Multivessel Coronary Artery Disease What Can Be Done
Multivessel Coronary Artery Disease: What Can Be Done to Improve Outcomes? Jeffrey J. Popma, MD Director, Interventional Cardiology Clinical Services Beth Israel Deaconess Medical Center Associate Professor of Medicine Harvard Medical School Boston, MA 1
Conflict of Interest Statement Within the past 12 months, I have had a financial interest/arrangement or affiliation with the organization(s) listed below. Physician Name Jeffrey J. Popma, MD Company/Relationship Research Grants: Cordis, Boston Scientific, Medtronic, Abbott-Guidant, e. V 3, Lab. Coat Medical Advisory Board: Cordis, Boston Scientific, Abbot Vascular 2
Improving Outcomes • Demonstrate Ischemia • Assess Clinical and Angiographic Risk • Appropriateness Guidelines SYNTAX Scores for PCI v. CABG • Liberal Use of FFR • Complete v. Incomplete Revascularization • Left Ventricular Support in low LVEF patients 3
Stable CAD Ischemia Matters Boden WE et al N Engl J Med 2007; 356: 1503 -16 Shaw, LJ Circulation 2008; 117: 1283 -1291 4
European Guidelines: Indications for Revascularization The ESC Guidelines have supported the use of revascularization in those patients with a substantial portion of myocardium (> 10%) at risk Wijns et al EHJ 2010 5
ISCHEMIA Trial International Study Comparing Health Effectiveness with Medical and Invasive Approaches • Patients with ≥ moderate ischemia randomly assigned to “cath+revasc” or “no cath” after CTA excludes left main disease • MAVERIC AND WISDOM Investigators merged • Judith Hochman/William Boden/Gregg Stone 6
Improving Outcomes • Demonstrate Ischemia • Assess Clinical and Angiographic Risk • Appropriateness Guidelines SYNTAX Scores for PCI v. CABG • Liberal Use of FFR • Complete v. Incomplete Revascularization • Left Ventricular Support in low LVEF patients 7
Existing Clinical & Angiographic Scores: Lack of Consistency in Predicting the Risk Proposed Score Variables used in Score Outcomes Clinical Angiographic Euro. SCORE 17 0 Mortality Mayo Clinic Risk Score 7 0 MACE SYNTAX score 0 11 / Lesion Anatomy complexity Society of Thoracic Surgeons score 40 2 Mortality Northern New England 8 0 Mortality New York CABG risk index 10 0 Mortality ACEF score 3 0 Mortality Global risk classification 17 11 / Lesion Cardiac Mortality New Risk Classification Score (NERS) 17 33 MACE Functional Syntax Score 1 11 / Lesion MACE 8
Quantitating Three Vessel Disease: SYNTAX Score Local Heart team (surgeon & interventional cardiologist) assessed each patient in regards to: Patient’s operative risk (Euro. SCORE & Parsonnet score) Coronary lesion complexity (newly developed SYNTAX score) The goal of the SYNTAX score is to provide a tool to assist physicians in their revascularization strategies for patients with high risk lesions Sianos et al, Euro. Intervention 2005; 1: 219 -227 Valgimigli et al, Am J Cardiol 2007; 99: 1072 -1081 Serruys et al, Euro. Intervention 2007; 3: 450 -459 Coronary tree segments based on the classification proposed by the AHA and modified for the ARTS study Circulation 1975; 51: 31 -3 & Semin Interv Cardiol 1999; 4: 209 -19 Dominance Number & location of lesions Left Main Calcification SYNTAX Thrombus score 3 Vessel Total Occlusion Bifurcation Tortuosity Leaman score, Circ 1981; 63: 285 -299 Lesions classification ACC/AHA , Circ 2001; 103: 3019 -3041 Bifurcation classification, CCI 2000; 49: 274 -283 CTO classification, J Am Coll Cardiol 1997; 30: 649 -656 9
Lesions Complexity Predicts Outcomes SYNTAX Score in 645 LM Patients treated with PCI (DES) SYNTAX Score > 36 > 23 & 36 23 Death/MI/Stroke p=0. 005 20% 12. 4% 10% 8. 7% 3. 7% 0% 0 360 720 1080 Days Post PCI Kim et al. J Am Coll Cardiol Intv 2010; 3: 612 -236 10
