VIMS Journal: December 2015

Original Article

Comparison of Myocardial Tissue Doppler and Conventional Vessel Doppler in Predicting Perinatal Outcomes in Babies with Intrauterine Growth Restriction

Dr. Barnali Basu, Dr. A. Das, Dr. B. Choudhury

Abstract :
Introduction :
Myocardial Tissue Doppler in echocardiography is a new and upcoming technique being claimed to detect adverse outcomes in babies with intrauterine growth restriction and hence can act as a useful tool in their management. We undertake this study to see whether it is a better technique than Vessel Doppler which is used conventionally for this purpose.

Objectives :
The objective of the study was to compare conventional vessel Doppler and Myocardial tissue Doppler in predicting adverse outcomes in babies with intrauterine growth restriction.

Design:
It was a prospective case control study.

Population:
Patients in the third trimester of pregnancy.

Methods:
Fetal cardiac function was evaluated with the help of Myocardial Tissue Doppler in IUGR babies and correlated with vessel Doppler findings and neonatal outcomes.

Main Outcome Measures:
Right and Left Ventricular and Interventricular septal E', A, E'/A' and Myocardial performance index (MPI').

Results:
There were sixty two IUGR babies in the study. Twenty seven among them had abnormal vessel Doppler. They were found to have both significantly reduced Right Ventricular late diastolic velocity and Myocardial performance Index (p-0.05,p-0.019). The rest thirty five did not show any significant difference in their Myocardial tissue Doppler parameters. In eleven babies with abnormal vessel Doppler and adverse neonatal outcomes, right ventricular MPI' was found to be significantly lower. However, the variable had a poor sensitivity (40%) in detecting fetuses at risk for poor neonatal outcomes. Also the Myocardial tissue Doppler variables were also found to be significantly abnormal in nineteen (40%) of the forty seven babies with normal perinatal outcomes. Conventional vessel Doppler, on the other hand, was normal in only four of the fifteen babies with abnormal perinatal outcomes but normal in all babies with normal outcomes.

Conclusion:
Myocardial tissue Doppler shows subtle right sided cardiac dysfunction in IUGR babies with adverse perinatal outcomes. It is however not a sensitive indicator of adverse perinatal outcome in IUGR babies in comparison to Conventional vessel Doppler.

Keywords:
Cardiac dysfunction, IUGR, Myocardial tissue Doppler.

Introduction:
Intrauterine growth restriction (IUGR) affects about 3-5 % fetuses in India. It mainly occurs due to uteroplacental insufficiency. If present for prolonged periods, the chronic hypoxia can lead to abnormal manifestations in various fetal Original Article organ systems with continued adaptive mechanisms that tend to get decompensated with time leading to adverse outcomes in the baby. Several studies have proved the effect of the pathological process of placental dysfunction in IUGR on the fetal heart[1,2,3,4,5]. Fetal cardiac function is complex and depends on myocardial contractility as well as on extra-cardiac factors such as developmental maturation, loading conditions and fetal disease. With progressive prolonged hypoxia there is deterioration with impaired cardiac filling and drop in cardiac function.

Myocardial tissue Doppler ultrasonography is a technique that allows measurement of myocardial velocimetry in systole and diastole without the limitations of conventional Doppler which is influenced by cardiac rate and afterload conditions. As this technique involves assessment of tissue function, if used correctly it can provide us with valuable information regarding the functioning of fetal myocardium as it has done in case of adults and children. As the cardiovascular changes in IUGR with progressive deterioration of intracardiac perfusion and consequent function tend to occur sometime before the signs of fetal distress appear on biophysical tests, the technique can detect cardiac dysfunction and may prove to be of valuable help in deciding on the management of fetuses with growth restriction. From the studies done so far, tissue Doppler looks like a promising tool for the detection of IUGR babies at risk for adverse outcomes[6,7,8].

Conventionally Doppler ultrasound assessment of flow patterns and velocities in a number of fetal vessels particularly the umbilical artery is has been the test of choice in the management of IUGR babies. They often act as an important adjunct to fetal biometry in identifying the IUGR fetus at risk of numerous complications. IUGR has been postulated to develop from changes in the placental circulation different from the ones seen in normal babies resulting in reduced oxygen and blood supply to the fetus. These changes in the placental circulation soon lead to redistribution of the entire fetal circulation reflected as changes in the Doppler flow in the major vessels of the fetal circulation. Progressive Doppler studies have been found to have predictive values for fetal growth restriction[9,10,11]. The most widely used Doppler studies for this purpose are those conducted on Umbilical arteries, middle cerebral arteries and ductus venosus.

