How to improve prediction of waiting list mortality in heart transplant candidates?

The Journal of Heart and Lung Transplantation Volume 21, Number 1

Abstracts

BARK1 were determined by quantitative RT-PCR and imunohistochemical analysis in each group. Results: The results at 120 minutes of reperfusion are described in the table. LVPDP(%) CF(%)

BARK1

B2AR

Failing

Control

50 ⫾ 6* 78 ⫾ 4

89 ⫾ 5** 90 ⫾ 4

63 ⫾ 6 87 ⫾ 3

84 ⫾ 4 80 ⫾ 3

Data ⫽ Mean ⫾ SEM. Pretreatment values were defined as 100%. LVPDP ⫽ Left ventricular peak developed pressure, CF ⫽ Coronary flow, *p ⬍ 0.05 compared to Failing. **p ⬍ 0.05 compared to Control, ANOVA post hoc Tukey.

In summary, B2AR overexpression restored the myoprotective effects of IPC in failing hearts, and BARK1 abolished the myoprotective effects of IPC in normal hearts. Conclusion: These data indicate that BAR signal transduction pathway may be involved in IPC mechanisms and that B2AR gene transfer is effective in restoring the myoprotective effects of IPC in the failing hearts.

289 THE EFFECT OF OPEN LABEL UT15 OR BOSENTAN ON HOSPITALISATION DAYS IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION (PAH) A.M. Keogh, K.M. Brown, C.A. Corrigan, C. Allada, Y. Ten, St. Vincent’s Hospital, Sydney, Australia Two novel therapies, bosentan (endothelin antagonist) and UT15 (prostacycline analogue), have been shown in randomised trials to be efficacious in patients with PAH of varying etiologies. Following end of randomised trial, 49 Class III-IV patients (bosentan n⫽12 and UT15 n⫽37), were entered to open label therapy at a single centre and survived to followup 30 Sept 2001, allowing comparison of the effect of these two therapies on hospitalisation. Etiology of PAH was primary (24), scleroderma/SLE (7), Eisenmengers (7), embolic (7) and other (4). There were 29 females, 20 males: mean age at start of open label drug 49⫾16 years. Mean time from symptoms to diagnosis was 15⫾17 months for bosentan, and 33⫾98 months for UT15, reflecting the inclusion of Eisenmengers in the UT15, but not bosentan trial. Hospitalisation days, adjusted for months of followup were compared for the time from symptom onset to start open label drug, and from start open label drug to the followup date. Results: Time from symptom onset to start drug was shorter for bosentan than UT15 (46⫾40 months vs 78⫾122 months, p⬍0.05), and time on drug to followup was also shorter (6.5⫾0.5 months vs 15.9⫾7.2 months, p⬍0.001). When hospital days were adjusted for duration of disease, the mean total days/month for the index disease before and after start open label bosentan were 0.186 and 0.051 (76% reduction), and for UT15 0.146 and 0.182 (25% increase). For all cause hospitalisation, including index disease, but also ulceration and amputation, mean total hospital days/ month before and after start open label bosentan were 0.188 and 0.064 (66% reduction), and for UT15 0.207 vs 0.321 (55% increase). In addition, 17% of bosentan and 70% of UT15 patients were admitted to commence drug, resulting in trial-related hospital days of 0.58⫾1.38 vs 2.54⫾2.08, p⫽0.0044 respectively. Conclusions: Bosentan, but not UT15, appears to reduce timeadjusted hospitalisation rates in patients with PAH, both for the index disease and for inter-related causes.

