Preeclampsia is a Heart Disease

PREECLAMPSIA
IS A HEART DISEASE

HERBERT
VALENSISE
Tor Vergata University
Rome Italy

IUGR
preterm delivery
proteinuria abruptio placentae
decreased GFR
Glomerulo capillary endotheliosis
renal failure

alterated liver function test
subcapsular hemorrhage
fibrin deposition
HELLP
endothelium damage
hematological changes
humoral factors

decreased plasma volume leaky capillaries
pulmonary edema
increased SVR
ARDS
increased PA
decreased CVP
hypertensive encephalopathy
ischemia and vasospasm
hemorrhage
edema
eclampsia
multisystem changes in pre-eclampsia

CENTRAL HEATING DOESN’T WORK:
IS A BOILER PROBLEM OR THE PIPES ARE NOT
WORKING ?

WE SHOULD START OUR TALK
FROM THE END OF THE STORY

CONCLUSIONS
1- PATIENTS THAT DEVELOP PREECLAMPSIA HAVE
A SIGNIFICANT HIGH RISK
OF DEVELOPING CARDIOVASCULAR ISCHEMIC DISEASE
IN THE FOLLOWING YEARS OF THEIR LIFE

What are the effects of
preeclampsia on maternal
cardiac function?

Left Atrial Fractional Area Change
LA FAC %= (LAmax-LAmin)/LAmax

LAmax LAmin

LA FAC% in normal and hypertensive
60

50
*
40
* p <0.001
30
LA FAC%

20

10

0
I TRIM II TRIM III TRIM III TRIM
N/GH
LAFAC% is reduced in hypertensive patients,
suggesting a difficult voiding from left atrium in the
left ventricle Valensise et al Hypertension, 2001

Diastolic dysfunction in
HYPERTENSION
• Recent data suggest a diastolic dysfunction in
Gestational Hypertension
Vazquez Blanco Am J Hypertens
2001
Valensise et al. Hypertension; 2001
• Transmitral flow is altered with a prolongation
of IVRT and a bimodal distribution of DtE
2001
Valensise et al. Hypertension 2001
• Pulmonary vein flow shows a prevalence of
the systolic fraction (confirming the altered
compliance suggested by transmitral flow
modifications

Diastolic function: Transmitral flow and
IVRT
Normal
E A
E GH
A

Ao Ao
DtE dA DtE dA
IVRT IVRT

• IVRT is prolonged in GH patients because of a
higher left ventricular end-systolic pressure; a
longer time is therefore necessary for the left
ventricular pressure to fall below the atrial
pressure.

ISOVOLUMETRIC
RELAXATION TIME
100
90
*
80
70
60
IVRT

50
40
30
20
10
0
I TRIM II TRIM III TRIM III TRIM N/GH

NORMAL GH
Valensise Ultrasound Obstet Gynecol 2000
Valensise Hypertension 2001
* p<0.0001 GH III TRIM vs. NORM III TRIM

Left ventricular geometric pattern
and cardiac function
• Some Author suggest that the geometric
pattern may be altered in Gestational
Hypertension
2000
Valensise et al. Hypertension; 2001
Novelli et al. Hypertension 2003
• Concentric geometry appears to identify
patients at high risk for complications during
Gestational Hypertension
• Cardiac output and stroke volume may be
reduced during subsequently complicated
Gestational Hypertension compared to
uneventful gestational hypertension

GEOMETRIC ASPECTS OF LEFT VENTRICLE

Geometric pattern in complicated
hypertensive pregnancy

Normal Geometry Eccentric Hypertrophy
(LVMi<50g/m2.7, SRP<0.45) (LVMi>50g/m2.7, SRP<0.45)

Concentric Concentric
Remodeling Hypertrophy
(LVMi<50g/m2.7, (LVMi>50g/m2.7, SRP>0.45)
SRP>0.45)

