J. Dunning

Life supporting function for over one month of a transgenic porcine heart in a baboon

BACKGROUND Inhibition of hyperacute rejection (HAR) and sustained graft survival have been demonstrated in a pig-to-primate model of heterotopic cardiac xenotransplantation using pigs transgenic for human Decay Accelerating Factor (hDAF). Building on this work, an orthotopic model has been developed. This case records 39-day cardiac xenograft function in a life-supporting capacity with clinically applicable immunosuppression. METHODS Using a heart from an hDAF transgenic pig, an orthotopic cardiac transplant was performed on an adult baboon. The immunosuppressive regimen consisted of induction with a short course of cyclophosphamide, followed by maintenance therapy with cyclosporine A, mycophenolate mofetil and a tapering course of corticosteroids. Post-operative monitoring included daily anti-pig hemolytic antibody titer surveillance and endomyocardial biopsy. RESULTS The animal survived 39 days and was active and energetic throughout its postoperative course, remaining free of signs of cardiopulmonary failure. Endomyocardial biopsy performed on post-operative Day 36 revealed only patches of sub-endocardial fibrosis with no signs of active rejection. The baboon succumbed to an acute cardiopulmonary decompensation immediately following administration of medication via oral gavage. Post-mortem histopathology demonstrated well-preserved myocardial architecture with small foci of mild humoral rejection. CONCLUSIONS This case documents the longest survival recorded to date of a discordant orthotopic cardiac xenograft and illustrates that the hDAF transgene combined with a clinically acceptable maintenance immunosuppressive regimen enables sustained, life-supporting function of porcine cardiac xenografts in non-human primates. The inhibition of hyperacute rejection and the subsequent control of humoral and cellular rejection for over 1 month demonstrated in this experiment represent significant progress in the development of a viable strategy for clinical xenotransplantation.

S122 Outcome After Pulmonary Endarterectomy (pea): Long Term Follow-up Of The Uk National Cohort

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a life threatening condition that historically has a poor outcome with supportive medical treatment. Pulmonary endarterectomy (PEA) is the treatment of choice and offers the only chance of cure. Data on the predictors of long term survival after PEA are limited. We analysed the long-term data from the UK PEA cohort. Method All patients who underwent a PEA for CTEPH at Papworth hospital between January 1997 and December 2012 were included. Pre- and post-operative data on haemodynamics, exercise capacity, functional class and targeted PAH therapies taken were obtained from databases of the UK PH centres. The NHS spine summary care record tracking system was used for survival data and causes of death from the England and Scotland General Register Offices. The causes of death were further classified into 4 groups: 1. Post operative, 2. Right ventricular failure away from operative period, 3. Related to anticoagulation, 4. Unrelated to CTEPH e.g. malignancy. Results 880 patients underwent PEA over the 15 year period. The mean age was 57 (range 15–84) and 53% were male. 89% were in WHO functional class 3 or 4 before surgery with an mean mPAP of 47 mmHg and PVR of 830 dynes. Post surgery 84% of patients were in WHO functional class 1 or 2 and there was a reduction in the mean mPAP to 27 ± 9 mmHg and PVR to 286 ± 198 dynes/sec/cm5 by 12 months (p). Conclusion There was prolonged haemodynamic improvement but targeted therapy was used in 23% of patients with a mean follow-up of 4.3 years. The 10-year survival was 72% with mortality predominantly in the peri-operative period and later due to causes unrelated to CTEPH. Abstract S122 Table 1 First year post PEA haemodynamics and exercise capacity predict long term risk of death Predictor value Value Hazard ratio 95% confidence intervals 6 minute walk distance (m) 110 3.03 1.82–5.04 230 1.74 1.35–2.24 350 Reference 470 0.57 0.45–0.74 590 0.33 0.20–0.55 Mean pulmonary artery pressure (mmHg) 15 0.67 0.55–0.83 25 Reference 35 1.49 1.21–1.83 45 2.21 1.46–3.36 55 3.29 1.76–6.16 Cardiac index (L/min/m2) 1.5 1.60 1.00–2.56 2 1.26 1.00–1.60 2.5 Reference 3 0.79 0.62–1.00 3.5 0.63 0.39–1.00 4 0.49 0.24–1.00 Pulmonary vascular resistance(Dynes/sec/cm5) 50 0.51 0.37–0.70 250 Reference 450 1.95 1.43–2.67 650 3.81 2.03–7.14 850 7.44 2.90–19.08

Tricuspid Regurgitation after Cardiac Transplantation Does Not Affect Long Term Survival

Purpose Tricuspid regurgitation (TR) after orthotopic heart transplantation (OHT) may be associated with right ventricular dysfunction and increased mortality. This study addresses the fate of postoperative TR and its impact on long term survival. Methods and Materials Between 2002 and 2006, 118 patients were identified who underwent OHT at our institution. Detailed retrospective case-note review was undertaken. Data collected included demographic, perioperative and echocardiographic details. Patients were divided into two groups based on the degree of TR identified on echocardiography early postoperatively. Results Of the 118 pts, 23 (19%) had at least moderate TR in the early postoperative period. The two groups were otherwise similar with respect to age and sex, however the TR group had significantly higher preoperative mean pulmonary artery and capillary wedge pressure (33.4 vs. 25.6, p figure 1 ] Of the 23 patients with significant early postoperative TR, 17 (74%) demonstrated significant reduction in the grade of TR on serial annual echocardiographic follow-up. TR almost completely disappeared in 15 patients (65%) at 1-year follow-up. Conclusions This study reports no significant impact of early TR on long-term survival following OHT. In addition, in a significant proportion of patients the degree of TR improves significantly on follow-up echocardiography without any further intervention.

