Health & Medical Cardiovascular Health

A New Approach to Evaluate Fetal Myocardial Function

A New Approach to Evaluate Fetal Myocardial Function

Discussion


The objective of this study was to establish gestational age specific reference data for TVI measurements of the fetal myocardium. These data also reveal some new information regarding prenatal cardiac function as this study is the first to assess myocardial mechanics during fetal development by evaluating the different time intervals during a cardiac cycle according to the motion shifts of the AV-piston. The finding that the post ejection phase, measured from septum and the left ventricular free wall, decreased with gestational age, might reflect lactate dependent myocardial performance. During this phase the ventricular myocardium starts to relax, which paradoxically is an energy consuming process, caused by the repolarization process of the heart muscle cells, and consequently this phase will be very sensitive to low oxygen levels. In accordance adults exhibit a prolongation of post ejection during exercise and controlled hypoxia resulting in lactecaemia. In a recent study on fetal lamb we also observed a prolongation of post ejection at controlled hypoxia, suggesting an adaptive mechanism of the fetal heart to resolve to a more immature state at relative hypoxia. In the right ventricular free wall no significant change of the post ejection phase was observed throughout gestation, which is consistent with the absence of this phase for the corresponding cardiac wall in adults. The prolongation of the rapid filling phase throughout gestation is most likely due to an increase in size and volume. However, the maturational rate of e' was more prominent, which in accordance with recent findings indicate an improvement in active relaxation as pregnancy advances.

In concurrence with previous studies we observed that all peak velocities during the cardiac cycle were higher in the right ventricular free wall compared to septum and the left ventricular free wall - consistent with right ventricular dominance. As can be seen in Figure 4, the right ventricle also showed a greater stroke length compared to the left. We could also confirm the gestational increase in fetal myocardial velocities despite a maturational fall in fetal heart rate, and the increase of the e'/a' ratio, corresponding to a redistribution from A-wave towards E-wave dominance with gestational age. The higher ventricular filling velocities confirming the active Frank-Starling mechanism in the fetal heart, which is particularly apparent during fetal arrhythmias. The maturational rate of s' and e' was higher in the right ventricular free wall compared to the left ventricular free wall and septum, implying that the differential loading of the ventricles does influence the measures of myocardial maturation, unlike Gardiner et al. previously suggested. Sex was not decisive for any of the measured variables even though HR was observed to be significantly higher for the female fetus up until 30 weeks of gestation. Unlike Bilardo et al., we did not observe a relationship between sex and e', however, multiple regression analysis showed that a combination of HR and gestational age enhanced the correlation for the rapid filling phase. This would imply that an increased HR might affect the ability to measure e' accurately.

Previous studies that used spectral Doppler reported higher peak velocities compared to the present results, which is in agreement with the reported overestimation of velocity using this technique. Also the e'/a' ratio was higher in these studies, indicating a larger overestimation of e'. Using TVI, different studies have reported varying results. The measurements of e' and a' in the present study were in better compliance with previously reported results than the measurements of s'. An explanation for the observed discrepancies could be the angle dependency of the velocity measurements or the placement of the ROI. However, all aforementioned studies state acceptable reproducibility of their measurements. Which is also valid for the measurements made in this study, where reproducibility as well as intra- and inter-observer variability has been demonstrated to be acceptable in the controlled clinical setting, and may indicate that the equipment used is not interchangeable - previously demonstrated in both adult and fetal echocardiography. This implies that one should need to establish separate reference materials when measuring amplitudes of the myocardial velocity curve depending on which ultrasound system and is being used. A study demonstrating normal values and age related changes of pre' also suggest that pre' and post' are more reliable than s', as s' has shown to be preload and afterload dependent. Even though we demonstrate less distribution for pre', the peak velocity during such a short time interval is easy to miss. Further studies are needed in order to confirm the reasons for the discrepancies, and to establish whether this also applies for the timing of the mechanical events during a cardiac cycle.

As long as the timing of myocardial events can be represented accurately, time intervals could be more robust measurements than myocardial velocities as these measurements are less angle dependant and less influenced by tethering effects. Furthermore, time intervals have been described as markers of cardiac performance, where the myocardial performance index or Tei index, reflecting the relationship between the transition phases (pre and post ejection) and ventricular ejection, has been evaluated as a marker of fetal cardiac dysfunction. These time intervals were in the present study shown to be independent of heart rate within the studied heart rate interval. However, there was no gestational age related change of this index, despite a maturational shortening of the post ejection phase, which implies that the Tei index might not be as sensitive. Traditionally this index has been calculated from Doppler derived blood flow measurements, which are not comparable to tissue velocity measurements, and these measures should not be used interchangeably.

The transition phases mirror the hearts mechanical function and have been shown to be lactate sensitive markers for asphyxia and metabolic acidosis. Lactate is a metabolite in anaerobic metabolism and reflects tissue hypoxia. Determination of lactate in blood from the fetus's scalp during labor has been studied extensively and comparative studies of pH have shown that lactate analysis has similar or better predictive properties compared with pH analysis in the identification of short term neonatal morbidity. Thus non-invasive methods to determine the fetal lactate status is of great potential value in the area of fetal monitoring.

The timing of mechanical events has hitherto been difficult to ensure without a simultaneous ECG signal. To make the analysis of TVI measurements easier and more effective we introduced the CSD as a potential aid in fetal monitoring. Using this method we measure the time intervals according to the changes from static to dynamic work based on the DAPP-technology, and thus no longer require a simultaneous ECG signal. This means that in the future we can potentially provide a fully automated evaluation of the longitudinal myocardial velocity profile. Hypothetically this method could give early indications of myocardial dysfunction that should be beneficial in many patient groups where fetal myocardial function is affected and facilitate detection of risk pregnancies as well as aid in the assessment before and after intrauterine fetal therapy.

The provided reference material demonstrated the feasibility of the technique and that the measurements are sensitive enough to yield insight into maturational changes in myocardial function, which provides a foundation that will enable further investigations and potentially allow identification of fetuses with myocardial dysfunction.

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