Faculty Bibliography

In normal pediatric echocardiograms, the distance from the junction of superior vena cava (SVC) and right atrium to inferior vena cava (IVC) and right atrium is linearly related to height. We examine this relation in children listed for heart transplant with idiopathic dilated cardiomyopathy (IDC) compared with the previously defined normal distribution of SVC-IVC to improve matching of heart sizes. Measurements of SVC-IVC and left ventricular end-diastolic diameter in 55 pediatric patients with IDC were correlated with height, weight, and body surface area. Regression analyses were performed to find the best-fit equation and correlation coefficient. Generalized linear modeling compared SVC-IVC in patients with IDC with normal SVC-IVC values from 254 patients. There was a strong linear relation in patients with IDC between SVC-IVC and height (R2=0.84) and a logarithmic relation to weight (R2=0.80). Left ventricular end-diastolic diameter did not correlate with SVC-IVC or any other parameter. In 87% of patients with IDC, SVC-IVC was over 2 SDs above predicted normal values (mean z-score=4.3±2.1). In conclusion, predicted SVC-IVC in patients with IDC was different from published norms (p<0.001). SVC-IVC in pediatric patients with IDC, although linearly related to height, is consistently above normal values.

High pulmonary vascular resistance index (PVRI) can lead to right ventricular dysfunction and failure of the donor heart early after pediatric heart transplantation. Oral pulmonary vasodilators such as sildenafil have been shown to be effective modifiers of pulmonary vascular tone. We performed a retrospective, observational study comparing patients treated with sildenafil ("sildenafil group") to those not treated with sildenafil ("nonsildenafil group") after heart transplantation from 2007 to 2012. Pre- and posttransplant data were obtained, including hemodynamic data from right heart catheterizations. Twenty-four of 97 (25%) transplant recipients were transitioned to sildenafil from other systemic vasodilators. Pretransplant PVRI was higher in the sildenafil group (6.8 ± 3.9 indexed Woods units [WU]) as compared to the nonsildenafil group (2.5 ± 1.7 WU, p=0.002). In the sildenafil group posttransplant, there were significant decreases in systolic pulmonary artery pressure, mean pulmonary artery pressure, transpulmonary gradient and PVRI (4.7 ± 2.9 WU before sildenafil initiation to 2.7 ± 1 WU on sildenafil, p=0.0007). While intubation time, length of inotrope use and time to hospital discharge were longer in the sildenafil group, survival was similar between both groups. Oral sildenafil was associated with a significant improvement in right ventricular dysfunction and invasive hemodynamic measurements in pediatric heart transplant recipients with high PVRI early after transplant.

Severe thrombosis of a mechanical valve is a rare complication in pediatric patients. Thrombolytic therapy as treatment of mechanical mitral valve thrombosis has rarely been reported in young infants. We report the successful treatment with recombinant tissue-type plasminogen activator of a mechanical mitral valve thrombus in a 7 month-old patient with trisomy 21, complete atrioventricular canal defect and pulmonary hypertension status post complete atrioventricular canal repair and subsequent prosthetic mitral valve replacement. He presented with respiratory decompensation and shock secondary to severe mechanical mitral valve stenosis. Serial echocardiograms showed significant resolution of the thrombus within 18 h of infusion with no major bleeding complications during the treatment course. Although a rare complication of mechanical valve placement in pediatrics, thrombosis of mechanical valves may result in severe hemodynamic and respiratory compromise. This case demonstrates that thrombolytic therapy is a feasible option for the treatment of critical thrombosis in pediatric patients after MVR.

Pediatric donor hearts are regularly refused for donor quality with limited evidence as to which donor parameters are predictive of poor outcomes. We compare outcomes of recipients receiving hearts previously refused by other institutions for quality with the outcomes of recipients of primarily offered hearts. Data for recipients aged ≤18 and their donors were obtained. Specific UNOS refusal codes were used to place recipients into refusal and nonrefusal groups; demographics, morbidity and mortality were compared. Kaplan-Meier analysis with log-rank test was used to determine differences in graft survival. A multivariable Cox proportional hazards model was constructed to determine independent risk factors for postoperative mortality. From July 1, 2000 to April 30, 2011, 182 recipients were transplanted and included for analysis. One hundred thirty received a primarily offered heart; 52 received a refused heart. No difference in postoperative complications or graft survival between the two groups (p = 0.190) was found. Prior refusal was not an independent risk factor for recipient mortality. Analysis of this large pediatric cohort examining outcomes with quality-refused hearts shows that in-hospital morbidity and long-term mortality for recipients of quality-refused hearts are no different than recipients of primarily offered hearts, suggesting that donor hearts previously refused for quality are not necessarily unsuitable for transplant and often show excellent outcomes.

