2007 August: 혈관연구회 Aortic Stiffness, Central Aortic Pressure … · 2015. 7. 7. · Ees ratio (P/B) 1.76 ... Amlodipine 88 248 329 369 475 406 508 278 390 126 101 1042 15

Aortic Stiffness, Central Aortic Pressure and Ventriculo-Vascular

Interaction

Yonsei University

Seoul. Korea

Namsik Chung, MD

2007 August: 혈관연구회

Heart failure with preserved systolic function

• Fairly common

• Yet its pathophysiology remains uncertain

• Abnormal diastolic parameters are not

necessarily the sole or dominant factors

defining dysfunction, nor do they

necessarily guarantee clinical heart failure

or exertional dyspnea

Circulation. 2003;107:714-720

What Other contributing factors in HF with normal

or preserved LVEF ?

Older patients with isolated DHF have

reduced cardiac cycle-dependent changes

in proximal thoracic aortic area and

distensibility (beyond that which occurs

with normal aging), and this correlates

with and may contribute to their severe

exercise tolerance.

Hundley WG et al. JACC 2001

Hundley WG et al. JACC 2001

Heart (Ventricle)

Vascular System

Circulation; Continuous closed system

Ventricular-vascular coupling is…

the interaction of the heart and the

systemic vasculature

a central determinant of net cardiovascular

performance

David A. Kass, Heart failure review, 2002;7:51-62.

Combined systolic-ventricular and arterial stiffening

Can influence cardiovascular function in several ways..

Circulation. 2003;107:714-720

What is stiffness of chamber and artery ?

0

40

80

120

160

Pre

ssu

re (

mm

Hg

)

Volume (mL)

0 40 80 120 160

Ees

Ea

Eed

V0

•

Ees : Ventricular systolic elastance

(ESP/ESV)

Chamber systolic stiffness

Ea : Effective arterial elastance

(ESP/SV)

Vascular stiffness

EesWhether a high basal Ees itself

reflects intrinsic contractility is less

clear,

because structural changes from

hypertrophy or fibrosis can also

increase Ees.

Pak PH et al, Circulation. 1998;98:242–248

LV systolic stiffening (end-systolic elastance, Ees)

also rises with age and, combined with artery stiffening, and it can greatly amplify the effects of even small changes in blood volume on arterial pressure and cardiac workload.

Chen CH et al;J Am Coll Cardiol 1998;32:1221

Influenced by systemic vascular resistance, heart rate, and pulsatile load.

Kelly et al; Circulation. 1992;86:513

Elastance of Artery, Ea

Elastance of Artery, Ea

Aging raises Ea principally by its

effects on pulsatile loading,

with an additional but smaller

age-dependent effect from mean

resistance

Circulation 1983;68:50



0 50 100

19 y/o MLV

pre

ss

ure

(m

m H

g)

LV volume (mL)

Ees Ea

87 y/o F

0

50

100

150

0 50 100

LV volume (mL)

Kass: Hypertension 46:185, 2005

Ees

Ea

Implication of systolic-ventricular and arterial stiffening ?

Combined systolic-ventricular and arterial stiffening-1

Circulation. 2003;107:714-720

A high basal Ees blunts contractile

reserve, because further increase

coupled to positive inotropy is

limited and has only modest effects

on net ejection

High Ees and Ea augment systolic BP

sensitivity to cardiac loading,

exacerbating hypertensive responses

during exertion.

Enhanced sensitivity of BP

to circulating volume and diuretics is

common in HF-nlEF Pts and may

trigger rapid-onset pulmonary edema.

Gandhi SK et al N Engl J Med. 2001; 344:17–22Chen CH et al J Am Coll Cardiol. 1999;33:1602–1609


• Increased cardiac energy costs

to provide SV

• Arterial stiffening raises MV02

for a given SV, and ventricular

systolic stiffening amplifies this effect


Kelly RP et al, Circ Res. 1992;71:490–502

Kass Circulation. 2003;107:714-720

How to assess ventricular-vascular

coupling ?

David A. Kass, Heart failure review, 2002;7:51-62.

Stiffness of chamber and artery

0

40

80

120

160

Pre

ssu

re (

mm

Hg

)

Volume (mL)

0 40 80 120 160

Ees

Ea

Eed

V0

•

Ees : Ventricular systolic elastance

(ESP/ESV)

Chamber systolic stiffness

Ea : Effective arterial elastance

(ESP/SV)

Vascular stiffness

The ratio of Ea/Ees

: Ventricular – vascular coupling index !

Arterial elastance (Ea) = ESP/SV

LV systolic elastance (Ees) = ESP/ESV

Ventricular –vascular coupling index (VVI)

: ESP/SV / ESP/ESV

: Ea/ Ees = ESV / SV

Ventricular-vascular Uncoupling during

Exercise is Associated with Decreased Left

Ventricular Longitudinal Functional Reserve in

Hypertensive Patients

Shim CY, Park S, Seo HS, Choi EY, Kang S,

Choi D, Ha JW, Rim SJ, Chung N

Cardiology Division, Yonsei Cardiovascular Center

AHA 2006 Abstract

Backgrounds (1)

• Dyspnea on exertion is a common symptom in

hypertensive patients although normal resting

systolic function.

