Non-invasive hemodynamics in OB

Tom Archer, MD, MBA

Director, OB Anesthesia

UCSD

Non-invasive hemodynamic research at UCSD (1)

• Can emerging non-invasive hemodynamic

• measurement techniques be used to improve

• prediction or treatment of pre-eclampsia?

Two measurements and two technologies

• Cardiac output (CO) and systemic vascular resistance (SVR), from…

– Impedance cardiography (“Electrical velocimetry”)

• Central blood pressure and Augmentation index (AIx) from…

– Applanation tonometry and brachial BP

Why impedance cardiography and applanation tonometry?

Easier to perform than maternal echocardiography?

Give different information than uterine or umbilical artery Doppler.

Systemic vascular resistance does not = uterine artery velocimetry (UtAV)

or umbilical artery velocimetry (UmAV)

• UtAV looks at uterine artery and placenta

• SVR looks at “average” arteriolar tone (for all vascular beds).

• Does SVR add value beyond UtAV or UmAV?

Creasy and Resnik:

• “As many as 2/3 of of pre-eclamptic mothers have normal uterine artery Doppler tracings.”

• Probably their SVR is not normal.

Will CO and SVR become vital signs in OB?

• In OB clinic for pre-eclampsia prediction / detection?

• Inpatient management of pre-eclampsia?– Detection of deterioration of patient condition?– Titration of vasoactive meds (hydralazine,

labetalol)?– Titration of other Rx?

Bosio 1999

Hemodynamics of normal pregnancy:

CO rises early, plateaus at 28-32 weeks and falls slightly after that.

SVR falls early, plateaus at 28-32 weeks and rises slightly after that.

Bosio 1999

Gestational hypertension appears to involve persistent high CO and low-normal SVR.

Hemodynamically, gestational hypertension and pre-eclampsia are different diseases.

Bosio 1999

In pre-eclampsia, early phase (28-36 weeks) may involve an increased CO.

After 36 weeks, CO falls and SVR rises.

Is there a hyperdynamic early phase of pre-eclampsia, followed by arteriolar constriction (high SVR)?

Or did they simply fail to distinguish early and late-onset Pre-E, as in next study?

Hypertension 2008;52;873-880; originally published online Sep 29, 2008;Herbert Valensise, Barbara Vasapollo, Giulia Gagliardi and Gian Paolo Novelli

Italian study of hemodynamics of pre-eclampsia looks at normals, early and late onset pre-eclampsia.

Early pre-eclampsia group has UA notching, growth restriction and preterm delivery.

Late pre-eclampsia is relatively benign.

Hypertension 2008;52;873-880; originally published online Sep 29, 2008;Herbert Valensise, Barbara Vasapollo, Giulia Gagliardi and Gian Paolo Novelli

Early onset pre-E (< 34 weeks) is predicted at 24 weeks by high SVR and low CO.

Late onset pre-E

(> 34 weeks) is predicted at 24 weeks by low SVR and high CO.

Hypertension 2008;52;873-880; originally published online Sep 29, 2008;Herbert Valensise, Barbara Vasapollo, Giulia Gagliardi and Gian Paolo Novelli

Extremes of SVR at 24 weeks predict early and late onset pre-eclampsia

SVR > 1359 at 24 weeks predicts early onset (< 34 weeks) Pre-E.

SVR < 770 at 24 weeks predicts late onset (> 34 weeks) Pre-E.

Rang S, van Montfrans GA, Wolf H. Serial hemodynamic measurement in normal pregnancy, preeclampsia, and intrauterine growthrestriction. Am J Obstet Gynecol 2008;198:519.e1-519.e9.

Fetal growth restriction, with or without pre-eclampsia or gestational hypertension, is associated with high SVR and low CO.

Pre-eclampsia and gestational hypertension, without fetal growth restriction, are associated with low SVR and high CO.

Hence: Fetal growth restriction is associated with high SVR.

Early pre-eclampsia

• Associated with normal BMI, high SVR and low CO?

• Associated with fetal growth restriction.

Is SVR a “fundamental” prognostic or diagnostic

measurement?

Late pre-eclampsia

• Associated with increased BMI and increased CO?

• Relatively low impact on fetus (compared to early pre-eclampsia)?

Gestational hypertension (GH)vs. Pre-eclampsia (PE)

• GH associated with persistently high CO and low normal SVR and is not associated with certain VEGF haplotypes.

• Early onset PE associated with low CO and high SVR and certain VEGF haplotypes are protective.

• VEGF modulates vascular tone (SVR).

• Hypothesis: GH is not mediated by VEGF deficiency. PE is.

Molecular Human Reproduction, Vol.15, No.2 pp. 115–120, 2009Valeria C. Sandrim1, Ana C.T. Palei2, Ricardo C. Cavalli3,Francielle M. Arau´ jo3, Ester S. Ramos4, Geraldo Duarte3, andJose E. Tanus-Santos1,5

Should we be following SVR during pregnancy?

Does early (24 weeks) elevation of SVR predict early onset (<34

weeks) pre-eclampsia?

