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Cardiac Haemodynamics: Next Step in Fetal Monitoring
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
Cardiac Haemodynamics:
Next Step in Fetal Monitoring
Dr IE Bhorat
Outline of Presentation
• 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
Outline of Presentation
Pathophysiology of Diabetic Pregnancy
• Maternal hyperglycaemia
• fetal hyperglycaemia
• fetal pancreatic hyperplasia
• fetal hyperinsulinaemia
• macrosomia
Pathophysiology
Diabetic Pregnancy
Pathopysiology – Diabetic Pregnancy
• Fetal hyperinsulinaemiaincreased 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
Pathophysiology
Diabetic Pregnancy
Gestational Diabetes
• Macrosomia
• Increased metabolic demand
• Larger vascular cross sections
• FETO-MATERNAL METABOLIC PROBLEM AND
NOT A PLACENTAL PROBLEM
Gestational Diabetes
Gestational Diabetes
• 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
Gestational Diabetes
• 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?
Gestational Diabetes
Literature Survey
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
Literature Survey
Summary –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
Summary
Gestational Diabetes
Early Onset IUGR
• Fetal growth impairment
• Oligohydramnios
• Good fetal monitoring models
• Haemodynamic changes: alterations flow velocities in UA, MCA, DV, AoI Doppler
Early Onset 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
IUGR
Place for Additional Monitoring Parameters
• Hypoxia MCA RI < p5
• Tracking myocardial function
• Acidosis DV anomalies – myocardial necrosis + late compromised state
Place for Additional Monitoring
Parameters
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
IUGR
Pre-Eclampsia
• Cardiac dysfunction not conclusively demonstrated in Pre-Eclampsia
• Studies not distinguished early from late pre-eclampsia
• Not homogeneous group
• Early onset PET –part of Great Obstetric Syndromes
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
EO-PRE-ECLAMPSIA
Spiral Artery In Junctional Zone Myometrium Classification of Defective Deep Placentation- Brosens et al – Am J Obstet Gynecol :2011
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
•
PRE-ECLAMPSIA
Different Pathophysiologies Cardiac Dysfunction
• Diabetes IUGR PET
• AbnormalMetabolic milieu Hypoxia LV afterload
Cardiac Dysfunction
Different Pathophysiologies
Cardiac Dysfunction
Methodologies
Myocardial Performance Index
E/A ratio
Methodologies
Myocardial Performance 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 Index
Myocardial Performance Index
The time cursor is placed at the beginning of each Doppler click.
Myocardial Performance Index
Studies in Fetal Myocardial Performance –Research Group at UKZN
• 1. Reference Ranges of MPI – normograms -5th, 50th
and 95th percentiles.
• 2. MPI in Diabetes
• 3. MPI in IUGR
• 4. MPI in Pre-eclampsia
Studies in Fetal Myocardial Performance –
Research Group at UKZN
Reference Intervals of MPI –normal pregnancies
0.3
00
.35
0.4
00
.45
MP
I
20 25 30 35 40Gestational age (weeks)
Reference Intervals of MPI –
Normal Pregnancies
Reference Intervals of MPI – 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 Mod-
MPI noted with advancing gestation.
Reference Intervals of MPI –
Normal Pregnancies
Bhorat I, Bagratee R, Reddy T. Prenatal Diagnosis:2014;34 (11): 1031-1036
Gestational Diabetes
• Fetal myocardial performance in Gestational Diabetes and links to perinatal outcome
Gestational Diabetes
MPI and Gestational 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
MPI and Gestational Diabetes
MPI and Gestational Diabetes0
.30
.40
.50
.60
.7
MP
I
Control IDDM
MPI in Controls vs IDDM
MPI and Gestational Diabetes
Scatterplot of MPI vs Gestational age with linear predictions from quantile regression superimposed.
0.3
0.4
0.5
0.6
0.7
MP
I
31 32 33 34 35 36Gestational age (weeks)
Control IDDM
Linear prediction Linear prediction
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 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
Results
MPI and Gestational Diabetes
MPI and Gestational 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.
