Cardiac hemodynamics in fetuses with transposition of the great arteries and intact ventricular septum from diagnosis to end of pregnancy: longitudinal follow-up.

OBJECTIVES: Little is known about cardiac hemodynamics in the fetus with transposition of the great arteries and intact ventricular septum (TGA-IVS). Better understanding of the fetal physiology in TGA-IVS would help to provide insights into specific clinical complications observed after birth, in particular neonatal hypoxia and pulmonary hypertension. The aim of this study was to assess cardiac hemodynamics in fetuses with TGA-IVS by performing systematic longitudinal echocardiographic follow-up from diagnosis to delivery. METHODS: This was a longitudinal retrospective study of fetuses referred between 2010 and 2018 to the Sainte-Justine University Hospital Centre. Complete assessment of cardiac hemodynamics was performed in fetuses with TGA-IVS at 18-22, 28-32 and 35-38 weeks' gestation, which were compared with normal fetuses matched for gestational age. The maximum diameter of the foramen ovale was measured using two-dimensional echocardiography under the guidance of color Doppler echocardiography. Fetal cardiac hemodynamics were analyzed according to postnatal preductal transcutaneous oxygen saturation (TcSO2 ) < 65% or ≥ 65%, as a neonatal outcome, in fetuses with TGA-IVS. RESULTS: In total, 59 fetuses with TGA-IVS and 160 normal fetuses were included. Global cardiac output was significantly higher in fetuses with TGA-IVS than in controls, mainly owing to higher global pulmonary output, while global systemic cardiac output did not differ between TGA-IVS fetuses and controls throughout pregnancy. Aortic flow (right ventricular output in fetuses with TGA-IVS, left ventricular output in controls) was significantly higher in fetuses with TGA-IVS than in normal fetuses. Ductal flow was significantly lower in fetuses with TGA-IVS at every timepoint, and this difference increased considerably after 28-32 weeks. In parallel, the diameter of the foramen ovale was significantly smaller in fetuses with TGA-IVS at 28-32 and 35-38 weeks, with a stagnation in growth after 28 weeks, compared with continuous growth in normal fetuses. Most of these cardiac hemodynamic anomalies in fetuses with TGA-IVS were already present at 18-22 weeks, and the differences became greater at 28-32 weeks' gestation. TGA-IVS neonates with TcSO2 < 65% had lower fetal left ventricular output, higher diastolic ductal retrograde flow and smaller foramen ovale at 28-32 weeks, compared with fetal values in those with postnatal TcSO2 ≥ 65%. CONCLUSIONS: Compared with normal fetuses, those with TGA-IVS undergo a complex redistribution of blood flow during the second half of pregnancy, with higher global pulmonary flow, lower ductal flow (with negative diastolic flow at the end of pregnancy) and a smaller foramen ovale. In addition, fetal cardiac hemodynamic anomalies observed at 28-32 weeks' gestation were associated with lower postnatal TcSO2 . These observations may provide a better understanding of premature closure of the foramen ovale and postnatal hypoxia that are specific to TGA-IVS physiology. © 2019 International Society of Ultrasound in Obstetrics and Gynecology.

Early Initiation Rather Than Prolonged Duration of Antiretroviral Therapy in HIV Infection Contributes to the Normalization of CD8 T-Cell Counts.

BACKGROUND: CD8 T-cell counts remain elevated in human immunodeficiency virus (HIV) infection even after long-term antiretroviral therapy (ART), which is associated with an increased risk of non-AIDS-related events. We assessed the impact of ART initiation in early versus chronic HIV infection on trajectories of CD8 cell counts over time. METHODS: Of 280 individuals enrolled during primary HIV infection (PHI), 251 were followed up for 24 months; 84 started ART before 6 months of infection (eART), 49 started between 6 and 24 months, and 118 remained untreated. Plasma HIV viral load (VL), CD4 and CD8 cell counts were assessed at each study visit. CD8 counts were also examined in 182 age-matched HIV-infected individuals who started ART during chronic infection and maintained undetectable plasma VL for ≥5 years. RESULTS: At PHI baseline, higher CD8 cell counts were associated with more recent infection (P = .02), higher CD4 cell counts (P < .001), and higher VL (P < .001). The CD8 count in the eART group decreased from 797 to 588 cells/µL over 24 months (P < .001), to a level lower than that in untreated PHI (834 cells/µL; P = .004) or in long-term-treated patients with chronic HIV infection (743 cells/µL; P = .047). More prominent CD4 T-cell recovery was observed in the eART group than in the delayed ART group. CONCLUSIONS: ART initiated in early HIV infection is associated with improved resolution of CD8 T-cell elevation compared with long-term ART initiated in chronic infection. Early ART may help reduce the risk of non-AIDS-related events by alleviating this elevation.