1. Complex Coronary Cases
Supported by:
Abbott Vascular
Boston Scientific Corp
Vascular solution

2. Disclosures
Samin K. Sharma, MBBS, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, AngioScore, DSI/Lilly Inc., ABIOMED, CSI Annapoorna S. Kini, MBBS, FACC Nothing to disclose Sameer Mehta, MBBS, FACC Consulting Fees – The Medicines Company American College of Cardiology Foundation staff involved with this case have nothing to disclose

3. May 20th 2014 Case #59: AM, 62 yr M Presentation:
Patient presented on April 15th 2014 with cresendo angina CCS class III and stress MPI + for moderate anterior and mild lateral ischemia with LVEF 55%. A cardiac cath revealed 2 V CAD; multiple lesions of prox LAD/Diagonal bifurcation with TO of mid LAD filling distally via bridge collaterals and 80% lesion in OM3 and LVEF 55%. Pt underwent Promus Premier DES of OM3 without any complications. Pt was maximized on medical therapy but still has CCS class II angina.
Prior History:
Hypertension, Hyperlipidemia, + F/H, Paroxysmal AFib
Medications: All once daily dosage
Metoprolol XL 50mg, ISMN 60mg, Zestril 10mg, Clopidogrel 75mg, ASA 81mg, Atorvastatin 40mg, Warfarin 3

4. Case# 59: cont… Cardiac Cath 4/15/2014: Right Dominance
SYNTAX Score: 29
Cardiac Cath 4/15/2014: Right Dominance
2 V CAD with LVEF 55%
RCA: Severe diffuse disease, modertae size
LM: No obstruction
LAD: 80% prox LAD with 80% D1 bifurcation and 100% mid LAD with distal vessel fills via bridge collaterals and retrograde collaterals
LCx: 80% OM3 lesion moderate size and other vessels mild diffuse disease
Plan Today:
PCI of LAD/Diagonal bifurcation and mid LAD CTO 4

5. Appropriateness Criteria for Coronary Revascularization

6. Issues Involving The Case
EXPERT CTO Trial
Update in LM Revascularization

7. Issues Involving The Case
EXPERT CTO Trial
Update in LM Revascularization

8. Long-Term Outcome of PCI for CTO: Multicenter Registry
100
Overall success rate 68% 80
Success Rate (%) 60 40
# of cases
Success rate (%)
Annual Success Rates of CTO PCI in the Multinational CTO Registry
Mehran et al. JACC Interv 2011;4:952.

9. Temporal Trends in Cumulative Angiographic Success Rates and Major Procedural Complication Rates
80%
0.5%
Patel et al., JACC Cardiovasc Interv 2013;6:128 9

10. EXPERT CTO Trial Design
Prospective, multi-center, single-arm study
3 different study devices with three individual primary endpoints in CTO revascularization:
250 patients enrolled at 20 sites in the United States
Guide Wire
HT Pilot and HT Progress
Initial 138 pts
Angioplasty Balloon
Mini TREK
Initial 88 pts with successful guide wire crossing
Stent
Xience Prime and Xience V EES
250 pts

11. EXPERT CTO Trial: Study Population
Enrolled
N=250
28 Excluded from ITT in whom recanalization and pre-dilatation of the target lesion were not completed and/or study stent was not inserted into the coronary guiding catheter.
ITT
N=222 (89%)
6 Early Terminations
1 Withdrew consent
1 Death
4 Lost-to-follow-up
ITT at 1 Month
N=216
4 Early Terminations
2 Deaths
2 Lost-to-follow-up
ITT at 6 Months
N=212
3 Early Terminations
1 Death
2 Withdrew consent
ITT at 1 Year
N=209
Kini et al.; ACC i2 2014
Note: One year clinical follow-up rate was 97.3% (216/222)

