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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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slide1

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

endothelial balance

NO

PGI2

ET-1

AngII

“Endothelial Balance”

Normal Endothelial Function

NO Function

Vasodilatory

Antithrombotic

Antiproliferative

Anti-inflammatory

Vasodilation

Atheroprotective

endothelial balance1

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

endothelial dysfunction relationship to risk factors
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

endothelial dysfunction and ischemia

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.

cardiac events in patients with abnormal endothelial function with endopat
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

shear stress is atheroprotective
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

external counterpulsation suggested mechanisms of action

?

?

?

?

External Counterpulsation Suggested Mechanisms of Action

Neovascularization Remote PreconditioningEndothelial Function

?

Clinical Benefit

?

Peripheral Effects Passive Exercise?Placebo Effect

doppler ultrasound of descending aorta
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

vascular effects of eecp shear stress
Vascular Effects of EECP Shear Stress

Zhang et al, Circulation 2007

dose related no increase
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

shear effect of eecp plasma angiotensin ii levels
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

reactive hyperemia pat protocol

Cuff deflation

Cuffinflation

60 mm > SBP

10 minutes

5 minutes

10 minutes

Occlusion

Reactive Hyperemia-PAT Protocol
rh pat in patients with normal and abnormal coronary endothelial function
RH-PAT in Patients with Normal and Abnormal Coronary Endothelial Function

*p < 0.001

1.8

1.2

pat reactive hyperemia

p=0.006

p<0.001

1.2

PAT Reactive Hyperemia

Bonetti, Barsnesset al, JACC 2003

eecp effect on endothelial function

Pre-EECP

EECP Effect on Endothelial Function

* p < 0.05 vs. days 1, 17, and 35

*

Bonetti, Barsnesset al, JACC 2003

clinical benefit and rh pat index ccs angina class
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

clinical benefit and rh pat index duke activity status index dasi
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

circulating progenitor cells after eecp flow cytometric analysis facs
Circulating Progenitor Cells After EECPFlow Cytometric Analysis (FACS)

Boilson, Kiernan, Barsness, IJC 2011

external counterpulsation lv diastolic filling parameters rna
External Counterpulsation LV Diastolic Filling Parameters (RNA)

p<0.05

p<0.01

Uranoet al, JACC 2001

interventions that improve endothelial function and clinical outcome
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

the bottom line
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)