1. Complex Coronary Cases
Supported by:
Abbott Vascular Inc
Boston Scientific Corp
Terumo Vascular Corp
Trireme Medical Inc
Astra Zeneca
Spectranetics Corp

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

3. November 18th 2014 Case #65: PR, 74 yr M
Presentation:
Patient with new onset cresendo CCS Class III angina and severe inferior and moderate lateral wall ischemia on stress MPI. A cardiac cath on October 31st 2014 revealed 3 V CAD, LVEF 60% and Syntax score 22. Patient underwent RA and 2 Promus Premier DES to 90% calcified distal RCA lesion. Pt was maximized on medical therapy but still has CCS class II angina.
Prior History:
Hypertension, Hyperlipidemia, Ex-smoker
Medications: All once daily dosage
Metoprolol XL 50mg, ISMN 30mg, Clopidogrel 75mg, ASA 81mg, Atorvastatin 40mg 3

4. Case# 65: cont… Cardiac Cath 1031/2014: Right Dominance
3 V CAD with LVEF 60%
RCA: severely calcified 80-90% lesions in distal RCA LM: no obstruction
LAD: 60% mid LAD calcified lesions
LCx: 90% calcified lesion bifurcation lesions in prox LCx, 80% OM1 and 90% in OM2 (Medina 1,1,1)
SYNTAX Score was : 22
Course: Pt underwent RA+ DES x2 (Promus Premier) to dRCA
Plan Today:
PCI of moderately calcified bifurcation lesions of LCx and
OM branches using Chocolate balloon PTCA and planned
2 stents strategy.
SYNTAX Score now : 17 4

5. Appropriateness Criteria for Coronary Revascularization

6. Special Balloon Chocolate® PTCA TriReme Medical Inc.
Device description
Nitinol Constraining Structure Unique Dilatation Pillows and Grooves
Mechanism of operation
Controlled, Predictable, Uniform Inflation Reduced “Dog-Boning” Enhanced Dispersal of Dilatation Forces
Specifications
5F or 6F guide catheter compatible depending on balloon size
Range of balloon sizes (2.0/2.5/3.0/3.5mm x 10/15/20mm)
Product Approval and Indication
The Chocolate® PTCA Balloon Dilatation Catheter is indicated for balloon dilatation of the stenotic portion of coronary artery or bypass graft stenosis for the purpose of improving myocardial perfusion. FDA 510k clearance and CE MARK.

7. The Chocolate PTCA Balloon
Designed to provide predictable, uniform, and atraumatic dilatation
Unique nitinol “constraining structure” (CS)
Uniformly distributes circumferential forces (calcific or eccentric lesions) – no “dog boning”
Shields vessel wall from torsional shear stress caused by balloon “unfolding”
Modifies plaque via:
“Pillows”: vessel dilatation without cutting or scoring
“Grooves”: stress relief, plaque modification
Reduces dissections and recoil – improved lumen size
Fast deflation, concentric secondary profile
The Chocolate PTCA Balloon
Designed to provide predictable, uniform, and atraumatic dilatation
Unique nitinol “constraining structure” (CS)
Uniformly distributes circumferential forces (calcific or eccentric lesions) – no “dog boning”
Shields vessel wall from torsional shear stress caused by balloon “unfolding”
Modifies plaque via:
“Pillows”: vessel dilatation without cutting or scoring
“Grooves”: stress relief, plaque modification
Reduces dissections and recoil – improved lumen size
Fast deflation, concentric secondary profile

8. Flow-Limiting Dissections with PTCA
With conventional balloons, inflation can result in vessel trauma leading to dissections.
Three reasons are torsional, radial, and longitudinal stress!