12. EXPERT CTO Trial: Enrollment Criteria
Key Inclusion Criteria
– Symptomatic ischemic heart disease with clinical indication for CTO revascularization
– Maximum of one de novo native coronary artery lesion with TIMI 0/1 flow and estimated at least 3 months’ duration
– Suitability for placement of coronary stents in occluded segment” No severe tortuosity (angulation ≥ 45º) or location in excessively distal location
Key Exclusion Criteria
– Evidence of acute MI within 72 hours of the intended treatment
– Treatment with a device after successful crossing other than PTCA prior to stent placement (eg, directional or rotational coronary atherectomy, excimer laser, thrombectomy)
No restrictions regarding lesion length or treatment strategy (antegrade, retrograde, hybrid)

13. EXPERT CTO Trial Guide Wire Primary Endpoint: Angiographic Confirmation of Guide Wire in Distal True Lumen and Absence of In-Hospital MACE
Guide Wire Cohort
(%) [95%CI], N=138
Lower Bound (%)
Performance Goal (%)
P value
1o Analysis (ARC MI)
79.0
[71.2, 85.5]
72.8
62.5
<0.0001
Guide wire in distal lumen
89.9
[83.6, 94.3]
Absence of in-hospital MACE (ARC MI definition)
89.1
[82.7, 93.8]
2o Analysis (protocol MI)
87.7
[81.0, 92.7]
82.3
Absence of in-hospital MACE
97.8
[93.8, 99.5]
Kandazari et al.; SCAI 2013

14. Total Analysis Population
EXPERT CTO Trial Balloon Primary Endpoint: Successful Delivery, Performance and Absence of Angiographic and Clinical Complications
Evaluable Population
N=65
Total Analysis Population
N=88
Study Balloon Success (MINI-TREK)
(%) [95% CI]
93.8
[85.0, 98.3]
93.2
[85.7, 97.5]
Successful delivery to and across lesion
96.9
[89.3, 99.6]
96.6
[90.4, 99.3]
Successful inflation and deflation
100.0
[94.3, 100.0]
[95.8, 100.0]
Absence of clinically significant vessel perforation, flow-limiting dissection, reduction in TIMI flow, or clinically significant arrhythmias following pre-dilatation
97.7
[92.0, 99.7]
Achievement of final TIMI 3 flow at conclusion of procedure
[94.5, 100.0]
98.9
[93.8, 100.0]
Kandazari et al.; SCAI 2013

15. EXPERT CTO Trial: Baseline Clinical Characteristics
Age (years ± SD)
61.7 ± 10.4
Male (%)
81.1
Hypertension (%)
91.9
Dyslipidemia (%)
96.8
Diabetes (%)
40.1
Oral meds (% diabetics)
68.5
Insulin (% diabetics)
30.3
Current Tobacco Use (%)
26.0
Prior MI (%)
29.0
Previous PCI (%)
43.4
Prior CABG (%)
9.9
Number of Diseased Vessels (%)
One
76.6
Two
17.1
Three
6.3

16. EXPERT CTO Trial: Baseline Target Lesion Characteristics
Vessel Location (%)
LAD
LCX
RCA
LMCA
31.1
15.8
53.2
TIMI 0 (%)
95.9
% Stenosis (Mean ± SD)
99.7 ± 2.1
RVD (mm) (Mean ± SD)
2.7 ± 0.4
MLD (mm) (Mean ± SD)
0.01 ± 0.05
Lesion Length (mm) (Mean ± SD)
36.1 ± 18.5
Occlusion Length (mm) (Mean ± SD)
14.0 ± 10.6
Calcification (%)
None/Mild
Moderate to severe
50.9
48.8
Collaterals (%)
Ipsilateral
Contralateral
Bridging
92.8
92.6
86.5

17. EXPERT CTO Trial: Procedural Characteristics
N=222
Non-Target Lesions Treated (N) (Mean ± SD)
0.3 ± 0.05
Number of stents/lesion (Mean ± SD)
1.95 ± 0.98
Stent Length (mm) (Mean ± SD)
51.72 ± 27.16
Final TIMI 3 Flow (%)
97.7
Clinically Significant Perforation (%)
Procedure Time (minutes) (Mean ± SD)
79.9 ± 48.5
Contrast Volume (mL) (Mean ± SD)
259.0 ± 136.7
Fluoroscopy Duration (minutes) (Mean ± SD)
33.6 ± 23.3
Kini et al.; ACC i2 2014

