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2. Complex Coronary Cases
Supported by:
Abbott Vascular Inc
Boston Scientific Corp
Terumo Vascular Corp
Cardiovascular Science Inc
Abiomed Inc
Vascular Solution Corp
B-Braun Inc

3. Disclosures
Samin K. Sharma, MD, FSCAI, FACC Speaker’s Bureau – Boston Scientific Co Abbott Vascular Inc, ABIOMED, CSI Annapoorna S. Kini, MD, MRCP, FACC Nothing to disclose Sameer Mehta, MD, FACC Consulting Fees – Medtronic Inc

4. Nov 21st 2017 Case #101: KB 64 yrs M Presentation:
Presented with new onset CCS class II angina and a positive stress MPI for anterior, apical and septal ischemia. A cardiac cath on Nov 7th, 2017 revealed 2 V CAD: prox LAD CTO bifurcation (medina 1,1,1) with 80% D1 bifurcation, 70% LCx-OM2, Syntax score 30 and LVEF 60%. Pt underwent FFR of LCx-OM2 which was 0.91 (-). Pt was maximized on medical therapy with plan for LAD CTO PCI at a future date
Prior History: No CAD risk factors, SAQ-7 score 89
Medications: All once daily dosage started after cath
ASA 81mg, Clopidogrel 75mg, Metoprolol XL 50mg, Amlodipine 5mg, Atorvastatin 40mg 4

5. Case# 101: cont… Plan Today:
Cardiac Cath 11/7/2017: Right Dominance
II V CAD and LVEF 60%
LM: No obstruction
LAD: 100% occlusion proximally after a 80% bifurcating moderate size D1 (1,1,1)
LCx: 70% lesion in OM2 (FFR negative)
RCA: mild diffuse disease
SYNTAX Score: 30
Plan Today:
Planned for PCI of LAD CTO-D1 bifurcation with
dedicated 2-stent strategy by mini-crush technique 5

6. AUC 2017:Anatomic Two-Vessel Disease
Patel et al., J Am Coll Cardiol 2017;69:2212

7. AUC 2017: Physiologic One-Vessel Disease
Patel et al., J Am Coll Cardiol March 2017 Article in Press

8. BIFURCAID
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Google Play Store

9. Issues Involving The Case
Top Three Trials from TCT 2017:
DKCRUSH-V, ABSORB III-3Yr, CrossBoss First
ORBITA Trial- Sham Controlled Trial of PCI in
Stable Single Vessel CAD

10. Issues Involving The Case
Top Three Trials from TCT 2017:
DKCRUSH-V, ABSORB III-3Yr, CrossBoss First
ORBITA Trial- Sham Controlled Trial of PCI in
Stable Single Vessel CAD

12. 484 patients with unprotected LM bifurcations
DKCRUSH V Study Design
484 patients with unprotected LM bifurcations
Medina 1, 1, 1 and Medina 0, 1, 1 R
DK crush stenting
Provisional stenting
Clinical follow-up: 1, 6, 12 months
Angiographic follow-up: 13 months
Primary Endpoint: TLF at 12 months
Chen SL, TCT 2017

13. DKCRUSH V Trial: SYNTAX Score NERS II Score Provisional DK Crush
Chen SL, TCT 2017

14. DKCRUSH V Trial: Core Lab Data
(n=240)
Provisional
(n=242)
2- or 3-vessel disease
87.9
88.8
LM lesion
- Ostial
2.9
- Shaft/body
7.9
8.7
- Medina 1, 1, 1
85.0
78.5
- Medina 0, 1, 1
15.0
21.5
Calcification
37.1
39.7
Chronic total occlusion
12.1
12.4
TIMI flow grade <3
- Main vessel
20.4
19.8
- Side branch
7.0
Complex bifurcation lesion
35.8
27.3
IVUS assessment
28.3
28.9
Chen SL, TCT 2017

15. DKCRUSH V Trial: PCI Procedures
482 Patients, 637 Procedures, 1234 Stents in MV and SB
DK Crush (n=240)
Provisional (n=242)
Planned staged procedure
13.8
16.9
Transradial approach
77.9
74.8
6F guiding catheter
54.2
53.3
Side branch dilation*
68.3
39.7
MV stent length
27.9 ± 9.9 mm
28.8 ± 10.4 mm
SB stent length
21.0 ± 7.3 mm
21.4 ± 7.4 mm
Final kissing inflation*
99.6
78.9
POT
99.2
98.9
IVUS guidance
42.9
40.5
Complete revascularization
72.5
69.4
Procedural time, min*
81.9 ± 37.6
66.1 ± 34.5
Contrast volume, ml**
226.7 ± 81.4
190.9 ± 74.8
Angiographic success
98.3
97.1
* p<0.05, ** p<0.001
Chen SL, TCT 2017

