Interventional Cardiology חיים דננברג מערך הלב

Transcription

1 Interventional Cardiology חיים דננברג מערך הלב הדסה עין-כרם

2 History Claude Bernard. Introduced catheter through carotid artery of a horse into left ventricle to measure temperature Werner Forsmann. Introduced urologic catheter from brachial vein into right atrium.

3 WERNER FORSSMANN, M.D.

4 History

5 History 1940s- Cournand. Systematic investigation of right heart pressures in normal and diseased hearts Sones. Established technique for selective angiography of the coronary arteries Dotter. First balloon angioplasty for peripheral artery stenosis Judkins. Femoral approach coronary angiography Greuntzig. First human angioplasty for coronary artery stenosis.

6 The age of Intervention PTCA Percutaneous Transluminal Coronary Angioplasty

7

8

9

10

11 Mechanism of angioplasty i. Compression and redistribution of plaque ii. Embolization of plaque components iii. Arterial enlargement (aneurysm formation) iv. Disruption of plaque and arterial wall v. Intimal tears and dissections

12 Indication for PTCA according Andreas Gruntzig View Proximal stenosis Good left ventricular function No left main No calcified lesion

13 PTCA Indications for PTCA: Single vessel disease Proximal Lesions Contra- indications: Left main, Multivessel, Acute MI, Total occlusion, Bifurcation's, Tortuosity...

14 Indication 2010 for PCI There are in general no contraindications The only indication for CABG is a failed PTCA G.Hartzler

15 A wide variety of balloons

16 Timeline You Are Standing Here Phase 4 Phase 5 * 2010 Drug Drug Eluting stents Brachytherapy Phase 3 Primary Angioplasty for MI Phase 2 Stenting Phase 1 POBA

17 Simpson 1986: Coronary directional atherectomy in humans

18 Directional Coronary Atherectomy Debulking gives Less elastic recoil Less dissection Wider lumen Smoother lumen

19 Applications of DCA Type A lesion in large vessel (> 3mm) Severely eccentric lesion Abnormal contour (ulceration, flap, limited dissection) Ostial lesion Large bifurcation lesion Moderately lenghthy lesion in large vessel Salvage for failed PTCA

20 Auth 1988: rotablator

21 Applications for Rotablator Calcified lesions Tortuous lesions Ostial lesions Undilatable lesions Debulking in Instent restenosis

22 Coronary Dissections

23 Sigwart 1986: coronary stenting

24 Stents Better Stent Designs Customized Stents Bifurcation Stents Coated/Covered Stents Radioactive Stents

25 100% Guiding Catheter Interventional Cardiology Technical evolution Drug-eluting Stent Steerable guidewire DCA Balloon 9F 8F 7F 6F Rotablator Stent J. Simpson 5-8% Direct stenting Gruntzig Simpson Puel Bertrand BENESTENT Teirstein Sigwart STRESS King 5F Brachytherapy Modified from Michel Bertrand

26 Current Problems Platelet Activation Restenosis

27 Restenosis Data *Model based on 1555 patients in C-DAC stent trials Post-Procedure Lesion Length In-Stent MLD 10 mm 15 mm 20 mm 25 mm Diabetics 2.5 mm 35% 39% 43% 46% 3.0 mm 23% 26% 30% 33% 3.5 mm 15% 17% 19% 22% 4.0 mm 9% 10% 12% 14% Non-Diabetics 2.5 mm 27% 30% 33% 37% 3.0 mm 17% 19% 22% 25% 3.5 mm 10% 12% 14% 16% 4.0 mm 6% 7% 8% 10%

28

29 In-Stent Restenosis Compared to Pooled Palmaz-Schatz MULTI-LINK PS NIR PS MICRO II PS GR II PS Odds Ratio Serruys, 1998

30 Closed Cell Design

31 Open Cell Design

32 Closed Cell vs Open Cell Stents Closed Cell Open Cell

33 Pharmacological approches to prevent restenosis Antiplatelet and antithrombotic agents Anti-inflammatory drugs Specific growth factor antagonist Antiproliferatives and antineoplastics Vasodilators Lipid-lowering agents and antioxidants Local drug delivery and molecular strategies

34 Radiation Trials Study WRIST SVG-WRIST Long WRIST GAMMA-1 ARTISTIC Beta-WRIST INHIBIT START Source 192 Ir 192 Ir 192 Ir 192 Ir 192 Ir 90 Y 32 P 90 Sr/Y Dose (Gy) Patients

