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Effects of EECP on Endothelial Function

Ischemic Conditioning, Endothelial Function and Enhanced External Counterpulsation: From Research Studies to Patient Care Dallas, TX, November 17, 2013 . Effects of EECP on Endothelial Function. Gregory W. Barsness , MD, FACC, FAHA, FSCAI

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Effects of EECP on Endothelial Function

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  1. Ischemic Conditioning, Endothelial Function and Enhanced External Counterpulsation: From Research Studies to Patient Care Dallas, TX, November 17, 2013 Effects of EECP on Endothelial Function Gregory W. Barsness, MD, FACC, FAHA, FSCAI Consultant, Internal Medicine & Cardiology and Radiology Director, Mayo Clinic EECP Laboratory Director, Mayo Clinic Cardiac Intensive Care Unit Mayo Clinic College of Medicine Rochester, MN, USA barsness.gregory@mayo.edu

  2. NO PGI2 ET-1 AngII “Endothelial Balance” Normal Endothelial Function NO Function Vasodilatory Antithrombotic Antiproliferative Anti-inflammatory Vasodilation Atheroprotective

  3. Normal Endothelial Function Endothelial Dysfunction ET-1 AngII NO PGI2 ET-1 AngII NO PGI2 Vasoconstriction Atherogenic Vasodilation Atheroprotective “Endothelial Balance” ↓Endothelial repair Depletion of EPCs

  4. Endothelial Dysfunction Relationship to Risk Factors r=-0.73 P<0.0001 Slope of Ach dose response relationship (% diameter change/log Ach) Risk factors (no.) Vita et al: Circ 81:491, 1990

  5. NS Exercise thallium Normal Abnormal 400 P<0.005 Coronaryblood flowresponse(%) 300 P<0.01 200 100 0 Endothelial Dysfunction and Ischemia Zeiher, Circulation 1995;91:2345-52.

  6. Cardiac Events in Patients with Abnormal Endothelial Function with EndoPAT Endothelial Dysfunction Cardiac death/MI/ revasc/C hosp (%) Normal endothelial function Years from EndoPAT study L_RHI <0.4 129 109 100 83 69 56 36 25 L_RHI 0.4 140 123 115 104 86 66 55 44 Rubinshtein and Lerman, Euro Heart J 2010

  7. Shear Stress is Atheroprotective Shear stress Antithrombotic Antimigration NO PGI2 tPA Thrombomodulin NO Pro-survival Endothelium NO TGF Smoothmuscle Antigrowth Low mean shear Prothrombotic Promigration MCP-1 VCAM-1 Pro-apoptosis Endothelium Smoothmuscle Ang II PDGF Endothelin-1 Atherosclerotic lesion Pro-growth Trauband Berk, ArterioThrombVascBiol18:677, 1998

  8. ? ? ? ? External Counterpulsation Suggested Mechanisms of Action Neovascularization Remote PreconditioningEndothelial Function ? Clinical Benefit ? Peripheral Effects Passive Exercise?Placebo Effect

  9. Doppler Ultrasound of Descending Aorta • In aorta (like IABP) • Improved retrogradediastolic and enhanced antegrade systolic flow • Improved flow demonstrated in • Renal arteries • Carotid arteries • Internal mammary arteries • Coronary arteries Control ECP

  10. Shear Stress Increases with EECP13 Hypercholesterolemic Pigs Zhang et al, Circulation 2007

  11. Vascular Effects of EECP Shear Stress Zhang et al, Circulation 2007

  12. Dose-Related NO Increase 2.5 2.0 * * P<0.01 1.5 * 1.0 * * * 0.5 36 hours of ECP in 13 patients Ahktaret al, AJC 2006

  13. Shear Effect of EECP Plasma Angiotensin II Levels * * † *p < 0.05 vs controls;†p <0.05 vs CAD baseline Lawson et al,EurHeart J 2001;22(Abstr Suppl):538

  14. Peripheral Arterial Tonometry (PAT)

  15. Cuff deflation Cuffinflation 60 mm > SBP 10 minutes 5 minutes 10 minutes Occlusion Reactive Hyperemia-PAT Protocol

  16. RH-PAT in Patients with Normal and Abnormal Coronary Endothelial Function *p < 0.001 1.8 1.2

  17. p=0.006 p<0.001 1.2 PAT Reactive Hyperemia Bonetti, Barsnesset al, JACC 2003

  18. Pre-EECP EECP Effect on Endothelial Function * p < 0.05 vs. days 1, 17, and 35 * Bonetti, Barsnesset al, JACC 2003

  19. Clinical Benefit and RH-PAT Index CCS Angina Class * p < 0.05 vs. day 1 * Day 1 1-month follow-up Bonetti, Barsnesset al, JACC 2003

  20. Clinical Benefit and RH-PAT indexDuke Activity Status Index (DASI) * p < 0.05 vs. day 1 * Day 1 1-month follow-up Bonetti, Barsnesset al, JACC 2003

  21. Circulating Progenitor Cells After EECPFlow Cytometric Analysis (FACS) Boilson, Kiernan, Barsness, IJC 2011

  22. External Counterpulsation LV Diastolic Filling Parameters (RNA) p<0.05 p<0.01 Uranoet al, JACC 2001

  23. Interventions that Improve Endothelial Function and Clinical Outcome Lipid-Lowering ACE Inhibitors/ARBs Calcium Channel Blockers N-3 Fatty Acids Glycemic Control in Diabetes Blood Pressure Lowering Smoking Cessation Weight Reduction Exercise PDE-5 Inhibitors EECP

  24. The Bottom Line • Optimal medical therapy and risk factor modification are essential to improve endothelial function and outcome • EECP provides safe, effective, durable symptom relief and is associated with: • Improved QoL and vascular health • Potential pathway to improve prognosis via plaque modification, vascular function and myocardial performance effects (improved systolic and diastolic functional parameters)

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