16. DKCRUSH V Trial: Primary Endpoint
Target Lesion Failure
Chen SL, TCT 2017

17. DKCRUSH V Trial: Primary Endpoints at 1-Year
DK Crush (n=240)
Provisional (n=242)
p=0.06
p=0.02 %
p=0.03
p=0.48
Chen SL, TCT 2017

18. DKCRUSH V Trial: Stenting for LM Bifurcations
Chen et al., J Am Coll Cardiol 2017;70:2605

19. DKCRUSH V Trial: Quantitative Coronary Analysis
317 Patients Underwent 13-Month Angiographic Follow-Up
DK Crush (n=159)
Provisional (n=158)
P Value
SB lesion length ≥10 mm
50.0
42.9
0.14
SB diameter stenosis, %
65.8 ± 7.9
65.3 ± 8.3
0.87
MV lesion length, mm
22.4 ± 12.9
23.5 ± 12.8
0.36
MV diameter stenosis, %
60.8 ± 7.2
61.8 ± 8.1
0.51
Cross-over to 2 stents -
47.1
LM complex restenosis
7.1
14.6
0.10
- Main vessel
1.9
5.7
0.09
- Side branch*
5.0
12.0
Non-LM restenosis
7.6
0.41
*Restenosis within implanted stents was defined as a QCA DS >50% at FU.
Chen SL, TCT 2017

21. ABSORB II: 4-Year Patient Flowchart
311* and 154**
patients still in
the study but 5
missed 3 yr FUP
Baseline
1-year
2-year
3-year
4-year
1 death
2 withdrawal
7 withdrawal
4 death
3 withdrawal
1 LFU
3 withdrawal
4 death
3 withdrawal
2 LFU, 3 MV,
5 death, 1 LFU
2 MV
1 death,
2 MV, 1 withdrawal
11 no consent ,-2 still in study but missed 3yr FUP
2 death,
8 MV, 3 withdrawal
9 no consent, -3 still in study but missed 3yr FUP
At 4 years patients with missing visits (MV) were confirmed as alive and well by site PI.
20 patients did not sign protocol amendment for 4 & 5 year follow-up
Chevalier B, TCT 2017

22. ABSORB II: Device Oriented Composite Endpoint (DoCE)/ Target Lesion Failure (TLF)5 10 15 20 25
1152
1260
1440
1620
HR [95% CI]= 1.44 [0.15,13.80]
p=0.75 (Log rank test)
1.0%
0.7% 5 10 15 20 25
180
360
540
720
900
1080
1260
1440
1620
TLF per WHO (%)
Time Post Index Procedure (Days)
HR [95% CI]= 2.04 [0.98,4.24]
p=0.050 (Log rank test)
11.1%
5.6%
BVS (n=335)
XIENCE (n=166)
Δ = 0.3%
DoCE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization (TLR)
Chevalier B, TCT 2017

23. ABSORB II: 4-Year Clinical Outcomes Composite Endpoint
BVS (n=335)
XIENCE (n=116)
p=0.47
p=0.99
p=0.15
p=0.06
p=0.06
Chevalier et al., EuroIntervention Oct. 31, 2017 Epub

25. ABSORB III Study Flow and Follow-up
Randomized 2:1
N=2008 (ITT)
ABSORB
N=1322
N=1312
Xience
N=677
N=686
1-Year Follow-up
N=1296
N=671
2-Year Follow-up
N=4 lost to follow-up
N=6 withdrew consent
N=6 lost to follow-up
N=3 withdrew consent
N=10 lost to follow-up
N=2 withdrew consent
99.2% Complete
98.7% Complete
98.0% Complete
97.8% Complete
N=1276
N=661
3-Year Follow-up
N=14 lost to follow-up
N=3 withdrawn by physician/site
N=1 other
N=8 lost to follow-up
N=1 withdrew consent
N=1 withdrawn by physician/site
96.5% Complete
96.4% Complete
Kereiakes et al., J Am Coll Cardiol 2017 Article in Press

26. ABSORB III Trial: 3-Year Outcomes with Everolimus-Eluting Bioresorbable Scaffolds
Time-to-First Event Curves for TLF Through 3 Years
Time-to-First Event Curves for TLF Between 1 and 3 Years
Kereiakes et al., J Am Coll Cardiol 2017 Article in Press