9. Balloon Inflation Dynamics
Conventional Balloon
Chocolate Balloon
Nominal
> Nominal
Nominal
> Nominal
Chocolate’s unique design facilitates plaque modification
Valleys allow plaque extrusion & remodeling
Higher pressure enhances pillows
Pillows project beyond constraining structure

10. The Chocolate PTCA Balloon
Clinical indications
In situations where DES more problematic (DCB “friendly” lesions)
Small vessels
Bifurcations (esp. ostial branch)
DAPT contra-indications
Vessel preparation before BVS
For routine use, instead of conventional PTCA balloons

11. Issues Involving The Case
Update in Bifurcation Lesion PCI
Update on Revascularization in Diabetics

12. Issues Involving The Case
Update in Bifurcation Lesion PCI
Update on Revascularization in Diabetics

13. 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)

14. Significant Post Stenting SB Stenosis: QCA vs. FFR
(Jailed side branch lesions, n=94)
FFR
Functionally
significant
stenosis
38% of lesions
75%
% Stenosis
Koo et al. JACC 2005;46:633.

15. Randomized Comparison of FFR-Guided and Angiography-Guided Provisional Stenting for True Coronary Bifurcation Lesions:
The DKCRUSH-VI Trial

16. DKCRUSH VI Trial: Study Design
Medina 1,1,1/0,1,1 bifurcation lesions, SB≥2.5 mm
FFR group (n=160) Angio group (n=160)
Jailed wire, MV Stenting
SB FFR< Ostial SB: DS>70%, B/C dissection, TIMI<3
If yes, Kissing balloon inflation No No
If still yes, SB Stenting, FKBI
1-year clinical/13-m angio F/U
Chen and Stone, TCT 2014

17. DKCRUSH VI Trial: Procedural Findings
FFR group (n=160) Angio group (n=160)
Measuring SB-FFR SB stenting in 61 (38.1%) patients
Success (n=145, 90.6%) Failure (n=15) Success Failure
(n=51, 83.6%) (n=10, 16.4%)
FFR ≥ FFR < KBT
(n=70) (n=75)
KBI
FFR≥ FFR<0.8
(n=49) (n=26) Stenting SB (success in 22, 77.3%; failure in 8, 22.7%)
Stenting MV (100%)
FFR<0.8 (n=4) FFR≥0.8 (n=8) Failure (n=3)
SB PCI, any: 56.3%
SB stenting attempted: 25.9%
P=0.07
P=0.01
SB PCI, any: 63.1%
SB stenting attempted: 38.1%
Chen and Stone, TCT 2014

18. DKCRUSH VI Trial: 1-Year Clinical Outcomes
Angio Group (n=160)
FFR Group (n=160)
p=1.00
p=0.74 %
p=0.82
p=0.56
p=0.56
Chen and Stone, TCT 2014

19. DKCRUSH VI Trial: Distribution of Restenosis Pre-Specified Definition
Chen and Stone, TCT 2014

20. Post hoc definition DKCRUSH VI Trial: Distribution of Restenosis
Post hoc analysis if in-segment resetenosis*
Location
Angio group
FFR group
P Value
Proximal MV
3.4
1.7
0.68
Distal MV
9.2
0.01
Side Branch
11.8
21.2
0.037
* Defined as a QCA DS>50%; Segment=stented + P/D 5-mm MV, main vessel
Chen and Stone, TCT 2014

21. Medina 111/011 bifurcation with SB ≥2.5 mm Non-LM distal bifurcation
DEFINITION Study: Description of Complex Bifurcation Lesion Definitions
Medina 111/011 bifurcation with SB ≥2.5 mm
LM distal bifurcation
Non-LM distal bifurcation
SB DS ≥70%
SB lesion length ≥10 mm
SB DS ≥90%
SB lesion length ≥10 mm
Yes
Yes No
Yes
With any 2 minors
Simple
With any 2 minors
Yes
Yes
Complex
Chen et al., J Am Coll Cardiol Intv 2014; Article in Press

22. DEFINITION Study: Independent Factors of
MACE at 1 Y After Stenting by Regression Analysis (Training Group n=1,500)
Chen et al., J Am Coll Cardiol Intv 2014; Article in Press