P116 Outcomes of DCD Lung Offers: A Single Centre Experience in the UK

Introduction Lung transplantation is the treatment of choice for a variety of end stage lung diseases. It offers prognostic benefit and an improvement in quality of life for carefully selected patients. There sadly remains a critical shortage of lung donors. One way to increase the donor pool, and potentially the number of lung transplants, is to utilise organs which are Donated following Circulatory Death (DCD). Here we review our experience with DCD offers received during a two-and-a-half year period. Methods This is a retrospective study using data collected prospectively from all lung offers received between 01/2009 – 09/2011. We look at the proportion of DCD lung offers and track the fate of each of these down to transplantation. We look at the documented reasons for declining all DCD lung offers, the rate of DCD lung transplantation and the survival rate in this cohort. Results Overall, 80 lung transplants were performed during the study period. 7 were performed using DCDs, therefore, 9% of lung transplants are from DCD donors. Survival rate at 1 year post-DCD lung transplantation is approximately 80%. 233(86%) of DCD lung offers were initially declined. Numerous reasons were documented; the most common reason given (122 donors) was due to evidence of infection. In 37 cases, the donor was unlikely to meet extubation criteria. Interestingly, 42 donors were declined as a result of having no suitable recipient on the transplant waiting list alone. A large proportion of offers were initially accepted but not used. In 5 cases consent for transplantation was withdrawn from family, 7 cases were declined due to time/logistical factors and 10 donors were declined on inspection from the retrieval team. Conclusion Despite offering good short term outcomes, a large number of DCD lungs are declined for a variety reasons. Donors declined due to having no suitable recipient could be reduced by increasing the number of patients on the waiting list. Increased public awareness and better communication leading up to donation may lead to fewer cases of consent being withdrawn from family. A lower threshold for attending donors who might not meet criteria may also yield more organs. Abstract P116 Figure 1 Flow diagram of all lung offers and outcomes

S25 Incidence of surgically treated patients with chronic thromboembolic pulmonary hypertension in the UK during the last decade

Introduction Pulmonary endarterectomy (PEA) is the treatment of choice for patients with proximal chronic thromboembolic pulmonary hypertension (CTEPH). The UK has a single centre performing this operation and the program became nationally funded since 2000. Patients are referred from seven specialist pulmonary hypertension centres. Method All 625 patients treated with PEA from 2000 to 2010 were mapped according to their home postcode at the time of PEA surgery. Primary care trusts (PCTs) were assigned from these home postcodes. The incidence rate of each PCT and overall incidence were analysed. Mapinfo software was used to generate the referral maps. Results The new patient incidence ranges from no referrals in 123 PCTs in 2000–2002 to 90 in 2008–2010. The most recent period shows highest referral rates for PEA. From our PEA data mapping analysis we have calculated that the incidence of operated patients was 0.4 million population in 2000 (n=22) and 2 per million population in 2010 (n=122). Conclusion There has been a fivefold increase in PEA activity in the UK over the last decade. The analysis of our data are limited to surgical cases. The current incidence of PEA in the UK is already higher than historical estimation of the incidence of all CTEPH (0.1–0.5/million, Fedullo, N Engl J Med 2001). Since 30% of patients with CTEPH have distal disease distribution and some patients with proximal CTEPH do not proceed to surgery due to choice or comorbidities, the overall incidence of CTEPH is likely to be significantly higher than 2 per million/year and higher than previously suspected.Abstract S25 Table 1 Patient Incidence/million population/period Patient incidence in PCT/million 2000–2002 2003–2004 2005–2006 2007–2008 2008–2010 # of PCTs # of PCTs # of PCTs # of PCTs # of PCTs 0 123 136 124 113 90 0.1 to 2.4 16 13 10 18 12 2.5 to 4.9 40 29 37 37 50 5.0 to 7.4 10 9 19 15 20 7.5 to 9.9 2 4 0 3 11 10 to 35.6 3 3 4 8 11 Total incidence/million 0.56 0.65 1 1 1.6

Cardiopulmonary bypass does not increase the morbidity associated with lung transplantation for chronic obstructive airway disease

between the NIV group versus the control (non-NIV) group. Median stay in the intensive care unit and hospital was 2 days (range 1-56) and 25 (range 1-147) for the NIV group versus 2 days (range 1-70) and 29 (range 1-130) for the control group (p 0.27, 0.99 respectively). Median survival using Kaplan Meier survival analysis was 1322 days (3.6 years) in the NIV group and 1463 days (4.0 years) in the control group (p 0.96). There were no significant differences between the two groups in the rates of acute rejection or pulmonary infection in the first 12 months post-transplant. In terms of lung function, those on NIV had significantly lower percent-predicted FEV1 and FVC pre-operatively (17.7% vs 39.3% and 40.9% vs 52.5% respectively). FEV1 continued to remain lower in the NIV group at three months post-transplant (62.9% vs 72.1%) and at 12 months (75.9% vs 84.5%) but this did not achieve statistical significance. There were no significant differences in FVC post transplant. Conclusion: Provided standard nutritional and functional targets are achieved pre-transplant, prolonged use of NIV support does not impede obtaining a satisfactory outcome post-transplant.