27. ABSORB III Trial: TLF Stratified by Vessel Size
Kereiakes et al., J Am Coll Cardiol 2017 Article in Press

28. ABSORB III Trial: Time-to-First Event Curves for
Definite or Probable Device Thrombosis
Definite or Probable Thrombosis Through 3 Years
Definite or Probable Thrombosis Between 1 and 3 Years
Kereiakes et al., J Am Coll Cardiol 2017 Article in Press

29. ABSORB III Trial: Device Thrombosis Stratified by Vessel Size
Kereiakes et al., J Am Coll Cardiol 2017 Article in Press

30. Kereiakes et al., J Am Coll Cardiol 2017 Article in Press

31. Randomized Comparison of a CrossBoss First vs
Randomized Comparison of a CrossBoss First vs. Standard Wire Escalation Strategy for Crossing Coronary Chronic Total Occlusions: the “CrossBoss First” trial

32. CrossBoss 1st Trial: Study Flow Chart
Brilakis ES, TCT 2017

33. CrossBoss 1st Trial: Crossing Strategies
Variable
CrossBoss
Guidewire
P value
(n=122)
(n=124)
Technical Success, %
88.5
87.1
0.85
First Crossing Strategy, %
<.0001
▪ Antegrade wire escalation 22 98
▪ Antegrade dissection and re-entry 77 1
▪ Retrograde
Successful Crossing Strategy, % 24 51 50 18 17
▪ None 8 10
Brilakis ES, TCT 2017

34. CrossBoss 1st Trial: Primary Endpoints
Crossing Time
Procedural MACE
Randomized Technique
p= 1.0
p= 0.32
Variable
CrossBoss
Guidewire
P value
(n=122)
(n=124)
Crossing time (min)b
56 (33, 93)
66 (36, 105)
0.32
Standardized mean difference: 0.094
Brilakis ES, TCT 2017

35. CrossBoss 1st Trial: Primary Endpoints
ISR Cases
Crossing Time
Procedural MACE
Randomized Technique
p= 0.30
Variable
CrossBoss
Guidewire
P value
(n=25)
(n=24)
Crossing time (min)b
41 (23, 58)
66 (32, 111)
0.05
Standardized mean difference: 0.534
Brilakis ES, TCT 2017

36. CrossBoss 1st Trial: Procedural Characteristics and Outcomes
Variable
CrossBoss
Guidewire
P value
(n=122)
(n=124)
Procedural Success (%)
85.3
83.1
0.63
Total procedural time (min)
109
(78, 185)
(75, 161)
0.67
Total fluoroscopy time (min) 40
(28, 66) 37
(24, 65)
0.34
Total AK radiation dose
2.18
(1.23, 3.56)
2.34
(1.23, 3.91)
0.75
Contrast volume
260
(168, 350)
250
(155, 329)
0.49
Fluoroscopy time (min) at crossing 20
(11, 44) 25
(12, 48)
0.64
AK radiation dose at crossing
0.88
(0.48, 1.97)
1.08
(0.33, 2.44)
Brilakis ES, TCT 2017

37. CrossBoss 1st Trial: Procedural MACE
Variable, %
CrossBoss
Guidewire
P value
(n=122)
(n=124)
Procedural MACE
3.3
4.0
1.00
Death
1.6
0.8
0.62
Acute Q wave MI
0.0
0.50
Acute MI
2.5
0.37
Re-PCI
Stroke
Emergency CABG
Pericardiocentesis
3.2
0.06
Perforation
7.3
0.12
Brilakis ES, TCT 2017

38. CrossBoss 1st Trial: Equipment Costs
Brilakis ES, TCT 2017

39. Conclusions
As compared with a primary wire escalation strategy, upfront use of the CrossBoss catheter for crossing CTOs was associated with:
similar crossing time
similar success and procedural MACE rates
similar equipment costs
Further studies are needed to determine whether some subgroups (such as in-stent occlusions) are better suited for crossing using the CrossBoss catheter.
Brilakis ES, TCT 2017

40. Issues Involving The Case
Top Three Trials from TCT 2017:
DKCRUSH-V, ABSORB III-3Yr, CrossBoss First
ORBITA Trial- Sham Controlled Trial of PCI in
Stable Single Vessel CAD

