Cardiac Structure and Function in Children with Human Immunodeficiency Virus Infection Treated with Zidovudine

Abnormalities of cardiac structure and function are common in children infected with the human immunodeficiency virus (HIV). It is unclear, however, whether these abnormalities are attributable to the disease itself, associated infections, or possible cardiotoxic effects of the most commonly used treatment, zidovudine. We performed echocardiography in 24 children with symptomatic HIV infection immediately before they started zidovudine therapy and a mean of 1.32 years after therapy began. Sixteen of these children were also studied a mean of 1.26 years before starting zidovudine treatment. Comparison groups included 27 age-matched children with symptomatic HIV infection who had not received zidovudine and 191 normal children. As compared with the normal children, the children treated with zidovudine had progressive left ventricular dilatation and an increase in ventricular-wall stress at end-systole (a measure of ventricular afterload); dilatation and stress were significantly elevated both before and during zidovudine treatment. The ratio of ventricular thickness to internal dimension was below normal before zidovudine treatment began (P<0.001). After treatment with zidovudine, however, overall left ventricular mass was increased (P = 0.02), as was peak wall stress (a stimulus to ventricular hypertrophy) (P = 0.01). Ventricular contractility remained normal, but fractional shortening of the left ventricle was decreased (P = 0.004). No statistically significant differences were detected at follow-up in any of these measurements between HIV-infected children treated with zidovudine and those not so treated. Progressive left ventricular dilatation occurred in children with symptomatic HIV infection. Compensatory hypertrophy also occurred but was inadequate to maintain peak systolic wall stress within the normal range. The progressive elevation of ventricular afterload due to dilatation resulted in depressed ventricular performance, but intrinsic ventricular contractility remained normal. Zidovudine did not appear to worsen or ameliorate these cardiac changes. (N Engl J Med 1992;327: 1260–5.), CARDIOVASCULAR abnormalities are common in children with human immunodeficiency virus (HIV) infection,^{1 2 3 4 5 6} but little is known about their cause or clinical course. The cardiovascular effects of zidovudine, which is used to treat most children with symptomatic HIV infection in the United States,^{7 , 8} have also not been well characterized. This drug has been reported to affect cardiac muscle adversely in rats.^{9 10 11} The mechanism appears similar to that noted in skeletal muscle in humans, in which a distinct myopathy has been observed.^{12 13 14 15 16 17} Recent recommendations to withhold antiretroviral therapy in HIV-infected patients with cardiomyopathy or congestive heart failure^{18 , 19} and to consider serial endomyocardial…