Geometric pattern of the left ventricle
Novelli et al. Hypertension, 2003
Uneventful GH (101) Complicated GH (47)

n=31 n=10
30.7 % 22.3 %

n=70 n=37
69.3 % 78.7%
Non concentric Geometry Non concentric geometry

Concentric geometry Concentric Geometry

Hemodynamic features of the two groups :

Parameter Uneventful Complicated P-value
GH GH
N=101 N=47
Heart Rate(bpm) 84+/-11 82+/-14 ns
Systolic BP(mmHg) 144+/-11 146+/-9 ns
Diastolic BP (mmHg) 82+/-13 82+/-14 ns
Mean BP (mmHg) 103+/-9 103+/-11 ns
TVR (dyne•sec•cm-5) 1403+/-375 1653+/-536 0.002
EDV (mL) 104+/-13 101+/-15 Ns
ESV (mL) 30+/-8 33+/-8 0.023
Stroke Volume (mL) 74+/-12 67+/-16 0.007
Cardiac Output (L) 6.1+/-1.2 5.6+/-2.0 0.046

What is Total Vascular Resistance (TVR)?

TVR is the steady component of the cardiac
afterload determined by the cross-sectional
diameter of the resistance vasculature.

How is TVR calculated?
TVR is calculated by dividing Mean Blood
Pressure with Cardiac Output.

Diastolic BP+1/3(Systolic BP-Diastolic BP )
TVR= Cardiac Output (Stroke volume x Heart rate)
X 80

LVOT: Left ventricular outflow tract

Integral of the aortic flow

AOA
LV

LA

Cardiac Output

CO=5.664 L/min Blood Pressure=110/60 mmHg

Mean Blood Pressure=76.6 mmHg

TVR=80xMBP/CO

TVR=1083 dyn

Cardiac Output


Mean Blood Pressure=100 mmHg

TVR=80xMBP/CO

TVR=1412 dyn

Cardiac Output

CO=5.664 L/min
Blood Pressure=110/70 mmHg

Mean Blood Pressure=100 mmHg
Mean Blood Pressure=83.33 mmHg
TVR=80xMBP/CO

TVR=1412 dyn
TVR=1481 dyn

CONCLUSIONS
1- PATIENTS THAT DEVELOP PREECLAMPSIA HAVE

2.MATERNAL HEART DURING PREECLAMPSIA AND
HYPERTENSION ADAPTS SHOWING
- DIASTOLIC DYSFUNCTION
- REDUCED LA%FAC AND INCREASED IVRT
- INCREASED RELATIVE WALL THICKNESS
- REDUCED STROKE VOLUME
- REDUCED CARDIAC OUTPUT
- INCREASED TOTAL VASCULAR RESISTANCES

Is maternal cardiac function
different in patients that
will and will not develop
clinical complications?

Maternal heart
evaluation
268 emGH pregnancies
between 28 and 31 weeks Echocardiography:
TVR
Geometric pattern of LV

Follow up
for maternal andfeto-
neonatal
complications Valensise et al, BJOG 2006

Main maternal and fetal/neonatal complications
subsequently developed in women with gestational
hypertension

Valensise et al, BJOG 2006

M-mode-derived and 2D-derived
parameters at 28–31 weeks


Blood Pressure levels and TVR in
uncomplicated and complicated early mild
gestational hypertension
*P<0.05 vs controls; °P<0.05 vs. uncomplicated EMGH °*
* *
160 1800 1754
144 145
140 1600

120 1400 *
111
* * 1200 1138
100
83 85 1000 949
80
800
60
62
600
40 400

20 200

0 0
SBP DBP TVR

Controls Uncomplicated EMGH Complicated EMGH


Relative wall thickness of the left ventricle
(geometric pattern)
°*
00:50 * 00:46
00:43 00:41
00:38 RWT>0.45
00:36 Concentric
geometry of the
00:28 left ventricle
00:21

00:14

00:07

00:00
RWT
Controls Uncomplicated EMGH Complicated EMGH
*P<0.05 vs controls; °P<0.05 vs. uncomplicated EMGH


