2. Complex Coronary Cases
Supported by:
Abbott Vascular
Boston Scientific Corporation
Medtronic, Inc.
Astrazeneca

3. Disclosures
Samin K. Sharma, MBBS, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott, The Medicines Company, Daiichi Sankyo, Inc. and Lilly USA, LLC 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

4. March 19th 2013 Case #9: CS, 73 yr M Presentation: Prior History:
Presented on 2/8/2013 with cresendo CCS class III angina & exertional dyspnea. Pt had stress MPI revealing severe anterior and lateral ischemia. Echo in past revealed severe MR and minimal LV dysfunction; surgical repair recommended but declined. Cath revealed 3 V CAD and LVEF 55%. SYNTAX score 25. Cardiac surgery recommended but again declined after Heart-Team discussion. Pt underwent Xience Xpedition DES to LCx-HL and prox LAD and did well. Pt Still has residual class II angina.
Prior History:
Hyperlipidemia, Hypertension, H/o CVA
Medications: All once daily dosage
Aspirin 81mg, Clopidogrel 75mg, Metoprolol XL 100mg, Diltiazem CD 180mg, Rosuvastatin 20mg 4

5. Case# 9: cont… SYNTAX score 25 Cardiac Cath 2/8/2013: Left Dominance
3 Vessel CAD with LVEF 56%
Left Main: Mild diffuse disease
LAD: 80-90% lesion in prox, total D1 fills via collaterals
LCx: 90% distal LCx with 80% OM1 bifurcation lesion
Ramus Intermedius: 95% lesion, moderate size
PCI: Underwent Xience Xpedition DES (3/23mm) to pLAD and Xience Xpedition DES (2.5/28mm) to Ramus Intermedius
Plan Today:
- PCI of bifurcation lesion of circumflex (SYNTAX score 16) 5

6. Appropriateness Criteria for Coronary Revascularization

7. Issues Involving The Case
Two DES for bifurcation lesions
Newer devices for calcified lesions

8. Issues Involving The Case
Two DES for bifurcation lesions
Newer devices for calcified lesions

9. Coronary Artery Bifurcation Lesion Interventional Techniques
Interventional Bifurcation Techniques
One Stent
Technique (OST)
Kissing Stent
Technique (SKS)
Crush Stent
Technique (CrST)
OST with SBR
Dilatation (SBT)
‘T’ Stent
Technique (TST)
Culotte Stent
Technique (CUT) 9

10. Clinical Outcomes in Trials Comparing One-DES (1S) vs
Clinical Outcomes in Trials Comparing One-DES (1S) vs. Two-DES (2S) Strategy in Treating Coronary Bifurcations
MACE
TLR 19
18.0
15.8
15.2 15
13.6
12.9
2.1
12.8
4.5
11.4
11.9 %
12.0
10.9
9.5
8.0
8.0
8.9
7.2
5.6
5.8
5.6
3.4
4.5
2.9
4.0
1.9
1.0 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S
Colombo et al.
SES stents
(n=85)
Hildick et al.
BBC ONE
(n=500)
Ferenc et al.
T-stenting
(n=202)
Steigen et al.
NORDIC Trial
(n=413)
Colombo et al.
CACTUS trial
(n=85)
Pan et al.
SES stents
(n=91)
Sharma et al.
PRECISE-SKS
(n=100)

11. Incidence of Reported Stent Thrombosis
Clinical Outcomes in Trials Comparing One-DES (1S) vs.
Two-DES (2S) Strategy in Treating Coronary Bifurcations
Incidence of Reported Stent Thrombosis
1S group
2S group
3.5
3.0
3.0 %
2.0
2.0
1.7
1.1
0.5
0.4 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S 1S 2S
Colombo et al.
SES stents
(n=85)
Hildick et al.
BBC ONE
(n=500)
Ferenc et al.
T-stenting
(n=202)
Steigen et al.
NORDIC Trial
(n=413)
Colombo et al.
CACTUS trial
(n=85)
Pan et al.
SES stents
(n=91)
Sharma et al.
PRECISE-SKS
(n=100)

