Conquering the Complex Coronary Intervention… Lesions, Drugs, Devices and Stress William O. Suddath, M. D. Director, Interventional Cardiology Training Georgetown University Washington Hospital Center

I have no real or apparent conflicts of interest to report. William O. Suddath, MD I have no real or apparent conflicts of interest to report.

Evolution of Percutaneous Coronary Reperfusion FDA Approval DES CMS Approval DES Cypher FDA Approval Cook Stent-bail out JJIS stent-elective Introduction of Thrombolytic Therapy HFICA Approval Stent Brachytherapy 1st PTCA DES Thrombosis Introduction of IV NTG ACEI Statins Approval of PCI for AMI GUSTO, PACT trials Clinical Trials -Dir Atherectomy -Stent -Rotablator -Excimer Laser PCI for AMI BSC Approval TAXUS 3

Complex Lesions / Complex Disease AMI Calcification Multistenting Ostium Thrombus Long lesions CTO Unstable angina Multivessel Saphenous graft Bifurcation Diabetes Chronic renal failure Left main Diffuse disease “REAL WORLD”

Pathophysiology of ST-Elevation Myocardial Infarction Generally caused by a completely occlusive thrombus in a coronary artery Results from stabilization of a platelet aggregate at site of plaque rupture by fibrin mesh Review pathophysiology for STEMI. Contrast this with other ACS presentations (UA and non-STEMI). platelet RBC fibrin mesh GP IIb-IIIa 6

1. Time is Myocardium 2. Infarct Size is Outcome 100 D 80 60 Mortality Reduction (%) C 40 20 B A Extent of Myocardial Salvage 4 8 12 16 20 24 Time From Symptom Onset to Reperfusion Therapy, h Critical Time-dependent Period Goal: Myocardial Salvage Time-independent Period Goal: Open Infarct-Related Artery Gersh BJ, et al. JAMA. 2005;293:979.

MedSTAR Transport Washington Hospital Center Washington, DC 8 8

America’s Aging Society -- Over 65: 72 million, represents 20% of populace in next twenty years --Over 85: 18 million by 2050 --Only 20% are fully mobile --50% have some degree of dementia

Approach Understand, It’s a team effort… Know your teams strengths and weakness Anesthesia Surgery Recruit advice and opinion… it’s not a sign of weakness Put away your ego…

Anatomical Considerations Rational Anatomical Considerations Radial Cannulation Superficial artery Easy compression Early ambulation

Angiography 2D Longitudinal Lumen Imaging

New Technologies

IVUS Imaging 2D Cross-Sectional Imaging

IVUS Imaging: Plaque Surface and Volume Transverse Plane Longitudinal Plane

Pharmacology ASA Anticoagulation… bivalrudin, oral Xa Antiplatelet Therapy… which one? Adjunctive Therapy… vasodilators Lytic Therapy II B, III A Inhibition

Indirect vs Direct Thrombin Inhibition Indirect inhibition by heparin requires the presence of antithrombin (AT), the actual inhibitor. Heparin (long yellow strand) binds to AT, causing a shape change that increases the ability of AT to inhibit thrombin. Direct inhibition with Angiomax® (bivalirudin) inhibits thrombin directly with high affinity and specificity. It requires no cofactor, and acts alone. Bivalirudin’s effectiveness is not affected by variability in the concentration of a co-factor like AT. Key Message: Angiomax inhibits thrombin directly; therefore, it does not promote coagulation. On the left panel, heparin is not labeled but is represented by the long strand. Several “antithrombin” agents have been developed to prevent coagulation for many clinical circumstances. Heparin is a ubiquitous agent in the hospital and outpatient settings that is an imprecise and inefficient anticlotting agent. Indirect inhibition by heparin requires the presence of antithrombin (AT), the actual inhibitor in the clotting cascade. The panel on the left shows heparin (see the long strand) binding to AT and causing a shape change that increases the ability of AT to inhibit thrombin. Angiomax inhibits thrombin directly with high affinity and specificity. The panel on the right shows Angiomax binding to thrombin. Angiomax provides rapid, effective thrombin inhibition to prevent thrombosis and platelet effects. Hirsh J et al. Chest. 2001;119(1 suppl):64S-94S. Weitz JI et al. Thromb Res. 2002;106:V275-V284. Gibson CM, 2006

Bivalirudin is Cleaved by Thrombin, a Rapid Return to Hemostasis, a Safety Advantage Heparin’s effects on platelets and its reappearance as it dissociates from cells and proteins may explain the prolonged bleeding risk following discontinuation of heparin, when a return to normal hemostasis is essential. Angiomax® (bivalirudin) is cleaved by thrombin, allowing thrombin to quickly recover hemostatic activity upon discontinuation of Angiomax. The natural reversibility and the short, 25-minute half-life may explain the significantly lower bleeding rates seen in clinical trials. Key Message: The natural reversibility and the short, 25-minute half-life of Angiomax may explain the significantly lower bleeding rates seen in clinical trials. Heparin’s effects on platelets and its reappearance as it dissociates from cells and proteins may explain the prolonged bleeding risk following discontinuation of heparin, when a return to normal hemostasis is essential. Angiomax has a short half-life. It is actually cleaved by thrombin, allowing thrombin to quickly recover hemostatic activity upon discontinuation of Angiomax. Angiomax Prescribing Information, June 14 2005. Maraganore JM et al. Biochemistry. 1990;29:7095-7101. Hirsh J et al. Chest. 2001;119(1 suppl):64S-94S.