ROC CURVE for Blood Pressure Values

100%
80%
Sensitivity

60% SBP
DBP
40% MBP
20%
0%
0% 50% 100%
1-Specificity

ROC CURVE Relative Wall Thickness Cut off
0.45


ROC CURVE Total Vascular Resistance
Cut off 1340 dyn.s.cm-5


Cutoff values for TVR in multiparas e primiparas with
sensitivity, specificity, PPV, NPV and accuracy


Univariate and multivariate binary logistic regression
analysis for the prediction of complicated EMGH


TVR
in Intrauterine
Growth Restriction
and
Small for Gestational Age

ISOLATED FGR in
Normotensive
Total Vascular
Pregnancy Resistance
TVR=80 x MAP/CO
**
1800
1600
1400
1200
The high mean blood 1000
pressure and the low 800
600
cardiac output 400
explain the elevated 200

TVR in the IUGR 0
CONTROL IUGR
group
** p <0.0001

Parameter Normal Fetal FGR
Growth
Maternal Heart rate

Cardiac Output

Total Vascular
Resistance
Left Ventricular Mass

Differentiation through TVR
of FGR from SGA

TAKE HOME MESSAGE:

If we find a fetus with an AC <10 th
centile and normal PI of UA at 27-31
weeks

1. If the mother shows LOW TVR, the
pregnancy will probably procede without
complications (SGA).

2. If the mother shows HIGH TVR the
fetus will develop a Growth Restriction
(FGR).

TVR=80 x MAP/CO TVR
SGA:normal Cardiac
1800
Output coupled with a 1600 **
lower Mean Arterial 1400
Pressure contributes 1200
to maintain a reduced 1000
TVR 800
600
FGR: low cardiac 400
200
Output and relatively
0
high Mean Arterial SGA FGR
pressure
** p <0.0001

CONCLUSIONS
1. PATIENTS THAT DEVELOP PREECLAMPSIA HAVE

- DIASTOLIC DYSFUNCTION WITH REDUCED LA%FAC AND INCREASED IVRT
- REDUCED STROKE VOLUME AND CARDIAC OUTPUT

3. ALTERED CARDIAC FUNCTION MIGHT HELP
TO DIFFERENTIATE AMONG THE AFFECTED PATIENTS
THOSE WHO WILL DEVELOP COMPLICATIONS

altered prior to the onset
of preeclampsia?

Echocardiograpphy identifies
at 24 weeks gestation
Normotensive patients with subsequent maternal and/or fetal
complications through TVR

Uterine Artery Doppler and maternal Total
Vascular Resistance (TVR) and Left ventricular
Morphology

Vasapollo et al. Hypertension
2008

TVR and CO at 24 weeks’ gestation in the
asymptomatic phase

High TVR Low CO

1600
1570 7
6.57
1400
dyne 6
L/min
1200
5
1000
1009 4 4.51
L/min
800
600
dyne 3

2
400
200 1

0 0
Uncomplicated Complicated Uncomplicated Complicated

2008

•Total Vascular Resistance (>1400
dynes) appears to be the best
predictive parameter (PPV: 77%) for
complications in pregnancy at 24
weeks’ gestation in pts selected
through uterine artery Doppler.

2008

TVR in the latent
phase of
Early and Late
Preeclampsia
Valensise et al. Hypertension
2008

Model of the asymtomatic phase of Preeclampsia
•Our data show that early maternal and fetal complications are
associated to high TVR and low CO in the latent phase of the
disease

•Previous and recent data on the latent phase of preeclampsia
describe a model with low TVR and high CO.
Easterling 1990; Bosio 1999; Nicolaides 2008

•Early and late PE should be regarded as different forms of the
disease:
Early PE (before 34 weeks) associated with abnormal
uterine artery Doppler, FGR, and adverse maternal and
neonatal outcomes.
Late PE (after 34 weeks) associated with normal or slight
increase in uterine resistance index, mild maternal disease,
a low rate of fetal involvement.
Murphy 2000, Ness 2006, Sibai 2005

EARLY AND LATE PREECLAMPSIA

Are Early and Late PE hemodynamically
different?