159

290 CORRELATIONS BETWEEN BASIC FIBROBLAST GROWTH FACTOR (bFGF), VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF), AND CLINICAL FEATURES OF PULMONARY ARTERIAL HYPERTENSION (PAH) J.D. Rich,1 J. Benisty,2 V.V. McLaughlin,1 J. Folkman,2 S. Rich,1 1 Rush Heart Institute, Rush-Presbyterian-St. Lukes Medical Center, Chicago, IL; 2Harvard Childrens Hospital, Boston, MA PAH is the result of abnormal pulmonary vascular growth. Elevations in bFGF and VEGF have been noted in animal models, but growth factors that cause PAH in humans are unknown. We measured serum and urine bFGF and VEGF in 76 stable pts with PAH (primary pulmonary hypertension (PPH)⫽51, collagen vascular disease (CVD)⫽15, congenital heart disease (CHD)⫽10), and 10 controls. Growth factors were correlated against age, gender, etiology, NYHA Functional Class, current medications, and hemodynamics. Results: Pts with PAH had significant elevations in serum bFGF (6.9⫾14.1 vs. 0.53⫾0.7 ng/ml) and VEGF (72.9⫾16.6 vs. 21.9⫾2.5 pg/ml) from controls (p⬍0.01). There were differences in bFGF levels based on etiology (PPH⫽8.9, CHD⫽3.9, CVD⫽1.9) (p⬍0.01) (Figure), with highest levels in pts with the highest PA pressures (p⫽0.04). Elevations in VEGF were confined to those with PPH (PPH⫽92.8, CHD⫽27.1, CVD⫽37.4) (p⬍0.01), with the highest values in pts with the lowest cardiac outputs (p⫽0.05). Urinary bFGF and VEGF were elevated only in pts with PPH, and correlated poorly with serum levels. Conclusion: bFGF may play an important role in the myointimal proliferation noted in PAH. In contrast, VEGF, which has been associated with plexiform lesions in PPH, may increase as a result of localized angiogenesis in response to tissue hypoxia. The molecular pathways responsible for PPH appears to differ from those in other forms of PAH.

291 HOW TO IMPROVE PREDICTION OF WAITING LIST MORTALITY IN HEART TRANSPLANT CANDIDATES? J.M. Smits,1 M.C. Deng,2 J. De Meester,3 M. Hummel,4 F. Schoendube,5 H.H. Scheld,5 H.C. van Houwelingen,6 1 Eurotransplant, Leiden, Netherlands; 2Columbia University, New York, NY; 3Onze Lieve Vrouw Clinic, Aalst, Belgium; 4Berlin Heart Center, Berlin, Germany; 5University Hospital, University of Muenster, Muenster, Germany; 6LUMC

160

Abstracts

Current trends in medical management of advanced heart failure and transplant medicine and the enactment of a detailed national transplant laws forced a change towards allocation driven by disease severity. The aim of this study was (i) to examine whether the current UNOS status 1a/1b/2 classification could be improved, (ii) create a new model which allows the calculation of a continuous index based of a few easily obtained variables. The available clinical profile data were first classified into physiological subscores: (1) urgency score based on patient’s residency, administration of IV cathecholamines, VAD implant, requirement of hemodialysis and or hemofiltration, (2) left ventricular heart failure score, based on cardiac index and LVEF, (3) right ventricular heart failure score based on PAM, TPG, PVR, ZVD, (4) systemic heart failure score based on sodium, heart rate, creatinine, peak VO2 and MAP and the factors patient’s age, AB0 and body surface. All patients registered in Germany in 1997 [N⫽889] were used as derivation set, the total German 1998 cohort [N⫽897] was used as validation set. Only the urgency score and the left ventricular heart failure score were found to be significantly associated with mortality and retained in the model, a summarizing index called German Transplant Society score (GTS) was then calculated. The GTS score enabled a discrimination between high, medium and low risk patients. Results from a Cox PH model showed that the addition of the GTS score significantly improved a prediction model based on the UNOS classess (p⫽0.037). The use of this continuous disease severity index based on 7 objective variables would allow a perfect patient’s ranking, thereby enabling an urgency driven allocation without the necessity to downweigh it by waiting time. 292 THE URGENT HEART SCHEME IN THE UK—THE FIRST TWO YEARS F.M. Seeney, R.L. Potter, Statistical Services, UK Transplant NHS, Bristol, United Kingdom Background: The UK operates urgent heart Schemes for adult and paediatric patients. These enable centres to register needy or rapidly deteriorating patients to receive priority over other more stable patients in the organ offering process. A summary of activity throughout the Schemes’ first two years of operation is presented. The Schemes: The Schemes were introduced on 1 April 1999 since when, donor hearts are offered preferentially to urgent heart patients. In any one year no more than 38 urgent adult registrations are permitted but there is no restriction on the number of paediatric registerations allowed. A centre is only allowed to register one adult and one paediatric patient as urgent at any one time. For every urgent heart transplant performed using an adult donor heart the transplanting centre must payback an adult heart into the donor pool before they can register their next adult urgent patient. Activity: In the first two years, 77 patients were registered for an urgent heart transplant: 33 adult and 44 paediatric. Only one centre used their full urgent adult quota for a year. 24 adult and 25 paediatric patients received an urgent heart transplant and 2 adult and 11 paediatric patients died on the urgent list before receiving a transplant. A further 7 adult and 8 paediatric patients were returned to the routine waiting list, generally because they were either unfit for transplant or had recovered sufficiently to no longer be considered urgent. A total of 90 donor hearts were offered to urgent patients. Many of these hearts, 44%, were declined as the donor was an unsuitable size for the urgent patient. A further 24% were