A number of studies have come up recently questioning the usefulness of Doppler in IUGR fetuses and whether the absence of any Doppler changes can indeed be reliably taken as a sign of absence of any fetal decompensation and future neonatal morbidity[12,13,14]. This is more so in fetuses >34 weeks where despite normal Doppler findings, a sizeable proportion of SGA fetuses were found to have perinatal complications requiring intervention. Hence there is always a search for better studies than conventional vessel Doppler to detect dysfunction in babies with IUGR so that intervention can be taken in time for them balancing the complications of prematurity. We undertook this study to see if Myocardial tissue Doppler is a better investigative test than conventional vessel Doppler in the prediction of adverse outcomes in babies with intrauterine growth restriction.

The study was a prospective observational study, carried out between August 2011-August 2013, in the Department of Obstetrics and Gynaecology, Kasturba Hospital, Manipal. Patients in the third trimester of pregnancy who were identified as having IUGR were taken for the study. Written and informed consent was obtained from all patients. IUGR was diagnosed through ultrasound examination using the Haddock´┐Żs formula to calculate the estimated fetal weight and plotting of charts. The fetuses whose growth curve were below the 10th percentile or showed a fall in the expected growth curve were taken for the study. The growth curves were plotted with standardized custom made charts used in the hospital for the diagnosis and management of fetal growth restriction. Exclusion criteria were patients with multiple gestation and fetuses with cardiac anomalies.

Fetal echocardiography was done along with myocardial tissue Doppler in all these patients with help of Vivid GE machine. Sampling was done at the level of the basal part of the left ventricular free wall, right ventricular wall and interventricular septum.

The variables of tissue Doppler taken for all the three areas were[9] :

E'-the mean peak value of three early diastolic waves, A'-the mean value of three late diastolic or atrial filling waves, E'/A'-The ratio between the two.

Myocardial performance index (MPI') - Calculated by the formula ICT'+IRT'/ET' where: ICT' stands for isovolumetric contraction time, ET' stands for ejection time and IRT' for isovolumetric relaxation time.

Conventional Vessel Doppler examination was done for all of these patients. The vessels imaged were 1) Umbilical Artery, 2) Middle cerebral Artery, 3) DuctusVenosus.

Variables looked for were: Pulsatility index: Systolic end diastolic peak velocity/time averaged maximum velocity (PI),Resistance index: Systolic end diastolic peak velocity/systolic peak velocity (RI), Systolic to diastolic ratio: Systolic peak velocity/diastolic peak velocity. (S/D ratio) Peak Systolic velocity: Mean of three values of maximum systolic velocity in the middle cerebral artery.

Cerebroplacental ratio (CP ratio): Ratio of pulsatility index of Middle cerebral artery with that of umbilical artery. A value of more than 1 defined as adequate cerebral blood flow. The variables of the measurements made closest to delivery were taken.

All patients were followed up to 7 days postdelivery. Adverse neonatal outcomes were taken as: NICU admission for > 5 days, hypoglycemia, respiratory distress syndrome, presence of cardiomegaly, neonatal seizures and mortality. The variables obtained by myocardial tissue Doppler were compared those obtained by conventional Vessel Doppler. Comparison of the two tests was made between babies with normal and adverse outcomes. Statistical analysis was done with the help of SPSS software 16.

Results:
Among the patients attending the antenatal OPD, Sixty two patients with IUGR could be taken for the study (Table 1). Among them, twenty seven had abnormal vessel Doppler (defined as raised umbilical artery indices, absent or reversed end diastolic flow) while thirty five had normal vessel Doppler (Table 2). Myocardial tissue Doppler was performed on all these patients and its efficacy in detecting cardiac dysfunction compared with that of conventional vessel Doppler.

The Myocardial tissue Doppler parameters of the two groups of IUGR with normal and abnormal vessel Doppler were compared using the independent t-test (Table 3). The tissue Doppler parameters were lesser in the IUGR babies with abnormal vessel Doppler than the ones with normal. None of them were however statistically significant. This indicates that Myocardial tissue Doppler is not able to differentiate between the babies requiring more particular attention as defined by conventional Vessel Doppler.