Just 4 EKG electrodes connected to a small box.

Completely non-invasive.

Portable, usable in OB clinic or OR.

Electrical impedance (resistance) of the chest decreases during systole (inverted scale).

“Traditional” impedance cardiography assumes that impedance change with heartbeat is due to volume change in aorta.

Electrical velocimetry tries to improve on this assumption by assuming decrease in impedance is due to red cell alignment during acceleration of flow.

Opening of aortic valve and alignment of erythrocytes is associated with a decrease in impedance (resistance).

Oxytocin 10 U bolus at delivery decreases SVR and CO rises. Demonstrated with arterial line and pulse contour analysis:

Increase in CO due to delivery and oxytocin, detected by electrical velocimetry. No arterial line needed.

Research questions about CO and SVR

• Is Cardiotronic system useful and easy for routine outpatient use?

• Can we detect an early increase in SVR in pre-eclamptic pregnancies?

• How do hemodynamics of spinal anesthesia and CS compare in pre-eclamptics vs. normals?

Mean BP in 30 normals and 30 preeclamptic (preterm) women for C/S under SAB

Spinal anesthesia in pre-eclamptics causes less hypotension than in normals

• Is this true?

• Is it due to better maintained SVR or CO?

• The teaching used to be: pre-eclampsia is associated with hyperactive sympathetic nervous system probably not true.

Non-invasive hemodynamic research at UCSD (2)

• Applanation tonometry: an indirect way of measuring ascending aortic pressure (central blood pressure).

• Augmentation index: a measure of arterial pressure wave reflection and increased cardiac workload during systole.

health.yahoo.com/topic/heart/overview/article...

LV “sees” the systolic BP in the ascending aorta.

With normal aortic valve, LV wall tension depends on pressure in ascending aorta

(and diameter of LV chamber).

Heart “sees” central aortic systolic pressure, not brachial

artery pressure.

• Obviously, it’s hard to measure ascending aorta pressure directly.

• Ascending aortic (“central”) BP can be extrapolated from the radial pulse, using applanation tonometry and brachial BP.

Augmentation index

• A measure of wave reflection from muscular arteries.

• Chronically: a measure of endothelial function and muscular artery tone.

• Acute changes due to body temperature, posture, wine, other drugs

Augmentation Index (AIx)

• AIx = unnecessary heart work.

• High AIx leads to LVH and cardiomyopathy.

• Lower AIx is better.

• Treatments that lower AIx help the patient.

AIx increases in “inflammatory” states:

Obesity

• OSA

• Hyperglycemia

• Sepsis

• Pre-eclampsia

• Lupus

• Cocaine use

• Hypercholesterolemia

What makes AIx go down-- chronically?

• Exercise

• Weight loss

• Red wine

• Statins

• Control of blood pressure (ACEI and CCB)

• NTG

http://www.itmonline.org/image/pulse2.jpg

Pulse analysis is an ancient practice, now making a comeback.

http://www.mamweb.org/modules.php?name=Content&pa=showpage&pid=32000

Etienne-Jules Marey (1830-1904) invented the sphygmograph to record the arterial pulse on smoked paper. It was used by Engelmann, Mackenzie and Wenckebach.

Sphygmograph 1876

Pulse analysis was serious business in the 19th century

• Sphygmographs in common use.

• Insurance companies relied on their results.

Life insurance examination manual from 1891 discussed pulse analysis by sphygmography.

Tom Archer, 58 y.o., good general health.

Radial and predicted ascending aortic pressure waveform when subject is cold.

SphygmoCor system for measuring central blood pressures

Kozo Hirata, MD; Masanobu Kawakami, MD; Michael F O’Rourke, MD, DSc*Circ J 2006; 70: 1231–1239

AIx =

Augmentation Pressure /

Pulse Pressure

Augmentation index– extra cardiac work due to wave reflection

Extra cardiac work (“wasted energy”) causes LVH chronically and– perhaps– CHF acutely in pre-eclampsia.

Augmentation pressure is a deadly backdraft which exhausts the heart over time.

Augmentation pressure

• Reduces stroke volume and cardiac output. Creates illusion of hypovolemia?

• Activates renin-angiotensin-aldosterone system?

• Activates BNP?

AIR

BLOOD

#3 Systemic vascular resistance (resistance arterioles)

#2 Stiffness of aorta (“windkessel”)

heart

veins

arteries

#1 SV

#4 Wave reflection–

timing and amount

Muscular arteries

Central BP

What creates central BP?

Run animation

• Wave reflection animation can be found at:

• http://atcormedical.com/wave_reflection.html

“There is, however, much information in the velocity waveform. With

each heart beat a pressure pulse travels down the arterial tree, and

is the resultant of forward compression waves created by the

ejection pulse of the heart and reflected waves from arteriolar

terminations and other near branching points of the arterial tree

(Taylor 1965: McDonald 1974).”