SYNTAX Score Is Insufficient: Clinical Morbidity Further Discriminates the Risk SYNTAX score < 19 L L > 27 I 96. 1% 94. 6% 90 80 3 -6 >6 L L I I I H GRC = The Global Risk Classification * log rank test; n = 255 LM patients undergoing PCI 78. 1% P = 0. 004* 70 LOW INTERMEDIATE HIGH 6 0 SYNTAX score 1 2 Time (months) 0 2 4 100 Cardiac death free survival (%) Euro. SCORE 0 -2 19 -27 Cardiac death free survival (%) 100 98. 4% 90 84. 0% 80 P < 0. 001* 70 LOW INTERMEDIATE HIGH 6 0 68. 6% GRC 1 0 2 Time (months) Capodanno et al, Am Heart J 2010: 159: 103 -9 2 4 11
ENDEAVOR IV Multicenter Randomized Trial vs Taxus PI: M. Leon and D. Kandzari Single De Novo Native Coronary Artery Lesions Reference Vessel Diameter: 2. 5 – 3. 5 mm Lesion Length: ≤ 27 mm Pre-dilatation required N = 1548 patients 1: 1 Randomization 80 US sites Endeavor Stent N = 774 Taxus Stent N = 774 Clinical endpoints 30 d Angio/IVUS endpoints 6 mo 8 mo 9 mo 12 mo 2 yr 3 yr 4 yr 5 yr QCA and IVUS Subset (328 total = 21. 2%) Primary Endpoint: TVF (cardiac death, MI, TVR) at 9 mo Secondary Endpoints: In-segment % DS at 8 mo; TLR and TVR at 9 mo Drug Therapy: ASA and clopidogrel/ticlopidine ≥ 6 mo 12
ENDEAVOR IV Cumulative Incidence of TLR to 5 Years Endeavor ZES Log Rank P = 0. 70 0. 9% Taxus PES 10% Cumulative Incidence for TLR 1 year >1 year to 5 years E-ZES 4. 5% E-ZES 3. 2% 8. 6% (60) 7. 7% (56) PES 3. 3% PES 5. 1% 8% 6% 4% 2% 0% 0 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 773 695 661 636 594 Taxus 775 771 695 665 626 593 13
Improving Outcomes • Demonstrate Ischemia • Assess Clinical and Angiographic Risk • Appropriateness Guidelines SYNTAX Scores for PCI v. CABG • Liberal Use of FFR • Complete v. Incomplete Revascularization • Left Ventricular Support in low LVEF patients 14
European Guidelines: SYNTAX The ESC Guidelines Uses SYNTAX score and the completeness of revascularization of PCI v. CABG Wijns et al EHJ 2010 15
Improving Outcomes • Demonstrate Ischemia • Assess Clinical and Angiographic Risk • Appropriateness Guidelines SYNTAX Scores for PCI v. CABG • Liberal Use of FFR • Complete v. Incomplete Revascularization • Left Ventricular Support in low LVEF patients 16
FFR vs. Angiography for Multivessel Evaluation: FAME Two Year FU FFR-Guided Angio-Guided 730 days 4. 5% Fearon TCT 2010 17
Improving Outcomes • Demonstrate Ischemia • Assess Clinical and Angiographic Risk • Appropriateness Guidelines SYNTAX Scores for PCI v. CABG • Liberal Use of FFR • Complete v. Incomplete Revascularization • Left Ventricular Support in low LVEF patients 18
Anatomy vs. Morbidity Risk Stratification STS score SYNTAX score Low Medium High Low PCI PCI Medium PCI ± Support PCI & Support High SYNTAX CABG BCIS CABG PCI & II PROTECT Support Or No Options 19
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 N = 448 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 (>3 x. ULN 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
SYNTAX vs PROTECT II SYNTAX PROTECT II PCI arm (n=448) (n=903) Age (Mean±SD) 65± 10 67± 11 Male (%) 76 82 DM (%) 26 52 Prior MI (%) 32 68 CHF (%) 4 87 LVEF ≤ 30% (%) 1. 3 92 Euroscore 4± 3 18± 18 (Mean±SD)
PROTECT II Summary • Rates of 30 -d MAE in the ITT analysis were not different (40. 1% for IABP v. 35. 1% for Impella; P = 0. 277). • There was a trend toward lower 90 day MAE in ITT pts treated with the Impella device (49. 3% for IABP v. 40. 6% for Impella; vs, P = 0. 066). • In the per protocol patients, a trend toward fewer MAE were noted with the Impella vs. IABP at 30 days (34. 3% vs 42. 2% , p=0. 092) and MAE were significantly lower at 90 days (40. 0% vs 51. 0%; P = 0. 023).