18. EXPERT CTO Trial: Procedural Success and Outcomes According to Guide Wire Strategy
Per ARC MI
Per Protocol MI
Overall Procedure Success (%)
89.6% (198/221)
96.4% (213/221)
Success by Guide Wire Crossing Method (%)
Antegrade Only
90.1 (173/192)
97.9 (188/192)
Antegrade crossing
90.3 (168/186)
97.8 (182/186)
STAR
85.7 (6/7)
100.0 (7/7)
Knuckle wire
100.0 (1/1)
Bridgepoint/StingRay
78.3 (18/23)
96.7 (22/23)
Retrograde Only
91.7 (11/12)
Retrograde crossing
Combined Antegrade and Retrograde
81.8 (9/11)
CART
Reverse CART
77.8 (7/9)
Kissing wire technique
Multiple crossing techniques
80.0 (4/5)
Kini et al.; ACC i2 2014

19. EXPERT CTO Trial: MI According to
CK-MB Elevation (N=220) %
Kini et al.; ACC i2 2014

20. EXPERT CTO Trial: 1 Year Clinical Outcome%
Kini et al.; ACC i2 2014

21. EXPERT CTO Trial: Conclusions
As a rigorously conducted, multicenter registration trial representing contemporary CTO PCI, the EXPERT CTO clinical trial successfully met all 3 of its device primary endpoints:
Procedural success of 90%+ achieved with guide wires among highest reported and with favorable safety
Effectiveness of low-profile angioplasty catheters demonstrated by deliverability, lesion crossing, achievement of luminal gain, low rate of complications, and high rate of procedural success
Primary endpoint demonstrates excellent safety and efficacy of Xience EES in this very complex lesion subset of CTO
Xience EES was associated with a definite ST rate of 1% and a TLR rate of 6.3%
Overall MACE was largely driven by periprocedural MI that did not translate to other adverse events at 1 year
Kini et al.; ACC i2 2014

22. Issues Involving The Case
EXPERT CTO Trial
Update in LM Revascularization

23. LMCA Stenosis Location
LCX
About two third of LMCA
Lesions include distal bifurcation; 1/3rd are ostial/shaft lesions
66%
Bifurcation
LMCA
26%
Ostium 8%
Body-Shaft
LAD

24. Mohr et al., Lancet 2013;381:629

25. SYNTAX Trial: Patient Distribution at 5 Years FU
1800 patients enrolled
897 randomly assigned to CABG
903 randomly assigned to PCI
40 withdrew consent
8 lost to follow-up
7 withdrew consent
5 lost to follow-up
849 remained in the study at 1 year
891 remained in the study at 1 year
10 withdrew consent
33 lost to follow-up/other
1 early follow-up
4 withdrew consent
16 lost to follow-up/other
0 early follow-up
805 remained in the study at 5 years
871 remained in the study at 5 years
897 analyzed
903 analyzed
Mohr et al., Lancet 2013;381:629

26. SYNTAX Trial: MACCE Rates in Patients
with LM Disease vs. 3 V Disease at 5-Yr FU
Left Main Disease
3-Vessel Disease
Baseline SYNTAX Score 0-22
Baseline SYNTAX Score 0-22
Baseline SYNTAX Score 23-32
Baseline SYNTAX Score 23-32
Mohr et al., Lancet 2013;381:629

27. SYNTAX Trial: MACCE Rates in Patients
with LM Disease vs. 3 V Disease at 5-Yr FU
Left Main Disease
3-Vessel Disease
Baseline SYNTAX Score ≥33
Baseline SYNTAX Score ≥33
Mohr et al., Lancet 2013;381:629

