Expanding the donor pool: successful use of marginal donor lungs with a history of smoking

S130

Abstracts

diferences concerning any other clinical and laboratorial variables. Adverse symptoms were: headache (7%), sustained ventricular tachycardia (2%), dizziness(2%), fever (2%), thoracic pain (2%), unstable angina (2%), hemoptysis (2%), and phlebitis (4%). Conclusion: Our findings make LEVO an attractive option to treat CHF pts needing in inotropic drugs. The basal SSBP is associated with LEVO treatment efficacy. The lackness of response to LEVO is a marker of worse prognosis in CHF. 260 DECREASE OF WAITING LIST MORTALITY IN CARDIAC TRANSPLANTATION THOUGH TRANSPLANT NUMBERS ARE DROPPING. THE IMPACT OF OPTIMAL BRIDGING A. Mu ¨ hlbauer,1 A. Zuckermann,1 A. Bohdjalian,1 G. Wieselthaler,1 E. Wolner,1 M. Grimm,1 1Dept. of Cardio-Thoracic Surgery, University of Vienna, Vienna, Vienna, Austria Purpose: Transplant numbers have dropped markedly during the last years. Therefor the danger of increased waiting list mortality is obvious. The aim of the study was to examine incidence and cause of death on the waiting list and potential impact of different bridging therapies over the last decade. Procedures: Between 1992-2002 a total of 1065 patients (mean age 53.2 years, 15% females, 60% dil. CMP, 35% isch. CMP, 5% others) were put on the waiting list for cardiac transplantation. A total of 415 (39%) were bridged to transplantation (pharmacological: n ⫽ 199 (48%), AICD: n ⫽ 161 (39%) and mechanical: n ⫽ 55 (13%). Changes of waiting list mortality, causes of death, removal from the waiting list, transplant incidence and incidence of bridging amd bridging patterns were compared between two time periods: 1992-1997 and 1998-2002. Results: Waiting list mortality decreased significantly from 28% to 12% (p ⬍ 0.001) between the two time periods. While in the early time span 17% of listed patients died from SCD, these numbers dropped to 5% in the late period (p ⬍ 0.001). The risk of death from pump failure also decreased (8% to 2%; p ⫽ 0.002). Death from non cardiac reason has become the predominant cause of death (38%, p ⬍ 0.001). The number of bridged patients has markedly increased from 28% to 63% (p ⬍ 0.001). Within the group of bridged patients, assist devices underwent the biggest growth (7% vs. 19%, p ⬍ 0.01). Pharmacological bridging and AICD remained stable. The percentage of patients transplanted has remained stable (36% vs. 41%) while the total number of cardiac transplants (265 vs. 138) as well as patients put on the waiting list (732 vs. 333) and waiting time to transplantation (231 ⫾ 108 vs. 147 ⫾ 60, p ⬍ 0.01) has significantly decreased. Conclusion: Mortality on the waiting list for heart transplantation has decreased significantly although the total number of cardiac transplants has also dropped. Optimal bridging (pharmacological, mechanical and electrical) and heart failure therapy combined with a perfected local allocation system are responsible for this improvement. 261 ROLE OF LEFT VENTRCULAR ASSIST DEVICE FOR PATIENTS IN ACUTE MYOCARDIAL INFARCTION COMPLICATED BY CARDIOGENIC SHOCK S.J. Park,1 M. Colvin-Adams,2 S. Ormaza,3 K.K. Liao,3 R. Segurola,3 A. Boyle,2 L.W. Miller,2 1Joint Cardiac Program, California Pacific Medical Center, San Francisco, CA; 2Medicine, University of Minnesota, Minneapolis, MN; 3Surgery, University of Minnesota, Minneapolis, MN Purpose: The overall survival rate of patients who present with acute myocardial infarction (AMI) has improved over the years. Yet some of

