Recent histological and genoarray studies identified B cell signatures associated with renal transplant tolerance or chronic rejection. The role of B cells in cardiac rejection is poorly characterised. This prospective study applied serial phenotyping to determine B cell signatures within six months of cardiac transplantation.

Coronary Artery Vasculopathy (CAV) is the major life limiting factor in cardiac transplantation. There is a growing appreciation that mechanisms other than cellular rejection play a role in the development of CAV. Recent clinical data has demonstrated the presence of non-HLA IgM antibodies as a significant risk factor in it's development. While antibody, and ultimately complement activation are potential risk factors for CAV, few studies have investigated their distribution in advanced human CAV lesions. Here we investigate the distribution of complement, IgM and IgG within CAV lesions.

Comparison of outcome following heart/lung transplantation(H/L Tx) performed for idiopathic pulmonary arterial hypertension(IPAH) and chronic thromboembolic pulmonary hypertension(CTEPH) is unknown. The objective of this study is to compare the outcome of H/L Tx performed for CTEPH and IPAH.

25 years of heart transplantation data were used to identify factors associated with patient survival and investigate changes over time.Analysis was performed across 5 time eras -pre-triple therapy, post-triple therapy to 1990 and the remaining 15 years through 2005 divided into 3 groups of 5 years each.Both short-and long-term survival improved with the advent of triple therapy, but remained unchanged from the early 1990's.Mean donor and recipient age, proportion of female donors and recipients, transplants with two human leucocyte antigen (HLA)-DR mismatches, ischaemic and cardiopulmonary bypass times (CPB) have increased, while rates of rejection and infection have decreased over time.Female donor and recipient diagnosis were independent predictors of short-term mortality.Older age, recipient diagnosis, 2 or more early rejection episodes and number of HLA-A mismatches were independent predictors of mortality in the longterm.Survival rates after heart transplantation improved with advances in patient care, but have remained static since, during which time there have been increases in risk factors and use of more marginal donors.

The Organ Care System (OCS) is a portable organ perfusion and monitoring system designed to preserve donor hearts in near-physiologic states for clinical transplantation. The PROTECT Study is a prospective, single-arm, non-randomized, safety and performance study of the OCS. The purpose of the current study is to report the 1-year clinical outcomes in heart transplant recipients who received donor hearts preserved and maintained with the OCS.

Purpose: Chronic rejection in the form of coronary artery vasculopathy (CAV) is the major life-limiting factor in cardiac transplant, post one year. The mechanisms behind the development of CAV are yet to be fully elucidated. Recent data has implicated humoral immune responses, demonstrated by complement activation, as key factors in the pathogenesis. This study analyses cardiac biopsies taken over the first two years post transplantation for the presence of complement (C4d), and analyses the relationships to the development of acute rejection and CAV.

Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardio-respiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4-171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1- and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome.

Purpose: To demonstrate the performance and safety of the Organ Care System (OCS) for donor heart preservation and transportation. OCS is a portable organ perfusion and monitoring system intended to preserve a donated heart in near-physiologic functioning state during transport for the eventual transplantation into a recipient. OCS maintains organ viability by continuously perfusing the donated heart with warm, oxygenated donor's blood, supplemented with a maintenance solution.

Purpose: We examined the risk factors for and changes over time in, survival following heart-lung transplantation (HLT) between 1984 and 2005.

Purpose: PPMV is sometimes necessary following lung transplantation (LT). We examined the incidence, indications and outcomes of LT recipients requiring PPMV.

Purpose: Monitoring cyclosporin (CYA) C2 levels improves clinical outcomes following transplantation (Tx), and evidence has shown that targeting therapeutic C2 levels in the early post-Tx period significantly reduces the long-term incidence of acute rejection. We therefore performed an intention-to-treat analysis of 3, 6 and 12 month clinical outcomes from lung-Tx recipients initially monitored by traditional CYA C0 or by C2 levels.

