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Managing Angina and Risk via Improved Endothelial Function Nothing to Disclose Related to this Talk Gregory W.. Ischemic Heart Disease in Vietnam Growing and Costly Problem WHO Report

Managing Angina and Risk via

Improved Endothelial Function

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

15 th National Congress of Cardiology

Hanoi, Vietnam, October 9-11, 2016

Cardiovascular Diseases

Epidemiology and Economics

Leading global cause of death:

 17.3 m/yr, increasing to >23 million by 2030

 20-30% of global deaths (including US)

Most costly disease in US (> $320 b/yr)

 Affects >85 million in US

 Costs will double by 2030

Ischemic Heart Disease in Vietnam

Growing and Costly Problem

WHO Report 2011

Data from 2016 Pacific Cross Vietnam (Blue Cross Vietnam)

In 2011:

38% of Deaths related to CV Disease

23% of Deaths from Stroke 15% of Death attributable to Coronary Disease

By 2017:

20% prevalence of CV Disease and HTN

Patient Vulnerability to ACS

Smoking Hypertension Hypercholesterolemia Diabetes

New risk factors

Genomic predisposition

Endothelial Dysfunction ► The Vulnerable Patient

Dementia Heart failure Stroke Acute Coronary

syndrome Sudden death

Bonetti et al, ATVB 2003 Naghavi et al, Circulation 2003

The Endothelium

The Ideal Diagnostic and Therapeutic Target

Importance of Shear Stress

CTO Revascularization and 7 Mo FollowUp

NO

PGI2

ET-1 AngII Normal Endothelial Function

Vasodilation Atheroprotective

Endothelial Function

The Importance of Balance

Intact

Endothelium

Vascular smooth muscle

Impaired

Endothelium

Vascular smooth muscle

Functional Angiogram Protocol

Infusion catheter Doppler wire

Diagnostic Angiography *

Adenosine IC 24-36 µg

IVUS

Hemodynamic data Doppler velocity Diagnostic angiogram

Low fat diet

No smoking

Baseline

4-5 mm

CP1147604-1

Reactive Hyperemia - Endothelium (NO) Dependent

Time after cuff release (sec)

Reactive Hyperemia-Peripheral Tonometry

Cuff inflation

60 mm > SBP

Cuff deflation

Occlusion

Coronary Endothelial Dysfunction

Relationship to Risk Factors

Vita et al: Circ 81:491, 1990

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

Good Function

Bad Function

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

ECG-Gated Sequential Diastolic Activation

In aorta (like IABP)

• Improved retrograde diastolic and

enhanced antegrade systolic flow

Improved flow demonstrated in

• Renal arteries

• Carotid arteries

• Internal mammary arteries

• Coronary arteries

EECP Enhances Shear Stress Forces

Doppler Ultrasound of Descending Aorta

Shear Stress is Atheroprotective

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

P<0.01

36 hours of ECP in 13 patients

Ahktar et al, AJC 2006

EECP Effect on Endothelial Function

RH-PAT 1 Month Following Treatment

1.29

0 0.5

1 1.5

Day 1 Day 17 Day 35 1-month

Clinical Benefit and RH-PAT Index

Clinical Benefit and RH-PAT index

Duke Activity Status Index (DASI)

0 0.5 1 1.5 2

DASI improvement No DASI improvement

Endothelial Progenitor Cell Number

Impacts Endothelial Function

Change in brachial reactivity (%)

EPCs (colony-forming units)

r=-0.59 P<0.001

EPC Function Impacts Vascular Repair

Healing in Mouse Carotid Injury Model

Wang et al BMC Cardiovasc Disorders 2016;16:179

Transplantation of EPCs and EPCs Overexpressing PDGFR-β

Accelerates re-endothelialization and Mitigates neointima formation at 14 days

Circulating Progenitor Cells After EECP

Flow Cytometric Analysis (FACS)

10 20 30 40 50 60 70 80 90 100

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

Persistent Endothelial Dysfunction

is Associated with CV Events

Kitta Y et al: J Am Coll Cardiol 53:323, 2009 CP1343701-4

0.0 0.2 0.4 0.6 0.8 1.0

Conclusions

Endothelial dysfunction is associated with symptoms and impaired outcome

 Central and unifying disorder

Invasive and noninvasive testing can identify a high-risk population

Optimized medical therapy, risk factor modification and exercise are essential

to improve symptoms and outcome

 Modulated via endothelial function effects

CP1124540-1

barsness.gregory@mayo.edu

Mayo Clinic Rochester, MN

CAM ON