Role for immune monitoring to tailor induction prophylaxis in pediatric heart recipients.

UNLABELLED: rATG is used for HTx induction but is costly and associated with infection and PTLD. HYPOTHESIS: Tailoring rATG induction with CD3 monitoring results in less infection, reduced costs, and similar rejection. Retrospective review of HTx recipients receiving rATG induction. Control cases received "usual" rATG dosing (1.5 mg/kg/day typically × 5 days). Starting in October 2009, absolute CD3 monitoring (target <25 cells/mm(3) ) guided rATG dosing (study cases). Outcomes included first-year incidence of infection/rejection, direct costs of therapy, and incidence of PTLD/death. Study cases (n = 32) received fewer doses of rATG (median 4 vs. 5, p < 0.001) and less total rATG (median 3.2 vs. 7.4 mg/kg, p < 0.001) compared with controls (n = 17). There was no difference in incidence of infection, rejection, or patient survival during the first year post-HTx. There was one early death in both groups and one late case of PTLD in the control group. Drug savings were significant (median drug cost per patient $2718 vs. $4756, p < 0.001). CD3-tailored rATG induction in HTx recipients is associated with reduced drug costs and similar rates of rejection/infection. Longer follow-up will determine whether extended benefits are associated with this induction monitoring strategy.

Tissue Doppler septal Tei index indicates severity of illness in pediatric patients with congestive heart failure.

The Doppler Tei index is an independent predictor of outcomes in adult heart failure. Tissue Doppler imaging (TDI) may be a superior method to measure the Tei index in children because it is less affected by heart rate variability. We hypothesized that the TDI Tei index reflects severity of illness in pediatric heart failure. Twenty-five pediatric heart failure patients were prospectively enrolled. Listing for heart transplantation or death were the outcomes used to define severity of illness. Baseline demographics, brain natriuretic peptide (BNP), and standard echocardiographic and TDI-derived parameters were analyzed to determine outcome indicators. Ten of the 25 patients (40%) were listed for transplantation. There were no deaths. Multivariate analysis combining age, heart rate, standard echocardiographic parameters, and BNP resulted in shortening fraction (p = 0.002) as the best indicator of listing for transplantation (R(2) = 0.32). A second multivariate analysis combining age, heart rate, TDI parameters, and BNP resulted in age (p = 0.03) and septal Tei index (p = 0.03) as the best predictive model (R(2) = 0.36). The area under the receiver operating characteristic (ROC) curve for septal Tei index was 0.84 (95% confidence interval = 0.64-0.96,), and it was comparable with the ROC curve for shortening fraction, p = 0.76. Optimal values of sensitivity (100%) and specificity (60%) were obtained with septal Tei index values >0.51. The TDI septal Tei index is an indicator of disease severity in pediatric heart failure patients and offers potential advantages compared with standard echocardiographic measures of left-ventricular ejection.

ABO-incompatible heart transplantation in early childhood: an international multicenter study of clinical experiences and limits.

BACKGROUND: Intentional blood group (BG)-incompatible (ABOi) heart transplantation in childhood is emerging in many centers. Safety limits remain undetermined. In this multicenter study we have compiled experience on clinical and immunologic boundaries. METHODS: Data from six centers in Europe and North America on ABOi transplantation were collected in a standardized survey. RESULTS: Fifty-eight ABOi transplants were performed in 57 patients. Median age at transplant was 6.8 months (0.03 to 90 months); post-transplant follow-up was 37.7 months (0.46 to 117 months), accumulating 188 patient-years. Forty-seven percent of the patients received pretransplant mechanical circulatory support. Donors were either blood group A (n = 25), B (n = 18) or AB (n = 15). The median peak antibody titer to the donor BG pretransplant was 1:8 (0 to 1:64) for anti-A and 1:4 (0 to 1:32) for anti-B. Titers against the donor BG were lower post- than pretransplant in B recipients (p = 0.02), whereas third-party antibodies in BG O recipients developed normally post-transplant. Induction immunosuppression included anti-thymocyte globulin (61%), basiliximab (32%) or none (7%). All patients received calcineurin inhibitors, including 62% with mycophenolate mofetil, 10% with azathioprine, 2% with everolimus and 24% with steroids. There were 4 episodes of cellular rejection (Grade≥2R) and 7 antibody-mediated rejections. Five patients underwent antibody removal post-transplant. One patient developed severe graft vasculopathy. Freedom from death or retransplantation was 100%/96%/69% at 1/5/10 years. No graft loss was attributed to BG antibodies. CONCLUSIONS: Successful ABOi heart transplantation can be performed at an older age and with higher isohemagglutinin titers than initially assumed and using similar immunosuppressive regimens as for ABO-compatible transplants. Rejection and graft vasculopathy are rare. Persistently low titers of antibodies to the donor BG post-transplant suggest elements of tolerance and/or accommodation.