Cardiac Complications in Children With Human Immunodeficiency Virus Infection

Objective. Although numerous cardiac abnormalities have been reported in HIV-infected children, precise estimates of the incidence of cardiac disease in these children are not well-known. The objective of this report is to describe the 2-year cumulative incidence of cardiac abnormalities in HIV-infected children. Methodology: Design. Prospective cohort (Group I) and inception cohort (Group II) study design. Setting. A volunteer sample from 10 university and public hospitals. Participants. Group I consisted of 205 HIV vertically infected children enrolled at a median age of 22 months. This group was comprised of infants and children already known to be HIV-infected at the time of enrollment in the study. Most of the children were AfricanAmerican or Hispanic and 89% had symptomatic HIV infection at enrollment. The second group included 611 neonates born to HIV-infected mothers, enrolled during fetal life or before 28 days of age (Group II). In contrast to the older Group I children, all the Group II children were enrolled before their HIV status was ascertained. Interventions. According to the study protocol, children underwent a series of cardiac evaluations including two-dimensional echocardiogram and Doppler studies of cardiac function every 4 to 6 months. They also had a 12or 15-lead surface electrocardiogram (ECG), 24-hour ambulatory ECG monitoring, and a chest radiograph every 12 months. Outcome Measures. Main outcome measures were the cumulative incidence of an initial episode of left ventricular (LV) dysfunction, cardiac enlargement, and congestive heart failure (CHF). Because cardiac abnormalities tended to cluster in the same patients, we also determined the number of children who had cardiac impairment which we defined as having either left ventricular fractional shortening (LV FS) <25% after 6 months of age, CHF, or treatment with cardiac medications. Results: Cardiac Abnormalities. In Group I children (older cohort), the prevalence of decreased LV function (FS <25%) was 5.7% and the 2-year cumulative incidence (excluding prevalent cases) was 15.3%. The prevalence of echocardiographic LV enlargement (LV end-diastolic dimension z score >2) at the time of the first echocardiogram was 8.3%. The cumulative incidence of LV enddiastolic enlargement was 11.7% after 2 years. The cumulative incidence of CHF and/or the use of cardiac medications was 10.0% in Group I children. There were 14 prevalent cases of cardiac impairment (LV FS <25% after 6 months of age, CHF, or treatment with cardiac medications) in Group I. After excluding these prevalent cases, the 2-year cumulative incidence of cardiac impairment was 19.1% among Group I children and 80.9% remained free of cardiac impairment after 2 years of follow-up. Within Group II (neonatal cohort), the 2-year cumulative incidence of decreased LV FS was 10.7% in the HIVinfected children compared with 3.1% in the HIV-uninfected children. LV dilatation was also more common in Group II infected versus uninfected children (8.7% vs 2.1%). The cumulative incidence of CHF and/or the use of cardiac medications was 8.8% in Group II infected versus 0.5% in uninfected subjects. The 1and 2-year cumulative incidence rates of cardiac impairment for Group II infected children were 10.1% and 12.8%, respectively, with 87.2% free of cardiac impairment after the first 2 years of life. Mortality. In the Group I cohort, the 2-year cumulative death rate from all causes was 16.9% [95% CI: 11.7%– 22.1%]. The 1and 2-year mortality rates after the diagnosis of CHF (Kaplan-Meier estimates) were 69% and 100%, respectively. In the Group II cohort, the 2-year cumulative death rate from all causes was 16.3% [95% CI: 8.8%–23.9%] in the HIV-infected children compared with no deaths among the 463 uninfected Group II children. Two of the 4 Group II children with CHF died during the 2-year observation period and 1 more died within 2 years of the diagnosis of CHF. The 2-year mortality rate after the diagnosis of CHF was 75%. Conclusions. This study reports that in addition to subclinical cardiac abnormalities previously reported by the P2C2 Study Group, an important number of HIVinfected children develop clinical heart disease. Over a From the *Department of Pediatrics, Division of Pediatric Cardiology, Presbyterian Hospital/Columbia University School of Medicine, New York, New York; the ‡Department of Cardiology, Children’s Hospital, Boston, Massachusetts; the §Department of Pediatrics, Division of Pediatric Cardiology, University of California, Los Angeles Medical Center and School of Medicine, Los Angeles, California; the Departments of \Biostatistics and ¶Epidemiology and #Pediatrics, **Division of Pediatric Cardiology, Cleveland Clinic, Cleveland, Ohio; the ‡‡Department of Pediatrics, Division of Pediatric Cardiology, Baylor College of Medicine, Houston, Texas; the §§National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda, Maryland; and the \\Department of Pediatrics, Division of Pediatric Cardiology, Mt Sinai School of Medicine, New York, New York. aDr Lipshultz’ current affiliation is with the Division of Pediatric Cardiology, Children’s Hospital at Strong, University of Rochester Medical Center,