Fetal Heart Involvement
A recent study by Hornberger sought to determine whether vertically transmitted HIV infection and maternal infection with HIV are associated with altered cardiovascular structure and function in utero.
Fetal echocardiography was performed in 173 fetuses of 169 HIV-infected mothers (mean gestational age, 33.0 weeks; SD=3.7 weeks) at five centers. Fetuses determined after birth to be HIV-infected had similar echocardiographic findings as fetuses determined to be HIV-uninfected later, except for slightly smaller left ventricular diastolic dimensions (p=0.01). Differences in cardiovascular dimensions and Doppler velocities were identified between fetuses of HIV- infected women and previously published normal fetal data. The reason for the differences may be a result of maternal HIV infection, maternal risk factors, or selection bias in the external control data [54]. The P2C2 study describing the cardiovascular status of infants and children of HIV-infected women shows that children infected with HIV-1 had significantly more cardiac abnormalities than external control subjects [13]. Study analysis showed that HIV-1-infected children had a statistically significant higher heart rate at all ages. In addition, all children born to HIV-1-infected women had a low left ventricular fractional shortening at birth, which improved in the uninfected children by 8 months of age but not quite up to the normal level as seen in children in the external control group. The left ventricular fractional shortening remained persistently lower in the HIV-infected children for up to 20 months. Similarly, left ventricular mass was the same at birth for both HIV- infected and uninfected children but became significantly higher in HIV-infected children aged between 4 and 30 months. The study results extend previous reports from the P2C2 study showing that fetal echocardiograms indicated fetal cardiovascular abnormalities in pregnant HIV-1- infected women, irrespective of whether the children turned out to be HIV-1 infected after birth. Based on the results of the current cohort study, the authors conclude that irrespective of their HIV-1 status, infants born to HIV-1-infected women have significantly worse cardiac function than other infants, suggesting that the uterine environment has an important role in postnatal cardiovascular abnormalities. The authors also suggest that appropriate treatment strategies should be considered for all children born to HIV-1-infected women, as even mild left ventricular dysfunction has shown to effect mortality over time. The P2C2 study led to many commentaries dealing particularly with the reliability of the methods used to assess ventricular function. Indeed, in another P2C2 report, there was unacceptable variability of many M-mode cardiac measurements, including fractional shortening, between the local and central institutions [18]. A less variable method of measuring cardiac function should be identified and used in future studies that attempt to evaluate early treatment of HIV-associated cardiac depression with novel therapeutic approaches. Other groups have not confirmed the results of this study [10], which do no reflect the experience of European countries.The effects of maternal HIV infection and mother-infant HIV transmission on the prevalence and distribution of congenital cardiovascular malformations in the chil-
dren of HIV-infected mothers have been investigated in a few studies. The Italian Multicenter Study demonstrated a trend toward a higher prevalence of congenital cardiovascular malformations in HIV-infected children as compared to general population-based data, but the number of cases was small (5/165, 2.4%) [55]. There was no difference between HIV-infected and HIV- uninfected children. Vogel et al. reported a series of five patients with congenital heart disease from a population of 175 children exposed prenatally to maternal HIV infection (2.8%) [56]. The P2C2 HIV study indicates a congenital cardiovascular malformation prevalence of 12.3% in children of HIV- infected mothers [57].
Again, this proportion is very surprising and has not been confirmed. It is of note that in the first study [54], the methodology pertaining to the identification of cardiac defects was not provided and that in the P2C2 study, most of the lesions were clinically unapparent and were detected by routine echocardiography as part of the study protocol. Our personal experience shows that the prevalence of symptomatic heart defects in children born to HIV-infected mothers is comparable to the general population. The pathophysiologic factors leading to a higher prevalence of cardiac malformations in fetuses of HIV- infected mothers may include alterations of fetal flow patterns related to increased placental vascular resistances. Additional maternal risk factors that may significantly affect fetal organogenesis such as increased alcohol use, cocaine addiction, and poor nutritional status also have to be considered. There are no reports on cardiac teratogenicity related to zidovudine.Cardiac complications of AIDS or vertically transmitted HIV in children appear to be frequent. However, the actual prevalence of severe cardiac compromise remains difficult to assess and very few groups have reported their own experience. The P2C2 HIV study is the most important study sharing its data with the medical community in charge of these infants and children. This study presents very disquieting results regarding cardiac involvement in infants from HIV-infected mothers, but the numbers of commentaries published after these results were evidence of a rising controversy. The evolving antiviral therapy may change the profile of cardiac manifestations of HIV in the pediatric age group, as fewer children are infected in developed countries. The emerging concern is the vascular dysfunction that may lead to early atherosclerosis. Longitudinal studies are needed to address this worrisome issue in the pediatric population.
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