Can we link a particular type of PE with a
specific haemodynamic model?

PATIENT SELECTION

1345 normotensive
primigravidas with 24 weeks
notching at 20-22 weeks Uterine artery Doppler+
Maternal Echocardiography

X
119 other
1119 normal complications
outcome 107 PE (8%)
(9%)
(Controls)
32 Late
75 Early PE PE

ASYMPTOMATIC 24 WEEKS PATIENTS

TVR, CO, bilateral notching, and BMI in the
asymptomatic phase of Early and Late PE
EARLY PE

CO 40%
9,00
8,00 8.96 LATE PE
7,00 L/min 60% P<0.05 16%
6,00
5,00
4,00
3,00
4.49
2,00 L/min
1,00 84%
0,00 Bilateral Notch Normal Doppler
EARLY PE LATE PE
Pre-pregnancy

TVR BMI
28
1800 28
1600
1605 27
Kg/m²
1400
1200
dyne 26
1000
25
800
600 739
24
24
400
dyne
200 23 Kg/m²
0
EARLY PE LATE PE 22
EARLY PE LATE PE

EARLY AND LATE PREECLAMPSIA at 24 weeks’
(latent phase)

Controls Early PE Late PE

TVR 990±179 1605±248* 739±244*°

CO 6.61±1.10 4.49±1.09* 8.96±1.83*°

Pre-preg. 23±4 24±2 28±6*°
BMI
Bilateral 67 (6.0%) 45 (60.0%)* 5 (15.6%)*°
Notch
Birthweight 46±23 18±12* 48±20°
centile

*P<0.05 vs. controls; °P<0.05 vs. Early PE

CONCLUSIONS
EARLY AND LATE PREECLAMPSIA

Early and Late PE appear to be
hemodynamically different!

Early PE is characterized by high TVR and low CO

Late PE is charachterized by low TVR and high CO

IN THE FUTURE:
No more PE without CO and
TVR values!

CONCLUSIONS
1. PATIENTS THAT DEVELOP PREECLAMPSIA HAVE

- DIASTOLIC DYSFUNCTION WITH REDUCED LA%FAC AND INCREASED IVRT
- REDUCED STROKE VOLUME AND CARDIAC OUTPUT
3.ALTERED CARDIAC FUNCTION MIGHT HELP
TO DIFFERENTIATE AMONG THE AFFECTED PATIENTS
THOSE WHO WILL DEVELOP COMPLICATIONS

4. ALTERED CARDIAC FUNCTION IS ALREADY
IDENTIFIABLE
IN ASYMPTOMATIC PATIENTS BEFORE THE
APPEARANCE OF THE CLINICAL SIGNS

so difficult to investigate?

IS IT SO DIFFICULT TO GET INFORMATIONS
ON CARDIAC FUNCTION DURING PREGNANCY?

How to calculate Stroke Volume, Cardiac Output and
TVR?

E wave
A wave
IVRT DtE

Aortic flow
Left Ventricular Out-flow
Tract (LVOT) integral
(Ao int)
Stroke volume (SV)=Area LVOT x Ao int
Cardiac output (CO)=SV x heart rate
Calculation of Total Vascular Resistance:
TVR=80 x (Mean Arterial Pressure/Cardiac Output)

JUST ONE MINUTE OF TIME
TO MEASURE TOTAL SISTEMIC VASCULAR RESISTANCE

AND LATER?
• INDIVIDUAL CONTROL
• FOLLOW THE VALUE IN FOLLOWING
DAYS/WEEKS
• EVALUATE IF THERE IS A TENDENCY
TO REDUCE TVR OR INCREASE TVR
• ADAPT THERAPY?

To study or not to study the heart this is the question

IN THE FUTURE:
Please do take care of the
Maternal Cardiac function and be
able to evaluate its parameters
The heart function might be
A good key to understand
Preeclampsia vascular status

Preeclampsia is a Heart Disease

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