The Journal of Heart and Lung Transplantation February 2004

patients face exceedingly high mortality, in excess of 50%, when AMI is associated with cardiogenic shock. We hypothesize that left ventricular assist device (LVAD) implantation in this high risk population could improve their survival. Procedure: We treated 27 patients who presented in profound cardiogenic shock following AMI during the past 8 years. Their mean age was 55.3 years. Twenty-three patients were male. Majority of the patients required 2–3 inotropes or vasoactive drugs. Intra-aortic balloon pump support was required in 100% of patients and 5 patient were supported on extra-corporeal membrane oxygenator. Twentytwo patients were supported with mechanical ventilator. All patients had diagnostic coronary angiography and 16/27 (60%) underwent percutaneous transcatheter angioplasty without improvement in their condition. Their mean pulmonary capillary wedge pressure was 26, cardiac index of 2.1 l/min, their mean systolic blood pressure was 85, and mean heart rate was 110 beats/min. Results: The survival following LVAD implantation was 78% (21/26). The mean from the time of acute myocardial infarction to the LVAD implant was about 4 days. Except for one patient who is still being supported on LVAD, 20 out of 21 survivors underwent heart transplantation after mean of 180 days support. Seventeen out of 20 patients are long-term survivors following heart transplantation. Conclusion: Patients who present in cardiogenic shock with AMI have exceedingly high mortality with conventional treatment. LVAD can implanted with acceptable operative mortality, despite a fresh infarction. The use of an LVAD in this setting can translate into good long-term survival for patients who otherwise would have had dismal prognosis. 262 EXPANDING THE DONOR POOL: SUCCESSFUL USE OF MARGINAL DONOR LUNGS WITH A HISTORY OF SMOKING J.C. Mullen,1 D.C. Lien,1 M.J. Bentley,1 K.B. Jackson,1 K.C. Stewart,1 P.J. Brown,1 H.A. Taskinen,1 D.L. Modry,1 1Lung Transplant Program, University of Alberta, Edmonton, AB, Canada Purpose: The purpose of this study was to evaluate the effect of donor smoking history on outcomes in lung transplantation. Methods: We retrospectively reviewed the results of 111 consecutive single and double lung transplants performed between January 2000 and August 2003 for whom donor smoking history was available. Living donor lung transplants and heart/lung transplants were excluded. Patients were grouped by pack-year smoking history. All prospective donors were free from significant respiratory symptoms or known respiratory disease. They were deemed to have acceptable chest radiographic findings, bronchoscopy findings, and oxygen challenges (PO2 measured on FiO2 ⫽ 1.0). Some marginal donors also underwent chest CT scans. Results: Variable

0

0–10

N Intubation Time (h) Intensive Care Unit Stay (d) Hospital Stay (d) Follow-up (m) 1y FEV1 (L) 1y FVC (L) 1y FEV1/FVC Ratio Actuarial Survival (30d) Actuarial Survival (1y)

50 144 ⫾ 49 11 ⫾ 2

32 302 ⫾ 145 12 ⫾ 3

11–20 15 54 ⫾ 18 8⫾3

>20 14 91 ⫾ 35 8⫾2

45 ⫾ 7 35 ⫾ 7 30 ⫾ 5 34 ⫾ 5 17 ⫾ 2 15 ⫾ 2 18 ⫾ 3 14 ⫾ 3 2.13 ⫾ 0.17 2.63 ⫾ 0.15 2.27 ⫾ 0.20 2.09 ⫾ 0.21 3.29 ⫾ 0.24 3.27 ⫾ 0.20 3.36 ⫾ 0.22 3.07 ⫾ 0.33 0.66 ⫾ 0.03 0.81 ⫾ 0.03 0.68 ⫾ 0.05 0.69 ⫾ 0.02 96% 90% 93% 100% 82%

87%

Column headings are reported in pack-years.

86%

100%

p – 0.8 0.9 0.6 0.7 0.4 0.9 0.4 0.5 0.5

The Journal of Heart and Lung Transplantation Volume 23, Number 2S

Conclusion: We demonstrated no significant effect of donor smoking history alone on early patient outcome provided that the donors were acceptable by other criteria. The decision to use these organs should be considered on a case-by-case basis, and these results suggest that smoking history alone should not rule out lung donation.

263 MULTI-FREQUENCY FORCED OSCILLATION TECHNIQUE [FOT] FOR ASSESSMENT OF LUNG ALLOGRAFT FUNCTION: A PILOT STUDY D.J. Ross,1 M.D. Goldman,2 R.M. Strieter,1 J.A. Belperio,1 A. Ardehali,3 1Medicine, UCLA, Los Angeles, CA; 2Medicine, King Drew/UCLA, Los Angeles, CA; 3Surgery, UCLA, Los Angeles, CA Introduction: The forced impulse oscillation technique [FOT] measures impedance of the respiratory system to forced acoustic oscillations. Resistance [Rrs; Normal: 1.8-3 cm H2O/L/s] and reactance [Xrs], the vector of elastic and inertial tissue forces, can be determined with 7-10% variability. Normative data exist for normal subjects, smokers and both healthy and asthmatic children. We postulate that FOT may allow enhanced discrimination of larger versus smaller airway dysfunction after LT. Methods: Prospective, cross-sectional pilot study of FOT in combination with spirometric and FOB assessments. A Jaeger IOS system allowed determination of Rrs; an integrated response index for reactance [AX; Normal: ⬍3 cm H20/L]; frequency dependence of resistance [f-d Rrs:Normal ⬍20%] and Resonant Frequency [Normal: ⬍12 hz]. Results: Eleven patients [SLT ⫽ 4, BLT ⫽ 7] between 6 weeks and 10 years post-LT. “Healthy” [N ⫽ 4] BLT had normal values for AX, Rrs and absent f-d Rrs. With ACR Grades 2-3 [N ⫽ 3], increased AX [6.0 ⫾ 2], Resonant Frequency [15.4 ⫾ 0.4] and evident f-d Rrs were observed. With BOS, an increased AX [7.3 ⫾ 0.4], Rrs [5.4 ⫾ 0.1], Resonant Frequency [15.7 ⫾ 0.4] and f-d Rrs were detected. Two patients with segmental bronchial strictures had increased resistance at all frequencies without f-d Rrs evident. SLT patients represented a hybrid airway physiology with abnormal values for Rrs, AX and Resonant Frequency. Conclusions: FOT spectral analyses suggest normal resistance and reactance for “healthy” lung allografts while abnormal measures of smaller airway function [AX, f-d Rrs] and Rrs in ACR and BOS. Bronchial strictures were distinctly evident by FOT and characterized by increased Rrs across all oscillation frequencies. We propose that serial mensuration by this easily performed and brief study (60 seconds) may enhance detection of airway complications or BOS after LT. A prospective study is in progress at our center.