OBJECTIVES/OBJECTIVE:To assess the differences in rejection and infection complications between the most common contemporary immunosuppression regimen in pediatric heart transplantation (cytolytic induction, tacrolimus based) and classic triple-therapy (cyclosporine based without induction). STUDY DESIGN/METHODS:We performed a retrospective, historical-control, observational study comparing outcomes in patients who underwent traditional immunosuppression (control group, n = 64) with those for whom the contemporary protocol was used (n = 39). Episodes of rejection, viremia (cytomegalovirus or Epstein-Barr virus), serious bacterial or fungal infections, anemia or neutropenia requiring treatment in the first year after heart transplantation, and 1-year survival were compared between traditional and contemporary immunosuppression groups. RESULTS:The 2 groups were similar with respect to baseline demographics. There were no differences in risk of cytomegalovirus, Epstein-Barr virus, or bacterial or fungal infections in the first year post-transplantation. Patients in the contemporary group were more likely to need therapy for anemia (51% vs 14%, P < .001) or neutropenia (10% vs 0%, P = .019). However, more contemporary protocol patients were rejection-free in the first year post-transplantation (63% vs 41%, P = .03). Overall graft survival was similar between groups (P = .15). CONCLUSIONS:A contemporary immunosuppression regimen using tacrolimus, mycophenolate mofetil, and induction was associated with less rejection in the first year, with no difference in the risk of infection but greater risk of anemia and neutropenia requiring treatment. Long-term follow-up on these patients will evaluate the impact of the immunosuppression regimen on survival.

Orthotopic heart transplantation remains the definitive treatment of choice for patients with end-stage heart failure; however, elevated PVRI is a reported risk factor for mortality after heart transplant and, when severely elevated, is considered an absolute contraindication. Use of a ventricular assist device has been proposed as one treatment for reducing pulmonary vascular resistance index in potential heart transplant candidates refractory to medical vasodilator therapies. We report on a teenage patient with dilated cardiomyopathy and severely elevated PVRI, unresponsive to pulmonary vasodilator therapy, who underwent left ventricular assist device implantation to safely allow for aggressive pulmonary vasodilator therapy and to decrease PVRI. The resulting dramatic improvement in PVRI in a relatively short period of time allowed for successful heart transplantation, avoiding the need for heart-lung transplant.

BACKGROUND:ABO incompatible (ABOi) heart transplantation is an accepted approach to increasing organ availability for young patients. Previous studies have suggested that early survival for ABOi transplants is similar to ABO compatible (ABOc) transplants. We analyzed the Pediatric Heart Transplant Study (PHTS) database from 1/96 to 12/08 to further assess this strategy. METHODS:We analyzed the numbers of ABOi and ABOc done at the PHTS centers. We then compared the clinical characteristics, and short-term freedom from death, rejection and infection in the ABOi patients with the patients that had an ABOc heart transplant during the same period. All patients were less than or equal to 15 months of age at listing (the age of the oldest ABOi patient). We adjusted for co-variates shown to increase risk for mortality (age less than 1 month, extracorporeal membrane oxygenation (ECMO), ventilator, previous sternotomy, and congenital heart disease). RESULTS:There were 931 total transplants done at 34 PHTS centers during the 12 year time period in patients ≤15 months of age. Of these, 502 transplants were performed at 20 PHTS centers that did at least one ABOi heart transplant. Eighty-five of the 502 (17%) were ABOi. At time of transplant, ABOi recipients compared with ABOc were more likely to be on a ventilator (49.4% vs 36.5%, p=0.025), and more often supported with ECMO (23.5% vs 13.4%, p=0.018). There was similar survival at 12 months (82% vs 84%, p=0.7). In risk adjusted analysis ABOi status was not associated with 1 year mortality (HR 0.85, 95% CI 0.45-1.6, p=0.61). The ABOi patients had greater freedom from rejection when compared with ABOc patients for all 34 centers (75% vs 62%, p=0.016), but the difference was not significant when limited only to the 20 centers doing ABOi transplants (75% vs 69%, p=0.4). The ABOi cohort had lower infection rates (23.5% vs 37.9%, p = 0.013). This difference remained after adjusting for center and other covariates. CONCLUSIONS:In center and risk adjusted analysis, young children who received an ABOi transplant had equivalent one-year survival and freedom from rejection compared with those who received an ABOc transplant. In spite of the favorable outcome for ABOi recipients, many centers appear to reserve ABOi transplantation for sicker patients. These data mandate reexamination of the current United Network for Organ Sharing (UNOS) policy that gives priority to ABOc over ABOi transplantation in the United States.