Christoph Bara

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.

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

A European, multicenter, prospective, non-randomized, clinical pilot trial was designed to evaluate the feasibility of the Perceval S sutureless aortic valve prosthesis. A clinical and echocardiographic follow up was performed at the time of hospital discharge and subsequently after one, three, six, and 12 months. The valve was implanted following sternotomy, extracorporeal circulation (ECC), aortic cross-clamping, cardioplegic arrest, and removal of the native valve. Implantation suturing was not required. Optimal annular sealing was obtained with brief low-pressure balloon dilation. If coronary bypass was indicated, a distal anastomosis was performed first. Between April 2007 and February 2008, 30 patients (mean age: 81 +/- 4 years) underwent aortic valve replacement. The prevalence of pure aortic stenosis was 76.7%, and that of mixed lesion 23.3%. The mean logistic EuroSCORE was 13.18%, and the NYHA class was III and IV in 93.3% and 6.7% of patients, respectively. The implanted valve size was 21 and 23 mm in 37% and 63% of patients, respectively, and 14 (46.7%) underwent coronary artery bypass grafting (11 internal mammary artery, nine vein grafts). The mean aortic cross-clamp and ECC times were 34 +/- 15 min and 59 +/- 21 min, respectively. There was one in-hospital death (3.3%), and three deaths occurred within 12 months of follow up (one death was valve-related, and two deaths were independent of the valve implantation). A total of 28 patients was assessed at one month post-implantation, and 23 after 12 months. No migration or dislodgement of the valve had occurred, but there were two mild paravalvular leakages and two mild intravalvular insufficiencies. The preliminary results of the trial confirmed the safety and efficacy of the Perceval S sutureless aortic valve. In this high-risk subset of patients, shortening the aortic cross-clamp and ECC times may help to reduce mortality and morbidity.

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.

As a consequence of the growing number of elderly people, the incidence of degenerative aortic diseases continues to increase. Often, artificial aortic roots are needed to replace the native tissue. Some physical characteristics of the artificial aortic root, however, are quite different from native aorta and need to be optimized. The supposed benefit of a prosthesis with artificial sinuses of Valsalva could first be checked by numerical calculations. Two simplified base geometries were used for simulating the flow and pressure distributions, especially in the coronary arteries. One model approximates the ascending aorta as a tube, and the other uses a design with toroidal dilation of the aortic root to approximate the native geometry of the sinuses of Valsalva. The flow and pressure distributions in both models were compared in the ascending aorta as well as in the right and the left coronary arteries. Both the pressure and the velocity distribution in the coronary artery region were not significantly higher in the model with the sinus design compared to the tube model. The sinus design only slightly increased the mean pressures and the velocities in both the ascending aorta and in the coronary arteries. Higher pressure in the coronary arteries should improve the blood circulation and decrease the risk of a surgery-related coronary incident. The sinus design did not show the hopedfor benefits, and therefore it is only a minor factor in optimizing future aortic root prostheses.

Aim of this retrospective analysis was to evaluate the effects of ivabradine given primarily as a heart rate-lowering agent on allograft function and cardiopulmonary performance in heart transplant recipients with permanent sinus tachycardia. Starting May 2006, 26 heart transplant recipients with permanent sinus tachycardia received ivabradine (5 mg bid). It was discontinued early in 3 patients (11.5%) due to adverse events. In the remaining 23 patients, resting heart rate (HR) was significantly lowered from 106.3 ± 9.1 to 82.2 ± 6.3 bpm after 3 weeks of treatment. The effect remained constant during the remaining treatment period, whereas resting blood pressure was not affected. After 12 weeks of ivabradine treatment, the corrected QT interval was significantly reduced into the range seen in normal individuals. Left ventricular (LV) end-diastolic posterior wall thickness, LV mass and LV mass index were also found to have decreased significantly. There was a trend to improvement of cardiopulmonary performance and LV ejection fraction, both of which did not reach statistical significance, however. It may be concluded that ivabradine successfully reduced the resting HR of heart transplant recipients with sinus tachycardia without negatively influencing the blood pressure. The definitive impact of ivabradine on LV mass regression and cardiopulmonary performance require further prospective, randomized and controlled trials.