1. Complex Coronary Cases
Supported by:
Abbott Vascular Inc
Boston Scientific Corp
Terumo Vascular Corp
Vascular Solutions Inc
Cardiovascular Science Inc
AstraZeneca Pharmaceuticals
The Medicines Company

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. February 17th 2015 Case #68: MW, 60 yrs M
Presentation:
Patient without prior history of MI, presented with new onset CCS Class II angina and high-risk stress MPI for anterior and inferior ischemia with infarction and TID. A cardiac cath on Jan 8th 2015 revealed 2 V CAD and LVEF 40% and SYNTAX score 21. Pt underwent PCI using Promus Premier DES to mid RCA and did well. Still has moderate angina largely due to residual multiple diffuse LAD lesions
Prior History:
Hypertension, NIDDM, Hyperlipidemia, +F/H, Ankylosing Spondylitis
Medications: All once daily dosage
Metoprolol XL 50mg, Amlodipine 5mg, Metformin XL 1000mg, ASA 81mg, Atorvastatin 40mg, Clopidogrel 75mg, Methotrexate 5mg 3

4. Case# 68: cont… Cardiac Cath 1/8/2015: Right Dominance
II V CAD with LVEF 40%
RCA: 90% lesion in mid, large size
LM: No obstruction
LAD: 90% heavily calcified mid LAD with % distal lesion; moderate size with diffuse disease, mild diffuse D1
LCx: 80% heavily calcified prox LCx lesion, large size vessel
Pt underwent PCI of mid RCA with Promus Pr DES (3/28mm)
SYNTAX Score was : 21
Plan Today:
PCI of diffusely diseased multiple calcified lesions of mid and distal LAD. Now SYNTAX score is 17. 4

5. Appropriateness Criteria for Coronary Revascularization

6. Issues Involving The Case
Complete vs. Incomplete Revascularization
in Stable CAD
Management Options in Refractory Angina

7. Issues Involving The Case
Complete vs. Incomplete Revascularization
in Stable CAD
Management Options in Refractory Angina

8. Arms of “All-Comers” SYNTAX Population
Flow Chart of Frequency of Complete Revascularization (CR) vs In-Complete Revascularization (ICR) in PCI and CABG;
Arms of “All-Comers” SYNTAX Population
Farooq et . al., J Am Coll Cardiol 2013;61:282 8

9. SYNTAX Trial PCI Group: 4-Year Clinical Outcomes
by Complete vs. Incomplete Revascularization
Complete Revascularization (n=578)
Patients (%)
p=<0.001
Incomplete Revascularization (n=510)
p=0.011
p=0.052
p=0.059
p=0.046
p=0.23
Farooq et . al., J Am Coll Cardiol 2013;61:282 9

10. SYNTAX Trial CABG Group: 4-Year Clinical Outcomes by Complete vs
SYNTAX Trial CABG Group: 4-Year Clinical Outcomes by Complete vs. Incomplete Revascularization
Complete Revascularization (n=1031)
Patients (%)
Incomplete Revascularization (n=483)
p=0.013
p=0.07
p=0.039
p=0.026
p=0.64
p=0.01
p=0.076
p=0.98
Farooq et . al., J Am Coll Cardiol 2013;61:282 10

11. Four-Year MACCE in the SYNTAX Trial: Stratified
by Presence of ICR vs. CR in Patients with CTOs
PCI Group: CTO (N= 286)
CABG Group: CTO (N= 554)
P-value 0.024
P-value 0.015
ICR: 39.9%
ICR: 27.8%
CR: 26.6%
CR: 18.7%
Farooq et . al., J Am Coll Cardiol 2013;61:282 11

12. The Residual SYNTAX Score (rSS)
Rationale: Calculated as the SYNTAX score of untreated lesions after the procedure
Strengths: The residual SYNTAX Score (rSS) has the potential to get a standardized quantification of incomplete revascularization linked to potential prognostic implications.
º rSS = 0 means complete revascularization
º rSS > 0 quantifies increasing levels of
incomplete revascularization
Minus the Lesions underwent revascularization
SYNTAX Score

13. SYNTAX Trial: The Residual SYNTAX Score (rSS)
Généreux et al., J Am Coll Cardiol 2012;59:2165

14. The Residual SYNTAX Score Components in Patients
with Incomplete Revascularization According to Tertile
Residual SS
1-2 (n=523)
Residual SS >2-8 (n=578)
Residual SS >8 (n=501)
P Value
Severe calcification
0.0
1.7
11.8
<0.001
CTO
0.2
10.0
43.1
Bifurcation/trifurcation
30.9
57.3
Aorto-ostial lesion
0.7
0.3
Lesion length >20 mm
0.6
24.7
70.1
Small vessel/diffuse dz
78.2
52.4
52.7
Généreux et al., J Am Coll Cardiol 2012;59:2165