All patients were followed upto 7 days postdelivery to look for neonatal outcome. The babies were looked for the development of any complications like: NICU admission for > 5 days, Hypoglycemia, Hyperbilirubinemia, Need for ventilator, Respiratory distress syndrome, Presence of cardiomegaly, Need for ionotropes, Necrotizing enterocolitis, Neonatal seizures, Mortality.

Twenty six IUGR babies required prolonged NICU admission however only fifteen had severe complications of respiratory distress requiring ventilator care. Among these nine were found to be asphyxiated at birth, five of them acidotic. Other adverse neonatal outcomes like hypoglycemia and cardiomegaly were not found to be in sufficient number among the IUGR babies. Three of the IUGR babies died, one of pulmonary hemorrhage and another of cardiac failure. In the case of the 3rd baby, in view of poor prognosis the mother refused any intervention leading to intrauterine death. On comparing the Myocardial tissue Doppler parameters between the babies with adverse and normal outcomes, only the right ventricle Myocardial performance index was found to be significantly lesser in babies who developed severe morbidity (Table 4). This probably indicates the presence of right ventricular dysfunction in IUGR babies who develop adverse neonatal outcomes.

The two babies who died also developed cardiac failure and they were also found to have abnormal Myocardial tissue Doppler variables for the right ventricle.

Hence, among all the Myocardial tissue Doppler variables, the right ventricular tissue Doppler variables are significantly affected and could act as markers of cardiac dysfunction or adverse neonatal outcome in IUGR.

As there is no defined cutoff as yet for fetuses for these parameters, the sensitivity of these variables in predicting adverse outcomes was assessed with Correlation curves.

On preparing a correlation curve of Right MPI' with neonatal outcomes, a negative correlation of was found (Figure 1). Lower the MPI', worse is the outcome of the baby. However the sensitivity as per the curve obtained is only 40% at a cutoff value of 0.65. Hence this value is likely to miss a lot of patients with adverse neonatal outcomes.

ROC Curve

As there are no fixed cutoffs for Myocardial tissue Doppler, the ones obtained by this curve was used for comparison with conventional vessel Doppler.

Among the Twenty seven babies with IUGR and abnormal vessel Doppler, nineteen had values less than the defined cutoff values as per the sensitivity curve. Out of these, eleven babies had adverse neonatal outcomes.

When the same cutoffs for Myocardial Tissue Doppler were applied to IUGR babies with normal outcomes, there were still significant numbers of babies with abnormal values (Table 5). Conventional Vessel Doppler in comparison to myocardial tissue Doppler had less false positives as well as negatives showing both more sensitivity and specificity than the latter. Statistically significant difference between babies with adverse and normal outcomes with the Doppler values were found with Conventional Vessel Doppler (Table 6) which is thus more sensitive in predicting adverse neonatal outcomes than Myocardial Tissue Doppler.

Discussion:
It was a prospective observational study conducted to compare the efficacy of conventional Vessel Doppler and Myocardial Tissue Doppler in detecting adverse perinatal outcome in IUGR. Sixty two IUGR patients were taken for the study. Dating forms an important consideration in the diagnosis of IUGR. In our data, most of the patients had excellent or good dating, so it can be reliably said that no patient was falsely categorized.

Myocardial tissue Doppler was used for the study which uses the high amplitude and low frequency signals generated by the myocardial tissue while movement during the cardiac cycle giving an impartial view of the actual functioning of the different ventricles of the heart without being biased by the load conditions. This can enable us to identify if there is actual cardiac dysfunction or just altered functioning as a compensation to tide over unfavorable circulatory changes. All measurements were made on the same machine and were carried out by the same trained person. Hence the chances of interobserver variations and the problems of expertise and knowledge were nullified.


Vessel Doppler making use of flow patterns in the fetal circulation to look for abnormalities in circulation has been used for a long time to assess the uteroplacental insufficiency seen in intrauterine growth restriction. The major vessels used for this purpose are the umbilical artery, middle cerebral artery and the ductusvenosus. The changes of uteroplacental insufficiency and the resultant compensatory mechanisms in the fetal circulation are reflected in the different indices of these vessels. These are followed by changes in the non-stress test and biophysical profile which can lead to fetal death if not acted timely. Hence Vessel Doppler can act as indicator of adverse neonatal outcome.

In the present study 35 IUGR babies were found to have normal vessel Doppler. Four of these had adverse neonatal outcomes. The 27 babies with abnormal vessel Doppler on the other hand showed significant reduction in Right ventricle MPI'. This essentially shows that all abnormalities of Myocardial tissue Doppler seen in IUGR are only confined to the ones with abnormal Vessel Doppler. Hence conventional Vessel Doppler is as efficacious in detecting the babies with cardiac dysfunction.