12. DKCRUSH Technique for Bifurcation Lesions1.
SBr stenting 2.
Balloon crush 3.
1st Kissing balloon inflation 4.
MV stent and crush 5.
Final Kissing balloon inflation
Chen S et al. J Interven Cardiol 2009;22:127

13. A Randomized Clinical Study Comparing Double Kissing
Crush With Provisional Stenting for Treatment of Coronary Bifurcation Lesions: DK Crush II Study
Conventional (n= 185) %
p<0.001
DK Crush (n=185)
22.2
p=0.017
p=0.07
17.3
14.6
p=0.036
10.3
9.7
p=0.37
6.5
4.9
3.8
2.2
0.5
Main Vessel
Side Vessel
TVR
MACE ST
Angiographic Restenosis
Chen S et al, JACC 2011;57:914
Confidential Material 13 13

14. Flowchart of Study Design
DK-CRUSH III Study
Flowchart of Study Design
Chen et al., JACC 2013 In Press 14

15. TVR-Free Survival Rate at 12 M MACE-Free Survival Rate at 12 M
DK-CRUSH III Study
TVR-Free Survival Rate at 12 M
MACE-Free Survival Rate at 12 M
Chen et al., JACC 2013 In Press 15

16. DK-CRUSH III Study: Clinical F/U at 12 Months
DK Group (N = 210)
p=0.001
Culotte Group (N = 209)
p=0.03 %
p=0.38
p=1.00
p=0.62
Chen et al., JACC 2013 In Press 16

17. Forest Plots of 1-Year MACE Rate in Pre-Specifies Subgroups
DK-CRUSH III Study
Forest Plots of 1-Year MACE Rate in Pre-Specifies Subgroups
Chen et al., JACC 2013 In Press 17

18. BBC One Study: 9-Month Post-PCI Scores on SAQ for Simple and Complex Groups
Sirker et al., JACC Cardiovasc Interv 2013;6:139 18

19. BBC One Study: Direction of Change in Individual Patients’ Scores on SAQ
Sirker et al., JACC Cardiovasc Interv 2013;6:139 19

20. Issues Involving The Case
Two DES for bifurcation lesions
Newer devices for calcified lesions

21. Facts about Calcified Lesions
Angiography underestimates the presence, extent and axial depth of calcium
Calcium significantly increases procedural complications
Most studies have excluded calcified lesions
While rotational atherectomy (RA) allows for greater stent expansion, studies have reported increased late loss and restenosis, likely due to platelet activation and thermal injury from the device
Thus, at the present time, RA is mainly reserved for undilatable or extremely calcified lesions.
Mintz et al., Circ 1995;01:1959, Lofberg et al., Cardiovasc Interv Radiol 1998;19:317, Davies et al., J Am Coll Surg 2005;201:275, Gallino et al., Circ 1984;70:619, Becquemin et al., J Endovasc Surg, 1995;2:42, Zdanowski et al., Int Angio 1999;18:251, Vroegindeweij et al., Cardiovasc Interv Radiol 1997;20:420 21

22. Impact of Severity of Coronary Calcification on 1-Year Outcomes After PCI in NSTEMI/STEMI:
Insight from an angiographic pooled analysis from ACUITY and HORIZONS Trials
Généreux, TCT 2012 22

23. Frequency of Moderate/Severe Calcification in ACS Population
n = 6,855 patients
Moderate/Severe
None/Mild
Généreux, TCT 2012 23

24. 1-Year Ischemic Outcomes: ACS Population (N= 6855 patients)
None/Mild
Moderate/Severe %
p=0.22
p=0.002
p=0.0002
p=0.001
p=0.007
Généreux, TCT 2012 24

25. Device Selection for Various Coronary Lesions Type
All Comers/Fibrotic Undilatable/Mild-Mod Calcified Heavily Calcified *
AngioSculpt
Compliant or
Non-compliant Balloon