BJOG January 1985. Vol. 92, pp. 23-30

Fetal umbilical artery flow velocity waveforms andplacental resistance : clinical significance

BRIAN J. TRUDINGER Senior Lecturer, WARWICK B. GTLES Postgraduate Scholar, COLLEEN M. COOK Technical Oflcer, JOHN BOMBARDIER1 Biomedical Engineer & LEE COLLINS Medical Physicist, Fetal Welfare Laboratory, Westmead Hospital, Westmead, New South Wdes 21 45, Australia

BJOG January 1985. Vol. 92, pp. 23-30

Fetal umbilical artery flow velocity waveforms andplacental resistance : clinical significance

BRIAN J. TRUDINGER Senior Lecturer, WARWICK B. GTLES Postgraduate Scholar, COLLEEN M. COOK Technical Oflcer, JOHN BOMBARDIER1 Biomedical Engineer & LEE COLLINS Medical Physicist, Fetal Welfare Laboratory, Westmead Hospital, Westmead, New South Wdes 21 45, Australia

Trudinger BJ et al BJOG January 1985. Vol. 92, pp. 23-30

Diseased, high resistance umbilical arteries. Much wave reflection.

Trudinger et al BJOG January 1985. Vol. 92, pp. 23-30

Healthy, low resistance umbilical arteries. Little wave reflection.

Trudinger et al BJOG January 1985. Vol. 92, pp. 23-30

Trudinger et al BJOG January 1985. Vol. 92, pp. 23-30

Trudinger et al BJOG January 1985. Vol. 92, pp. 23-30

Tom Archer, 58 yo, after work, seated comfortably. Aix = 11%.

Tom Archer, 58 y.o., while squatting.

Aix = 21%

Tom Archer, seated, very cold from being outside in winter.

Aix = 27%

Tom Archer, 58 yo, after exercise and wine.

AIx = 1%

Ted Archer, 30 y.o., at rest. Subject runs marathons. Aix = -14%.

Reflected pressure wave arrives late and perfuses coronaries in diastole.

Statins and ACE inhibitors can lower central BPs

and AIx– is this part of their therapeutic effect?

6 months Rx with atorvastatin decreased central aortic pulse pressure and augmentation index.

WW Nichols Curr Opin Cardiol 2002, 17:543–551

Four months Rx with lisinopril decreased central aortic pulse pressure and augmentation index.

WW Nichols Curr Opin Cardiol 2002, 17:543–551

ACE inhibitors and aldosterone antagonists

can reverse LV hypertrophy.

Is this due to decreased AIx and strain on the heart?

Adams KF, Am J Health-Syst Pharm—Vol 61 May 1, 2004 Suppl 2

ACE inhibitors and aldosterone antagonists reverse LV hypertrophy– via central BP effects?.

DO, 56 yo female, hypertensive, diabetic May 31, 2007. Aix = 41%

DO, 56 yo female, hypertensive, diabetic January 3, 2008. After weight loss and 3 weeks Lipitor. AIx = 26%

Ayten Elvan-Tas¸ pinar, Arie Franx, Michiel L. Bots,Hein W. Bruinse, and Hein A. KoomansAm J Hypertens2004;17:941–946

Augmentation index increases in pre-eclampsia

Normotensive 29 y.o. pregnant woman

Pre-eclamptic patient,

29 yo.

MT, 22 yo, healthy, in labor, epidural in place and she is comfortable.

Aix = -1%.

JM, 21 yo, in labor, recent onset lupus, on prednisone and plaquenil

Aix = 6%

At UCSD: 25 y.o. woman at 26 weeks, chronic HTN and pre-eclampsia, on labetalol– pressure has been well controlled at time of this study. AIx (now 24%) might have been higher before BP control.

American Journal of Obstetrics and Gynecology (2005) 193, 450–4Evaluation of B-type natriuretic peptide (BNP) levels innormal and preeclamptic womenJamie L. Resnik, MD,* Christina Hong, MD, Robert Resnik, MD,Radmila Kazanegra, MD, Jennifer Beede, BA, Vikas Bhalla, MD,Alan Maisel, MD

BNP increases in severe pre-eclampsia– probably due to stretching of the left ventricle.

Cite this article as: Tihtonen KM, Kööbi T, Vuolteenaho O, et al. Natriuretic peptides and hemodynamics in preeclampsia. Am J Obstet Gynecol 2007;196:328.e1-328.e7.

In pre-eclampsia, we see increased SVR (arteriolar constriction), MAP and decreased CO. Atria and ventricles respond by increasing natriuretic peptide secretion.

Will BNP correlate with AIx and MAP, as indices of left

ventricular stretch?

Other questions for UCSD research:

• Can we develop a predictive model for pre-eclampsia based on non-invasive hemodynamic measurements, uterine artery Doppler and serum markers?

• Is there a role for non-invasive hemodynamics in patient management?

Questions:

In pre-eclampsia do increases in SVR and AIx precede changes in

umbilical artery Doppler?

Can SVR and AIx be endpoints for palliative treatment of pre-

eclampsia, to improve fetal and maternal outcomes?

Question:

For the Chronic Hypertension in Pregnancy Study (CHIPS) should you (ideally) measure brachial BP or central BP?

Thank you!

Questions?