1. Multivessel PCI: Pearls of Wisdom (?) for Success
Jeffrey W. Moses, MD
Professor of Medicine
Director, Interventional Cardiac Therapeutics
Columbia University Medical Center
Director Complex Coronary Interventions
St. Francis Hospital, Roslyn, LI

2. I have relevant financial relationships Consultant BSC Abiomed Abbott
Jeffrey Moses MD
I have relevant financial relationships
Consultant
BSC
Abiomed
Abbott

3. Can PCI be done as safely as CABG?
MVD Pearls
Can PCI be done as safely as CABG?

4. SYNTAX Score 5 Year MACCE Lowest SYNTAX Tertile (0-22) SYNTAX SCORE
No. &
Location
of lesion
Left
Main
Tortuosity
3 Vessel
Thrombus
Bifurcation
CTO
Calcification
SYNTAX
SCORE
SYNTAX Score
Dominance
5 Year MACCE
Lowest SYNTAX Tertile (0-22) 50
All Patients
p=0.43
3-Vessel CAD only
p=0.0005
CABG
33.3%
32.1%
PCI 25
Cumulative Event Rate (%)
Exhibit 33
28.6%
26.8% 12 24 36 48 60 12 24 36 48 60
Months Since Allocation
Months Since Allocation
Mohr, et al. Lancet 2013;381:629-38 3 3

5. SYNTAX Score 5 Year MACCE Middle SYNTAX Tertile (23-32) SYNTAX SCORE
No. &
Location
of lesion
Left
Main
Tortuosity
3 Vessel
Thrombus
Bifurcation
CTO
Calcification
SYNTAX
SCORE
SYNTAX Score
Dominance
5 Year MACCE
Middle SYNTAX Tertile (23-32) 50
All Patients
p=0.008
3-Vessel CAD only
p=0.0008
37.9%
36.0%
CABG (n=897)
PCI (n=903) 25
Cumulative Event Rate (%)
Exhibit 33
25.8%
22.6% 12 24 36 48 60 12 24 36 48 60
Months Since Allocation
Months Since Allocation
Mohr, et al. Lancet 2013;381:629-38 4 4

6. SYNTAX Score 5 Year MACCE Highest SYNTAX Tertile (33+) SYNTAX SCORE
No. &
Location
of lesion
Left
Main
Tortuosity
3 Vessel
Thrombus
Bifurcation
CTO
Calcification
SYNTAX
SCORE
SYNTAX Score
Dominance
5 Year MACCE
Highest SYNTAX Tertile (33+)
p<0.0001 50
All Patients
3-Vessel CAD only
p=0.0005
CABG (n=897)
PCI (n=903)
44.0%
41.9% 25
Cumulative Event Rate (%)
Exhibit 33
26.8%
24.1% 12 24 36 48 60 12 24 36 48 60
Months Since Allocation
Months Since Allocation
Mohr, et al. Lancet 2013;381:629-38 5 5

7. Farooq V et al. Lancet 2013;381:639-50
100 80 60
58.4%
4-year Mortality (%) 40
31.5% 20
15.1%
6.8% 3%
0.6%
1.3% 20 40 60 80
100
Total Points
Farooq V et al. Lancet 2013;381:639-50

8. MVD Pearls
Can I Completely Revascularize? (at least as well as the surgeon)

9. Complete Revascularization vs. Incomplete Revascularization in SYNTAX
Patients (%)
P=0.052
P=0.049
P=0.059
P=0.046
P=0.23
All-cause
Death
Cardiac
Death MI
CVA
All-cause
Revascul-arization
Stent
Throm- bosis
Death/CVA /MI
MACCE
Farooq et al, JACC 2013;xx:xxx-xxx 8

