Cardiac complications in children with human immunodeficiency virus infection

Objective. Although numerous cardiac abnormalities have been reported in HI V-infected children, precise estimates of the incidence of cardiac disease in these children are not well-known. The objective of this report is to de scribe the 2-year cumulative incidence of cardiac abnormalities in HIV-infe cted children. Methodology: Design. Prospective cohort (Group I) and inception cohort (Gro up II) study design. Setting. A volunteer sample from 10 university and public hospitals. Participants. Group I consisted of 205 HIV vertically infected children enr olled 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 African-American or Hispanic and 89% had symptomatic HIV infection at enrollment. The second group included 611 neon ates 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 Dopple r studies of cardiac function every 4 to 6 months. They also had a 12- or 1 5-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 t o cluster in the same patients, we also determined the number of children w ho had cardiac impairment which we defined as having either left ventricula r fractional shortening (LV FS) less than or equal to 25% after 6 months of age, CHF, or treatment with cardiac medications. Results: Cardiac Abnormalities. In Group I children (older cohort), the pre valence of decreased LV function (FS less than or equal to 25%) was 5.7% an d the 2-year cumulative incidence (excluding prevalent cases) was 15.3%. Th e prevalence of echocardiographic LV enlargement (LV end-diastolic dimensio n z score >2) at the time of the first echocardiogram was 8.3%. The cumulat ive incidence of LV end-diastolic enlargement was 11.7% after 2 years. The cumulative incidence of CHF and/or the use of cardiac medications was 1 0.0% in Group I children. There were 14 prevalent cases of cardiac impairme nt (LV FS less than or equal to 25% after 6 months of age, CHF, or treatmen t with cardiac medications) in Group I. After excluding these prevalent cas es, the 2-year cumulative incidence of cardiac impairment was 19.1% among G roup 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 decre ased LV FS was 10.7% in the HIV-infected children compared with 3.1% in the HIV-uninfected children. LV dilatation was also more common in Group II in fected 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 1- and 2-year cumulative incidence rates of cardiac impairment for Group II infected children were 10.1% and 1 2.8%, 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 1- and 2-year mortality rates after the diagnosis of CHF (Kaplan-Meier estimates) were 69% and 100%:, res pectively. In the Group II cohort, the 2-year cumulative death rate from al l causes was 16.3% [95% CI: 8.8%-23.9%] in the HIV-infected children compar ed 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 abn ormalities previously reported by the (PC2)-C-2 Study Group, an important n umber of HIV-infected children develop clinical heart disease. Over a 2-yea r period, approximately 10% of HIV-infected children had CHF or were treate d with cardiac medications. In addition, approximately 20% of HIV-infected children developed depressed LV function or LV dilatation and it is likely that these abnormalities are hallmarks of future clinically important cardi ac dysfunction. Cardiac abnormalities were found in both the older (Group I ) as well as the neonatal cohort (Group II) (whose HIV infection status was unknown before enrollment) thereby minimizing potential selection bias bas ed on previously known heart disease. Based on these findings, we recommend that clinicians need to maintain a hi gh degree of suspicion for heart disease in HIV-infected children. All HIV- infected infants and children should have a thorough baseline cardiac evalu ation. Patients who develop symptoms of heart or lung disease should underg o more detailed cardiac examinations including ECG and cardiac ultrasound.