MPI and Gestational Diabetes
Bhorat I, Bagratee J, Pillay M, Reddy T. Prenatal Diagnosis 2014; 34 (13): 1301-1306
IUGR and Fetal Myocardial 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?
IUGR and Fetal Myocardial
Performance
MPI and IUGR
Question 1: Is MPI altered in IUGR?
MPI and IUGR
MPI and IUGRMPI and 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) 0.9535
Gestational age (weeks) 33 (31 -34) 33 (31-34) 1
Gestational age of delivery (mean
SD)
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 (0.78-08) 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
MPI and IUGR
• Question 2: Does MPI correlate with degree of IUGR ?
MPI and IUGR
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.
Methods
Distribution of Mod-MPI in each of the IUGR grades
0.4
0.5
0.6
0.7
0.8
MP
I
Uncompensated Compensated Critical
MPI and IUGR
• Question 3: Is the MPI a prognostic indicator?
MPI and IUGR
Pregnancy and Perinatal OutcomesIUGR
ControlsUncompensated Compensated Critical
Number (n) 43 19 10 14
Gest age –mean
(delivery)
39w4d (38w3d-
40w3d)
37w1d (36w-
37w5d)
35w6d (34w3d-
36w3d)
30w2d (29w5d-
32w1d)
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) 3110 (2960-
3476)
2156 (1890-2314) 1910 (1623-2118) 920 (850-1103)
5-min APGAR <6 - 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 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
Adverse Perinatal Outcome
MPI and E/A ratio as markers of adverse outcome0
.00
0.2
50
.50
0.7
51
.00
Se
nsi
tivity
0.00 0.25 0.50 0.75 1.001-Specificity
MPI AUC: 0.939 E/A Ratio AUC: 0.761
Reference
ROC curve: comparing Mod-MPI and DV PIV in prediction of perinatal mortality , both being
significant predictors.
MPI in 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
MPI in IUGR
Bhorat I, Bagratee J, Pillay M, Reddy T. Prenatal Diagnosis: 2015:35(3); 266-273
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.
Conclusion
PET and 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 MPI
PET and MPI
• Question 1: Is MPI altered in severe EO –PET?
PET and MPI
ResultsResults
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 MPI
• Question 2: Does MPI alter with deteriorating placental vascular resistance in PET?
PET and MPI
Comparison of Mod-MPI values between the 4 levels of severity in Study (PET) Groups
0.5
0.5
50
.60
.65
0.7
MP
I
0.7<= UA <0.8 0.8<= UA <0.85 UA>= 0.85 AEDF
PET and MPI
• Question 3: Is the MPI a prognostic indicator of APO in severe EO-PET?
PET and MPI
Pregnancy and Perinatal Outcomes in the Control and Study Groups
Control
(normals)
Group 1
0.7<=UA <
0.8
Group 2
0.8<=UA
<0.85
Group 3
RI ≥0.85
Group 4
AEDF/REDF/
Abn DV PIV
N = 30 N = 9 N = 10 N = 5 N = 6
Median MPI0.38
(0.38-0.39)
0.54
(0.5-0.58)
0.62
(0.6-0.62)
0.65
(0.6-0.67)
0.68
(0.65-0.71)
Birth Weight (g)
mean
3085
(2989-3315)
1636
(1465- 1765)
1242
(1023-1356)
1196
(980-1236)
950
(855-1046)
Mean Gest age
(w) at delivery39.2 32w3d 31w3d 30w6d 30w2d
APGARS <6
(5min)
-3 5 3 5
Neonatal death-
- - 2 3
pH <7.15 - 1 2 2 4
HIE - - 2 1 1
IVH - - - - 1
BPD 1 -
Perinatal
complications- 33% 50% 60% 83%
Adverse Perinatal Outcome – 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
Adverse Perinatal Outcome - PET
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 PET
• For adverse perinatal outcome, a cut-off Mod-MPI value of >0.55 conferred a sensitivity of 100% (95% Confidence interval [CI] 82.3-100%), 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-eclampticgroup compared to controls (0.66 vs 0.79, p < 0.0001).No adverse outcomes were noted in the control group.
MPI and PET
MPI and Pre-eclampsia
• 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.
MPI and Pre-eclampsia
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 mod-MPI 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
Conclusions