Background: The establishment of lung transplantation as a treatment modality for end-stage lung disease has led to an imbalance in the demand and supply for such a procedure. Increasingly marginal donors are being accepted for transplantation. We assessed the short- and long-term outcomes with the use of lung donors with low PO2.Methods: All heart-lung and double lung transplantations (n = 362) carried out between 1984 and 2001 were included. Recipients were divided according to the optimized donor PO2 (on 100% Fio(2)): PO2 = 30 to 40 kPa = low PO2 donors (n = 50) and Po-2 > 40 kPa = normal PO2 donors (n = 312). There were no differences in the sex distribution, cytomegalovirus infection status, ischemic time, and intubation durations for the recipients and their respective donors between the 2 groups. The low PO2 donors were older (38 vs 32 years, p = 0.01) and the allografts were transplanted into younger recipients (33 vs 38 years, p = 0.01).Results: There was a trend toward an increase in the 30-day mortality between the 2 groups (22% vs 13%, odds ratio 1.92, 95% confidence interval 0.91-4.05 p = 0.08). The 1- and 5-year survival rates (standard error) were 66% (7%) and 52% (7%) for the low PO2 group and 72% (3%) and 44% (3%') for the normal PO2 group (p = 0.97). Similar infection rates were recorded for the groups. Although rejection rates were similar in the first 3 months, there was a lower rate of rejection in the low PO2 group thereafter, (hazard ratio, 0.52; p = 0.05). Risk of bronchiolitis obliterans syndrome (BOS) onset was marginally increased in the borderline donors (hazard ratio 1.05, 95% confidence interval 0.68-1.62), although this was not statistically significant.Conclusions: Donor lung allograft, with optimized PO2 between 30 and 40 kPa on 100% FiO(2) used for lung transplantation did compromise 30-day mortality, but the difference in mortality did not extend beyond 30 days in our patient group. Copyright (c) 2005 by the International Society for Heart and Lung Transplantation.

Infective endocarditis is a rare but life-threatening complication of heart and heart-lung transplantation. We describe a 32-year-old woman who developed aortic valvular endocarditis following heart-lung transplantation. Enterococcus was the infective organism. The patient's condition was successfully managed using prolonged intravenous antibiotic therapy and aortic valve replacement.

Background: Over 50,000 heart transplants have been performed in the last 3 decades. The global shortage of donor. organs and the relaxation of candidate selection criteria over time has resulted in recent controversy about the benefits of heart transplantation for some risk groups. We assessed the survival benefit acquired in the Papworth Hospital heart transplant population overall, taking into account resuscitated marginal donors and high-risk recipients.Methods: All heart transplant patients listed between 1979 and June 2002 were analyzed (n = 1,212). Of these, 931 cardiac transplantations were done, including the use of 126 marginal donors. High-risk recipients (n = 163) were defined as patients being in the hospital, on intravenous inotropic drugs, and/or with a high transpulmonary gradient (> 15 min Hg). Using Cox regression with transplantation as a time-dependent, covariate, we assessed the survival benefit of transplantation. In our model we assumed that after transplantation the initial risk of death is high relative to continued waiting, followed by an exponential decline in risk. The crossover point (COP) is the time at which the risk of death after transplantation is equal to that of continued waiting (i.e., the relative risk is 1). The equity point (EP) determines the time at which the early post-operative risk is offset by the later period of lower risk and, therefore, the time at which transplantation has a survival advantage.Results: Overall, the COP was at 54 days and EP at 141 days. In the marginal donor sub-group, COP was achieved at 32 days with EP at 72 days, indicating a survival benefit. The difference in the COP and EP between the borderline donor and normal donor sub-groups was not statistically significant. Post-transplant survival was not significantly different from recipients of normal cardiac allografts (p =.43). Likewise, for the high-risk recipient group, the COP and EP were at 72 and 203 days. Although post-op survival was significantly shorter than the normal-risk group, both groups achieved survival benefits.Conclusion: Heart transplantation provides survival benefit in these risk groups of recipients in our population. This is a reflection of our active donor management protocol and rigorous donor and recipient selection process.

Background: Acute rejection increases the inflammatory burden of the transplanted organ and predisposes to cardiac allograft vasculopathy (CAV). In this Study we aim to determine the magnitude of the association, and to differentiate between the effects of mild vs severe rejection episodes.Methods: Between 1988 and 2003, 489 1-year survivors of heart transplantation underwent 1,435 angiograms. These patients were classified as having no CAV (0% stenosis), mild/moderate CAV (< 70%) or severe CAV (> 70%). Acute rejection was considered either mild (Grades 1A, 1B and 2 untreated) or moderate/severe (Grade 2 treated on a clinical basis and Grades 3A, 3B and 4). We used multi-state Markov models to examine risk factors for the onset of CAV.Results: Expressed as relative risk, the onset of CAV was significantly increased by donor age (1.26 per 10 years, 95% confidence interval [CI] 1.12 to 1.42), male recipient (1.72, 95% CI 1.01 to 2.94), pre-transplant recipient ischemic disease (1.53, 95% CI 1.14 to 2.06) and cumulative number of moderate/severe rejections (1.10 per episode, 95% CI 1.03 to 1.18). Human leukocyte antigen (HLA) and cytomegalovirus (CMV) matching, donor gender, recipient age, smoking, cumulative CMV infections and mild rejections were not significant risk factors. Estimated annual onset rate of CAV was 11.3% for patients with no moderate/severe rejection, rising to 13.6% for those with two and 18.0% for those with five such rejections.Conclusions: Acute moderate/severe cellular rejection has a cumulative impact on CAV onset, whereas mild, untreated rejection is not associated with CAV.