The Journal of Heart and Lung Transplantation Volume 20, Number 2
Abstracts
268 NITRIC OXIDE INHALATION MODULATES ENDOTHELIN-1 AND BIG ENDOTHELIN-1 AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION F.D. Wagner1, S. Buz1, C. Knosalla1, M. Loebe1, R. Hetzer1, B. Hocher2; 1Deutsches Herzzentrum Berlin, Berlin, Germany; 2 Charite, Berlin, Germany Purpose: Nitric oxide inhalation therapy is now an established therapy in the treatment of right ventricular dysfunction due to pulmonary hypertension after left ventricular assist device (LVAD) implantation. Inhaled nitric oxide (iNO) decreases right ventricular afterload by its selective vasodilating effect on the pulmonary circulation. It is known that endothelin-1 (ET-1) contributes to pulmonary hypertension. The effects of iNO on circulating ET-1 and big endothelin (big ET-1) in LVAD-patients were investigated in this study. Methods: On weaning from cardiopulmonary bypass (CPB) 15 consecutive patients were treated with iNO because of right ventricular compromise secondary to pulmonary hypertension. Plasma ET-1 and big ET-1 concentrations were measured preoperatively, on CPB prior to iNO, 12, 24, and 48 hrs. postoperatively, as well as 72 hrs after cessation of iNO. Results: Mean initial iNO dose was 33 ppm (20-40 ppm). NO therapy was successfully weaned in all patients without a rebound phenomenon. ET-1 and big ET-1 were increased preoperatively (1.50 ⫹/- 1.9 and 3.87 ⫹/- 3.0 fmol/ml, respectively). ET-1 concentrations were highest on cardiopulmonary bypass (2.00⫹/1.56 fmol/ml). ET-1 and big ET-1 decreased significantly during iNO therapy and were lowest 72 hrs after cessation of iNO (Table 1). The iNO dose and plasma ET-1 levels correlated significantly (p⬍0.001). A significant correlation was also found between ET-1 and PA-pressures, PVR and PVR/SVR ratio, but not with CI and SVR. Conclusion: Since it is known, that ET-1 mediates pulmonary hypertension, we suggest a two-fold effect of iNO therapy: first a selective vasodilation of the pulmonary vasculature and second NO-mediated inhibition of one of the most potent vasoconstrictors of pulmonary vessels: ET-1. Table 1
ET-1 fmol/mL Big ET-1 fmol/mL
12h
24h
48h
72h post iNO
1.5⫹/-1.4 5.3⫹/-5.5
1.3⫹/-1.6 3.7⫹/-2.0
1.1⫹/-1.2 3.6⫹/-2.9
0.7⫹/-0.4 2.2⫹/-0.8
269 LVAD THERAPY IMPROVES UTILIZATION OF DONOR HEARTS: IMPLICATIONS FOR PROLONGED INOTROPIC THERAPY K. Aaronson, M. Eppinger, S. Wright, F.D. Pagani; University of Michigan, Ann Arbor, MI, USA Background: It is generally accepted that LVAD therapy improves post-transplant survival. However, the risk of LVAD implant generally discourages its use in favor of prolonged inotropic therapy. Methods: We investigated the impact of LVAD therapy on heart transplant outcomes in adult patients (age ⱖ 17 years) from January 1, 1995 to October 1, 2000. Sixty-two patients underwent LVAD implant as a bridge to transplant (TX). Survival (KM) for 50 patients with outcomes (death or TX) was calculated from the
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time of LVAD implant or time of TX and compared to survival for 29 patients who underwent TX with inotropic therapy (UNOS status 1,1A,1B), and 82 who underwent TX as UNOS status 2. Results: TX survival in patients with prior LVAD support was superior compared to survival in patients undergoing TX as UNOS status 1 with inotropic therapy or as UNOS status 2 (see Table; ( ) - no. at risk). Survival from the time of LVAD implant (includes TX operation) was equivalent to survival for patients undergoing TX as UNOS status I with inotropic therapy. Conclusions: Long-term survival in patients undergoing LVAD therapy from the time of LVAD implant was equivalent to survival of patients undergoing TX as UNOS status 1 with inotropic therapy from the time of transplant. However, there were fewer transplant deaths in patients receiving LVAD therapy. LVAD therapy yields similar long-term survival with conservation of donor hearts. Given the critical shortage of donor organs, LVAD therapy as opposed to prolonged inotropic therapy may be preferential. Group
1 Year
3 Year
5 Year
Survival for Status 1 with LVAD from TX Survival for Status 1 with LVAD from LVAD Implant Survival for Status 1 with Inotropic therapy from TX Survival for Status 2 from TX
95%(31)
92% (6)
92%(1)
80%(29)
77% (8)
77%(1)
