The primary specific aims of this study are to 1) establish the incidence, clinical spectrum, and natural history of cardiac dysautonomia as defined by heart rate spectral analysis in both HIV infected and noninfected children and 2) evaluate the value of heart rate spectral analysis for predicting dysrhythmias and sudden death in infants and children born to HIV infected mothers. The magnitude of clinical problems associated with autonomic dysfunction in children with symptomatic HIV infection appears to be great. Hemodynamic abnormalities, dysrhythmias, unexplained arrest and/or sudden death are common in HIV+ children, especially when acute deterioration, interventions or neurologic involvement is present. If this proposed study establishes that cardiac dysautonomia is predictive of adverse outcomes in HIV infected children, then a future prospective trial of beta-adrenergic antagonist therapy may be warranted. This will be accomplished by performing additional analysis of previously collected data under the NHLBI-sponsored multicenter study entitled """"""""Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted Human Immunodeficiency Virus (HIV) Infection and abbreviated P2C2. The P2C2 study is being performed in a prospectively defined cohort of 150 children with HIV infection and 350 uninfected control children born to HIV infected women who have been followed since the first month of life to provide understanding of cardiac dysautonomia in early HIV infection. In addition, 198 children with symptomatic HIV infection will be analyzed to provide an assessment of cardiac dysautonomia in later stages of pediatric HIV infection. Heart rate spectral analysis will be performed in the autonomic physiology research unit at Children's Hospital, Boston on 2196 Holter monitor recordings from these patients followed at the five P2C2 clinical centers to capture noninvasively the time varying contributions of the sympathetic and parasympathetic nervous system to the control of heart rate throughout the course of a day. The spectral balance parameters and the changing response of heart rate to the electrocardiogram-derived respiratory signal will characterize the responsiveness of the sympathetic and parasympathetic nervous system at rest and during the events of a normal day. Autonomic function data will be electronically transmitted to the P2C2 dam coordinating center at the Cleveland Clinic. Analysis of these data at the Cleveland Clinic and the Harvard School of Public Health with other factors collected in the P2C2 database (eg. infectious, immunologic, growth, renal, neuroendocrine, pulmonary and cardiac) will identify the interaction of these factors as to the risk they pose for cardiac dysautonomia. Should significant cardiac dysautonomia be detected then groups at particularly high risk will be identified as a cohort for future trials to test the feasibility of using beta-adrenergic blockade to alter the clinical significance of cardiac dysautonomia.
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