10. Residual SS in SYNTAX Trial
Low Baseline SYNTAX Score (0-22)
Intermediate Baseline SYNTAX Score (23-32)
High Baseline SYNTAX Score (≥33)
60%
60%
60%
Residual
SYNTAX Score
Log–rank
P value .022
Log–rank
P value <.001
Log–rank
P value <.001
50%
50%
>0–4
>4–8
>8
50%
40%
40%
40%
39.1%
34.1%
Estimated Event Rate
30%
30%
30%
23.8%
20%
20%
20%
13.8%
12.9%
11.5%
10%
10%
10.1%
10%
10.2%
7.7%
8.2%
9.3%
6.7% 0% 0% 0% 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5
All-Cause Death (y)
All-Cause Death (y)
All-Cause Death (y)
Farooq Circ 2013;128:141
Kereiakes et al, Rev Cardiovasc Med. 2014;15:24-30 9

11. Residual SS in SYNTAX Trial
All-cause Death
All-cause Revascularization
MACCE
60%
Log–rank
P value <.001
60%
Log–rank
P value <.001
60%
Log–rank
P value <.001
Residual
SYNTAX Score
59.5%
50%
50%
0 (n–386)
>0–4 (n–184)
>4–8 (n–167)
>8 (n–153)
50%
40%
40%
40%
41.3%
35.3%
32.0%
35.3%
Estimated Event Rate
30%
30%
29.9%
30%
27.7%
27.2%
20%
20%
20%
18.1%
11.4%
10%
8.7%
10%
10%
8.5% 0% 0% 0% 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5
All-Cause Death (y)
All-cause Revascularization (y)
MACCE (y)
Farooq Circ 2013;128:141
Kereiakes et al, Rev Cardiovasc Med. 2014;15:24-30 10

12. MVD Pearls
Aggressively approach CTOs

13. 13,443 stable patients who underwent 14,439 procedures, 2005 to 2009
Long-term Follow-up of Elective CTO Angioplasty: Analysis from the UK Central Cardiac Audit Database
13,443 stable patients who underwent 14,439 procedures, 2005 to 2009
Procedural success was 70.6% and mortality 5.6%
Successful revascularization of at least 1 CTO decreased mortality (adjusted HR 0.72; 95% CI ; P < .001)
Mortality risk was lower in patients who had complete revascularization of all vessels than in those whose procedures were partial (adjusted HR 0.70; 95% CI ; P =.002) or failed (adjusted HR 0.61; 95% CI ; P < .001)
Implications: Successful PCI and complete revascularization of all vessels both improve long-term survival in patients with CTO.
George S, et al. J Am Coll Cardiol. 2014;64:

14. MVD Pearls
SYNTAX score is not an absolute indicator of MACE especially with newer generation stents

15. Girasis et al, Euro Heart J 2011; “in press”
SIRTAX: SYNTAX Score Is Not a Measure of Absolute Risk: Different Stent, Different Outcomes % 60 60
SES
PES
SES
PES 50 50
P=0.46
P=0.98
P=0.001
P=0.95
P=0.35
P=0.21 40 40
MACE 1Y
DEATH 1Y 30 30
23.9 20 20
9.0
7.5
8.6
4.9 10
6.6
7.3 10
1.5
1.4
0.7
2.1
0.0
CSSLOW
n=282
CSSMID
n=283
CSSHIGH
n=283
CSSLOW
n=282
CSSMID
n=283
CSSHIGH
n=283
Girasis et al, Euro Heart J 2011; “in press” 14

16. Adjusted Event Rates: Death
BMS vs 1st Gen DES vs. 2nd Gen DES SCAAR: 94,384 consecutive pts in Sweden (BMS 64,631; 1st gen DES 19,202; 2nd gen DES 10,551
1st gen = Cypher, Taxus , Endeavor. 2nd gen = Resolute, Xience, Promus Element
Adjusted Event Rates: Death
Months
Adj HR of 2nd gen DES
vs. 1st gen DES: 0.77 [0.63–0.95]
vs. BMS: 0.55 [0.46–0.67]
BMS
1st gen DES
2nd gen DES 6% 5% 4% 3% 2% 1% 0% 3 6 9 12 15 18 21 24
Death (%)
Current and future DES and Past/Present/Future DES Fellows
Sarno G et al. EHJ 2012;33:606–13 15

