Haemodynamics:
CardiacCardiac
Haemodynamics:
Next Step in
Next Step
Fetal Monitoring
FetalinMonitoring
Dr IE Bhorat
MBChB(Ntl), B.SC (UDW), DA (SA), Dip Mid COG (SA), FCOG (SA), PhD.
Subspecialist:
Fetal –Maternal Medicine
Head:
Fetal Medicine, Dept of Obstetrics and Gynaecology, Nelson R
Mandela School of Medicine, University of Kwa-Zulu Natal, Durban,
South Africa
Outline of
of Presentation
Presentation
Outline
• 1. Pathophysiology of Gestational Diabetes, IUGR
and PET –> Different pathways  Link to Cardiac
Dysfunction
• 2. Methodologies and Techniques to Assess Fetal
Cardiac Function: Mod MPI and E/A ratio
• 3. Studies Supporting Use of Functional Cardiac
Assessment - ? Integration in Routine Fetal
Assessment
Pathophysiology
Pathophysiology
of Diabetic Pregnancy
Diabetic Pregnancy
• Maternal hyperglycaemia
•  fetal hyperglycaemia
•  fetal pancreatic hyperplasia
•  fetal hyperinsulinaemia
•  macrosomia
Pathophysiology
Pathopysiology
– Diabetic Pregnancy
Diabetic Pregnancy
•
Fetal hyperinsulinaemia increased glucose oxidation + oxygen consumption
•
 fetus has reduced capacity for oxidative metabolism and low pyruvate dehydrogenase
activity
•
 when capacity is reached  anaerobic metabolism lacticaemia  fetal acidosis 
death
•
Bradley and Salvesan (early 90’s) –cordocentesis - fetuses of diabetic pregnancies 
SIGNIFICANT ACIDEMIA AND HYPERLACTICAEMIA IN ABSENCE OF HYPOXAEMIA -  offers an
explanation of so-called “unexplained” fetal deaths  consequence of increased metabolic
rate
•
DIABETES: Concept of: ACIDOSIS IN ABSENCE OF HYPOXIA
•
Implications for antenatal surveillance
Gestational Diabetes
Diabetes
Gestational
• Macrosomia
• Increased metabolic demand
• Larger vascular cross sections
• FETO-MATERNAL METABOLIC PROBLEM AND
NOT A PLACENTAL PROBLEM
Gestational Diabetes
Diabetes
Gestational
• What antenatal tools do we presently have in fetal
surveillance?
• Umbilical Artery Doppler velocimetry – widely used
method of antenatal surveillance in high risk
pregnancies including diabetic pregnancies.
• But what does Umbilical Artery Doppler velocimetry
measure?- resistance to placental blood flow
Gestational Diabetes
Diabetes
Gestational
• Most of our conventional antenatal surveillance techniques
– Umbilical artery PI/RI, Middle cerebral artery PI/RI and
Ductus venosus PIV – revolve around placental insufficiency
– NOT THE PROBLEM IN DIABETIC PREGNANCIES
• CONCLUSION: NOT APPROPRIATE OR SUFFICIENT AS A
MONITORING MODEL IN DIABETES.
• What about cardiac dysfunction?
Literature Survey
Literature
Literature: Cardiac Haemodynamics:
•
1. Fetal interventricular septal thickness increases – alterations in diastole (occur
even in well controlled diabetics)-Rizzo G et al – (1991)
•
2. Impaired ventricular compliance in fetuses of diabetic pregnancie Rizzo G et al
(1994), Weiner Z et al (1999)
•
3. LV and RV hypertrophy – Weiner et al
•
4. Hypertrophic CMO
•
5. Increased Preload Index in IVC – associated with lower pH at birth and
polycythaemia – Nicolaides KH et al
•
6. Abnormal metabolism – direct cardiac effect on function
Summary Diabetes
Summary –Gestational
Gestational Diabetes
• 1. Pathophysiology – metabolic problem and not
placental insufficiency.