23. DEFINITION Study: Flow Chart
2058 patients with Medina
111/011 bifurcation lesions
3828 patients with Medina
111/011 bifurcation lesions
558 patients excluded
SB <2.5 mm
-- 14 lost during F/U
558 patients excluded
SB <2.5 mm
-- 14 lost during F/U
1550 patients with Medina 111/011 bifurcation and SB ≥2.5 mm
(Training Group)
3660 patients with Medina 111/011 bifurcation and SB ≥2.5 mm
(Study Group)
To build criteria of lesions complexity
To test the predictive value for worse clinical events
Chen et al., J Am Coll Cardiol Intv 2014; Article in Press

24. DEFINITION Study: Clinical Outcomes in
Complex and Simple Groups (n=3660)
Complex (n=1108)
Simple (n=2552)
In-Hospital Outcomes
At 1-Year Outcomes
p=<0.001
p=0.004 %
p=<0.0001
p=<0.001 %
p=<0.001
p=<0.001
p=0.12
p=0.26
p=0.08
p=0.07
MI Cardiac TVR MACE ST
death
MI Cardiac TVR MACE ST
death
Chen et al., J Am Coll Cardiol Intv 2014; Article in Press

25. DEFINITION Study: Clinical Outcomes in 2-Stent
and Provisional Stent in Complex Groups (n=1108)
Two Stent (n=537)
Provisional Stent (n=571)
In-Hospital Outcomes
At 1-Year Outcomes
p=0.14
p=1.34 %
p=0.03
p=0.03 %
p=0.07
p=0.04
p=0.90
p=0.37 NS NS
MI Cardiac TVR MACE ST
death
MI Cardiac TVR MACE ST
death
Chen et al., J Am Coll Cardiol Intv 2014; Article in Press

27. BABILON Trial: Flow Chart
Randomization
Drug-eluting Balloon (DEB)
DES
Sequential MB/SB dilatation with plain balloon
Sequential MB/SB dilatation with DEB
(1:1 balloon:artery relation
2. Provisional T-stenting with BMS/MB
Provisional T-stenting with DES (everolimus)/MB
Final Kissing with regular balloons at operator’s discretion
3 months dual antiplatelet therapy
12 months dual antiplatelet therapy
9-month angiographic follow-up (primary endpoint: late luminal loss, LLL), and global restenosis
2-year clinical follow-up (secondary endpoint: MACE, clinical events)
López Minguez et al., EuroIntervention 2014;10:50

28. BABILON Trial: 24-Month Clinical Events
pDEB group (n=52)
DES group (n=56)
p=0.11
p=0.05
p=0.03 %
p=0.67
p=1.0
p=1.0
López Minguez et al., EuroIntervention 2014;10:50

29. Issues Involving The Case
Update in Bifurcation Lesion PCI
Update on Revascularization in Diabetics

30. MASS II Study: Mortality Rate at 10-Year F/U
for Diabetic and Non-Diabetic Patients
Diabetic (n=232)
Non-Diabetic (n=399)
N=88
N=115
N=64
N=141
N=80
N=123
Hueb et al., Circulation 2010;122:949

31. VA CARDS Study: CONSORT Flow Diagram
Enrollment
6678 Pts screened for eligibility
6471 Excluded
● 6080 Not angiography eligible
● 173 Declined to participate
● 218 Other reasons
207 Randomized
Allocation
103 Assigned to CABG group
104 Assigned to PCI group
1 Misrandomized
5 Withdrawn due to
early study termination
2 Misrandomized
1 Withdrawn due to
early study termination
Follow-up
Analysis
97 Included in the
intention-to-treat analyses
101 Included in the intention-to-treat analyses
Kamalesh et al., JACC;2013:61:808

32. VA CARDS Study: Primary Endpoints Occurrence Rate at 2Years
CABG (n=97)
PCI (n=101)
95% CI
[ ]
95% CI
[ ] %
95% CI
[ ]
Kamalesh et al., JACC;2013:61:808

