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105 TIGHT PERIOPERATIVE GLUCOSE CONTROL IS ASSOCIATED WITH FEWER LVAD RELATED INFECTIONS AND BETTER POST-VAD SURVIVAL T.P. Martens,1 M.J. Russo,1 F.H. Cheema,1 I. George,1 M.Y. Tabksblat,1 S. Alison-Mayne,1 J.B. Goldberg,1 R. Wang,1 S.H. Bailey,1 M. Argenziano,1 A.S. Stewart,1 M.C. Oz,1 D.M. Mancini,2 Y. Naka,1 1Surgery, Columbia University College of Physicians and Surgeons—New York Presbyterian Hospital, New York, NY; 2Medicine, Columbia University College of Physicians and Surgeons—New York Presbyterian Hospital, New York, NY Background: Tight glucose control in critically ill patients is associated with a reduction in long term morbidity and mortality. The purpose of this study is to determine if a similar relationship exists in left ventricular assist device (LVAD) patients. Methods: We retrospectively reviewed 158 consecutive patients undergoing Heartmate I LVAD-implant at our center. The average blood glucose (BG) at four time intervals—3 days prior (3PRE) and 3 (3POST), 7 (7POST), and 10 days (10POST) following LVAD-implantation —were calculated. As the median BGs at 3PRE, 3POST, 7POST, 10POST were 139, 151, 139, and 137 mg/dl, respectively, BG of 140mg/dl was selected for analysis. Local device infection (LDI) was defined by clinical signs with positive culture(s) from the abdominal wound, driveline, pocket, or pump. Results: There was a strong statistical association between BG ⬍ 140 and fewer LDIs at 3PRE (37 vs 19%, p⫽0.010), 3POST (33 vs 20%, p⫽0.066), 7POST (37 vs 21%, p⫽0.027), 10POST (38 vs 22%, p⫽0.022) and bacteremia post-implant [3POST, 41 vs. 26%, (p⫽0.055), 7POST, 47 vs 25%, (p⫽0.003), 10POST, 45 vs 28%, (p⫽0.020)]. Multivariate regression controlling for diabetes demonstrated an inverse relationship between BG as a continuous variable and LDI at 3PRE(p⫽0.005), 3POST(p⫽0.157), 7POST(p⫽0.006), 10POST(p⫽0.001) and bacteremia at 3POST(p⫽0.008), 7POST(p⫽0.028), 10POST(p⫽0.047). Preop BG was also associated with increased postop ICU length of stay (p⫽0.026). Finally, with BG ⬍ 140, there was a trend toward improved survival at 30 days, 90 days, and to transplant at 3POST (91 vs 80% p⫽0.071, 84 vs 68% p⫽0.025, 82 vs 72% p⫽0.185) and 7POST (93 vs 81% p⫽0.031, 84 vs 69% p ⫽0.035, 84 vs 74% p⫽0.154). Conclusions: BG levels under 140 mg/dl in the perioperative period are associated with fewer LDIs, fewer episodes of bacteremia, and better long term survival in LVAD recipients. Improved pre and post-op glucose control may reduce infectious morbidity and improve post-implant outcomes. 106 HEPARIN-INDUCED THROMBOCYTOPENIA ADVERSELY AFFECTS CLINICAL OUTCOMES IN PATIENTS ON MECHANICAL CIRCULATORY SUPPORT S. Schenk,1 A. El-Banyosy,1 M. Morshuis,1 W. Prohaska,1 L. Arusoglu,1 R. Koerfer,1 1Thoracic and Cardiovascular Surgery, Heart Center NRW, Bad Oeynhausen, Germany Purpose: Patients on mechanical circulatory support are at risk of developing heparin-induced thrombocytopenia (HIT) due to the liberal use of heparin peri-operatively. We evaluated antibody status and outcome. Procedures: Between 2003 and 2004, 115 patients were placed on mechanical circulatory support for ⬎5 days. Blood samples from postoperative day 7 were retrospectively analyzed for anti-PF4/ heparin antibodies and heparin-induced platelet activation. Results: Overall, 12 (10.6%) patients were HIT positive as defined by in vitro platelet activation, 28 (24.8%) patients classified as antibody