In fetal life it is the right side of the heart which plays the dominant role in the circulation of blood. As a result this is the area to be more in requirement of oxygen and nutrients and also more susceptible for hypoxia and ischemia. This therefore explains the observation of right sided parameters to be abnormal with IUGR.

Despite indicating the presence of cardiac dysfunction in IUGR babies, the Myocardial tissue Doppler parameters fared poorly in sensitivity and specificity in predicting the babies with increased chances of developing adverse neonatal outcomes. On account of its still being in the research phase, cutoff levels as to what is defined as abnormal tissue Doppler are not present. To enable looking for the level above which adverse neonatal outcome could be predicted, ROC curves were prepared for assessing the sensitivity of Tissue Doppler in predicting adverse neonatal outcomes. Using the cutoff as obtained by these curves to define normal and abnormal tissue Doppler, not only do the curves in themselves show a poor sensitivity of 40% only for Right ventricle MPI', but also these values tag lot of IUGR babies with normal outcomes as having abnormal tissue Doppler.

Undoubtedly, the babies with serious adverse outcomes seen in our study were all found to have abnormal Myocardial tissue Doppler values, but these were also detected as easily by vessel Doppler. On the other hand Myocardial tissue Doppler showed an unacceptable number of abnormal values both in IUGR babies with normal outcome and normal vessel Doppler. Myocardial Tissue Doppler has hence high numbers of false positives and low sensitivity in babies with IUGR.

There were as many as 15 babies with adverse neonatal outcomes of mainly respiratory distress and birth asphyxia. Comparable number of babies in this group had both abnormal Myocardial and conventional vessel Doppler. The babies with adverse neonatal outcomes also conformed to the findings of IUGR babies with abnormal vessel Doppler in having lower right ventricle MPI' in comparison to IUGR babies with normal outcomes. This shows good reliability of the technique in predicting adverse perinatal outcome in IUGR babies. Of note however is the presence of a number of IUGR babies with normal neonatal outcome who still had abnormal Myocardial tissue Doppler. The Right ventricular MPI' has been found to have low sensitivity on statistical analysis in this study and this could be a reflection of the same.

There have been a lot of studies[12,13,14] questioning the effectiveness of Conventional vessel Doppler with some finding abnormal myocardial tissue Doppler variables in patients with normal vessel Doppler[15]. However there has been hardly any study that looks at the neonatal outcomes of the babies taken up. In our study, even though the babies with serious adverse outcomes seen in our study like mortality, cardiomegaly, acidosis and birth asphyxia were all found to have abnormal Myocardial tissue Doppler values, these were also detected as easily by vessel Doppler. On the other hand Myocardial tissue Doppler showed an unacceptable number of abnormal values both in babies with normal outcome and normal vessel Doppler. This makes the Myocardial tissue Doppler a poor predictor for adverse neonatal outcomes as well as poor indicator in deciding the time of delivery in IUGR babies which is a critical decision.

The present study was undertaken to see if the upcoming technique of Myocardial tissue Doppler which already has proved its mettle in adults and children could be applied successfully in fetuses as well. But trying to correlate this investigation with conventional vessel Doppler and has not yielded very good results. The conventional vessel Doppler still remains the test to be carried out when faced with the dilemma of whether to deliver or observe when faced with the problem of IUGR in a patient.

Even though Myocardial tissue Doppler had a low sensitivity in predicting adverse perinatal outcome, it did indicate cardiac dysfunction in IUGR. Further research is needed with a larger sample size to further determine its usefulness.

Conclusion:
We conclude that Myocardial tissue Doppler shows right ventricular dysfunction in IUGR. Myocardial tissue Doppler is however not a sensitive indicator of adverse perinatal outcome in IUGR babies. Hence it is only a research tool and not useful in the clinical management of IUGR babies where conventional vessel Doppler is more useful.

Limitations:
As the babies were not followed up for a long period of time it is not known whether the abnormal tissue Doppler values found in the babies with normal vessel Doppler are indicative of cardiac dysfunction in future life. Also Troponin T levels of these babies were not checked and hence it cannot be confirmed if the abnormal values were incidental findings or subtle cardiac dysfunction. More research is needed in this regard.

Acknowledgements:
The authors would like to thank Dr. Lavanya Rai, Dr. Pratap Kumar and Dr. Muralidhar V. Pai for their valuable help and guidance in conducting this study.