The Journal of Heart and Lung Transplantation January 2002 declined as the donor was unsuitable for other reasons such as, age, medical reasons and their past history. A payback was required, and made, for 17 of the urgent heart transplants; 10 were offered to the centres that donated the urgent hearts. Conclusions: Both Schemes appear to be working well with 73% of adult, and 57% of paediatric, urgent patients receiving an urgent heart transplant. The destination of payback hearts will continue to be monitored to ensure that donating centres are not disadvantaged by offering a heart for an urgent transplant. 293 THE SEROPOSITIVE DONOR HEART M.C. Deng,1 H. Hauff,2 S. Itescu,2 S. Taranto,3 B. Scully,1 R.S. Brown,4 J.M.A. Smits,5 N.M. Edwards,2 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY; 3OPTN, United Network for Organ Sharing, Richmond, VA; 4Center for Liver Disease and Transplantation, Columbia University, New York, NY; 5Eurotransplant International Foundation, Leiden, Netherlands Purpose: Donor heart acceptance criteria need to be continuously revised with respect to donor age, donor heart dysfunction, donor heart structural changes, donor malignancies and donor infection in order to responsibly increase the donor pool. In this context, we review available data on donor hepatitis B (HBV) and C virus (HCV) infection. Methods: We performed a retrospective query and analysis of all OPTN/UNOS data since 1994. Results: Based on the cumulative OPTN experience including the time period between 1994 and 1999 including 13,309 heart transplants, 37(0.3%) cardiac transplants were completed with HBsAg⫹ donor hearts, 363(2.7%) with anti-HBC positive donor organs, and 231(1.7%) with HCV ⫹ donor hearts. Conditioning on the assumption that the distribution of prognostic factors for survival is equal for the HBV/HCV positive and HBV/HCV negative subgroups, transplants performed with an anti HBC positive donor organ have a similar 5 year survival (66% versus 70%;P⫽ns), while transplants performed with an anti HCV positive donor organ have a lower 5 year survival (58% versus 68%;P⬍0.05). Conclusion: 1) Data with regard to pretransplantation heart failure risk profile are not available precluding exact conclusions with respect to the effect of the infection on outcome and should be collected in the future. 2) Currently, a practicable recommendation is the matched allocation of HBV and HCV positive donor organs and recipients. HBsAg-positive hearts, indicating active infection in the donor, could be considered for HBV positive recipients who should undergo HB immune globuline and lamivudine treatment. Donor hearts which are anti-HBcAg positive and thus indicate resolved HBV infection in the donor, could be considered for all HBV positive recipients as well as HBV negative high risk recipients who should undergo lamivudine treatment. Donor HCV positive organs could be used either for HCV positive recipients or for HCV negative recipients at high risk of dying from heart failure without transplantation. Interferon-2b/ribavirin therapy may be considered for these recipients. 294 HEPATITIS B CORE ANTIBODY BUT SURFACE ANTIGEN NEGATIVE DONORS REPRESENT A VIABLE THERAPEUTIC OPTION TO INCREASE AVAILABLE ORGANS FOR LUNG TRANSPLANT RECIPIENTS