ABSTRACT
Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.
Subject(s)
Biomarkers/metabolism , Coronary Artery Disease/diagnosis , Graft Rejection/diagnosis , Heart Diseases/surgery , Heart Transplantation/adverse effects , Adult , Blotting, Western , Case-Control Studies , Clinical Trials as Topic , Coronary Artery Disease/etiology , Coronary Artery Disease/metabolism , Endothelin-1/metabolism , Female , Gene Expression Profiling , Graft Rejection/etiology , Graft Rejection/metabolism , Humans , Male , Middle Aged , Prospective Studies , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Vascular Endothelial Growth Factor AABSTRACT
The National Organ Transplant Act stipulates that deceased donor organs should be justly and wisely allocated based on sound medical criteria. Allocation schemes are consistent across the country, and specific policies are publicly vetted. Patient selection criteria are largely in the hands of individual organ transplant programs, and consistent standards are less evident. This has been particularly apparent for patients with developmental disabilities (DDs). In response to concerns regarding the fairness of transplant evaluations for patients with DDs, we developed a transplant centerwide policy using a multidisciplinary, community-based approach. This publication details the particular policy of our center. All patients should receive individualized assessments using consistent standards; disability should be neither a relative nor an absolute contraindication to transplantation. External review can increase trust in the selection process. Patients in persistent vegetative states should not be listed for transplantation.
Subject(s)
Developmental Disabilities/physiopathology , Organ Transplantation/methods , Patient Selection , Tissue and Organ Procurement , Child , Humans , Intelligence Tests , Organ Transplantation/ethics , Prognosis , Waiting ListsABSTRACT
Hematopoietic SCT (HSCT) is a life-saving therapy in children, but has been associated with heart failure. Little is known about subclinical changes in cardiac function. We examined changes in systolic and diastolic function from pre- to 1-year post HSCT by echocardiography. All patients (n=74, 61% men, median age 9.1 years, mean left-ventricular (LV) ejection fraction 61.3±4.9%) who underwent HSCT at Children's Hospital Boston between 2005 and 2008, were <21 years at time of HSCT, and had routine pre- and 1-year post echocardiograms were included. Systolic function parameters, including LV ejection fraction, rate-corrected velocity of fiber shortening (Vcfc) and stress-velocity index and diastolic parameters, including tissue Doppler imaging (TDI)-derived velocities, and left-ventricular flow propagation, were compared before and after transplant. At 1-year post HSCT, systolic function, as measured by Vcfc (1.10±0.15 vs 1.04±0.12 circ/s; P=0.03) and stress-velocity index (z-score 0.40±1.4 vs -0.20±1.1; P=0.02), had worsened; diastolic function parameters, including mitral E' velocity (16.6±3.9 vs 15.0±3.4 cm/s; P=0.01) and tricuspid E' velocity (14.3±3.6 vs 12.4±2.8 cm/s; P=0.002) had also decreased. At 1-year post HSCT, children have subclinical declines in systolic and diastolic function. These small changes might become clinically important over time. Serial non-invasive assessment of cardiac function should be considered in all children following HSCT.