State of Respiratory Syncytial Virus Prophylaxis in Congenital Heart Disease Patients and Some of the Questions That Linger

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Abstract

Lower respiratory illness that results from respiratory syncytial virus (RSV) infection has long been recognized as a serious health risk to infants and children with congenital heart disease (CHD).1,2 In particular, RSVtriggered pulmonary hypertension, complications in managing heart failure, and prolonged mechanical ventilatory assistance may all delay or jeopardize the successful cardiac surgical palliation or repair of these children. Many of the health concerns for these children mirror those for premature infants. Not surprisingly, the history of prevention of RSV disease in CHD infants and young children parallels that of premature infants with chronic lung disease.

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Following an efficacy trial that included premature infants and children with CHD, hyperimmune RSV globulin (RSV-IGIV, RespiGam├óÔÇŞ╦İ MedImmune Inc., US) was approved by the US Food and Drug Administration (FDA) for the prevention of RSV lower respiratory illness in premature infants.3 Due to the small number of CHD patients and some safety concerns, a subsequent trial tested the safety and efficacy of RSV-IGIV in CHD patients specifically.4 This study failed to achieve its primary efficacy end-point of reduced RSV hospitalizations, although it did demonstrate the efficacy of this treatment in CHD patients below six months of age. There were significant safety concerns found in this study as there were an unexpectedly high number of surgically related adverse events in infants with cyanotic cardiac lesions. This was possibly due to altered blood viscosity in the treated patients.

Palivizumab (Synagis├óÔÇŞ╦İ MedImmune, Inc., US) is a monoclonal antibody (mAb) directed at the F surface glycoprotein of RSV that interrupts viral binding to cells in both RSV subtypes A and B. It was approved by the FDA for the prevention of RSV hospitalization in premature infants following an extensive multicenter clinical trial.5 Subsequently, in what remains the largest drug trial conducted in CHD patients, over four RSV seasons (1998├óÔé¼ÔÇ£2002) 1,287 CHD patients were randomized to a double-blind, placebo-controlled clinical trial powered to test the efficacy and safety of palivizumab.6 The primary efficacy end-point of reduced RSV hospitalizations was met (45% relative reduction in treated group) and, unlike RSV-IVIG, no serious safety concerns for palivizumab were observed, leading to the addition of infants and children <24 months of age with hemodynamically significant CHD to prophylaxis indications.7

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