Left ventricular structure and function in children infected with human immunodeficiency virus: the prospective P2C2 HIV Multicenter Study. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2 HIV) Study Group

Abstract

Background: The frequency of, course of, and factors associated with cardiovascular abnormalities in pediatric HIV are incompletely understood.

Methods and results: A baseline echocardiogram (median age, 2.1 years) and 2 years of follow-up every 4 months were obtained as part of a prospective study on 196 vertically HIV-infected children. Age- or body surface area-adjusted z scores were calculated by use of data from normal control subjects. Although 88% had symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were abnormal at baseline (decreased left ventricular fractional shortening [LV FS] and contractility and increased heart rate and LV dimension, mass, and wall stresses). Most of the abnormal baseline cardiac measurements correlated with depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart rate and LV mass showed significantly progressive abnormalities, whereas FS and contractility tended to decline. No association was seen between longitudinal changes in FS and CD4 cell count z score. Children who developed encephalopathy during follow-up had depressed initial FS, and FS continued to decline during follow-up.

Conclusions: Subclinical cardiac abnormalities in HIV-infected children are common, persistent, and often progressive. Dilated cardiomyopathy (depressed contractility and dilatation) and inappropriate LV hypertrophy (elevated LV mass in the setting of decreased height and weight) were noted. Depressed LV function correlated with immune dysfunction at baseline but not longitudinally, suggesting that the CD4 cell count may not be a useful surrogate marker of HIV-associated LV dysfunction. However, the development of encephalopathy may signal a decline in FS.

Figure 1

Initial echocardiographic measurements for HIV-infected infants and children plotted on regression lines with 95% prediction intervals for 285 normal children. A, LV FS percent vs age in years. B, LV end-systolic wall stress in g/cm² vs age in years. C, LV end-diastolic dimension in centimeters vs BSA in square meters. D, LV peak wall stress in g/cm² vs BSA in square meters. E, LV contractility z score vs age in years. F, Heart rate in bpm vs age in years.

Figure 2

Longitudinal change in echocardiographic parameters by age group using repeated-measures analysis. Time trend lines represent model-based means adjusted for time on study, age, age by time on study, digitizer and baseline CD4 cell count z score for LV mass and z score, LV end-systolic wall stress and z score, LV peak-systolic wall stress and z score, and LV contractility (stress velocity index).