• Therefore, it is important to evaluate the net

cardiovascular performance during exercise in

hypertensive patients.

Backgrounds (2)

• The increased vascular stiffness is one of

characteristics in hypertensive patients. But also

the chamber stiffness is also increased due to

adaptive response. Therefore, the VV index at rest

is in normal range.

• But, there is no study about the VV response

during exercise in hypertensive patients.

Backgrounds (3)

Pump (Ventricle) Tube (Vascular)

Ees Ea


Ees ↑↑ Ea ↑↔


Ees ↑↑ Ea ↑↑

Normal - Rest Normal - Exercise

HTN - Rest HTN - Exercise

?

Hypothesis

• Ventricular-vascular coupling response to

exercise can be abnormal in hypertensive

patients.

• Abnormal ventricular-vascular coupling

response to exercise is associated with

decreased LV longitudinal functional reserve.

Methods

• 140 treated hypertensive pts older than 40 yrs

• Echocardiography with supine bicycle exercise

(25W, 3-min increments)

• Group I : Normal V-V coupling response

• Group II : Abnormal V-V coupling response

(defined as increased VVI during exercise)

AHA 2006 Abstract

Exercise stress echo

Baseline Peak Ex : 25W

LVEDV 72.77

LVESV 32.33

VV coupling index 0.80

61.33

35.28

1.354

Ventricular-vascular coupling

Group I

(n = 103)

Group II

(n = 37)P-value

VVI Base 0.72 ± 0.20 0.58 ± 0.16 0.003

Peak 0.51 ± 0.19 0.66 ± 0.15 0.002

VVI ratio (P/B) 0.71 ± 0.17 1.16 ± 0.21 <0.001

Ea Base 1.98 ± 0.47 1.93 ± 0.44 0.611

Peak 2.33 ± 0.58 2.69 ± 0.61 0.017

Ea ratio (P/B) 1.20 ± 0.24 1.40 ± 0.16 <0.001

Ees Base 2.90 ± 0.89 3.54 ± 1.20 0.008

Peak 5.01 ± 1.87 4.30 ± 1.26 0.110

Ees ratio (P/B) 1.76 ± 0.49 1.26 ± 0.20 <0.001

AHA 2006 Abstract

Correlation of VVI ratio and Systolic and Diastolic Reserve

Peak Exercise/ Base VVI ratio Peak Exercise/ Base VVI ratioS’ velo

cit

y (

cm

/s)

at

peak e

xerc

ise

E’ velo

cit

y (

cm

/s)

at

peak e

xerc

ise

r= -0.412

p < 0.001

r= -0.434

p < 0.001

AHA 2006 Abstract

• In hypertensive patients, VVI response

during exercise can be abnormal (peak

exercise/base VVI ratio >1.0) despite of

normal VV coupling at rest.

• Abnormal VVI response during exercise

was associated with decreased LV

longitudinal systolic and diastolic

functional reserve in patients with

hypertension. AHA 2006 Abstract

Summary

Aortic Stiffness

Femoral artery

Iliac artery

Abdominal aorta

Ascending aorta

Renalartery

Thoracic aorta

50

100

150

50

100

150

50

100

150

Nichols WW, et al. Arterial Vasodilation. Philadelphia,1993;32.

(mm

Hg

)(m

m H

g)

(mm

Hg

)

Age 68 years

Age 54 years

Age 24 yearsMaximum

Amplification

Maximum

Early Wave

Reflection

Blood pressure curves

J Hypertens 23:1745–1750,2005

CHEN-HUAN CHEN, DAVID A. KASS , J Am Coll Cardiol 1998;32:1221

Human aging……….

Increased vascular and

myocaridal stiffening

Elevation of systolic BP

and widening of PP

CHEN-HUAN CHEN, DAVID A. KASS , J Am Coll Cardiol 1998;32:1221

Increased vascular stiffening

Increased risk for CV disease

and stroke

Aortic Stiffness

Young adults Older adults

Young normal aorta

Old stiff aorta

Resistance

artery

Young normal aorta

Resistance

artery

Old stiff aorta

Courtesy of JB Seward

Pressure during

systole is a major

determinant of

myocardial O2

requirement

Pressure during

diastole is a major

determinant of CBF

Efficient arterial

system

Inefficient

arterial system

“Continuity Disease”

Heart

Conduit vesselsStiffening

“Forward stiffening”Wave reflection

Muscular arteries

Capillary Microvasc End organ

Brain, kidney, heart

Physiological

model

Ea, Ees, Ed

Increased with Age

& higher in Women

than men

Circulation 112: 2254, 2005

Courtesy of AJ Tajik

“Continuity Disease”