78%(14)
78% (8)
78%(4)
86%(66)
78%(35)
72%(8)
270 LVAD BLOOD STREAM INFECTION: THERAPEUTIC RATIONALE FOR TRANSPLANTATION R.S. Poston, D.N. Sorce, S. Husain, E.A. Stanford, S. Winowich, S. Kusne, B.P. Griffith, R.L. Kormos; University of Pittsburgh, Pittsburgh, PA, USA Blood stream infections (BSI) in VADpatients have a reportedly high mortality. UNOS currently grants 1a status to these patients, although reports of poor outcome following heart transplantation (HTrx) raises concerns about organ utilization. A predictor of mortality might be the inability to clear BSI prior to HTrx. Of the 146 patients who received a VAD implant, (1987-2000), 103 (71%) received a HTrx. The medical records of 21 (20%) with BSI prior to HTrx were retrospectively reviewed. Ten had definitive VAD infection (explanted pump cultures positive, Grp I), and 11 had only presumed VAD infection (bacteremia with negative pump cultures at explant Grp II). Grp I infection was associated with an 80% rate of persistent bacteremia at transplant with 30-day 1 year mortality rates of 20 and 40%, respectively. Grp II showed persistent bacteremia in 18% with a 30-day and 1 year mortality rate of 9% each. Grp I vs grp II patients had greater malnutrition (pre-VAD albumin 2.9⫹/-0.5 vs 3.3⫹/-0.8, p⬍0.05). The post-HTrx morbidity in Grp I was higher with longer post-HTrx intubation (9⫹/-11.2 vs. 3.6⫹/-5.5 days) and a greater rise in creatinine over the first postoperative week (1.5⫹/-1.0 vs. 0.22⫹/-0.3 mg/dl). No difference was seen in blood loss (2471⫹/-1310 vs. 2005⫹/-2548 cc), transfusion requirements (PRBC 1487⫹/-1012 vs. 1788⫹/-1701 cc; FFP 1714⫹/-1455 vs. 1333⫹/-1007; platelets 329⫹/-192 vs. 359⫹/-201 cc) or need for inotropic support. Although triple therapy (CSA/FK, prednisone, Imuran/Cellcept) was used in only 2/10 patients in Grp I vs. 6/11 in Grp II, there was no difference in the number of grade 2 or 3 rejections (0.45 vs. 0.91 events/year). Postoperative infections were common, but infection with the preoperative blood stream
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Abstracts
organism occurred in only 1 patient per group. The mortality and morbidity of pump explantation and urgent HTrx following VAD infection is great. These data suggest that a subgroup of VAD patients with BSI may be managed medically prior to HTrx with an acceptable outcome. 271 CHANGES IN THE SOLID ORGAN DONOR POOL AND THE EFFECT ON CARDIOTHORACIC DONATION? F.M. Seeney, M.A. Belger, F.C. Fordham; UK Transplant, Bristol, United Kingdom Background During the 1990’s the numbers of heart beating cadaveric solid organ and cardiothoracic donors have declined. Until recently fluctuations in the number of solid organ and cardiothoracic donors have mirrored each other. This study aimed to identify factors that influenced the probability of a solid organ donor donating cardiothoracic organs. Methods Data on 8442 adult heart beating cadaveric solid organ donors in the UK and Republic of Ireland during 1 January 1990 to 30 June 2000 were analysed. Logistic regression was used to assess the influence of donation year and zone, donor age, cause of death and blood group on the probability that a solid organ donor would become a cardiothoracic donor. Results In the first half of 1999 there were 344 solid organ and 129 cardiothoracic donors, this increased in the second half by 10% to 381and by 9% to 180, respectively. In the next 6 months solid organ donors remained stable, 379, but cardiothoracic declined by 10% to 162. In 1990 40% of solid organ donors provided cardiothoracic organs but this has steadily decreased to 34% in the first half of 2000. All factors investigated were found to be significant. Donors from road traffic accidents (RTAs) were more likely to donate cardiothoracic organs than those dying from cerebrovascular accidents (CVAs). Donor numbers from RTAs declined from 93 in the first half of 1990 to 43 in 2000 and from CVAs increased from 216 to 255. Proportionally fewer RTA donors provided cardiothoracic organs; 58% in 1990, 44% in 2000. Older solid organ donors were less likely to donate cardiothoracic organs than younger ones. Donors aged over 50 now constitute 19% of cardiothoracic donors compared with 2% in 1990. Conclusion Cardiothoracic organs are more likely to be retrieved from young RTA donors than any other group. This is a reducing donor pool as the median age of solid organ donors increases and fewer deaths occur from RTAs. Increased deaths from CVAs have recently helped maintain solid organ donor numbers but these donors are not always suitable as cardiothoracic donors due to the nature of their death. 