23 Angiographic Analysis: Objectives • To characterize the complexity of patients enrolled in PROTECT-II based on the extent of anatomic ischemia at the time of coronary revascularization • To related the extent of revascularization with the occurrence of 90 -day clinical events • To assess whethere are treatment effect differences with IMPELLA that related to the extent of revascularization performed
Ischemia Zone Score (IZ) • 396 angiograms • SYNTAX Scores were determined for all patients without prior CABG • Ischemia zone (IZ) scores were calculated using an 11 -point scoring system. • Scores include credit for patent SVGs and collaterals LCx=3 LAD= 6 RCA=2 Range of Ischemia Zone Score = [0 -11]
Limited Revascularization – Subject 039 -120 A-F Pre-procedure Post-procedure Pre-PCI IZ = 3 Post-PCI IZ =1 Delta (∆) IZ = 2 IZ = Ischemia Zone score
Extensive Revascularization – Subject 008 -142 M-B Pre-PCI IZ = 10 Pre-procedure Post-PCI IZ = 0 Delta (∆) IZ = 10 IZ = Ischemia Zone score Post-procedure
Was the Extent of Revascularization Similar in Both Treatment Groups?
Extent of Revascularization IABP Impella (N=211) (N=216) pvalue Average number of lesion tx 2. 87± 1. 2 2. 88± 1. 2 0. 98 Average lesion length 35. 1± 26. 3 36. 3± 27 0. 658 % of patients with 3 or more stents 41. 7% 51. 2% 0. 05 Pre PCI Syntax Score 30± 14 30± 13 0. 595 Post PCI Syntax Score 15± 13 0. 988 D (Pre- Post) in Syntax Score 16± 9 15± 10 0. 490 Pre PCI Ischemia zone score 8. 9± 2. 1 0. 662 Post PCI Ischemia zone score 4. 2± 2. 9 4. 4± 3. 2 0. 537 D Pre-Post Ischemia zone 4. 7± 2. 8 4. 4± 2. 9 0. 318 Procedural Characteristics
What Were the Predictors of Limited v. Extensive Revascularization?
Predictors of Limited Revascularization-I Δ IZ 0 -2 Δ IZ 3 -11 N=118 N-278 68. 0± 9. 7 88. 1 84. 7 38/17 43. 2 74. 6 67. 2± 11. 3 78. 8 88. 5 15. 4/11. 0 29. 2 65. 3 Prior CABG, % 55. 9 22. 7 Prior PCI, % PVD, % Diabetes mellitus, % 47. 5 26. 5 56. 8 35. 1 27. 2 50. 7 Characteristics Age, years Male Gender, % Unstable Angina, % NYHA Class III/IV, % Pacemaker / ICD Prior Infarction, % pvalue 0. 496 0. 028 0. 305 0. 720 0. 007 0. 072 < 0. 001 0. 022 0. 890 0. 269
Predictors of Limited Revascularization Characteristics COPD, % Renal Insufficiency, % LVEF, % Prior Stroke, Arrhythmia STS PROM, % Logistic Euroscore Additive Euroscore Surgical Refusal, % Δ IZ 0 -2 Δ IZ 3 -11 N=118 N-278 pvalue 19. 7 28. 2 23. 4 5. 7 17. 8 49. 2 6. 94± 7. 65 20. 1± 16. 9 9. 04 56. 8 29. 7 25. 5 23. 7 6. 6 14. 0 47. 8 5. 57± 6. 17 17. 7± 15. 6 8. 49 67. 3 0. 039 0. 583 0. 590 0. 339 0. 809 0. 086 0. 221 0. 232 0. 047
Was there a difference in the outcome based on the extent of revascularization?
MAE Outcomes Based on the Extent of Revascularization Extensive Revasc. Limited Revasc. p=0. 03 90 day MAE 1 st Tercile Limited Revasc D IZ [0 -2] 2 nd Tercile More Extensive Revasc D IZ [3 -5] 3 rd Tercile Most Extensive Revasc D IZ[6 -11] Extent of Revascularization (by Terciles of D IZS ) MAE= Major Adverse Event Rate; D IZ = Delta Ischemia Zone score (Pre. PCI - Post. PCI)
90 day Outcome By Extent of Revascularization Characteristics Δ IZ 0Δ IZ 6Δ IZ 3 -5 2 11 N=133 N=119 1 N=145 pvalue MAE 55. 1 40. 6 41. 4 0. 036 Death/MI/Stroke/Reva sc 40. 7 25. 6 26. 2 0. 014 MACCE 1 33. 9 24. 1 20. 033 MACCE = Death, Stroke, Large MI*, Revasc. (*Stone et al. Circulation 2001; 104: 642 -647)
Was there a difference in the treatment effect based on the extent of revascularization?