29. DELTA Registry: Cumulative Incidence of MACCE
at Follow-up of 5 Yrs
PCI Overall (n=1874)
CABG Overall (n=900) %
Chieffo et al., J Am Coll Cardiol Intev 2012;5:718

31. DELTA Registry: Study Population Flow Chart
Naganuma et al., J Am Coll Cardiol Intev 2014;7:354

32. DELTA Registry: Cumulative Incidence of
In-Hospital MACCE
PCI group (n=482)
CABG group (n=374) %
Naganuma et al., J Am Coll Cardiol Intev 2014;7:354

33. DELTA Registry: Cumulative Incidence of
Follow-Up MACCE at 5 Yrs
PCI group (n=482)
P= 0.06
CABG group (n=374) %
P= 0.009
Naganuma et al., J Am Coll Cardiol Intev 2014;7:354

34. Freedom from All-cause death
DELTA Registry: Death and MACCE event Free in PCI Group vs. CABG Group for ULMCA in Propensity Score-Matched Groups
Freedom from All-cause death
Freedom from MACCE
Naganuma et al., J Am Coll Cardiol Intev 2014;7:354

35. FINE Registry: MACE at 2-Year Clinical Follow-Up; First-Generation vs
FINE Registry: MACE at 2-Year Clinical Follow-Up; First-Generation vs. New-Generation DES
First-Generation DES (n=93)
p=0.07
New-Generation DES (n=93)
p=0.04 %
p=0.08
p=0.46
p=1.04
Buchanan et al., EuroIntervention 2013;9:809

37. ISAR LEFT-MAIN 2 Study: 30 Days Clinical Outcomes
p=>0.99
ZES (n=324)
EES (n=326)
p=0.74 %
p=0.47
p=>0.99
p=>0.99
Mehilli et al., JACC 2013;62:2075

38. ISAR-LEFT-MAIN 2 Study: ZES vs
ISAR-LEFT-MAIN 2 Study: ZES vs. EES for Unprotected LM CAD at 1 Year Clinical Outcomes
ST (Def/Prob)
0.9%
0.6%
ZES (n=324)
p=0.24
EES (n=326)
p=0.25 %
p=0.35
p=0.98
p=0.16
N=237
N=226
Death MI TLR Death, MI Angiographic
or TLR restenosis
Mehilli et al., JACC 2013;62:2075

39. Method of Revascularization of Multi-vessel and LM Coronary Artery disease
CABG
PCI
Two-vessel CAD with proximal LAD stenosis A
Three Vessel CAD with low CAD burden (i.e., three
focal stenosis, low SYNTAX score)
Three-vessel CAD with intermediate to high CAD burden (i.e., multiple diffuse lesions, presence of CTO, or high SYNTAX score >32)/DM
U/I
Isolated left main stenosis U
Left main stenosis and additional CAD with low CAD burden (i.e., one to two vessel additional involvement, low SYNTAX score <33)
Left main stenosis and additional CAD with intermediate to high
CAD burden (i.e., three vessel involvement, presence of CTO, or high SYNTAX score >32) I 39

41. Method of Revascularization of Multi-vessel and LM Coronary Artery disease
CABG
PCI
Two-vessel CAD with proximal LAD stenosis A
Three Vessel CAD with low CAD burden (i.e., three
focal stenosis, low SYNTAX score)
Three-vessel CAD with intermediate to high CAD burden (i.e., multiple diffuse lesions, presence of CTO, or high SYNTAX score >32)/DM
U/I
Isolated left main stenosis/ Ostial & shaft lesion
U/A
Left main stenosis and additional CAD with low CAD burden (i.e., one to two vessel additional involvement, low SYNTAX score <33) U
Left main stenosis and additional CAD with intermediate to high
CAD burden (i.e., three vessel involvement, presence of CTO, or high SYNTAX score >32) I 41

42. LM disease (±1, 2 or 3 vessel disease) and SYNTAX score of ≤32
EXCEL Trial (Evaluation of Xience Prime vs. CABG
for Examination of LM Disease)
LM disease (±1, 2 or 3 vessel disease)
and SYNTAX score of ≤32
Randomize 2600 pts
Trial finished enrollment
after 1800 cases
ABBOTT Vascular XIENCE Prime stent
CABG
The primary endpoint is the composite incidence of death, large MI or stroke at a median FU duration of 3 years, powered for sequential non-inferiority and superiority testing.
The major secondary endpoint is the composite incidence of death, MI, stroke or unplanned repeat revascularization. All patients will be followed for 5 years total.