15. Residual SYNTAX Score: 1-Year Outcomes According to the rSS
P = 0.006
P = 0.32
(%)
P = 0.007
P = 0.001
P = 0.23
Death
UTVR
MACE MI ST
Généreux et al., J Am Coll Cardiol 2012;59:2165

16. The Residual SYNTAX Score: Death
Généreux et al., J Am Coll Cardiol 2012;59:2165

18. SYNTAX Trial-PCI arm: Complete and Incomplete Revascularization Stratified by Baseline SYNTAX Score
Residual SYNTAX Score
0 (n=386)
>0-4 (n=184)
>4-8 (n=167)
>8 (n=153)
p=<0.001
p=0.06
p=<0.001 %
n=290
n=310
Farooq et al., Circulation 2013;128:141

19. SYNTAX Trial-PCI Arm: 5-Year Clinical Outcomes
Based on the Residual Syntax Score after TAXUS DES
Farooq et al., Circulation 2013;128:141

20. SYNTAX Trial-PCI Arm: 5-Year Clinical Outcomes
Based on the Residual Syntax Score after TAXUS DES
Farooq et al., Circulation 2013;128:141

21. SYNTAX Trial-PCI Arm: 5-Year Clinical Outcomes
Based on the Residual Syntax Score after TAXUS DES
Farooq et al., Circulation 2013;128:141

22. SYNTAX Trial-PCI Arm: 5-Year Clinical Outcomes
Based on the Residual Syntax Score after TAXUS DES
Farooq et al., Circulation 2013;128:141

24. Issues Involving The Case
Complete vs. Incomplete Revascularization
in Stable CAD
Management Options in Refractory Angina

25. Refractory Angina Pectoris
Definition
By the ESC Joint Study Group Refractory Angina is defined as:
“a chronic condition (≥3 months) characterized by the presence of angina caused by coronary insufficiency in the presence of CAD, which is not amenable to a combination of medical therapy, angioplasty, or coronary bypass surgery” in patients with evidence of ischemia.
Patients can be suboptimal candidates for revascularization for many reasons, including having unsuitable coronary anatomy (severe diffuse atherosclerosis, or the absence of targets or lack of graft conduits for CABG surgery), the presence of substantial comorbidities (severe left ventricular dysfunction, peripheral artery disease, or chronic kidney disease), or because of advanced age.

26. Management Options in Refractory Angina
Pharmacologic
Non-Invasive
Invasive
Oral nitrate
Enhanced External Counterpulsation (EECP)
Trans-myocardial Revascularization (TMR)
β-blockers
Cardiac Rehabilitation
Angiogenesis
Calcium Channel blockers
Exercise Programs
Transcutaneous Electrical Nerve Stimulation (TEMS)
Ranolazine: MARS, CARISA
Self Management Training
Spinal Cord Stimulation (SCS)
Trimetazidine
Thoracic Epidural Anesthesia (TEA)
L-Arginine
Endoscopic Thoracic Sympathectomy (ETS)
Nicorandil
Left Stellate Ganglion Block (LSGB)
Ivabradine
Coronary Sinus Reduction Stent
Heart
Transplantation

29. Management Options for Refractory Angina
Henry et al., Nat Rev Cardiol 2014;11:78

30. Emerging Pharmacological Therapies for Refractory Angina
Pharmacological Agent
Proposed Mechanism of Action
Comments
Chelation Therapy
EDTA (associated with carious vitamins)
Mechanism of action uncertain, possibly associated with reduced oxidation of low-density lipoprotein, vasodilatory effects, and enhanced production of tissue plasminogen activator.
Remains controversial despite data from the TACT trial. No efficacy on angina per se, but frequently administered to pts with advanced CAD unsuitable for revascularization. Class IIb
Rheological agents
Intermittent thrombolytics (urokinase)
Depletion of plasma fibrinogen, which reduces blood viscosity and improves the rheological properties of blood in the microcirculation.
Historical interest. Administered in some of Europe to treat patients with refractory angina.
Testosterone
Promotes endothelium-dependent relaxation of coronary arteries.
Inadequately investigated in patients with ischemic heart disease.