17. MVD Pearls
Evaluate Diabetes in the overall context of the patient and anatomy

18. 1 Endpoint: Death, Stroke, or MI
FREEDOM: 1900 pts with diabetes
+MVD randomized to SES/PES vs. CABG
1 Endpoint: Death, Stroke, or MI 30
PCI/DES
CABG
26.6% 20
18.7%
Death, Stroke, MI, %
13.0% 10
11.9%
P = 0.005 1 2 3 4 5 6
Years
PCI/DES
953
848
788
625
416
219 40
CABG
943
814
758
613
422
221 44
Farkouh ME et al. NEJM 2012 17

19. SYNTAX Score I vs II: The SYNTAX Trial
Interactions: Diabetes
Diabetes was not an independent predictor of mortality or MACE in either the CABG or PCI arm, and had a negative interaction effect
Pinteraction = 0.67
Log HR
PCI
CABG No
Yes
Farooq V et al. Lancet 2013;381:639-50

20. Network Plot of Treatment Comparisons DES
SES
BMS
POBA
PES
CABG
CoCrEES
Network plot of treatment comparisons. Nodes and lines are weighted according to the number of studies providing direct comparisons between 2 treatments. BMS indicates bare metal stent; CABG, coronary artery bypass graft surgery; CoCrEES, cobalt–chromium everolimus-eluting stent; PES, paclitaxel-eluting stent; POBA, plain old balloon angioplasty; PtCrEES, platinum–chromium everolimus-eluting stent; SES, sirolimus-eluting stent; ZES-E, zotarolimus-eluting stent-endeavor; and ZES-R, zotarolimus-eluting stent-resolute.
ZES-R
ZES-E
PtCrEES
Copyright© American Heart Association, Inc. All rights reserved.
Bangalore S et al. Circ Cardiovasc Interv. 2014;7:

21. Bangalore S et al. Circ Cardiovasc Interv. 2014;7:518-525
Mixed treatment comparison analyses for coronary artery bypass graft surgery (CABG) vs percuDEs vs CABG in DMtaneous coronary intervention (PCI) for the outcome of all-cause mortality
Outcome: Mortality
Treatment
Control
Favor PCI
Favor CABG
Rate Ratio
95%
Crl
POBA
BMS
PES
SES
ZES-E
ZES-R
CoCr EES
vs. CABG
1.25
1.29
1.57
1.43
1.32
1.45
1.11
0.81
0.95
1.15
1.06
1.82
0.31
0.67
1.82
1.79
2.19
1.97
2.32
8.81
1.84
Mixed treatment comparison analyses for coronary artery bypass graft surgery (CABG) vs percutaneous coronary intervention (PCI) for the outcome of all-cause mortality. BMS indicates bare metal stent; CoCr EES, cobalt–chromium everolimus-eluting stent; CrI, credibility interval; PES, paclitaxel-eluting stent; POBA, plain old balloon angioplasty; RR, rate ratio; SES, sirolimus-eluting stent; ZES-E, zotarolimus-eluting stent-endeavor; and ZES-R, zotarolimus-eluting stent-resolute.
0.00
1.00
2.00
3.00
RR (95% Crl)
Copyright© American Heart Association, Inc. All rights reserved.
Bangalore S et al. Circ Cardiovasc Interv. 2014;7:

22. Bangalore S et al. Circ Cardiovasc Interv. 2014;7:518-525
Mixed treatment comparison analyses for coronary artery bypass graft surgery (CABG) vs percutaneous coronary intervention (PCI) for the outcome of myocardial infarction
Outcome: MI
Treatment
Control
Favor PCI
Favor CABG
Rate Ratio
95%
Crl
POBA
BMS
PES
SES
ZES-E
ZES-R
CoCr EES
vs. CABG
1.16
1.50
1.43
1.22
1.55
0.72
0.35
0.77
0.76
0.66
0.63
0.24
0.27
3.56
2.65
2.44
2.04
3.60
5.03
1.60
Mixed treatment comparison analyses for coronary artery bypass graft surgery (CABG) vs percutaneous coronary intervention (PCI) for the outcome of myocardial infarction. BMS indicates bare metal stent; CoCr EES, cobalt–chromium everolimus-eluting stent; CrI, credibility interval; PES, paclitaxel-eluting stent; POBA, plain old balloon angioplasty; RR, rate ratio; SES, sirolimus-eluting stent; ZES-E, zotarolimus-eluting stent-endeavor; and ZES-R, zotarolimus-eluting stent-resolute.
0.10
1.00
10.00
RR (95% Crl)
Copyright© American Heart Association, Inc. All rights reserved.
Bangalore S et al. Circ Cardiovasc Interv. 2014;7:

23. Bangalore S et al. Circ Cardiovasc Interv. 2014;7:518-525
Mixed treatment comparison analyses for coronary artery bypass graft surgery (CABG) vs percutaneous coronary intervention (PCI) for the outcome of repeat revascularization
Outcome: Repeat revascularization
Treatment
Control
Favor PCI
Favor CABG
Rate Ratio
95%
Crl
POBA
BMS
PES
SES
ZES-E
ZES-R
PtCr EES
CoCr EES
vs. CABG
4.41
3.18
1.81
1.47
2.35
2.40
3.02
1.31
1.80
2.11
1.19
0.95
1.30
1.01
0.72
0.74
10.97
5.01
2.77
2.23
4.18
5.84
13.26
2.29
Mixed treatment comparison analyses for coronary artery bypass graft surgery (CABG) vs percutaneous coronary intervention (PCI) for the outcome of repeat revascularization. BMS indicates bare metal stent; CoCr EES, cobalt–chromium everolimus-eluting stent; CrI, credibility interval; PES, paclitaxel-eluting stent; POBA, plain old balloon angioplasty; PtCr EES, platinum–chromium everolimus-eluting stent; RR, rate ratio; SES, sirolimus-eluting stent; ZES-E, zotarolimus-eluting stent-endeavor; and ZES-R, zotarolimus-eluting stent-resolute.
RR (95% Crl)
0.10
1.00
10.00
Copyright© American Heart
Association, Inc. All rights reserved.
Bangalore S et al. Circ Cardiovasc Interv. 2014;7:

24. MVD Pearls Carefully decide on treatment order
If staging make sure to treat the “culprit” in the first session in symptomatic patients
Try to bootstrap for complex lesions to minimize risk of an ultracomplex vessel
For CTO consider treating donor vessel to allow for retrograde option

25. MVD Pearls Optimize lesion preparation
MVD has a higher propensity for calcification
Think
Angiosculpt, CB
Roto, Orbital

26. MVD Pearls
Rational use of hemodynamic support

27. When Do I Consider Support?
Last Remaining Vessel
Severe LV dysfunction: support for ischemic stress and contrast load
LV dysfunction with prospect of uncontrolled interruption of coronary flow
Difficult wiring
Difficult stent delivery
High risk of no reflow (i.e., SVGs, Roto, thrombus)

28. Comparison of Support Devices
IABP
ECMO
TandemHeart
Impella CP
Catheter Size
21/18
21/17/15 9
Cannula Size
8.5-10 13
# Insertion Sites 1 2
Anticoagulation +
+++
++/+++
Transeptal No
Yes
Limb ischemia
Priming volume
Unloads Directly LV
Requires stable rhythm
Improve hemodynamics 27

29. PROTECT II Trial Design
Patients Requiring Prophylactic Hemodynamic Support
During Non-Emergent High Risk PCI on
Unprotected LM/Last Patent Conduit and LVEF≤35% OR
3 Vessel Disease and LVEF≤30% R
1:1
IABP +
PCI
IMPELLA 2.5 +
PCI
Primary Endpoint = 30-day Composite MAE* rate
Follow-up of the Composite MAE* rate at 90 days
* Major Adverse Events (MAE):
Death, MI (>3xULN CK-MB or Troponin) , Stroke/TIA, Repeat Revasc, Cardiac or Vascular Operation of Vasc. Operation for limb ischemia, Acute Renal Dysfunction, Increase in Aortic insufficiency, Severe Hypotension, CPR/VT, Angio Failure