26. Cutting Balloon (Flextome)
Balloon Atherotomy
Cutting Balloon (Flextome)
- Security & performance are engineered to:
Reduce vessel wall expansion
Maximize plaque compression
Relief hoop stress
- Better results with lower inflation pressure
compared to plain old balloon angioplasty
Longitudinal
microtomes
Indications:
-Mild calcified
-Inelastic/chronic
-Ostial
-ISR
AngioSculpt balloon

27. Post-procedure Stent Luminal Area ≥5.0 mm2%
Costa et al., Am J Cardiol 2007;100:812 27

28. Stent Expansion by Plaque Morphology
% Optimal Stent Expansion
Pre-dilatation with AngioSculpt
Pre-dilatation with POBA
Direct Stent
Soft 87 75 74
Calcific 90 72
Fibrotic 82 77
Mixed 76
Costa et al., Am J Cardiol 2007;100:812 28

29. ROTAXUS
240 patients with calcified lesions enrolled between August 2006 and March 2010 at 3 clinical sites in Germany
Mean age 71
DM 28%
MVD 74%
1:1 randomization
Ostial 18%
Bifurc 48%
B2/C 90%
IVUS not used
Rotoblator + PES
(n=120)
PTCA + PES
(n=120)
- 2 patients died in-hospital
- 6 patients withdrew consent
- 5 patients lost at follow-up
Clinical follow-up at
9 months in 96.2%
(n=227)
Angio follow-up at
9 months in 80.5%
(n=190)
*Primary endpoint: In-stent late loss
Richert, TCT 2011 29

30. ROTAXUS: 9-month Follow-up * Defined as death, MI and TVR
ROTA + PES (n=123)
PTCA + PES (n=132)
p=0.73 %
p=0.84
p=0.79
p=0.78
p=1.0
* Defined as death, MI and TVR
Richert, TCT 2011 30

31. ORBITAL ATHERECTOMY: Unique Mechanism of Action
Differential Orbital Sanding
Crown will only sand the hard components of plaque
Soft components (plaque/tissue) flex away from crown
Orbital Mechanism
Increased speed = Increased centrifugal force
Greater centrifugal force = Larger orbital diameter
CF=Mass X Rotational speed2
Radius of the orbit 31

32. Orbital Atherectomy Technology for Calcified Coronary Arteries
Easy setup and use
Control of device in operating field
.012” OAS guide wire
Compatible with 6 French guiding catheters 32

33. ORBITAL Atherectomy: Unique Mechanism
of Action
Orbiting Crown Enables
Continous flow of blood and saline
Minimizes thermal injury
Potentially decreases no-reflow and periprocedural cardiac enzyme elevation
One crown treats different vessel diameters based on orbiting speed 33

34. The Differences Between Sanding and Drilling
Orbital
Rotational
Mechanism of Action
Direction
Bi-directional
Uni-directional 34

35. ORBIT I Trial
First-in-man study using orbital atherectomy in coronary arteries
Designed to demonstrate safety and performance in calcified coronary lesions
Prospective, single-arm
2 centers OUS
50 subjects with >90⁰ of calcium via IVUS
Compared to ORBIT II
Shorter lesions
Less B2/C lesions
MACE Rate
30 days1
6 months1
2 years2
3 years2 6% 8%
15%
18.2%
Cardiac Death 0% 2%
9.1%
Q-wave MI
Non Q-wave MI 9%
TLR 3%
Parikh et al., Catheter Cardiovasc Interv 2012, March 5
2. Parikh et al., JACC Cardiovasc Interv 2013;6:Suppl 5 35

36. 443 patients enrolled in 49 US sites
ORBIT II Study Design
To evaluate safety and efficacy of coronary OAS to prepare de novo severely calcified coronary lesions for enabling stent placement
Prospective
Multi-center trial
Single arm – FDA recommendation as there are no FDA-approved percutaneous treatments for patients with severely calcified lesions.
443 patients enrolled in 49 US sites
30 days follow-up
Complete in 97.7 % (N=430/443)
Chambers, ACC 2013 36