41. Benefit of PCI over MT in Stable CAD
Decreased angina and antianginal meds (ACME I)
Improved exercise tolerance (ACME I)
Decreases ischemia on MPI (Nuclear sub-study of Courage Trial)
Better quality of life parameter (FAME-2 Trial)
Reduce urgent revascularization in FFR <0.81 (FAME-2 Trial)
Properly done may reduce 5-Yr death/MI (US gp of Courage Trial)

43. ORBITA Trial: Background
Over PCIs per year for stable angina
Primarily for angina relief
Size of angina relief beyond placebo unknown
Unblinded PCI +96 seconds (NEJM 1992)
Single drug +55 seconds (JACC 2004)

44. ORBITA Trial: Principal Hypothesis Symptom Relief in Stable Angina
PCI increases exercise time more than placebo procedure
Primary endpoint Difference in exercise time increment between the arms
For patients to be willing to participate in this first placebo- controlled trial of PCI, duration must be long enough for full hemodynamic effect but not so long as to inhibit recruitment
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

45. Sample Size Calculation
ORBITA Trial
Inclusion Criteria
To detect 30 sec,
at 80% power,
within-arm SD 75 sec,
Needs 200 randomized patients
Stable angina
One or more ≥ 70% stenosis in a single vessel
Suitable for PCI
This sample size is comparable to other trials assessing this question.
Sample Size Calculation
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

46. ORBITA Trial Design
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

47. ORBITA Trial Profile
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

48. ORBITA Trial: Blinding Techniques
Patient:
Headphones and music Sedation
Minimum 15 min wait
Both arms: DAPT
Same post-procedural instructions
Same discharge letter
Clinical Team:
Standardised handover Ward team blinded
Both arms: Treated as if PCI
No access to cath report Same discharge letter
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

49. ORBITA Trial: Stenosis Severity
PCI
n = 105
Placebo n = 95 P
Area stenosis by QCA (%)
84.6
(SD 10.2)
84.2
(SD 10.3)
0.781
FFR
0.69
(SD 0.16)
0.778
iFR
0.76
(SD 0.22)
(SD 0.21)
0.751
Al-Lamee R, TCT 2017

50. ORBITA Trial: Primary Endpoint Change in Total Exercise Time40 35 30 25 20 15 10 5
PCI
Placebo
Change in exercise time
(seconds)
28.4
(SD 86.3)
p=0.001
11.8
(SD 93.3) p=0.235
+16.6 sec
(-8.9 to 42.0)
p=0.20
Error bars are standard errors of the mean
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

51. ORBITA Trial: Secondary Endpoint Results
Blinded Evaluation of Ischemia Reduction
Peak Stress Wall Motion Index Score
PCI
(n=80)
Placebo
(n=57)
Pre-randomization
0.18
Follow-up
0.06
0.19
∆ (Pre-randomization to follow-up)
-0.08
(0.17)
p=<0.0001
0.02
(0.16)
p=0.43
Difference in ∆ between arms
-0.09 (-0.15 to -0.04)
p=0.001
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

52. ORBITA Trial: Secondary Endpoint Results
CCS Class Improved in Both Groups
CCS Class at Enrollment
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

53. ORBITA Trial Endpoints
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

54. ORBITA Trial Endpoints
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

55. ORBITA Trial Endpoints
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

56. ORBITA Trial: Changes in CCS Angina Grade
PCI
Placebo
P Value
Enrolment to pre-randomization
---
0.92
Patients assessed (n)
105 95
No change or deterioration (%) 60 62
1 class improvement (%) 26 23
≥2 class improvement (%) 14 15
Pre-randomization to follow-up
0.63 91 49 55 24 21
Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

57. Conclusions
ORBITA is the first placebo-controlled randomized trial of PCI in stable angina
Area stenosis QCA 84.4%, FFR 0.69, iFR 0.76
PCI was safe and physiologically effective
PCI significantly reduced ischemic burden as assessed by stress echo
In this single vessel, angiographically guided trial there was no difference in exercise time increment between PCI and placebo
Al-Lamee R, TCT 2017

58. ORBITA in Context Single vessel PCI guided by angina + angiogram
To allow complete revascularization
PCI guided by angina + angiogram
In line with common practice
Focus is on symptomatic relief
Not risk or events
Intensive medical therapy
In line with Guidelines

62. Al-Lamee, et al., Lancet Nov. 2, 2017 Epub

64. Limitations of the ORBITA Trial:
Small sample size
Short duration (only 6 weeks as benefit of PCI in FAME2 occurred at 6 months)
Super selective 1V CAD population. On MMT & baseline exercise tolerance of >9 min (>10% of PCI population)
29-31% of physiologically negative lesions underwent PCI
It will be difficult to replicate sham PCI
After 6 weeks, many of these patients will undergo “True PCI” on patients and MD’s preference