Heart

Conduit vesselsStiffening

“Forward stiffening”Wave reflection

Muscular arteries

Capillary Microvasc End organ

Brain, kidney, heart

Physiological

model

Ea, Ees, Ed

Increased with Age

& higher in Women

than men

Circulation 112: 2254, 2005

Systolic BP

Widened PP

Concentric LVH

DD—LAV---DHF

Courtesy of AJ Tajik

Aortic stiffening

Central aortic SBP Central aortic DBP

LV afterload Coronary perfusion

Myocyte hypertrophySubendocardial

ischaemia

Impaired Relaxation Myocardial Fibrosis

Diastolic Dysfunction

Increased V-V stiffening and the

consequent rise in systolic BP during

stress or small change of volume

Delayed Ventricular relaxation and elevated

Systolic BP Increased LVEDP

Elevated Ees and Ea likely exacerbate

hypertensive stress responses , delaying

relaxation, limiting filling, and raising diastolic

pressures.Circulation. 2003;107:714-720

Cardiovasc Res. 1999;43:344–353

Increased ventricular-arterial stiffening

• A 59 year old male presented

with chest discomfort ,DOE

and puffy face

• DM and hypertension

medication for 10 years

Case

Baseline Leg up

Baseline E/E’ = 19.0BP 120/77

Leg up E/E’ = 23.6BP 156/80

• A 77 year old female

presented with dyspnea on

exertion

• DM and hypertension on

medication for 20 years

Case

Leg up E/E’ = 18.3BP 142/78

Baseline E/E’ = 14.8BP 122/72

25 W E/E’ = 21.7BP 172/78

Differential Impact of BP-Lowering Drugs on Central Arterial

Pressure Influences Clinical Outcomes - Principal Results of

the Conduit Artery Function Evaluation (CAFE) Study in

ASCOT

CAFE

Primary Objective

: The different BP-lowering regimens in

ASCOT (atenolol thiazide vs. amlodipine

perindopril) would produce different effects on

central aortic pressures and hemodynamics

despite similar effects on brachial BP.

Radial Tonometry

Pulse Wave Analysis

Sensor

Artery

Bone

Brachial Blood

Pressure

140

70Radial

140

70Central Aortic

Transfer

function

P2

P1

Augmentation index = P2-P1

Pulse pressure

Pulse pressure

Brachial and Central Aortic Pulse

Pressure by Treatment Arm

Time (Years)

Atenolol 86 243 324 356 445 372 462 270 339 128 85 1031

Amlodipine 88 248 329 369 475 406 508 278 390 126 101 1042

38

43

48

53

58

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6

mm

Hg

AUC

56.2

55.3

46.4

P=.06

43.4

P<.0001

Amlodipine

Atenolol

Central PP

Diff Mean (AUC) =3(2.1, 3.9) mm Hg

Brachial SBP

Diff Mean (AUC)= -0.9 (-1.9,0)mm Hg

Augmentation Index (%) by

Treatment Arm

Time (Years)

Atenolol 86 243 324 356 445 372 462 270 339 128 85 1031

Amlodipine 88 248 329 369 475 406 508 278 390 126 101 1042

15

20

25

30

35

40

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 AUC

Amlodipine

Atenolol

25.3

31.9

Diff Mean (AUC) = -6.5(5.8,7.3) mm Hg

P<.0001

Alx

(%

)

Impact of Blood Pressure and Central Aortic Hemodynamics on Clinical Outcomes in the CAFÉ Study (Hazard/10 mm Hg)

Updated Cox proportional hazard model for the composite endpoint,

unadjusted

Factor X2 P HR CI

Peripheral PP 21.0 <.0001 1.21 1.12-1.30

Central PP 17.8 <.0001 1.20 1.11-1.30

Augmentation 7.10 .008 1.22 1.06-1.4

P1 height 19.0 <.0001 1.37 1.20-1.54

• Despite similar brachial systolic blood pressure, Amlodipine +

perindopril-based treatment was more effective than

atenolol+thiazide-based treatment at lowering central aortic

systolic blood pressure and central aortic pulse pressure

• Central aortic pressure may be an important independent

determinant of clinical outcomes

• Results of the CAFÉ study suggest that the “central aortic

blood pressure hypothesis” is a plausible mechanism to

explain the better clinical outcomes for hypertensive patients

treated with amlodipine+perindopril-based therapy in ASCOT

CAFÉ Study Conclusion

ConclusionConcept of reducing the abnormal

ventriculo-vascular stiffness in

hypertension, diabetes mellitus,

CAD, and elderly patients would further

help in the search for optimum treatment.

Thank you for your attention !

Documents

2007 August: 혈관연구회 Aortic Stiffness, Central Aortic Pressure … · 2015. 7. 7. · Ees ratio (P/B) 1.76 ... Amlodipine 88 248 329 369 475 406 508 278 390 126 101 1042 15