Myocardial Involvement
Dilated cardiomyopathy is the most common cardiac complication of HIV infection in children and is an adverse prognostic indicator in patients with HIV infection. The Prospective Pediatric Pulmonary and Cardiac Complications Study of HIV (P2C2) showed a 5-year cumulative incidence of dilated cardiomyopathy as high as 28% in vertically HIV-infected children [12].
Further, the mortality rate in children who exhibited congestive heart failure was 52.5% (95% CI, 30.5-74.5) in this study. In addition, the authors suggest that the incidence of left ventricular dysfunction in HIV-infected children is underestimated in this population because of the low sensitivity of the commonly used noninvasive echocardiographic techniques to examine left ventricular performance [18].The reported incidence of cardiac involvement in HIV-infected children varies from 0.9% of congestive heart failure in a study using hospital diagnosis codes [19] to 14% in later studies using the shortening fraction of the left ventricle as an indicator of systolic function [20]. Lipshultz et al. reported that cardiac abnormalities were seen in up to 93% of patients who had undergone more extensive cardiac testing at a referral center [16]. Two patterns of left ventricular function abnormalities were described when using load-independent indexes of contractility: (1) hyperdynamic left ventricular performance with enhanced contractility and reduced afterload, and (2) diminished contractility associated with symptomatic cardiomyopathy. Serial evaluations revealed that 89% of the patients had progressive left ventricular dysfunction.
The most important study designed to assess the incidence of cardiac dysfunction in HIV-infected children is the P2C2 HIV study [10, 12, 21-23]. This study began in 1990 and data collection continued through January 1997. Left ventricular function was evaluated every 4-6 months for up to 5 years in a birth cohort of 805 infants born to women infected with HIV-1.
In total, 205 vertically HIV-infected children (group I) and 600 subjects enrolled during fetal life (group II, neonatal inception cohort; n=432) or before 28 days of age (n=168) were included in the study. Their final HIV status was unknown at the time of enrolment in the study. Of these, 93 were finally HIV- infected and 463 HIV-uninfected. In addition, a cross-sectionally measured comparison group of 195 healthy children born to mothers who were not infected with HIV was also recruited as external controls. Main outcome measures were the cumulative incidence of an initial episode of left ventricular dysfunction, cardiac enlargement, and congestive heart failure. Because cardiac abnormalities tended to cluster in the same patients, the number of children who had cardiac impairment defined as having left ventricular fractional shortening (LV FS) zidovudine was not associated with acute or chronic abnormalities in left ventricular structure or function in infants exposed to the drug in the perinatal period. While controversial, these results suggest that careful follow-up is necessary in an HIV-infected child with cardiomyopathy receiving zidovudine. Finally, nutritional deficiencies such as selenium deficiency and prolonged immunosuppression have also been proposed to be causal or deleterious additional factors [32].The treatment of congestive heart failure in children with HIV should begin with routine anticongestive measures. Although not formally studied in HIV-infected children, angiotensin-converting inhibitors can be used judiciously. Recent nonrandomized studies using chronic β-blockers in children yielded encouraging preliminary results [33]. Lipshultz et al. reported normalization of the left ventricular dilatation and diminished wall thickness of HIV- infected children with monthly intravenous immunoglobulin infusion, possibly because of an improvement in immunologically mediated left ventricular dysfunction [34]. The question of whether asymptomatic HIV-infected children with left ventricular dilatation should be treated with angiotensin-converting inhibitors is unresolved.