Limited Revascularization (Δ 0 -1) Characteristics Age, years Male Gender, % Unstable Angina, % NYHA Class III/IV, % Pacemaker / ICD Prior Infarction, % Prior CABG, % Prior PCI, % PVD, % Diabetes mellitus, % IABP IMPELLA N=53 N=65 pvalue 66. 4± 9. 6 69. 3± 9. 7 0. 112 88. 7 87. 7 0. 869 41. 7 42. 2 0. 960 48. 8 59. 6 0. 282 37. 7 47. 7 0. 277 69. 8 78. 5 0. 283 50. 9 60. 0 0. 324 47. 2 47. 7 0. 955 26. 4 26. 6 0. 986 47. 2 64. 6 0. 057 Limited Revascularization =DIZS[0 -2]; D IZS = Delta Ischemia score (Pre. PCI - Post. PCI)
Limited Revascularization (Δ 0 -1) Characteristics COPD, % Renal Insufficiency, % LVEF, % Prior Stroke, % Arrhythmia, % STS PROM, % Logistic Euroscore Additive Euroscore Surgical Refusal, % IABP IMPELLA N=53 N=65 pvalue 21. 2% 18. 5 0. 715 26. 9 29. 2 0. 783 23. 6± 6. 0 23. 2± 5. 4 0. 703 17. 0 18. 5 0. 834 49. 1 49. 2 0. 985 6. 8± 9. 2 7. 1± 6. 2 0. 855 17. 8± 14. 9 21. 9± 18. 2 0. 197 8. 4± 3. 1 9. 6± 3. 7 0. 60 37. 7 46. 2 0. 357 Limited Revascularization = DIZS[0 -2]; D IZS = Delta Ischemia score (Pre. PCI - Post. PCI)
90 day Outcomes With Limited Revascularization (Δ 0 -2) 1 N=65 Relative Difference pvalue 50. 9 58. 5 13% 0. 414 Death/Stroke/ MI/Revasc 35. 8 44. 6 20% 0. 335 MACCE 1 32. 1 35. 2 8% 0. 706 Events IABP IMPELLA N=54 MAE MACCE = Death, Stroke, Large MI*, Revasc. (*Stone et al. Circulation 2001; 104: 642 -647)
Extensive Revascularization (Δ 3 -11) Characteristics Age, years Male Gender, % CHF, % NYHA Class III/IV, % Pacemaker / ICD Prior Infarction, % Prior CABG, % Prior PCI, % PVD, % Diabetes mellitus, % IABP N=145 IMPELLA p-value N=133 67. 3± 11. 4 67. 1± 11. 4 0. 887 80. 7 76. 7 0. 415 84. 1 93. 2 0. 018 54. 9 57. 3 0. 712 29. 9 28. 6 0. 814 66. 2 64. 4 0. 751 20. 7 24. 8 0. 412 34. 0 36. 4 0. 685 27. 6 26. 7 0. 871 51. 0 50. 4 0. 913
Extensive Revascularization (Δ 3 -11) Characteristics COPD, % Renal Insufficiency, % IABP N=145 IMPELLA p-value N=133 29. 9 29. 5 0. 954 29. 7 21. 1 0. 100 LVEF, % Prior Stroke, Arrhythmia STS PROM, % 23. 9± 6. 5 23. 5± 6. 6 0. 615 17. 9 9. 8 0. 050 45. 8 50. 0 0. 489 5. 9± 6. 4 5. 2± 5. 9 0. 307 Logistic Euroscore 18. 0± 17. 5± 17. 2 0. 813 Additive Euroscore Surgical Refusal, % 8. 2± 3. 7 8. 7± 7. 1 0. 476 51. 0 46. 6 0. 462 Extensive Revascularization =DIZS[3 -11]; D IZS = Delta Ischemia score (Pre. PCI - Post. PCI)
90 -Day Outcome With Extensive Revascularization (combined 2 nd and 3 rd terciles) 1 N=133 Relative Difference pvalue 49. 0 32. 3 34% 0. 005 Death/Stroke/ MI/Revasc 31. 0 20. 3 35% 0. 041 MACCE 1 28. 3 15. 0 47% 0. 008 Events IABP IMPELLA N=145 MAE MACCE = Death, Stroke, Large MI*, Revasc. (*Stone et al. Circulation 2001; 104: 642 -647)
42 Protect-II Analysis: Conclusions • The extent of revascularization was similar in patients randomized to IABP and IMPELLA • Patients with more extensive revascularization had improved outcomes at 90 -days than patients with limited revascularization • There was no difference in outcomes between IMPELLA and IABP in patients with limited revascularization • In patients undergoing extensive revascularization, IMPELLA substantially reduced 90 -day events compared with IABP by 34%
Improving Outcomes After PCI • Documentation of ischemia is essential when deciding on revascularization in patients with mutlivessel CAD • SYNTAX and STS scores are important risk criteria • FFR can you used in intermediate lesions • In patients with extensive CAD and reduced LV function undergoing PCI, the goal should be to perform as much revascularization as possible in order to reduce 90 -day event rates, including death, MI, and revascularization • Temporary left ventricular support substantially improves clinical outcomes in patients undergoing extensive revascularization 43
- Slides: 43