A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0–40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. Clinicaltrials.gov identifier NCT00761787

Objective: Ex vivo organ perfusion is an advanced preservation technique that allows graft assessment and extended ex situ intervals. We hypothesized that its properties might be especially beneficial for high-risk recipients and/or donors with extended criteria. Methods: We reviewed the outcomes of 119 consecutive heart transplant patients, which were divided into two groups: A (OCS) vs. B (conventional). Ex vivo organ perfusion was performed using the Organ Care System (OCS). Indications for OCS-usage were expected ischemic time of >4 h or >2 h plus given extended donor criteria. Results: Both groups included mostly redo cases (A: 89.7% vs. B: 78.4%; p = 0.121). Incidences of donors with previous cardiac arrest (%) (A: 32.4 vs. B: 22.2; p < 0.05) or LV-hypertrophy (%) (A: 19.1 vs. B: 8.3; p = 0.119) were also increased in Group A. Ex situ time (min) was significantly longer in Group A (A: 381 (74) vs. B: 228 (43); p < 0.05). Ventilation time (days) (A: 10.0 (19.9) vs. B: 24.3 (43.2); p = 0.057), postoperative need for ECLS (%) (A: 25.0 vs. B: 39.2; p = 0.112) and postoperative dialysis (chronic) (%) (A: 4.4 vs. B: 27.5; p < 0.001) were numerically better in the OCS group, without any difference in the occurrence of early graft rejection. The 30-d-survival (A: 92.4% vs. B: 90.2%; p = 0.745) and mid-term survival were statistically not different between both groups. Conclusions: OCS heart allowed safe transplantation of surgically complex recipients with excellent one-year outcomes, despite long preservation times and unfavourable donor characteristics. Furthermore, we observed trends towards decreased ventilation times and fewer ECLS treatments. In times of reduced organ availability and increasing recipient complexity, OCS heart is a valuable instrument that enables otherwise infeasible allocations and contributes to increase surgical safety.

Objective: Various patch materials currently used for cardiac reconstruction represent non-viable tissue with high susceptibility to infection and degeneration. We therefore introduce an innovative, autologous vascularized matrix with high regenerative potential for myocardial reconstruction. Methods: Autologous small bowel segments without mucosa, but with both the adjacent jejunal artery and vein, were harvested and used in a single-stage procedure for the replacement of right ventricular transmural defects (2 cm × 3 cm) in pigs (group A; n = 3). The autografts were revascularized by connecting jejunal vessels to the right internal thoracic artery and vein. Autologous pericardium was used as controls (group B; n = 3). All procedures were performed on beating hearts using a right heart bypass. After explantation (up to 6 months), the patches were investigated by standard histological analyses, immunohistochemistry and confocal microscopy. Results: Postoperative complications, for example excessive bleeding, graft rupture or dislodgement due to the dynamic cardiac contractions, did not occur. In group A, newly formed cardiomyocytes positively stained for Nkx 2.5 and myosin heavy chain were identified 1 month after operation. The cardiomyocytes were localized in close proximity to mesenteric capillaries in a disseminated-like pattern and showed a strong tendency to form islets. In contrast, explanted pericardial patches appeared as fibrotic tissue without evidence of myocardial cells inside the patch. Conclusion: We developed a novel autologous graft with preserved vascularity that can be used for myocardial grafting. This vascularized matrix undergoes autologous repopulation with cardiomyocytes after transmural myocardial replacement. Vascularization represents an important prerequisite for myocardial guided tissue regeneration.