65. Conclusion of the ORBITA Trial
“Too much hype for too little gain”
Unlike to change our clinical practice

67. FAME 2 Trial: Cumulative Incidence of MACEs
Fearon et al.,Circulation Nov. 2017, Epub

68. FAME 2 Trial: Clinical Outcomes at 3-Year F/U
PCI+MT (n=447)
MT alone (n=441) %
p=<0.001
p=0.10
p=0.33
p=0.41
p=0.43
Fearon et al.,Circulation Nov. 2017, Epub

69. FAME 2 Trial: Differences in Angina Patient with CCS II-IV (%)
PCI+MT
MT alone
p=0.42
Patient with CCS II-IV (%)
p=<0.001
p=<0.001
p=<0.001
p=0.002
p=0.02
Fearon et al.,Circulation Nov. 2017, Epub

70. FAME 2 Trial: Differences in Costs
PCI+MT Cumulative Cost
MT Cumulative Cost
PCI+MT Annual Follow-Up Cost
MT Annual Follow-Up Cost
Fearon et al.,Circulation Nov. 2017, Epub

71. FAME 2 Trial: Costs During Index Admission
and 3-Year Follow-Up
Fearon et al.,Circulation Nov. 2017, Epub

72. FAME 2 Trial: Changes in European Quality of Life-5 Dimensions (EQ-5D)
PCI+MT
MT alone
EQ-5D Index No
(%) (98%) (98%) (94%) (96%) (91%) (91%) (85%) (87%)
*p<0.05 vs Baseline
Fearon et al.,Circulation Nov. 2017, Epub

73. Fearon et al.,Circulation Nov. 2017, Epub

74. Take Home Message: Recent Interventional Trials of DKCRUSH-V, ABSORB-III, CROSSBOSS 1st, ORBITA, FAME-2
DKCRUSH-V showed that 2-stent strategy is better then provisional-stent strategy (47% required 2 stents) in dLM bifurcation. ABSORB II and III long-term data continued to show scaffold being inferior to Xience DES. Crossboss 1st strategt of CTO recanalization failed show any advantage over routine wire escalation strategy
ORBITA trial of one vessel CAD after optimal maximal medical stabilization failed to show any benefit of PCI on exercise duration and angina relief compared to sham PCI at 6-week follow-up. Trial did show improvement in echo wall motion scores on exercise. ORBITA trial on ground of only 6-weeks duration is unlikely to change our practice as PCI benefit may/will occur after 4-6mths in reducing urgent TLR our MMT alone in lesions <0.80.

75. Question # 1
DKCRUSH V trial dLM bifurcation PCI revealed the following except:
Lower revascularization vs conventional strategy
Lower MI vs conventional strategy
C. Lower ST vs conventional strategy
2-stents were compared with 1-stent strategy in all cases
E. Similar mortality vs conventional strategy

76. Question # 2
CrossBoss 1st trial of CTO recanalization showed the following except;
Similar technical success as wire escalation
Similar MACE rates as wire escalation
Similar cost as wire escalation
Lower pericardial tamponade vs wire escalation
Similar procedure time as wire escalation

77. Question # 3
ORBITA trial comparing True PCI with Sham PCI showed the following except:
A. Similar exercise time improvement
B. No difference in angina class at follow-up
C. Similar medication use at follow-up
D. Similar echo wall motion index during exercise
E. Similar MACE at follow-up

78. Question # 1 The correct answer is D
DKCRUSH V trial dLM bifurcation PCI revealed the following except:
Lower revascularization vs conventional strategy
Lower MI vs conventional strategy
C. Lower ST vs conventional strategy
2-stents were compared with 1-stent strategy in all cases
E. Similar mortality vs conventional strategy
The correct answer is D

79. Question # 2 The correct answer is C
CrossBoss 1st trial of CTO recanalization showed the following except;
Similar technical success as wire escalation
Similar MACE rates as wire escalation
Similar cost as wire escalation
Lower pericardial tamponade vs wire escalation
Similar procedure time as wire escalation
The correct answer is C

80. Question # 3 The correct answer is E
ORBITA trial comparing True PCI with Sham PCI showed the following except:
A. Similar exercise time improvement
B. No difference in angina class at follow-up
C. Similar medication use at follow-up
D. Similar MACE rates at 6-week follow-up
E. Similar echo wall motion index during exercise
The correct answer is E