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Managing Angina and Risk via Improved Endothelial Function: The EECP Model Nothing to Disclose Related to this Talk Gregory W.. NO FunctionVasodilatory Antithrombotic Antiproliferativ

Managing Angina and Risk via

Improved Endothelial Function:

The EECP Model

Nothing to Disclose Related to this Talk

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

14th Vietnam National Congress of Cardiology

Da Nang, Vietnam October 11-14, 2014

NO Function

Vasodilatory Antithrombotic Antiproliferative Anti-inflammatory Endothelial Function

The Importance of Balance

↓Endothelial repair

Depletion of EPCs Endothelial Function

The Importance of Balance

Coronary Endothelial Dysfunction

Relationship to Risk Factors

Vita et al: Circ 81:491, 1990

-30 -25 -20 -15 -10 -5 0 5 10 15

0 100 200 300 400

0 50 100 150 200 250 300 350

CTL AC1 AC2 AC3 PAPA

P<0.01

P<0.005

NS Exercise thallium

Normal Abnormal

Normal Endothelial Function

Abnormal Peripheral Endothelial Function

Relationship to Cardiac Events

Rubinshtein and Lerman, Euro Heart J 2010

Endothelial Dysfunction

Vulnerability

New risk factors

Genomic predisposition

Endothelial Dysfunction ► The Vulnerable Patient

syndrome Sudden death

Importance of Shear Stress

CTO Revascularization and 7 Mo FollowUp

Shear Stress is Atheroprotective

ECG-Gated Sequential Diastolic Activation

In aorta (like IABP)

diastolic and enhanced antegrade systolic flow

Improved flow demonstrated in

EECP Enhances Shear Stress Forces

Doppler Ultrasound of Descending Aorta

Shear Stress Effect of EECP

Dose-Related NO Increase in Humans

0 50

Po st-EEC

P 1-Mo

nth

3-Mo nth

Endothelin-1 (pg/L) Nitric Oxide (mg/L) ET-1/NO Ratio

2.5 2.0 1.5 1.0 0.5

36 hours of ECP in 13 patients

Ahktar et al, AJC 2006

Reactive Hyperemia-PAT Protocol

Cuff inflation

60 mm > SBP

Cuff deflation

Occlusion

Quantitation of RH-PAT (RH-PAT index)

Post-occlusion PAT-amplitude

RH-PAT index =

Pre-occlusion PAT-amplitude

0 0.5 1 1.5 2 2.5

EECP Effect on Endothelial Function

RH-PAT During Treatment

EECP Effect on Endothelial Function

RH-PAT 1 Month Following Treatment

1.29

0 0.5

1 1.5

Clinical Benefit and RH-PAT Index

Clinical Benefit and RH-PAT index

Duke Activity Status Index (DASI)

0 0.5 1 1.5 2

Relation Between the Number of Endothelial Progenitor Cells

and Endothelial Function

Change in brachial reactivity (%)

Endothelial progenitor cells (colony-forming units) r=-0.59

P<0.001

Circulating Progenitor Cells After EECP

Flow Cytometric Analysis (FACS)

10 20 30 40 50 60 70 80 90 100

Where do we go from here?

Persistent Endothelial Dysfunction

is Associated with CV Events

0.0 0.2 0.4 0.6 0.8 1.0

Interventions that Improve Endothelial

Function and Clinical Outcome

Statins/Low Fat Diet

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

Aspirin

EECP

The Bottom Line

Optimal medical therapy and risk factor modification are essential to improve

endothelial function and outcome

Exercise and EECP provide safe,

effective, durable symptom relief:

plaque modification, vascular function and

myocardial performance effects (improved

systolic and diastolic functional parameters)

CP1124540-1

barsness.gregory@mayo.edu

Mayo Clinic Rochester, MN, USA