• 2. Acidosis in absence of hypoxia
• 3. Fetal monitoring models revolve –hypoxia detection
• 4. Evidence of cardiac dysfunction
• 5. Possible –channel cardiac dysfunction into a
monitoring model
Early
Early Onset
Onset IUGR
IUGR
• Fetal growth impairment
• Oligohydramnios
• Good fetal monitoring models
• Haemodynamic changes: alterations flow
velocities in UA, MCA, DV, AoI Doppler
IUGR
IUGR
• Ductus venosus and Aortic Isthmus – Late
Doppler changes – cascade of deterioration
• DV Doppler anomaly  fetal acidosis 
anomalies in forward flow cardiac
haemodynamics.
• DV and AoI flow anomalies  extrapolations
 compromised cardiac state
Place
for
Additional
Monitoring
Place for Additional Monitoring
Parameters
Parameters
• Hypoxia 
•
MCA RI < p5
Tracking myocardial function
• Acidosis  DV anomalies – myocardial
necrosis + late compromised state
IUGR
IUGR
• Pivotal role  intrinsic myocardial function
 Compensatory mechanism of the IUGR
fetus  establishment of arterial
redistribution or Brain –Sparing effect
• Direct functional assessment of fetal heart 
based on pathophysiology  clinical value
PRE-ECLAMPSIA
Pre-Eclampsia
• Cardiac dysfunction not conclusively
demonstrated in Pre-Eclampsia
• Studies not distinguished early from late preeclampsia
• Not homogeneous group
• Early onset PET –part of Great Obstetric
Syndromes
EO-PRE-ECLAMPSIA
EO-PRE-ECLAMPSIA
Placental maladaptation + Vascular Transformation
Reduced perfusion
Placental Ischaemia
------------------------------------------ PLGF + VEGF / sFLT -1
Vessel Injury + vasoconstriction
Increased PVR
Increased Fetal Cardiac Afterload
Spiral Artery In Junctional Zone Myometrium Classification of Defective
Deep Placentation- Brosens et al – Am J Obstet Gynecol :2011
PRE-ECLAMPSIA
PRE-ECLAMPSIA
• EO-PET >> placental pathological state >> IUGR  more serious clinical phenotype
• IUGR  intrinsic myocardial function  pivotal
role - compensatory mechanisms
• Hypothesise - alterations in cardiac function in
PET – Increased Cardiac Afterload
•
Different
Pathophysiologies
 Cardiac
Different
Pathophysiologies

Dysfunction
Cardiac
Dysfunction
• Diabetes
IUGR
• Abnormal
Metabolic milieu
Hypoxia
PET
LV afterload
Cardiac Dysfunction
Methodologies
Methodologies
Myocardial Performance Index
E/A ratio
Myocardial Performance
Performance Index
Myocardial
Index
• The Myocardial Performance Index (MPI)
– Tei et al (TEI Index) – in adults to assess ventricular dysfunction (1995)
• Ratio between the duration of the isovolumetric periods (composed of 2
periods: contraction and relaxation ie ICT and IRT) and duration of ejection
(ET)
• MPI= (ICT+IRT)/ET
• Tei Index- used in fetus and newborn (Tsutsumi and Ichizuka )
• Valve –click method: Hernandez-Andrade = Mod MPI
Myocardial Performance
Performance Index
Myocardial
Index
The time cursor is placed at the beginning of each Doppler click.
StudiesininFetal
FetalMyocardial
MyocardialPerformance
Performance ––
Studies
ResearchGroup
Group at
atUKZN
UKZN
Research
• 1. Reference Ranges of MPI – normograms -5th, 50th
and 95th percentiles.
• 2. MPI in Diabetes
• 3. MPI in IUGR
• 4. MPI in Pre-eclampsia
0.30
0.35
MPI
0.40
0.45
Reference Intervals of MPI –normal
Reference
Intervals
of
MPI
–
pregnancies
Normal Pregnancies
20
25
30
Gestational age (weeks)
35
40
Reference Intervals of MPI – Normal
Reference
Intervals
of
MPI
–
Pregnancies
Normal Pregnancies
• Reference intervals of the Mod-MPI evaluating
fetal cardiac function have been established.
Maturational and developmental alterations in
the myocardial performance in utero resulting in
better ventricular compliance is most likely
responsible for the decreasing trend of the ModMPI noted with advancing gestation.