30. MACCE Outcomes Based on the Extent of Revascularization
(All Patients, N=413)
IABP
IMPELLA
p=0.489
p=0.007
90 Day MACCE
↓ 46% MACCE
N=54
N=65
N=145
N=133
Limited Revascularization
D IZ [0-2]
Extensive Revascularization
D IZ [3-11]
Extent of Revascularization

31. Be Prepared to Consider Certain Cases for PCI after Heart Team Evaluation
High CABG risk
Low EF
Severe COPD
CKD
Unusual comorbidities

32. MVD Pearls Consider the patient’s point of view
While “Death and MI” may be key to clinical trialists the patient may believe otherwise

33. Two Very Different Procedures…

34. How Do Patients Weigh Outcomes?
224 respondents “SYNTAX eligible” for 3VD revascularization
Attribute
Relative Weight
Risk of Death within 3 yrs
0.23
Risk of Stroke within 3 yrs
0.18
Risk of MI within 3 yrs
0.14
Risk of Revasc. within 3 yrs
0.11
Expected ΔLife Expectancy over 7 yrs
0.17
Extent of Procedure (length, hospital stay, recovery time)
66% Captured by MACCE Endpoint
34% of total weight is not captured
Tong et al, Ann Thor Surg 2012 33

35. Scenario Presented PCI CABG Hospital stay 2 day 4 day Recovery 1 week
6 weeks
Death 6% 3% MI 7%
CVA 2%
Revasc
20%
10%
Life expectancy
1 year?
Blinded – 83% CABG
Open – 73% CABG
PCI Choice: more familiarity with PCI,
High socioeconomic status
Tong et al, Ann Thor Surgery 2012;94:1908

36. Palmerini et al. JACC 2012;60:798-805
Risk of Stroke with CABG vs PCI: Meta-analysis of 8 RCTs: 30-day Follow-up
MASS II
2/205
3.09 (0.62, 15.50)
6/203
GABI
0/182
5.20 (0.25, )
2/177
BARI
2/915
3.52 (0.73, 17.01)
7/914
ERACI 2
0/225
5.04 (0.24, )
2/225
AWESOME
2/222
1.44 (0.24, 8.71)
3/232
ARTS 1
4/600
1.49 (0.42, 5.32)
6/605
EAST
1/198
3.09 (0.32, 30.01)
3/194 1
.00574
174
Study
PCI
OR (95% CI)
CABG
PCI worse
CABG worse
4.02 (0.85, 19.03)
2/546
8/549
SYNTAX 3VD
I-squared=0%
2.62 (1.40, 4.91)
13/3093
37/3099
Fixed effects
Random effects
0.42%
1.19%
∆=0.77%
Palmerini et al. JACC 2012;60:

37. Is it Really 3 VD ? FAME: “Downgrading” Multivessel Disease with FFR
86% 3VD and 57% 2VD reclassified >1 vessel
Tonino et al, JACC 2010;55:

38. FAME 3: Study Flow: All Comers with 3 V CAD (not involving LM)
Heart team identifies lesions for PCI/CABG
and then patient is randomized
FFR-Guided PCI with Resolute DES
Stent all lesions with FFR ≤ 0.80
(n=750)
Perform CABG based on
coronary angiogram
(n=750)
Primary: One Year follow-up for Death, MI, CVA, Revascularization
Key Secondary: Three Year follow-up for Death/MI/CVA
Non-inferior Design
NCT

39. Conclusions
Multivessel PCI is appropriate for a large group of patients
Reflexive CABG referral is unwarranted
Careful assessment of patient, anatomy and treatment plan are essential for optimal results