33. FREEDOM Trial: Estimates of Key Outcomes at 5 Years after Randomization
PCI (n=943)
p=0.005
CABG (n=957)
p=0.049
p=<0.001
p=0.12 %
p=0.003
Primary End Death MI Stroke Yr TVR
Farkouh et al., N Engl J Med 2012;367:2375 33

34. FREEDOM Trial: Estimates of the Composite Primary Outcome
Farkouh et al., N Engl J Med 2012;367:2375 34

35. SPIRIT V Trial: 1 Year Clinical Outcome in Diabetics
EES (n=215)
PES (n=104)
p=0.71
p=0.05
p=0.25 %
p=0.40
p=0.11
Grube et al., Am Heart J 2012;163:867

36. ESSENCE-DIABETES Trial: Clinical Outcomes
At 12 Months
EES (n=149)
SES (n=151)
p=0.22
p=0.12
p=0.45
p=0.50
p=1.0
Death MI ST Ischemia MACE
driven TVR
Kim et al., Circulation 2011;124:886

37. ISAR-LEFT-MAIN 2 Study: ZES vs
ISAR-LEFT-MAIN 2 Study: ZES vs. EES for Unprotected LM CAD 1 Year Clinical Outcomes
ST (Def/Prob)
0.93%
0.61%
ZES (n=324)
EES (n=326)
p=0.24
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. Network Plot of Treatment Comparisons
Banglore et al., Circ Cardiovasc Interv 2014;7:518

40. Median Rate of Primary and Secondary Outcomes From Mixed Treatment Comparison Analysis
Banglore et al., Circ Cardiovasc Interv 2014;7:518

41. Mixed Treatment Comparison Analyses for CABG vs. PCI in Diabetics
Outcome of All-Cause Mortality
Bangalore et al., Circ Cardiovasc Interv. 2014;7:518

42. Mixed Treatment Comparison Analyses for CABG vs. PCI in Diabetics
Outcome of MI
Outcome of Stroke
Bangalore et al., Circ Cardiovasc Interv. 2014;7:518

43. Mixed Treatment Comparison Analyses for CABG vs. PCI in Diabetics
Outcome of Repeat Revascularization
Bangalore et al., Circ Cardiovasc Interv. 2014;7:518

44. Sensitivity Analysis: Mixed Treatment Comparison
Analyses for CABG vs. PCI in Diabetics
Outcome of All-Cause Mortality Using Counts Data and
Frequentlist-Based Approach
Bangalore et al., Circ Cardiovasc Interv. 2014;7:518

45. FREEDOM Trial: Estimates of the Composite Primary Outcome at 5 yrs
Farkouh et al., N Engl J Med 2012;367:2375 45

46. Potential Primary Outcome of Death, MI or Stroke
if FREEDOM Trial is done with CoCr EES

48. The FREEDOM Insulin Subgroup Analysis
Estimates of the Primary Endpoint by Treatment Received and Insulin Use
Primary Composite Outcome at
5 Years by Insulin Use
Primary Composite Outcome at
5 Years by Treatment and Insulin Use
Dangas et al., J Am Coll Cardiol 2014;64:1189

49. Treatment Effect of CABG vs PCI in Non-ITDM and ITDM Groups
The FREEDOM Insulin Subgroup Analysis
Treatment Effect of CABG vs PCI in Non-ITDM and ITDM Groups
PCI (n=631)
CABG (n=617)
PCI (n=325)
CABG (n=277)
Non-ITDM
ITDM
p=0.40
p=0.40 %
p=0.64
p=0.81
p=0.81
p=0.64 %
p=0.33
p=0.33
Death/ Mortality 1-Y MACCE 1-Y TVR stroke/MI
Death/ Mortality Y MACCE 1-Y TVR
stroke/MI
Dangas et al., J Am Coll Cardiol 2014;64:1189

