Dysfunction
Author
Study
Population/ N (%) CTO
Study Duration
HR (95% CI) for Mortality
P Value
Claessen JACC Intv 2009
Single Center
3,277 STEMI/ 420 (13%)
5 years
1.9 ( )
<0.001
Lexis
CCI 2011
TAPAS
1,071 STEMI/ 90 (8%)
2.1 years
2.41* ( )
0.008
Claessen
EHJ 2012
HORIZONS-AMI
3,602 STEMI/ 297 (8%)
3 years
1.97 ( )
<0.01
Ramunddal
CRT 2012
SCAAR
17,730 NSTEMI/
1,621 (9%)
6 years
1.69 ( )
Tajstra
JACC Intv 2016
COMMIT HF
675 LVEF <35/ 278 (41%
1 year
1.84 RR ( )
0.006
*Cardiovascular mortality

24. Impact of CTO in Patient Survival
Hazard of CTO highest in:
Younger patients (<70 yrs)
STEMI

25. Impact of CTO in Patients with ACS EXPLORE Trial
300 STEMI Pts with Non-Infarct Related Artery CTO
RANDOMIZE
CTO PCI within 7 days of STEMI
Optimal Medical Therapy
Primary Endpoints: 1. LVEF by MRI
2. LVEDV by MRI
Clinical Outcomes at 1 Through 5 Years
van der Schaaf et al. Trials 2010;

26. Impact of CTO in Patients with ACS EXPLORE Trial
CTO Success 72% (predicted 80%)
No difference in clinical outcome at 4 months
CTO-PCI (n=136)
No CTO-PCI (n=144)
Difference (95%CI) p
LVEF (%)
44∙1
(12∙2)
44∙8
(11∙9)
-0∙8
(-3∙6 to 2∙1)
0∙597
Henriques et al. TCT 2015; JACC 2016

27. Clinical Outcomes Following CTO PCI Summary
In absence of randomized trial data, successful CTO PCI is consistently associated with survival advantage compared with failed CTO PCI
Mechanism translating benefit: completeness of revascularization, target vessel identity, improvement in LV function, reduction in arrhythmic potential
Trial design and conduct remains a limitation
CTO PCI is associated with durable reductions in repeat (surgical) revascularization
CTO treatment results in at least similar improvement in health status and quality of life as non-CTO PCI
With contemporary DES, the ‘gap’ in clinical outcome between CTO and non- CTO PCI has been bridged
Despite greater lesion complexity, similar rates of TLR, ST, MACE compared with non- CTO PCI
Benefit of CTO PCI may be especially relevant in selected pts with high ischemic burden, MVD, recent ACS