MH testing is a safe and useful tool to assess the pulmonary vasculature in fetuses with HLHS. There were no adverse consequences associated with MH testing. Through all phases of testing, qualitative assessments of right ventricular function and degree of tricuspid regurgitation remained the same. Moreover, there was no significant change in right ventricular cardiac output with MH. Finally, there was no ductal constriction noted in during MH or during the recovery period.
MH testing correctly identified HLHS fetuses that required urgent intervention on the inter-atrial septum at birth. None of the HLHS fetuses with appropriate vasoreactivity on the last scan prior to delivery required an urgent intervention on the inter-atrial septum at birth. In fact, two fetuses deemed to have a restrictive inter-atrial communication by previously published criteria3, 26, 28
were vasoreactive in response to MH in late third-trimester testing. At birth, both babies had good oxygen saturations while breathing room air. illustrates the pulmonary venous Doppler flow patterns and vasoreactivity testing for one of these fetuses. Rasanen defined vasoreactivity as a decrease in the pulsatility index of the branch pulmonary artery > 20% after 31 weeks gestation in normal fetuses15
. Based upon review of our results, however, we defined vasoreactivity in our HLHS cohort as a decline in the PI of greater than 10% at any branch point. HLHS fetuses with no decline in the PI at any branch point greater than 10% were considered to be non-vasoreactive in response to MH. Vasoreactivity was noted as early as 24 weeks gestation in one fetus with a restrictive inter-atrial communication. A second fetus with a restrictive inter-atrial communication demonstrated vasoreactivity at 26 weeks gestation, but lost vasoreactivity by 32 weeks gestation. Indeed, by providing a window for intervention, MH testing may prove useful when deciding upon a fetal intervention to open up a restrictive inter-atrial communication. We propose the routine incorporation of MH testing for late 3rd
trimester HLHS fetuses to assess the health of the pulmonary vasculature and to identify fetuses at greatest risk for postnatal pulmonary venous obstruction.
Figure 3 The top panel illustrates the pulmonary venous Doppler flow pattern in a fetus with HLHS and a restrictive inter-atrial communication. The bottom two panels demonstrate MH testing for this same fetus. The middle panel demonstrates the distal branch pulmonary (more ...)
Our study suggests that pulmonary vascular impedance is similar in HLHS fetuses compared to normal controls at baseline. The PI at the proximal, mid, and distal branch pulmonary artery was higher in our HLHS population compared to our normal control population at baseline; however, none met statistical significance (). Histopathologic changes within the pulmonary vasculature in HLHS fetuses have been well described in the postnatal literature12-14, 30, 31
. It is conceivable that subtle changes within the pulmonary vasculature are present in HLHS fetuses in utero, accounting for the mildly elevated PI at each branch pulmonary artery site compared to normal controls. Alternatively, the mildly elevated PI seen within the pulmonary vasculature may simply reflect altered flow patterns within the HLHS fetus. As we have previously reported, fetuses with HLHS have statistically lower cardiac outputs compared to normal control fetuses29
(see ). In the setting of a reduced cardiac output, blood may be preferentially shunted away from less vital organs, such as the lungs, and toward more vital structures, such as the brain, accounting for the overall mild increase in pulmonary vascular impedance and lower resistance in the cerebral vasculature compared to normal controls.
HLHS fetuses with an open inter-atrial communication acquire vasoreactivity over the course of gestation. However, fetuses with a restrictive inter-atrial septum did not demonstrate a significant change in vasoreactivity over the course of gestation (). One fetus with a restrictive inter-atrial septum demonstrated vasoreactivity at 26 weeks gestation, but lost vasoreactivity by 32 weeks gestation. We hypothesize that HLHS fetuses with a restrictive inter-atrial communication have elevated pressures within the pulmonary vasculature at earlier gestational ages. These elevated pressures may be a trigger for the acquisition of a muscular adventitial coat, thereby enabling vasoreactivity in response to MH at an earlier gestational age compared to normal fetuses or compared to fetuses with HLHS and an open inter-atrial communication. With continued obstruction to pulmonary venous egress, we hypothesize that the pulmonary veins become “arterialized” over the course of gestation leading to marked hypoxemia and hypercarbia at birth. In the absence of elevated pressures within the pulmonary vasculature, fetuses with HLHS and an open inter-atrial communication may acquire a muscular adventitial coat at a similar gestational age as normal fetuses without HLHS.
In response to MH, the MCA PI increased, but did not meet statistical significance. A previous investigator proposed that the cerebrovasculature vasodilates in response to hypoxia32
. If this explanation were true, one would expect the PI within the MCA to normalize in response to 10 minutes of MH, which raises the mixed venous oxygen content by approximately 10-15 torr. In fact, although the MCA PI increased with MH, it did not normalize, suggesting that the vasodilation of the cerebral vasculature may more related to flow than to hypoxemia.
Our study is limited by the small number of HLHS fetuses with a restrictive inter-atrial communication within our study cohort. Consequently, we may have insufficient power to detect changes in our parameters with MH testing within our subgroup analysis. Similarly, we may be underpowered to detect a change in vasoreactivity over the course of gestation. Based upon the results of our MH testing, we defined a cutoff for lack of vasoreactivity as a change in PI of < 10% with MH. However, we did not confirm this finding in our normal control population. Finally, we did not invasively check to determine that MH testing raised the fetal oxygen content. As a result, we have failed to detect changes in our parameters with MH testing on account of inadequate oxygen delivery to the fetus.