50. FREEDOM Follow-On Registry
Protocol Title
Long-term Outcomes in patients who underwent revascularization in the FREEDOM Trial
Abbreviated Title
FREEDOM Follow-On Registry
Name of Sponsor
Valentin Fuster Mount Sinai School Of Medicine Foundation
Study Objective
To assess the long-term event rate (death, non-fatal MI, or non-fatal stroke) following revascularization by PCI/DES or CABG in subjects with diabetes and multivessel CAD
Study Design
Prospective, multicenter observational registry
Study Centers
Up to 91 sites that participated in the FREEDOM main trial
Study Population
Approximately 1,000 subjects will be enrolled in the Follow-On registry, comprised of FREEDOM Trial survivors who consent to this registry
Duration of Participation
Subjects will be evaluated at Baseline (in-person) and annually thereafter via telephone up to 36-months
Eligibility Criteria
Inclusion Criteria:
Subjects of the FREEDOM trial in the past and agreed for Follow-up
Signed written informed consent
There are no exclusion criteria for this observational registry.
Primary Endpoint
The primary endpoint is the composite of death, non-fatal MI, or non-fatal stroke, the same as for the FREEDOM main trial
Secondary Endpoints
Secondary endpoints include: all-cause mortality, cardiovascular mortality, non-fatal MI, non-fatal stroke, and repeat revascularization

51. Take Home Message: Updates in Bifurcation Lesion PCI and Revascularization in Diabetics
Bifurcation lesion PCI involving FFR has limited value
but a prospective strategy of identifying complex bifurcation lesion is useful and has better outcomes with the use of 2-stents. Drug eluting balloon is inferior to DES in bifurcation lesion even as the provisional side branch strategy
Despite the superior outcomes of CABG in FREEDOM trial using first generation DES, data are emerging that newer generation DES especially CoCr EES has potential to have similar outcomes to CABG in multivessel diabetic pts. Future trials of revascularization in complex CAD in diabetic patients will be needed for the final answer.

52. Question # 1
Following is the true statement regarding DK CRUSH VI trial:
Higher MACE rate with Angio guided PCI
Lower Stent Thrombosis with FFR guided PCI
Higher overall TVR in Angio guided PCI
Higher side branch restenosis in FFR guided PCI
Higher MACE rates with Angio guided PCI

53. Question # 2
Following is the true statement from the DEFINITION study of bifurcation lesion PCI:
MACE rates were similar in simple vs. complex group
Outcomes were better with 2-stent strategy vs. Provisional strategy in Complex group
Rates of MI are similar in simple vs. complex group
Rates of Stent Thrombosis are similar in simple vs. complex group
It is tough to predict which bifurcation lesion is simple or complex

54. Question # 3
Mixed treatment comparison analysis of various PCI types and CABG have shown the following not to be true:
A. Higher mortality with SES/PES vs. CABG
B. Higher TVR with PCI vs. CABG
C. Lower stroke rates with PCI vs. CABG
D. Higher MI rates with PCI vs. CABG
E. PCI with CoCr EES has higher mortality and TVR vs. CABG

55. Question # 1 The correct answer is D
Following is the true statement regarding DK CRUSH VI trial:
Higher MACE rate with Angio guided PCI
Lower Stent Thrombosis with FFR guided PCI
Higher overall TVR in Angio guided PCI
Higher side branch restenosis in FFR guided PCI
Higher MACE rates with Angio guided PCI
The correct answer is D

56. Question # 2 The correct answer is B
Following is the true statement from the DEFINITION study of bifurcation lesion PCI:
MACE rates were similar in simple vs. complex group
Outcomes were better with 2-stent strategy vs. Provisional strategy in Complex group
Rates of MI are similar in simple vs. complex group
Rates of Stent Thrombosis are similar in simple vs. complex group
It is tough to predict which bifurcation lesion is simple or complex
The correct answer is B

57. Question # 3 The correct answer is E
Mixed treatment comparison analysis of various PCI types and CABG have shown the following not to be true:
A. Higher mortality with SES/PES vs. CABG
B. Higher TVR with PCI vs. CABG
C. Lower stroke rates with PCI vs. CABG
D. Higher MI rates with PCI vs. CABG
E. PCI with CoCr EES has higher mortality and TVR vs. CABG
The correct answer is E