IS PVR THE RIGHT METRIC FOR RV AFTERLOAD · Echo Doppler Assessment of PVR Robin Shandas Professor of Pediatrics, Cardiology ... Upstream vascular compliance is an important component

Shandas UCSF Presentation 3/14/2009

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The Children’s Hospital

Denver, CO

The Children’s Hospital

Denver, CO

Affiliated with

University of Colorado Health Sciences Center

Echo Doppler Assessment of PVR

Robin Shandas

Professor of Pediatrics, Cardiology

Professor of Mechanical Engineering

Director, Center for Bioengineering

University of Colorado

No disclosures

IS PVR THE RIGHT METRIC FOR RV AFTERLOAD ?

Ventricle Upstream Arteries

(Capacitance)

Resistance

(Arterioles and microcirculation)

Veins(Exit)

v

� Coupling between ventricle and proximal vasculature is important in efficiently transporting blood.

� Assumption: Proximal vessels are NOT simply conduits.

Components of load on the RV pump Hypothesis

Upstream vascular compliance is an important component of RV afterload.

Shandas UCSF Presentation 3/14/2009

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Decreased Hemodynamic Efficiency

Normotensive Hypertensive

Importance in the adult systemic circulation

� Growing body of evidence documenting the importance of arterial stiffness as an independent factor in predicting morbidity and mortality.

Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, and London GM. Impact of aortic stiffness on survival in end-stage renal disease. Circulation 99: 2434-2439, 1999.

Cheng LT, Chen HM, Tang LJ, Huang HY, Gu Y, Wang T : The study of aortic stiffness in different hypertension subtypes in dialysis patients. Hypertension Res 2008;31(4):593-599.

Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekam MA, Asmar R, Reneman RS, Hoeks AP, Breteler MM, Witteman JC: Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam study, Circulation 2006;113(5)657-663.

Many, many others….

Methods for Measuring Stiffness

� Most conventional methods fall into those that measure or estimate pressure, flow, compliance (stiffness).• Pulse pressure (stress)• Distensibility / pulsatility (strain)

• Arterial wave velocity (indirect estimate of compliance)• Flow or pressure augmentation (indirect estimate of compliance

and effect of wave reflection)

� Newer methods• Correlates of endothelial function

� Flow mediated dilation

Issues to Consider

Pulse wave speed measurement techniques:� Biological variability

• Ex: Arterial wave velocities range from 2 - 10 m/sec.• Assumptions of pulse wave speed methods:

� Constant wave speed over length of vessel.� No “complicating” influences (ex: derivation of the wave speed

equation)– No blood viscosity– Only “small” deformations of vessel wall– Simple relationship between pressure and vessel area

» Usually linear

� Measurement uncertainty• Typical sampling rate is 200 Hz - gives a inherent measurement

uncertainty of +/- 2.5 msec.• In 5 msec, a wave traveling at 10 m/sec will travel 5 cm.

� 2 m/sec wave will travel 1 cm.• Length of vessel thus becomes critical.

Shandas UCSF Presentation 3/14/2009

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RV failure due to elevated afterload is the proxima te

cause of death in patients with PAH

Reproduced from Ghio S et al. JACC Vol. 37, No 1, 2001. Jan 2001:183-8

Two basic loads on the right heart: 1. Vascul ar resistance

PCWP

PV Resistance =

MPAP

CO

Two basic loads on the right heart: 2. Vascul ar distension/stiffness

PV Impedance =

Impedance quantifies both vascular resistance and stiffness

PCWP

PV Resistance =

MPAP

CO

PV Impedance =

Shandas UCSF Presentation 3/14/2009

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� Measure of static (PVR) + dynamic (PVS) resistance imposed by vasculature on cardiac pump.

� First described by Milnor (‘66, ‘69)• Separated total right heart work into mean + oscillatory• Showed significance of oscillatory component• Performed first impedance study in the human• Showed right and upward shift in impedance curves for PAH

indicative of vascular stiffening.

� Difficult to obtain clinically since instantaneous pressure and flow are required.

Impedance Noninvasive measurement of systemic impedance

� Combination of Doppler (aortic flow) and carotid applanation tonometery� Attempted in 95 healthy subjects (successfully obtained data in 71).

� Only correlate found was minimum frequency of the impedance spectrum.

QuickTime™ and a decompressor

are needed to see this picture.