Bhorat I, Bagratee R, Reddy T. Prenatal Diagnosis:2014;34 (11):
1031-1036
Gestational Diabetes
Gestational
Diabetes
• Fetal myocardial performance in Gestational
Diabetes and links to perinatal outcome
MPIand
andGestational
Gestational Diabetes
MPI
Diabetes
• To determine whether the MPI is altered in fetuses in
pregnancies complicated by severe gestational
diabetes (GDM)
• To determine whether MPI is of value in fetal
surveillance in Diabetic pregnancy
• To determine whether MPI is of value in predicting
adverse perinatal outcome
MPIand
andGestational
Gestational Diabetes
MPI
Diabetes
0.5
0.4
0.3
MPI
0.6
0.7
MPI in Controls vs IDDM
Control
IDDM
0.5
0.4
0.3
MPI
0.6
0.7
Scatterplot of MPI vs Gestational age with linear predictions
from quantile regression superimposed.
31
32
33
34
Gestational age (weeks)
Control
Linear prediction
35
IDDM
Linear prediction
36
Outcomes in Study and Control Groups
Outcomes
Study Group (n=29)
Controls (n=29)
Stillbirth
1
-
Neonatal death
1
-
NICU admission
16
-
Tachypnoea + pulmonary
oedema
8
-
Apgar < 7 (5 min)
13
-
pH <7.15
13
-
Cardiomyopathy
1
-
Normal outcome
12
29
Distribution of MPI between normal and abnormal outcomes in the study
group and correlation to the 95th percentile of MPI from normal ranges
study
Results – MPI and Gestational
Results
Diabetes
MPI and Gestational Diabetes
All 17 fetuses showing abnormal outcome had:
MPI’s > 0.52 - sensitivity of 1 (0.8-1), specificity of
91.67% (0.61-0.998)
Additional risk factors: Increased Birthweight and low
E/A ratios and increased AFI
MPIand
andGestational
Gestational Diabetes
MPI
Diabetes
• To our knowledge this is the first study to
demonstrate a clear relationship between an
altered MPI and adverse fetal and neonatal
outcome in diabetic pregnancies.
Bhorat I, Bagratee J, Pillay M, Reddy T. Prenatal Diagnosis
2014; 34 (13): 1301-1306
IUGR and Fetal Myocardial
IUGR and
Fetal
Myocardial
Performance
Performance
• Question 1: Is MPI altered in IUGR
• Question 2: Does MPI correlate with degree
of IUGR
• Question 3: Is MPI a prognostic indicator of
APO?
MPI and
and IUGR
MPI
IUGR
Question 1: Is MPI altered in IUGR?
MPI and
and IUGR
MPI
IUGR
Demographic, Sonographic Data and Cardiac Doppler Data
between Control and Study Groups
Control (n=43)
IUGR (n=43)
p-value
Median (IQR)
Median (IQR)
Maternal age (mean(SD))
29.62 (3.61)
29.67(3.59)
Gestational age (weeks)
33 (31 -34)
33 (31-34)
1
Gestational age of delivery (mean
39.20 (0.45)
36.76 (1.18)
<0.0001
AFI (cm)
12.8
(12.2 - 13.4)
8.95 (7.95 - 10.1)
<0.0001
EWF (g)
2214
(1788 – 2436)
1559.5 (1042 - 1897.5)
<0.0001
E/A ratio
0.79
0.63 (0.57-0.67)
<0.0001
Median MPI (IQR)
0.37 (0.36-0.38)
0.59 (0.52-0.69)
<0.001
0.9535
SD)
(0.78-08)
MPI and
and IUGR
MPI
IUGR
• Question 2: Does MPI correlate with degree
of IUGR ?
Methods
Methods
• Uncompensated IUGR: AC < 10th percentile for gestational
age, elevated umbilical artery RI at > 2 standard deviations
for gestational age with no arterial redistribution and
normal venous Doppler.
• Compensated IUGR had in addition a middle cerebral
artery RI below the 5th centile for gestational age reflecting
arterial redistribution.
• Critical status IUGR: absent (AEDF) or reversed end
diastolic flow (RAEDF) in the umbilical artery and/or severe
venous Doppler anomalies: high suspicion of acidosis.