43. Take Home Message: EXPERT CTO Trial and Status of ULM PCI
Contemporary trial of CTO recanalization has shown to have success rate over 90% with very low complication rates and 1 year MACE rates of <10% using Xience EES including 1% ST and 6% TVR rates
Recent trials of ULM PCI involving ostial or shaft lesions have shown long-term outcomes similar to the CABG cohort. Hence PCI is a viable option in ostial/shaft ULM lesions with non-extensive concomitant other vessel disease.

44. Question # 1
Following are the false statements regarding Expert CTO trial:
DES is superior to BMS
Crossing with Minitrek balloon was achieved in >95% cases
Successful guide wire crossing occurred in 90% of cases
One year MACE rate was 20%
A and D

45. Question # 2
Following are the false conclusions of 5 year F/U of SYNTAX trial:
SYNTAX score predicted MACCE in LM cohort in each tertile
MACCE outcomes were similar in LM vs. 3 V CAD cohort
LM cohort had higher death rate
Incidence of CVA was similar in PCI vs. CABG group
All of the above

46. Question # 3
In the DELTA registry, Ostial/shaft ULM lesions have similar outcomes to CABG except:
A. Death rate
B. TVR
C. MACE
D. MACCE
E. MI

47. Question # 1
Following are the false statements regarding Expert CTO trial:
DES is superior to BMS
Crossing with Minitreck balloon was achieved in >95% cases
Successful guide wire crossing occurred in 90% of cases
One year MACE rate was 20%
A and D
The correct answer is E as EXPERT CTO used Xience DES only and MACE rate was 10% at one year.
Kini et al, ACCi2 Summit 2014

48. The correct answer is E as all are the false statements
Question # 2
Following are the false conclusions of 5 year F/U of SYNTAX trial:
SYNTAX score predicted MACCE in LM cohort in each tertile
MACCE outcomes were similar in LM vs. 3 V CAD cohort
LM cohort had higher death rate
Incidence of CVA was similar in PCI vs. CABG group
All of the above
The correct answer is E as all are the false statements
Mohr et al., Lancet 2013;381:629

49. The correct answer is B as all others were equal between 2 groups
Question # 3
In the DELTA registry, Ostial/shaft ULM lesions have similar outcomes to CABG except:
A. Death rate
B. TVR
C. MACE
D. CVA
E. MI
The correct answer is B as all others were equal between 2 groups
Naganuma et al., J Am Coll Cardiol Intev 2014;7:354

50. Question # 1
Following are the true statements regarding IMA PCI except:
2nd generation DES is superior to BMS in lowering TLR
PTCA of IMA anastomosis is associated with higher MACE
DES use has shown to improve survival
IMA PCI is associated with higher complications then native V
IMA PCI is technically challenging
The correct answer is B as PTCA of IMA anastomosis have shown to have lower MACE rates compared to stent
Gruberg et al., JACC 2000;35:944

51. Question # 2
Following are the recent randomized trials of Bivalirudin except :
HEAT PPCI
NAPLES III
BRAVE 4
REPLACE 2
BRIGHT
The correct answer is D as all other 4 trials are recent and REPLACE trial was done in 2002
ACC i2Summit 2014

52. Question # 3
Recent RCT of Bivalirudin vs. UFH have shown the following:
A. Lower bleeding rates
B. Lower MACE rates
C. Higher Stent Thrombosis in some trials
D. Higher TLR rates
E. Lower MI rates
The correct answer is C as HEAT PPCI trial has shown higher ST rate in the Bivalirudin arm
ACC i2 summit 2014