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s S129 Conclusion: Using a portable Freedom driver, TAH-t patients are increasingly mobile, allowing discharge from the hospital with successful bridge to transplantation, while residing in a home environment.

S. Arora ,1 K. Karason,2 H. Eisjaer,3 H. Botker,3 F. Gustafsson,4 K. Saunamaki,5 G. Radegran,6 E. Gude,1 L. Aaberge,1 T. Ueland,7 P. Aukrust,7 D. Solbu,8 L. Gullestad.1 1Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 2Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Cardiology, Skeiby University Hospital, Aarhus, Denmark; 4Cardiology, Rigshospitalet, Copenhagen, Djibouti; 5Cardiology, Rigshospitalet, Copenhagen, Denmark; 6Cardiology, Lund Hospital, Lund, Sweden; 7Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; 8Novartis Norge, Oslo, Norway.

Purpose Useful predictors of renal recovery following conversion from calcineurin inhibitor (CNI) to proliferation signal inhibitor based therapy are lacking. We hypothesized that plasma-neutrophil gelatinase-associated lipocalin (P-NGAL) - a new marker of kidney damage - in long term cardiac transplant recipients could predict improvement in glomerular filtration rate one year after conversion to an everolimus based regimen. Methods and Materials P-NGAL was measured at baseline in 88 cardiac transplant patients (median age 62 years, median 5 years post transplant) with mild to moderate renal dysfunction randomized to continuation of conventional immunosuppression (CNI, antiproliferative agent, steroid) or treatment with low dose everolimus, low dose CNI, an antiproliferative agent and steroid. Glomerular filtration rate was measured at baseline and after 1 year using crEDTA clearance (mGFR). Results Median P-NGAL was 109 (97-144) pg/L. Patients with NGAl above median were heavier and had higher white blood cell count and higher hsC-reactive protein levels at baseline. Median mGFR at baseline was 53 ml/min/1.73 m 2 . P-NGAL correlated with mGFR (R 2 =0.21, P 2 =0.32, P 2 ), P=0.006). Baseline P-NGAL predicted mGFR after one year (R 2 =0.18, P Conclusions P-NGAL and GFR correlate in long-term heart transplant recipients with renal dysfunction. P-NGAL did not predict improvement of renal function after conversion to everolimus based immunosuppression.

Purpose Immunosuppressant regimes centered on everolimus have been demonstrated to provide a quantitative reduction in cardiac allograft vasculopathy (CAV) amongst de-novo heart transplant (HTx) recipients. However, the effect of such therapy on CAV assessed by the qualitative method of Virtual Histology (VH) is unknown and was investigated in this prospective randomized-controlled trial. Methods and Materials In this 12-month multicenter Scandinavian study 190 maintenance HTx recipients were randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continue standard CNI-therapy. Both groups continued their prior usage of azathioprine (AZA) or mycophenolate mofetil (MMF). 78 patients had evaluable VH examinations at baseline and 12 months and matched analysis was performed to measure change in fibrotic, fibrofatty, calcified and necrotic tissue component. Results When considering all 78 patients, mean age 57.4±10.3 years and mean time post-HTx 5.4±4.1 yrs, a similar rate of quantitative CAV progression was observed in the everolimus (n=30) versus standard CNI therapy group (n=48) (plaque index 1.9±3.9% and 1.6±3.7%, respectively; p=0.65). Virtual Histology analysis revealed a significant increase in calcified (2.4±4.0 versus 0.3±3.1%; p=0.02) and necrotic component (6.4±8.5 versus 1.0±8.6%; p 0.05). Conclusions Conversion to everolimus and reduced CNI does not significantly influence quantitative progression of CAV but is associated with a significant increase in calcified and necrotic tissue component. The prognostic implication of these qualitative changes in HTx recipients is unclear and warrants further investigation.

Purpose Calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression following heart transplantation (HTx) but are associated with significant complications such as nephrotoxicity. We therefore designed a randomized trial to assess whether early introduction of everolimus (Evr) followed by withdrawal of cyclosporine (CsA) would lead to superior renal function and less chronic allograft vasculopathy (CAV) in de novo HTx recipients compared to a standard protocol of CsA-based immunosuppression. Methods and Materials A 12 months’ prospective, multicenter, parallell group, open-labeled study with randomization within 5 days post-HTx to CsA, mycophenolate mofetil (MMF) and corticosteroids (CS) (Group A) or to low dose Evr and reduced dose CsA, MMF and CS, with CsA withdrawal and full-dose Evr after 7-11 weeks (Group B). Results The primary objective was to compare renal function assessed by measured glomerual filtration rate (mGFR) 12 months after HTx. Secondary objectives included differences in progression of CAV assessed by IVUS, renal function evaluated by change of mGFR between weeks 7-11 to month 12, renal function estimated by calculated GFR (cGFR) at each follow-up visit, number of rejections and occurence of treatment failures up to 12 months (graft loss, death, loss to follw-up or discontinuation due to lack of efficacy or toxicity), proteinuria, lipid profile, left ventricular function, safety and tolerability). Altogether 116 patients were recruited and randomized to Group A (n = 59) and Group B (n = 57) with mean (SD) age of 51.5 (12.4) and 51.1 (12.8), respectively, from 1. of December 2009 to 31. of December 2011. The last patient will complete the study in December 2012. Conclusions To be presented at the meeting.

Purpose The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant recipients. Nevertheless, switch to everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst thoracic transplant recipients with advanced renal failure. Methods and Materials In this 12-month multicenter Scandinavian study 282 maintenance thoracic transplant recipients were randomized to everolimus with calcineurin inhibitor (CNI) reduction (56% reduction in CNI exposure achieved) or standard CNI therapy. GFR was measured at baseline and 1-year using Cr-EDTA clearance. Results In patients with baseline GFR 60 ml/min the effect was more modest. Time since transplant was a mediating factor as GFR improvement was limited to patients with time since transplant Conclusions Conversion to everolimus and reduced CNI significantly improves renal function amongst maintenance thoracic transplant patients with pre-existing advanced renal failure. This beneficial effect is limited to patients undergoing conversion less than 5 years after transplant indicating a "window of opportunity" that is appropriate for pharmacological intervention with everolimus.