The Journal of Heart and Lung Transplantation February 2006

epiphenomenon, and 73 (64.6%) patients were HIT negative. HIT positive patients had highest levels of anti-PF4/heparin antibodies, predominantly of pathogenic IgG subclasses. However, neither platelet counts nor standard coagulation monitoring distinguished between the groups. Freedom from thromboembolism was 33%, 33%, and 16% at 1, 3, and 6 months for HIT positive patients, 77%, 68%, and 55% for HIT negative patients (positive vs negative, P ⬍0.001), and 70%, 53%, and 53% for patients with antibody epiphenomenon (positive vs epiphenomenon, P⫽0.068), respectively. The relative risk for thromboembolism in antibody positive patients peaked in the first month of support (odds ratio 7.46, P ⫽ 0.002). Independent risk factors for thromboembolism by multivariate regression includedhigher anti-PF4/heparin antibody titers, female gender, and higher fibrinogen levels. Conclusion: Heparin-induced thrombocytopenia was more prevalent in patients on mechanical circulatory support than in other cardiac patients. Frequent antibody screening is recommended due to the increased risk of thromboembolism. Heparin-alternatives should undergo clinical trials in these high-risk patients. 107 ANTIBODY SENSITISATION FOLLOWING LVAD IMPLANTATION IS NOT DUE TO HLA ANTIBODIES H. Newell,1 J.D. Smith,1 A.J. Danskine,1 R.E. Fawson,1 E. Birks,1 M.L. Rose,1 1Heart Science Centre, Royal Brompton & Harefield NHS Trust, Harefield, Middlesex, United Kingdom Implantation of left ventricular assist devices (LVAD) is associated with HLA antibody sensitisation. The purpose of this study was to investigate whether LVAD patients receiving leukodepleted blood make HLA antibodies. Fifty-one patients, who received LVADs (from 1998) were studied, the mean period of implantation was 307.6 ⫹/⫺224.5 days. Serum samples were screened for HLA antibodies using ELISA (One Lambda), Luminex (Tepnel Lifecodes) and microcytotoxicity assays. 24/51 patients made IgG antibodies detected by ELISA, but this only in patients implanted since May 2003. These were not HLA antibodies as they were not only positive in wells coated with class I and class II antigens but also positive in wells containing no antigen. Prior to May 2003, the mean OD readings of LVAD recipients in the LAT-ELISA was 111 ⫹/⫺ 39.88 compared to 995 ⫹/⫺ 250.87 for later patients p ⬍0.0001. In Luminex assays these samples were positive with negative control beads (mean MFI ⫽ 4196⫹/⫺ 2225) compared to those implanted prior to May 2003 (205.88⫹/⫺96.38), p ⬍0.0001. None of the samples were cytotoxic to PBMC. All 24 patients demonstrated antibodies to albumin (commonly used to coat ELISA plates and Luminex beads) mean OD 930 ⫹/⫺ 360, compared to the 27 patients negative in the solid phase assays, mean OD 58⫹/⫺ 103 (p ⬍0.0001). Adsorption of the sera with albumin-coated beads eliminated reactivity in the commercial HLA antibody assays, but not in 4 HLA positive controls. Ten of the 24 patients with anti-albumin antibodies have been transplanted; their one year graft survival (69%) was not significantly different to fifteen LVAD patients transplanted without anti-albumin antibodies (80%) and 138 cardiac transplants performed within the same period (84%, p⫽0.45). In conclusion, this study demonstrates an anti-albumin antibody response in LVAD patients, which reacts in HLA antibody solid phase assays, giving the false impression of high HLA reactivity. This response does not appear to effect subsequent cardiac allograft survival. 108 EVALUATION OF THE VENTRICULAR ASSIST DEVICE PROGRAMME IN THE UNITED KINGDOM