0.6
0.5
0.4
MPI
0.7
0.8
Distribution of Mod-MPI in each of the IUGR grades
Uncompensated
Compensated
Critical
MPI and
and IUGR
MPI
IUGR
• Question 3: Is the MPI a prognostic indicator?
Pregnancy and Perinatal Outcomes
IUGR
Controls
Uncompensated
Compensated
Critical
Number (n)
43
19
10
14
Gest age –mean
(delivery)
39w4d (38w3d40w3d)
37w1d (36w37w5d)
35w6d (34w3d36w3d)
30w2d (29w5d32w1d)
Median MPI
0.37 (0.36-0.38)
0.52 (0.50-0.54)
0.63 (0.6-0.65)
0.7 (0.7-0.73)
Mode of Delivery –
C/S (%)
6
35
68
100
Birth Weight (g)
2156 (1890-2314)
1910 (1623-2118)
920 (850-1103)
5-min APGAR <6
3110 (29603476)
-
5
6
11
Perinatal Deaths
-
-
1
4
HIE
-
-
2
3
Neonatal Resuscit
-
5
5
11
Cord pH <7.15
-
1
3
10
IVH
-
-
-
2
BPD
-
-
-
2
Adverse outcome
0%
26%
60%
79%
Adverse Perinatal
Perinatal Outcome
Adverse
Outcome
• Severity of growth restriction
• Prematurity
• Cardiac dysfunction (hypoxaemia/acidaemia)
• Logistic regression analysis: MPI remained
significant predictor for APO –adjusting GA, EFW,
UA RI, DV, AFI and E/A ratio:
• Adjusted OR 95% CI:2.60 (1.15-5.83), p-0.02
0.00
0.25
0.50
0.75
1.00
MPI and E/A ratio as markers of adverse outcome
0.00
0.25
0.50
1-Specificity
MPI AUC: 0.939
Reference
0.75
E/A Ratio AUC: 0.761
1.00
ROC curve: comparing Mod-MPI and DV PIV in
prediction of perinatal mortality , both being
significant predictors.
MPI in
in IUGR
MPI
IUGR
• A cut-off Mod-MPI value of 0.54 : sensitivity of
87% (CI:66-97%), specificity of 75%(CI:55-91%)
and a likelihood ratio (LR) of 3.47 for an adverse
outcome.
• A cut-off Mod-MPI value of 0.67 conferred a
sensitivity of 100% (CI:54-100%), specificity of
81%(CI:65-92%) and LR of 5.28 for perinatal
death.
• No abnormal outcomes occurred in controls
Bhorat I, Bagratee J, Pillay M, Reddy T. Prenatal Diagnosis:
2015:35(3); 266-273
Conclusion:
Conclusion
• 1. Link between severity of MPI and adverse
outcomes in IUGR.
• 2. Cut-off MPI values for adverse outcomes
and perinatal death have been suggested.
• 3. MPI – allows tracking of cardiovascular
deterioration between hypoxia and acidosis.
PET and
PET
andMPI
MPI
• To determine whether fetuses in severe early
onset pre-eclampsia (EO-PET) have cardiac
dysfunction
• Does MPI deteriorate across stages of
increasing placental vascular resistance in PET
• Whether this dysfunction influences perinatal
outcome.
PET and
PET
andMPI
MPI
• Question 1: Is MPI altered in severe EO –PET?
Results
Results
Demographic and Sonographic Data and Cardiac
Doppler Data
Control Group
PET (Study) Group
p-value
Maternal age (years)
28.91 (3.80)
28 95 (3.70)
0.523
Gest age (w) (IQR)
30 (30.57-31.28)
29.98 (30.43-32)
0.454
EWF (g) at assessment
1629 (1597 - 1713)
1214 (913 - 1354)
0.0001
AFI (cm)
12.83 (1.11)
11.46 (3.29)
0.0697
E/A ratio
0.79 (0.02)
0.66 (0.03)
<0.0001
Median MOD-MPI (IQR)
0.38 (0.38-0.39)
0.62 (0.54-0.67)
<0.001
ICT (ms)
28 (27-29)
35 (34-38)
<0.001
IRT (ms)
39 (38-39)
58 (56-64)
<0.001
ET (ms)
172 (171-172)
152 (150-156)
<0.001
PET and
PET
andMPI
MPI
• Question 2: Does MPI alter with deteriorating
placental vascular resistance in PET?