35 In-Stent Restenosis

36 Sirolimus (Rapamycin) A naturally occurring antimicrobial first found on Easter Island Potent immunosuppressive activity Developed and marketed by Wyeth Ayerst Labs for prevention of renal transplant rejection (Rapamune )* Novel inhibitor of growth factor & cytokine-stimulated cell proliferation Mechanism of action: cell-cycle inhibition *Rapamune is a registered trademark of Wyeth Ayerst. Sirolimus, mw = 914

37 Histology of Sirolimus stent 3 days 30 days Control Sirolimus-coated

38 The DES Revolution

39 Paclitaxel

40 Components of the Endeavor Stent Cobalt Alloy Modular stent Strut thickness Delivery based on discrete, secure Technology ABT-578 (Sirolimus analogue) 10 µg/mm stent dosage Biocompatible PC Technology (phosphorylcholinepolymer)

41 SIRIUS Clinical Data: Odds Ratio for TLR by Subgroup at 9 Months Sirolimus Control P value Overall Male Female Diabetes No Diabetes LAD Non-LAD Small Vessel (<2.75) Large Vessel Short Lesion Long Lesion (>13.5) Overlap No Overlap # events prevented per 1,000 patients Hazards Ratio 95% CI E. Perin, Challenging Decisions in the Use of Drug-Eluting Stents, The Journal of Invasive Cardiology, Volume 16/Supplement F, Sept

42 TAXUS IV Clinical Data: Odds Ratio for TLR by Subgroup at 9 Months Taxus Control P value # events prevented per 1,000 patients Overall Diabetes - oral < Diabetes - insulin No Diabetes LAD Non LAD RVD <2.5 RVD >3.0 Lesion >20 mm Lesion <10 mm Overlap No Overlap Odds Ratio + 95% CI < < < E. Perin, Challenging Decisions in the Use of Drug-Eluting Stents, The Journal of Invasive Cardiology, Volume 16/Supplement F, Sept 2004

43

44 ENDEAVOR II TLR-Free Survival at 360 Days Freedom from TLR 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% DRIVER (Event Free ±1.5 SE) ENDEAVOR 94.0% 86.9% p<0.001, log rank Time after Initial Procedure (days)

45 To DES or not to DES?

46

47 Choice of DES: Release Kinetics

48 Stent 14 d. Rabbit Iliac

49 Late Loss & TLR Vs. Stent Type Mauri et al. Circ 2005

50 Late Loss and stent type t al. Circulation 2005 Adjusted to DM and lesion length

51 Choice of Stent CYPHER Sirolimus-eluting Stent TAXUS paclitaxel-eluting stent 140 µg/cm 2 sirolimus 100 µg/cm 2 paclitaxel ABT-578 ENDEAVOR ABT-578 eluting Stent Cytostatic MoA antiproliferative and anti-inflammatory action Released from closed-cell stent system Cytotoxic MoA antiproliferative effect Closed-cell stent system Sirolimus analogue Open cell system

52 RCTs Comparing Cypher to Taxus Study design Multicenter Clininical primary endpoint Primary endpoint Time of PE Parameter Patients Lesion length Vessel diameter Restenosis in Segment Late lumen Loss in Stent TVR MACE Primary Endpoint reached Major limitation TAXi not defined no n/a n/a 6 months n/a 102/100 not mentioned (3.2/3.2) n/a n/a 2.0/ /4.0 n/a no primary endpoint REALITY Cypher superior yes no angiographic 8 months in lesion RR 684/669 (17.0/17.3)10<;15< (2.4/2.4) /11.1 *0.09/ / /10.8 no no clinical primary endpoint SIRTAX Cypher superior no yes clinical 9 months MACE 503/509 "all"(12.4/13.4) (2.8/2.8) *6.7/11.9 *0.13/0.25 *6.0/9.2 *6.2/10.8 yes no multicenter trial ISAR-Diabetes non-inferior no no angiographic 6 months in-segment LLL 125/ / /2.8 *6.9/16.5 *0.43/ /12.2TLR No; in Seg LL(0.19/0.46*) no clinical primary endpoint The only study reaching the primary endpoint was SIRTAX, but it was not a multicenter study. There is no randomized, controlled multicenter trial with a primary clinical endpoint and adequate power showing that one DES is superior to another.

53

54

55 STENT THROMBOSIS Stent Stent

56

57

58

59 New Stents: Everolimus eluting stents

60 New Stents: Microporous Yukon (Translumina) Before After

61

62 New stents: Bioabsorbable

63 BVS bioabsorbable stent

64

65 New Stents: EPC surface capture

66 EPC capture: 1h.

67

68 Dedicated small vessel stent

69 ..There are costs and risks to a program of action but they are far less than the long-range costs and risks of comfortable inaction.. J.F.K