Conflict of Interest:
The authors wish to report no conflict of interest over this study.

Table 1. Demographic Characteristics of the Patients (N-62):

n-62
Mean SD
Age in years 28.10 4.74
Gestational age in weeks 33.1 0.41
Parity N %
primi 33 53.2%
Multiple abortions 9 14.5%
multi 20 32.3
Preeclampsia Present 17 27.4%
Absent 45 72.6%

Table 2: Comparison of Vessel Doppler Parameters Among the IUGR Babies:

IUGR(62) p-value
Abnormal Doppler(N-27) Normal Doppler (N-35)
Mean SD Mean SD
UA PI 1.100 0.615 0.87 0.20 0.07NS
UA RI 0.64 0.22 0.61 0.22 0.69 NS
UA S/D 3.16 1.33 2.28 0.36 0.002Sig
MCA PSV 53.8 17.6 51.4 12.7 0.53 NS
MCA PI 1.58 0.41 1.54 0.42 0.73NS

Test used: Independent t test, p value < 0.05 considered significant


Table 3: Myocardial Tissue Doppler Parameters Among IUGR Fetuses with Normal and Abnormal Vessel Doppler:

IUGR(62) p-value
Abnormal Doppler(N-27) Normal Doppler (N-35)
Mean SD Mean SD
IV-E' 0.037 0.009 0.039 0.01 0.28NS
IV-A' 0.0481 0.13 0.486 0.11 0.88 NS
IV-E'/A' 0.79 0.37 0.84 0.26 0.56NS
IV-MPI' 0.60 0.10 0.63 0.08 0.27 NS
LV-E' 0.05 0.01 0.06 0.04 0.40NS
LV-A' 0.068 0.02 0.061 0.02 0.23 NS
LV-E'/A' 0.76 0.37 0.92 0.32 0.08NS
LV-MPI' 0.62 0.17 0.64 0.09 0.68 NS
RV-E' 0.06 0.01 0.08 0.11 0.37 NS
RV-A' 0.09 0.02 0.094 0.02 0.50 NS
RV-E'/A' 0.64 0.15 0.62 0.22 0.74 NS
RV-MPI' 0.58 0.14 0.650.16 0.16 0.06 NS

Test used: Independent t test, p value < 0.05 considered significant. E', A' in m/sec, E'/A' and MPI' are ratios


Table 4: Myocardial Tissue Parameters Among IUGR Babies Who Developed Morbidities:

IUGR(62) p-value
Morbidity(N-15) Normal Outcome (N-47)
Mean SD Mean SD
IV-E' 0.04 0.0078 0.039 0.01 0.85NS
IV-A' 0.05 0.13 0.49 0.13 0.64 NS
IV-E'/A' 0.81 0.33 0.85 0.30 0.52NS
IV-MPI' 0.61 0.10 0.62 0.09 0.68 NS
LV-E' 0.05 0.017 0.055 0.027 0.49NS
LV-A' 0.066 0.023 0.068 0.022 0.73 NS
LV-E'/A' 0.80 0.36 0.80 0.28 0.99NS
LV-MPI' 0.628 0.17 0.647 0.11 0.59 NS
RV-E' 0.06 0.01 0.07 0.007 0.56 NS
RV-A' 0.09 0.017 0.09 0.02 0.14 NS
RV-E'/A' 0.63 0.15 0.62 0.24 0.93 NS
RV-MPI' 0.59 0.16 0.65 0.13 0.05Sig

Test used: Independent t test, p value < 0.05 considered significant. E', A' in m/sec, E'/A' and MPI' are ratios. Values in m/sec


Table 5: Efficacy of Myocardial Tissue Doppler in Detecting IUGR Babies with Adverse Neonatal Outcomes

Abnormal Myocardial Tissue Doppler Normal Myocardial Tissue Doppler p Value
IUGR babies with morbidity(15) 12 13 0.21
IUGR babies with normal outcome(47) 28 19

Test used: Chi Square test, p Value < 0.05 considered significant


Table 6: Efficacy of Conventional Vessel Doppler in Detecting IUGR Babies with Adverse Neonatal Outcomes

Abnormal Vessel Doppler Normal Vessel Doppler p Value
IUGR babies with morbidity(15) 11 4 0.05
IUGR babies with normal outcome(47) 4 43

Test used: Chi Square test, p Value < 0.05 considered significant


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