0.6
0.5
0.55
MPI
0.65
0.7
Comparison of Mod-MPI values between the 4 levels of
severity in Study (PET) Groups
0.7<= UA <0.8
0.8<= UA <0.85
UA>= 0.85
AEDF
PET and
PET
andMPI
MPI
• Question 3: Is the MPI a prognostic indicator
of APO in severe EO-PET?
Pregnancy and Perinatal Outcomes in the Control and Study
Groups
Control
(normals)
Median MPI
Birth Weight (g)
mean
Mean Gest age
(w) at delivery
APGARS <6
(5min)
Neonatal death
pH <7.15
HIE
IVH
BPD
Perinatal
complications
N = 30
0.38
(0.38-0.39)
Group 1
0.7<=UA <
0.8
N=9
0.54
(0.5-0.58)
Group 2
0.8<=UA
<0.85
N = 10
0.62
(0.6-0.62)
N=5
0.65
(0.6-0.67)
Group 4
AEDF/REDF/
Abn DV PIV
N=6
0.68
(0.65-0.71)
3085
(2989-3315)
1636
(1465- 1765)
1242
(1023-1356)
1196
(980-1236)
950
(855-1046)
39.2
32w3d
31w3d
30w6d
30w2d
3
5
3
5
-
Group 3
RI ≥0.85
-
-
-
2
3
1
-
2
2
-
2
1
1
4
1
1
-
-
33%
50%
60%
83%
Adverse Perinatal
Perinatal Outcome
Adverse
Outcome–-PET
PET
•
•
•
•
Worsening placental vascular resistance
Prematurity
Cardiac dysfunction
Logistic regression analysis MPI remained
significant predictor after adjusting for
gestational age and E/A ratio
• Adjusted OR 95% CI: 1.82 (1.06-3.11), p- value
0.03
Significant relationship between the myocardial performance
index and adverse outcome (area under the curve of 0.95)
ROC: Significant relationship depicted between myocardial
performance index and prediction of perinatal death (area
under the curve of 0.95)
MPI and
and PET
MPI
PET
• For adverse perinatal outcome, a cut-off Mod-MPI value of >0.55
conferred a sensitivity of 100% (95% Confidence interval [CI] 82.3100%), specificity of 82% (95% CI 51-96.5%) and a LR of 5.5.
• For perinatal death, a cut-off Mod-MPI value of 0.67 conferred a
sensitivity of 100% (95% CI 52-100%), specificity of 84% (95% CI
62.5-94%) and an LR of 6.25.
• The E/A ratios were significantly decreased in the pre-eclamptic
group compared to controls (0.66 vs 0.79, p < 0.0001).No adverse
outcomes were noted in the control group.
MPIand
and Pre-eclampsia
Pre-eclampsia
MPI
• 1. Fetal cardiac function is significantly impaired
in severe EO-PET
• 2. Tracking MPI measurements may allow the
clinician to monitor myocardial performance of
fetuses in severe EO-PET across deteriorating
placental vascular resistances.
• 3.Specific cut-off Mod-MPI values for prediction
of adverse perinatal outcome and perinatal death
have been suggested.
Conclusions
Conclusions
1. Mod-MPI may be the only non-invasive technique in monitoring
fetuses in gestational diabetes in order to detect a significantly
abnormal metabolic milieu.
2. Monitoring tool for assessing deteriorating cardiovascular function
in IUGR fetuses, and thereby guide the physician to optimal timing of
delivery before overt acidosis, myocardial necrosis or perinatal death
sets in.
3. Pre-eclampsia: evaluation of fetal cardiac function using the modMPI and E/A ratios together with the evaluation of umbilical artery
Doppler flow could be included into an integrated monitoring model in
the management of PET pregnancies
Conclusions
Conclusions
• These studies of fetal cardiac dysfunction in
high risk obstetric conditions makes the
argument for fetal cardiac function to being
part of an integrated approach to establish
fetal wellbeing in high risk obstetrics