Mazzaro L, et al: Aortic input impedance increases with age in healthy men and women, Hypertension 2005;45:1-6

Impedance

Beam Line

Input impedance found from corresponding harmonics of pressure

and flow|Z(w)| = |P(w)| / |Q(w)|

Flow Q(t) found from midline velocity in MPA Vecho(t), mean flow Qcath, and the expressions

Acorr = Vecho / Qcath

Q(t) = Acorr Vecho(t)

Typical Impedance Curves

� Significant differences between groups in both zero harmonic (Z0) and first two higher harmonics (Z1, Z2)

Shandas UCSF Presentation 3/14/2009

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Impedance and Proximal Stiffness

0

5

10

15

20

25

0 1 2

Effect of PA Stiffness on Input Impedance

Normal ComplianceStiff PA

Impe

danc

e M

odul

us (

mm

Hg

/ L /

min

)

Harmonic

p<0.001*

p<0.001*

p<0.001

*

PVR

PVS

PVR –vs– Zero Harmonic of Impedance (Z 0)

� Z0 shows exceptional correlation (R2 = 0.974) to hemodynamically measured PVR

� Reduces need for wedge pressure measurements.

Z1 + Z2 -vs- PVS -

� Z1+Z2 correlates well to global measure of vascular stiffness, PP/SV

Impedance demonstrates proportionally greater after load from vascular stiffening in patients with PAH

Z1+Z2=Stiffness

Z0=Resistance

Shandas UCSF Presentation 3/14/2009

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Impedance provides increased sensitivity to outcomes than PVR

Impedance

PVR

Reactive in Resistance?

Reactive in Stiffness?

Free of Complications at 1 year?

Patient 1 Yes Yes Yes

Patient 2 Yes Yes Yes

Patient 3 Yes Yes Yes

Patient 4 Yes Yes Yes

Patient 5 Yes Yes Yes

Patient 6 Yes Yes Yes

Patient 7 Yes No No

Patient 8 Yes No No

Patient 9 No No No

Patient 10 No No No

Does pulmonary vascular stiffness (PVS) increase in PAH ?

How do pulmonary arteries stiffen ?

�Strain stiffening.�Remodeling.�SMC activation.

How do pulmonary arteries stiffen ?� Strain stiffening.� Remodeling.� SMC activation.

Stress-Strain, RPA Normoxic Calf

Pressure-Diameter, RPA PAH patient challenged with 100% O2.

Shandas UCSF Presentation 3/14/2009

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Role of Elastin

2-Photon 3D image reconstruction

How do pulmonary arteries stiffen ?� Strain Stiffening� Remodeling.� SMC activation.

0

5

10

15

20

1 1.2 1.4 1.6 1.8

?

Pre

ssur

e (k

Pa)

CL

L C

1592 HLMB

2101 NLMB

λ

Media Elastin Area Fraction

MPA

H-1 41%

H-2 36%

N 29%

Elastin in the MPA stiffens and its

fractional area decreases in PAH

Role of Elastin in Arterial Stiffening

Shandas UCSF Presentation 3/14/2009

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How do pulmonary arteries stiffen ?� Strain Stiffening.� Remodeling.� SMC Activation.

0

5

10

15

20

25

30

You

ng's

Mod

ulus

(k

Pa)

10 15 20 25

% Strain

SMC EffectControl Nifedipine Fasudil

RPA - Normoxic Rat

Impedance - Hypoxic Rat

Pulmonary vascular stiffness is a critical yet overlooked component in the evaluation of PAH.

Proximal Artery Pressure-Diameter Loops

� Simultaneous acquisition of arterial diameter and pressure -vs- time.

� Information on local artery stiffness.

� May be useful in evaluating proximal vascular remodeling.

� Suprasternal short-axis.� Combination of conventional

and tissue-Doppler M-mode to obtain diameter.

� Pressure signal digitized simultaneously into ultrasound system.

Clinical Acquisition and Analysis of P-D and Impedance

Shandas UCSF Presentation 3/14/2009

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Non-invasive measurement of PA stiffness

B-Mode Image

Upper & Lower RPA Walls +

Computed Trace = RPA Diameter

Pressure (yellow) and ECG (blue) traces

Clinical measurement of pulmonary vascular stiffness (PVS)

� Growing body of evidence regarding its importance. Vascular mechanics easier to understand than myocardial mechanics.

� Cardiac catheterization laboratory is well-suited to making routine vascular function measurements.

� Measurements are relatively simple to implement clinically.• Do not need significant additional equipment

� Need pressure to maintain robustness in mechanical calculations.

� Awareness of measurement uncertainty.� Validation is important.

Acknowledgements

Supported by:NIH (HL 067393, HL 072738, MO1 RR00069, SCCOR HL084923, K24 HL 081506)Children’s Hospital Heart Institute, Denver, CO