The Journal of Heart and Lung Transplantation Volume 25, Number 2S

L.D. Sharples,1 M.J. Buxton,2 N. Caine,3 for the EVAD UK Research 4 1 Group, R&D Unit, Papworth Hospital NHS Trust, Papworth Everard, Cambridge, United Kingdom; 2Health Economics Research Group, Brunel University, Uxbridge, Middlesex, United Kingdom; 3R&D Unit, HM Government Department of Health, London, United Kingdom This study estimates cost-effectiveness of the UK government-funded VAD programme and identifies cost drivers. All patients implanted with a VAD for bridge to transplant (BTT) April 2002 to December 2004 were studied up to April 2005. Survival, quality of life and resource use were recorded. In the absence of a true comparison group, costs and survival were assessed against inotrope-dependent non-VAD transplant candidates from the same time period and against a hypothetical worst-case in which all potential VAD patients would die in ITU within 1 month without the technology. For life-time estimates a multistate model of VAD activity, transplant activity and survival was developed with data from the UK programme and long-term survival from the UK Transplant registry. Of the 70 VAD patients 30 (43%) died pre-transplant, 31 (44%) underwent transplantation and 4 (6%) were bridged to recovery. Five (7%) remained on VADs median 279 days. Survival from VAD implant was 52% at 12 months. Common adverse events were bleeding, infection and respiratory dysfunction. 29 patients were discharged with a VAD. One-year survival post-transplant was 84%. In the same period there were 71 inotrope-dependent patients, 10% died whilst listed, median waiting time was 16 days. One-year survival post-transplant was 85%. VAD and non-VAD patients had poor quality of life pre-transplantation and similar, significantly improved values afterwards (p ⬍0.001). Mean VAD implant cost, including the device, was £63,830. Main cost drivers were the device, ITU stay, hospital stay and treatment of adverse events. Modelled over their lifetime the mean cost for a VAD patient was £173,841 with mean survival 5.6 years, and when quality-adjusted 3.3 QALYs. Costs for inotrope-dependent patients would be £130,905 with mean survival 8.6 years, or 5.0 QALYs. Compared with the worst-case VADs would cost £49,384 per QALY. In the UK context VADs as BTT are expensive but result in improved survival compared to the worst-case. 109 PREOPERATIVE RENAL FAILURE DOES NOT AFFECT OUTCOME IN BRIDGE-TO-TRANSPLANTATION WITH A VENTRICULAR ASSIST DEVICE IMPLANTATION H. Tsukui,1 J.J. Teuteberg,2 S. Winowich,1 E. Stanford,1 S. Weaver,1 S. Murali,2 M.A. Mathier,2 D.M. McNamara,2 L.M. Cadaret,2 M.A. Simon,2 Y. Toyoda,1 R.L. Kormos,1 1Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA; 2 Cardiology, University of Pittsburgh Medical Center, Pittsburgh, PA Purpose: To clarify whether renal failure (RF) is a risk factor for bridge-to-transplant (BTT) ventricular assist device (VAD) implantation. Methods: We reviewed pre- and post-VAD implantation data including serum creatinine (s-Cre) levels and survival rate to and after heart transplantation (OHTX). Results: Eighty-one patients (pts) excluding acute cardiogenic shock received VADs (45 LVADs, 36 BiVADs) from January 2000 to September 2005 (age 51.3 yrs, 85% male, 44% ischemic). Pts were divided into Group A (pre-VAD s-Cre⬍2.0 mg/dl: 65 pts, mean 1.3⫾0.3 mg/dl [0.6 –1.9]) and Group B (pre-VAD s-Creⱖ2.0 mg/dl: 16 pts, mean 3.0⫾0.9 mg/dl [2.1– 6.0]). Two pts in Group B required preoperative hemodialysis (HD) for fluid control. Seven (mean 17 days [2–35]) and 5 (mean 8 days [2–19]) pts required postoperative HD in Group A and B, respectively (p⫽0.0538). Two months post-VAD implantation,

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s-Cre level in Group B recovered to normal (1.3⫾0.5 mg/dl). There was no significant difference in s-Cre between the two Groups at 4 months post-VAD implantation (Figure). Three pts were weaned from VAD in Group A. Seven pts and 2 pts are currently supported on VAD in Group A and B, respectively. Twelve pts and 5 pts died on VAD in Group A and B, respectively (p⫽NS). Forty-three pts (78%) in Group A and 9 pts (64%) in Group B received OHTX (p⫽NS). 1-year survival rate after OHTX was 88% and 78% in Group A and B, respectively (p⫽NS). Conclusion: VAD support improved preoperative RF at 2 months post-VAD implantation and did not prohibit successful OHTX. The need for temporary HD is high, but preoperative RF is not a risk factor for outcome.

Disclosure: The author has received a fellowship supported by Thoratec Corporation. 110 SURFACTANT PROTEIN A GENE POLYMORPHISM PREDICTS BOS F. D’Ovidio,1 H. Kaneda,1 C. Andrade,1 L.G. Singer,1 C. Chaparro,1 C. Gutierrez,1 M. Hutcheon,1 A. Pierre,1 M. Liu,1 T.K. Waddell,1 J. Floros,2 S. Keshavjee,1 1Toronto Lung Transplant Program, University of Toronto, Toronto, ON, Canada; 2Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA Bronchiolitis obliterans is the major factor limiting long-term success of lung transplantation. Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. We studied SP-A gene polymorphism as a predictor of BOS. Methods: Lung-Tx pts (34) were prospectively followed by PFTs, and bronchoscopies with BAL and biopsies. Donor lung were assayed for SP-A1 and SP-A2 gene polymorphism, pre implantation mRNA expression and post-Tx BAL protein levels. Results: BOS was diagnosed in 16 pts. No significant association was noted for SP-A1. The table shows the SP-A2 genotype frequency. SP-A2 Genotype Frequency 1A0-1A 1A0-1A0 1A0-1A2 1A0-1A3 1A0-1A5 1A0-1A9 1A1-1A0 1A1-1A3 1A1-1A8 1A1-1A10

12% (4) 41% (14) 3% (1) 3% (1) 6% (2) 6% (2) 17% (6) 6% (2) 3% (1) 3% (1)