272 PREDICTORS OF DEATH ON THE UNOS LUNG TRANSPLANT WAITING LIST: RESULTS OF A MULTIVARIATE ANALYSIS T.M. Egan1, L.E. Bennett2, E.R. Garrity3, F.L. Grover4, W.S. Ring5, R.C. Robbins6, E. Trulock7, D.E. Wood8; 1University of North Carolina, Chapel Hill, NC; 2UNOS, Richmond, VA; 3 Loyola University, Maywood, IL; 4University of Colorado, Boulder, CO; 5University of Texas Southwestern, Dallas, TX; 6 Stanford University, Stanford, CA; 7Washington University, St. Louis, MO; 8University of Washington, Seattle, WA, USA
The Journal of Heart and Lung Transplantation February 2001 We sought to determine whether data collected at the time of listing patients (pts) for lung transplantation (LTX) with UNOS was useful in predicting the risk of death on the waiting list. Data on pts added to the UNOS LTX list over the two years between 1/1/97 and 12/31/98 (n⫽3104) with the following diagnoses: COPD/alpha 1-antitrypsin deficiency (EMP) (n⫽1461), cystic fibrosis (CF) (n⫽708), idiopathic pulmonary fibrosis (IPF) (n⫽608), or primary pulmonary hypertension (PPH) (n⫽327) were analyzed in August 2000. A Cox proportional hazards regression model was fitted for each diagnosis using death on the waiting list as the outcome. 30 variables collected at the time of listing from the candidate registration form were considered for inclusion in each model. Variables were demographic (age, height, weight, body mass index [BMI]), hemodynamic (PA systolic, diastolic, mean, CO, wedge), pulmonary function (% predicted FVC, FEV-1) or clinical (eg, in hospital or ICU at time of listing, functional status, etc.). A p value ⬍0.05 was considered significant. Death on the LTX waiting list occurred in 202 IPF pts (33%), 99 PPH pts (30%), 198 CF pts (28%), but only 201 EMP pts (13.8%). The percentage of pts who died within 1 or 2 years of listing differed significantly among diagnoses (p⬍0.001). Being in ICU or in hospital at the time of listing was a significant predictor of death for all 4 diagnoses, but the number of pts was relatively small (n⫽180). Factors that were significant predictors of death, by diagnosis category, are as follows: for EMP pts: lower % predicted FEV-1, lower BMI, higher PA diastolic pressure, older age; for CF pts: presence of diabetes, lower % predicted FVC, higher O2 requirement at rest, decreasing height; for IPF pts: lower % predicted FVC, older age, higher PA systolic; for PPH pts: no physiologic data was predictive of death. In the multivariate models, % predicted FEV-1 at the time of listing was not predictive of death in CF pts, and extent of pulmonary hypertension was also not predictive of death in PPH pts. The probability of death for patients listed for LTX in the US differs depending on the diagnosis. We identified clinical, hemodynamic and pulmonary function factors that are predictive of the probability of death for pts with EMP, CF and IPF. These probability functions may be useful to develop a revised donor distribution algorithm that may reduce the number of deaths on the UNOS LTX waiting list. 273 THE IMPACT OF CHANGES IN RADIOGRAPHIC ABNORMALITIES IN ORGAN DONORS ON SUCCESSFUL LUNG DONATION M. McCowin1, T.S. Hall1, W. Babcock2, L.L. Solinger2, K.W. Hall1, D. Jablons1; 1University of California at San Francisco, San Francisco, CA; 2CTDN, San Francisco, CA, USA Objective The study purpose was to determine the impact of thoracic radiographic abnormalities on successful lung donation in a large study group. Methods 110 potential lung donors were evaluated. 417 chest radiographs taken during the initial 24 hours after admission and prior to organ harvest were evaluated for 9 radiographic criteria and radiographic diagnoses. Clinical characteristics and organ procurement were evaluated from hospital records and UNOS database. Results Initial lung densities were present in 38% of right and 36% of left lungs. During the evaluation period (mean 69.7⫹ 60 hours) 38% of right lungs and 28% left lungs improved radiographically. Up to 62% of initial infiltrates completely resolved.