Dual Antiplatelet Rx for PCI Circ 102: 624,2000 Dual Antiplatelet Rx for PCI % MACE 1.5 1.2 0.9 ISAR FANTASTIC STARS MATTIS CLASSICS

85% Inactive Metabolites Esterases Considerations N S O Cl CH3 C N S O C H 3 F Pro-drug Clopidogrel Prasugrel Hydrolysis (Esterases) 85% Inactive Metabolites Esterases N S O Cl CH3 C N S O F Oxidation (Cytochrome P450) HOOC * HS N O F Active Metabolite O N S Cl CH3 C Active Metabolite HOOC * HS N O Cl OCH3

Devices

Support Systems

Shock Categories Ventricular Septal Rupture 4.6% “Isolated” RV Shock 3.4% Tamponade/ Rupture 1.7% Acute Severe MR 8.3% Other 7.5% Predominant LV Failure 74.5% Shock Registry Hochman, JACC 36: 1063, 2000

Impella Axial flow pump Much simpler to use Increases cardiac output & unloads LV LP 2.5 12 F percutaneous approach; Maximum 2.5 L flow LP 5.0 21 F surgical cutdown; Maximum 5L flow Cost: 3-5K Blood Inlet Blood outlet Motor Pressure Lumen 43

ECMO

The Future This is not your standard Cath Lab….

CAD and Intervention… the Future Age Prior PCI / CABG Calcium Sex PVD… access LV dysfunction LM Valvular disease

Education / Preparation

Cath Lab VRTM Simulator Percutaneous Coronary Interventions (PCI) PTCA Percutaneous Peripheral Interventions (PPI) SFA Cardiac Rhythm Management (CRM) Heart Failure Bradycardia

The full Vascular simulation set-up

Summary A… Anticipate B… Be prepared C… Communicate D… Deep Breaths

Disasters

“SKS” Stenting of Unprotected Left Main Bifurcation Lesion 70% distal LMCA & 70-80% ostial LAD & 80-90% prox LCX 0-10% residual LMCA/LAD & 0-10% LMCA/LCX post 3.25/9 mm NC Monorail 3.0/13 mm Zeta in LMCA/LAD & 3.0/12 mm Express in LMCA/LCX

I II III Future Directions First Conclusion Future Recommendations ? Radial: I A Femoral: I C Future Recommendations ? AHA/ACC/ESC Future Directions I II III Evidence &/or Agreement (Beneficial, Useful, Effective) Conflicting Evidence Divergence of opinion (Usefulness, Efficacy) II a weight in favor II b less well established Not Useful/Effective Potentially Harmful First Conclusion Multiple randomized trials or meta-analyses Single randomized trial or non-randomized studies C. Only consensus opinion of experts, case studies or standard of care

Causes of Cardiogenic Shock Tamponade/rupture 1.7% Other 7.5% Isolated RV Shock 3.4% VSD 4.6% Acute Severe MR 8.3% Predominant LV Failure 74.5% Shock Registry JACC 2000 35:1063 66

Management of Patients in Cardiogenic Shock: Recommendations Early shock, Diagnosed on Hospital Presentation Delayed onset shock Echocardiogram to rule out mechanical defects IABP Fibrinolytic therapy if all of the following are present: >90 minutes to PCI 2. <3 hours post MI onset No contraindications Arrange rapid trnsfer to PCI/CABG Center Arrange rapid transfer to PCI/CABG Center Cardiac Catheterization and Coronary Angiography Hochman, Circulation 107: 2998, 2003

SHOCK Trial Acute Myocardial Infarction Randomization Emergency Revascularization Initial Medical Stabilization IABP/Pharmacoligic Support Possible Prior Thrombolysis Emergency Early PTCA/CABG ≤6 hrs IABP/Pharmacoligic Support Thrombolysis Unless Absolute Contraindication Possible Delayed Revascularization > 54 hrs Hochman, AHJ 137: 313, 1999

Training center: Simulation Set-up

Algorithm for Coronary Spasm

Definition That which is referred That which makes you stronger…. That which requires additional underwear That which requires a team approach In the end, knowing when to stop