A randomized controlled trial of motavizumab versus palivizumab for the prophylaxis of serious respiratory syncytial virus disease in children with hemodynamically significant congenital heart disease.

Children with hemodynamically significant congenital heart disease (CHD) are at risk for serious respiratory syncytial virus (RSV) disease. This study was designed to assess the safety and tolerability of motavizumab versus palivizumab in children with CHD and was not powered for efficacy. Patients (n = 1236) aged ≤24 mo were randomized to receive five monthly doses (15 mg/kg) of motavizumab or palivizumab during the RSV season. Adverse events (AEs) and serious AEs (SAEs) were recorded through 30 d after the last dose. RSV hospitalizations and RSV outpatient medically attended lower respiratory tract infections (MALRI; season 2) were summarized. Approximately 93 and 50% of patients reported an AE or SAE, respectively. Skin events occurred in 19.3% of motavizumab recipients and 16.2% of palivizumab recipients. Rates of hospitalizations and RSV MALRI were similar between treatment groups [relative risk (RR): 0.75; 95% CI, 0.34-1.59 and RR: 0.49; 95% CI, 0.10-1.99, respectively; both p > 0.05]. Motavizumab and palivizumab had similar safety profiles in children with hemodynamically significantly CHD; with the exception of skin events which were increased in motavizumab recipients. Safety and efficacy were consistent with another study comparing motavizumab with palivizumab in premature infants without CHD.

Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure.

OBJECTIVES: Elevated pulmonary vascular resistance may contribute to late Fontan circulation failure but is difficult to assess in such patients. Our aims were to assess outcomes of patients with failed Fontan circulation after heart transplantation and to determine whether elevated pulmonary vascular resistance might have contributed to the failure. METHODS: Fifteen patients (14 Fontan circulations, 1 Kawashima circulation) underwent transplantation. The most common indication was ventricular dysfunction (mean ventricular end-diastolic pressure 12.5 mm Hg). Patients with early failures (n = 4) required transplantation less than 1 year after the Fontan operation. Those with late failures (n = 11) underwent transplantation at least 1 year after the Fontan operation. Mean age at transplantation was 11.6 years. Mean Fontan-transplantation interval was 7.4 years. Mean pulmonary arterial pressure, transpulmonary gradient, and pulmonary vascular resistance before and after transplantation were assessed. Paired t tests of variable differences were used to compare variables. Survival was estimated by the Kaplan-Meier method. RESULTS: In-hospital mortality was 7%. There were 2 late events (1 death, 1 retransplantation) related to compliance or rejection issues. Graft survivals were 93%, 82%, and 82% at 3, 5, and 7 years, respectively. Posttransplantation pulmonary vascular resistance was elevated (>2.0 Wood units . m 2 ) in 11 of 14 survivors past initial hospitalization (mean 3.3 +/- 1.7 Wood units . m 2 ). Only patients with early Fontan failures (3 of 4) had normal posttransplantation pulmonary vascular resistance. In paired comparisons, posttransplantation transpulmonary gradient was increased by a mean of 6.8 mm Hg ( P < .0001) relative to pretransplantation value. CONCLUSIONS: Outcomes after heart transplantation for failed Fontan circulation were good. Mild-to-moderate pulmonary vascular disease was evident after heart transplantation for late failure. Elevated pulmonary vascular resistance is a likely contributor to Fontan circulation failure.

Mechanical limitation of pulmonary blood flow facilitates heart transplantation in older infants with hypoplastic left heart syndrome.

OBJECTIVES: Progression of pulmonary vascular disease limits heart transplantation for hypoplastic left heart syndrome (HLHS) to early infancy. Our objective was to assess the impact of bilateral pulmonary artery banding (PAB) on the operative courses of HLHS infants transplanted at ages older than 4 months. METHODS: Courses of all HLHS patients in our center who remained listed to age >or=120 days before heart transplantation were assessed. Patients undergoing transplantation after standard management (control group) were compared to patients having a prior pulmonary blood flow limiting procedure (PAB group). RESULTS: Of 16 identified patients, one crossed over to stage I Norwood on day 185 and died post-operatively. Fifteen patients were transplanted at age >or=120 days (control group n=9, PAB group n=6). Four PAB patients had open PA band placement. Two PAB patients underwent experimental percutaneous bilateral internal pulmonary artery flow limiting device insertion. The PAB group mean age at banding was 141+/-54 days, and mean interval from PAB to transplant was 35+/-31 days (range 1.5-68 days). No differences in age at transplant, weight at transplant, warm graft ischemia time or total graft ischemia time were detected between groups. Mean times of mechanical ventilation (control 143+/-69h vs. PAB 44+/-13h), inhaled nitric oxide (control 126+/-70h vs. PAB 37+/-9h), inotropic support (control 171+/-64h vs. PAB 87+/-17h), intensive care unit (ICU) stay (control 8.3+/-2.7 days vs. PAB 4.5+/-1.4 days), and hospital stay (control 10.4+/-3.9 days vs. PAB 7.0+/-1.1 days) were all lower in the PAB group (P<0.05 all comparisons). Two control patients died, three required extracorporeal membrane oxygenation (ECMO), and six did not tolerate primary chest closure. No PAB patient died or required ECMO. All PAB patients tolerated primary chest closure. All PAB patients had widely patent branch pulmonary arteries with no re-interventions to date. All hospital survivors remain alive (mean follow-up, control 50.2 months, PAB 11.5 months). CONCLUSIONS: Pre-transplant mechanical limitation of pulmonary blood flow simplified management and reduced morbidity for HLHS patients undergoing heart transplantation at ages >or=4 months. This strategy extends the permissible transplant waiting time in older infants with HLHS.