31. Neurogenic Components of Angina & Treatment Options
Henry et al., Nat Rev Cardiol 2014;11:78

32. Effect of Spinal Cord Stimulation (SCS) on
Exercise Capacity
Henry et al., Nat Rev Cardiol 2014;11:78

34. Surgical Operations for Angina
Placing a suture around the coronary sinus
Partial ligation of the
coronary sinus
Beck et al., JAMA 1954;156:1226

36. Coronary Sinus Reducer System
Complete system for coronary-sinus reducing device comprises of metal mesh premounted on a balloon catheter shaped like an hour glass when expanded
Verhehye et al., N Engl J Med 2015;372:519

37. Schematic Illustration Describing the Implantation Process of the CS Reducer
Konigstein et al., EuroIntervention 2014;9:1158

38. CT Angiogram of the Device in the Coronary Sinus Denotes Patency at 6 Months
Longitudinal CT angiographic view of the device in the coronary sinus show flow of contrast material
Cross-sectional CT angiographic view of the device in the coronary sinus show flow of contrast material
Verhehye et al., N Engl J Med 2015;372:519

39. Coronary Sinus Reducer System
The most commonly proposed mechanism
of benefit are mediated via elevated CS pressure causing:
recruitment of coronary collateral flow
redistribution of blood from the less-ischemic epicardium to the ischemic sub-endocardium
development of new collaterals/blood vessels
facilitate the dilatation of constricted sub-endocardial capillaries/arteriole
Net result being enhanced perfusion of the ischemic myocardium
and consequently hemodynamic parameters and angina symptoms
will improve

40. Change in Canadian Cardiovascular Society (CSS) Angina Class
Improvement in CCS Class
Mean Change in CCS Class
Verhehye et al., N Engl J Med 2015;372:519

41. CCS Angina Class at Baseline and 6 Months After Randomization
Verhehye et al., N Engl J Med 2015;372:519

42. Changes from Baseline to 6 Months Follow-up Exercise Tolerance Test
Verhehye et al., N Engl J Med 2015;372:519

43. Changes from Baseline to 6 Months Follow-up
Dobutamine Stress Echocardiography
Verhehye et al., N Engl J Med 2015;372:519

44. Death/MI were not different between 2 groups; 3 MI / 1 death in Control gp
1 MI / 0 death in Treatment gp

45. Take Home Message: Complete vs
Take Home Message: Complete vs. In-Complete Revascularization (ICR) and Management Options for Refractory Angina
Complete revascularization (CR) compared to ICR after PCI or CABG, is associated with lower long-term MACE including death. CABG is associated with lower ICR vs. PCI. Residual Syntax score of >8 is associated with higher death and other major cardiac events. Hence in PCI of complex lesions with high Syntax score, efforts should be made to optimize PCI procedures towards eye for CR
Of the various emerging treatment options for refractory angina despite MMT, coronary sinus reducing device seems to have the best potential in reducing angina severity and improving exercise tolerance.

46. Question # 1
In the SYNTAX trial increasing residual Syntax score is associated with increasing all adverse cardiac events except:
Stent thrombosis
Target vessel revascularization
Myocardial infarction
Death
MACCE

47. Question # 2
In pts with high Syntax score, following strategies are associated with higher complete vs. incomplete revascularization except:
PCI of all lesions including bifurcation lesion
Refer pt preferentially to CABG
PCI of all lesions except one difficult mid LAD CTO
PCI of all lesions except of non-dominant RCA CTO
PCI of ULM lesion including LAD bifurcation except of OM1

48. Question # 3
Recent randomized trial of Coronary sinus reducer device compared to placebo showed the following:
A. Lower incidence of MI
B. Higher CCS class III at follow-up
C. Lower mortality
D. Higher device related complications
E. Higher >2 CCS angina class improvement

49. Question # 1 The correct answer is A
In the SYNTAX trial increasing residual Syntax score is associated with increasing all adverse cardiac events except:
Stent thrombosis
Target vessel revascularization
Myocardial infarction
Death
MACCE
The correct answer is A

50. Question # 2 The correct answer is C
In pts with high Syntax score, following strategies are associated with higher complete vs. incomplete revascularization except:
PCI of all lesions including bifurcation lesion
Refer pt preferentially to CABG
PCI of all lesions except one difficult mid LAD CTO
PCI of all lesions except of non-dominant RCA CTO
PCI of ULM lesion including LAD bifurcation except of OM1
The correct answer is C

51. Question # 3 The correct answer is E
Recent randomized trial of Coronary sinus reducer device compared to placebo showed the following:
A. Lower incidence of MI
B. Higher CCS class III at follow-up
C. Lower mortality
D. Higher device related complications
E. Higher >2 CCS angina class improvement
The correct answer is E