264 DIFFERENTIAL GENE EXPRESSION PROFILING IN LUNG TRANSPLANT RECIPIENTS WITH CHRONIC REJECTION B.S. Lu,1 A.D. Yu,1 G.C. Cao,2 E.R. Garrity,1 W.T. Vigneswaran,3 S.M. Bhorade,1 1Pulmonary and Critical Care Medicine, Loyola University Medical Center, Maywood, IL; 2Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL; 3Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, IL Purpose: Chronic rejection, clinically manifested by bronchiolitis obliterans syndrome (BOS), is the leading cause of death after the first

Abstracts

S131

year of lung transplantation. To better understand the genetic markers that may be associated with BOS, we compared gene expression patterns of cytokines in lung transplant (LT) recipients with and without BOS. Methods: Six LT recipients with BOS were matched with six control LT recipients by underlying diagnosis and time from transplantation; none of the patients had documented infection or acute rejection. All LT recipients underwent bronchoscopy with bronchoalveolar lavage (BAL). BAL mRNA was isolated, purified and processed for hybridization with the SuperArray gene chip. Using microarray technology, gene expression profiles for 96 cytokines were determined. Gene expression values were normalized to GAPDH and analyzed by the unpaired Student’s t-test and randomization testing. Expression ratios were calculated by the mean of pairwise comparisons. Results: A total of 12/96 genes were differentially expressed between the two groups. The genes that were upregulated included T cell activators, regulators of interferon gamma production, and mesenchymal growth factors (IL-2, -4, -10, -12, -17, and TNF-␣) (p ⬍ 0.05). FGF 11 and 20 were downregulated (p ⬍ 0.05) in LT recipients with BOS. Specifically, IL-4, -12, -17, and TNF-␣ showed a greater than two-fold increase while FGF 11 showed a greater than two-fold decrease in expression. Conclusion: Using a novel approach we were able to identify a differential expression pattern of cytokines in LT recipients with BOS compared with control LT recipients. This study provides the first microarray analysis of gene expression of cytokines in lung transplant recipients with chronic rejection. Further evaluation of the function of these particular genes may provide further insight into the pathogenesis of chronic rejection.

265 DONOR CAUSE OF DEATH DOES NOT INFLUENCE MID-TERM SURVIVAL IN LUNG TRANSPLANT RECIPIENTS J.S. Ganesh,1 C.A. Rogers,1 N.R. Banner,1 R.S. Bonser,1 1On Behalf of the Steering Group, UK Cardiothoracic Transplant Audit, Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, United Kingdom Non-traumatic brainstem death may be a risk factor for bronchiolitis obliterans syndrome following lung transplantation (LTx). The influence of donor cause of death (DCD) on medium post-transplant survival is unknown. This was investigated using data from a national prospective cohort study of adult single and bilateral LTx undertaken between July 1995 and June 2002. DCD was categorised a priori into: vascular and tumour (V), traumatic (T), hypoxic brain damage (H) and infective (I) causes. All T donors resulted from blunt trauma. Risk factors for 3-year mortality were identified using Cox regression analysis. Of 552 eligible transplants DCD was classified V (357), T (143), H (35) and I (17). V donors were older (median 42 years) than others (medians ⬍27 years) (p ⬍ 0.001). T donors were more likely to be of male gender (p ⬍ 0.001). Overall, 207 patients died within 3 years of surgery. The median follow up time of survivors was 1.9 years. Unadjusted 3-year Kaplan-Meier survival curves did not vary with DCD (p ⫽ 0.8). Cox analysis identified recipient diagnosis (p ⫽ 0.01), CMV mismatch (p ⫽ 0.04), donor diabetes (p ⫽ 0.03), and donor age group (p ⫽ 0.05) as predictors of mortality. After adjustment for these risk factors, DCD was not identified as a predictor of mid-term mortality in LTx recipients (p ⫽ 0.79). Although DCD may be a risk factor for late complications following LTx it does not affect mid-term survival. This finding may be attributable to the absence of gun shot wounds to