37. ORBIT II Study Design Primary Safety Endpoint: 30-Day MACE
Cardiac death
MI defined as CK-MB level > 3 times upper limit of lab normal (ULN) value
With or without abnormal Q-wave
Target vessel revascularization (TVR)
Primary Efficacy Endpoint: Procedural Success
Success in facilitating stent delivery with a final residual stenosis of <50% and without in-hospital MACE
Chambers, TCT 2012 37

38. The ORBIT II Trial: An Historic SEVERELY CALCIFIED ARTERIES
Coronary Study
ORBIT II
Study
Unique Study Design to Evaluate Higher Risk CAD Patients
SEVERELY CALCIFIED ARTERIES
DIALYSIS
PATIENTS
INCLUDED
EF < 35%
INCLUDED
Chambers, TCT 2012 38

39. The ORBIT II Trial: Primary Safety Endpoint
30 Day MACE Rate Components:
MI (CK-MB >3x ULN): 9.7%
Non Q-wave %
Q-wave 0.9%
TVR/TLR: 1.4%
TVR %
TLR %
Cardiac death: %
Freedom from 30 Day MACE = 89.8%
Performance Goal = 83%
95% CI = 87.0%, 92.7%
80% % % % %
Chambers, ACC 2013 39

40. The ORBIT II Trial: Primary Efficacy Endpoint
Procedural Success Components:
Successful Stent Delivery: 97.7%
Less than 50% residual stenosis: %
In-hospital MACE: 9.5%
MI (CK-MB >3x ULN)/TVR/TLR: %
Non- Q-wave %
Q-wave %
TVR %
Cardiac death: %
Procedural Success = 89.1%
Performance Goal = 82%
95% CI = 85.8%, 91.8%
80% % % % %
Chambers, ACC 2013 40

41. The ORBIT II Trial: 30 Day Results (N=443) Patients with Severely Calcified Coronary Lesions Underwent Diamondback 360⁰ Orbital Atherectomy at 49 States
Primary Safety Endpoint of Freedom from MACE
Primary Efficacy Endpoint of Procedural Success % %
Successful <50% In-hospital MI TVR Cardiac
stent residual MACE death
delivery stenosis
Chambers, ACC 2013 41

42. Take Home Message: Two stent strategy and devices for calcified lesions
Appropriately done 2 stent treatment strategy is emerging as the superior strategy over 1 stent in large coronary bifurcation lesions. Hence no longer the issue should 1 or 2 DES; rather we should identify lesions which will need 2 DES and plan accordingly (rather then bailout strategy)
Orbital atherectomy system in heavily calcified coronary lesions appears very promising and once available, has a chance for wider acceptance because of effectiveness and simple setup and easy learning curve.

43. Question # 1
DK-Crush technique has shown to be superior to other stent strategy for bifurcation lesions except :
Lower restenosis
Lower TVR
Lower MACE
Lower stent thrombosis

44. Question # 2 Orbital atherectomy trials have shown 9-12M MACE rate of:
6-10%
11-15%
16-20%
21-25%
E. >25%

45. Question # 3 Statement about mechanism of Orbital atherectomy is true:
A. Lumen gain is proportional to the size of the burr
B. Lumen gain is proportional to burr movement
C. Lumen gain is proportional to the burr speed

46. Question # 1
DK-Crush technique has shown to be superior to other stent strategy for bifurcation lesions except :
Lower restenosis
Lower TVR
Lower MACE
Lower stent thrombosis
The correct answer is D. While DK Crush trials have shown lower MACE and restenosis, thee has been no difference in the incidence of stent thrombosis.

47. Question # 2
Orbital atherectomy trials have shown 9-12M MACE rate of:
6-10%
11-15%
16-20%
21-25%
E. >25%
The correct answer is A. Both ORBIT I and II trials showed MACE rate of <10% at 1 year follow-up. All was largely due to small non-Q wave MI.

48. Question # 3
Statement about mechanism of Orbital atherectomy is true:
A. Lumen gain is proportional to the size of the burr
B. Lumen gain is proportional to burr movement
C. Lumen gain is proportional to the burr speed
The correct answer is C. Lumen gain after Orbital atherectomy is dependent on the burr speed; faster it is, more arc it covers and larger is the lumen gain.