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The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
tomatic surveillance ICA is performed in our institution. CTA is effective for the diagnosis of coronary disease in non-transplant patients, but few studies have been done after HT. Methods and Materials: 118 HT patients, 1 to 24 years post transplant (mean⫽12years SD⫾ 6) underwent retrospective ECG gated 64-slice CTA without the use of any beta-blockers to slow the heart rate. Fifteen coronary segments were analyzed and reported by an independent investigator blinded to the results of ICA. Results: CTA images were systematically analyzed for image quality and the presence of CAV. Despite a mean resting heart rate of 82 bpm SD⫾ 13 and body mass index of 27kg/m2 SD ⫾ 5, 81% of the CTA images were graded as excellent or satisfactory. The status of each of the 1755 segments assessed by CTA irrespective of the image quality was compared with the findings from ICA. CTA had sensitivity, specificity, positive and negative predictive values of 71%, 79%, 72% and 78% respectively for the detection of any CAV found by ICA. On a patient basis, CTA best performed in diagnosing CAV with more than 25% stenosis with sensitivity, specificity, positive and negative predictive values of 74%, 94%, 79%, and 92% respectively. None of the 61 patients with completely normal CTA had CAV on ICA. Non-coronary cardiac and non-cardiac abnormalities were identified in 18% and 14% of patients respectively. 83 (92%) out of 90 patients who responded to a patient survey preferred CTA to ICA as a screening test for CAV. Conclusions: The study shows that CTA compares favourably with ICA in detecting CAV in Heart Transplant recipients, and may be a preferable screening technique because of its non invasive nature, patient preference and yield of additional information.
rejection episodes within the first year. 19 patients without any pre-defined risk factors experienced late rejection. Conclusions: Even among a low-risk cohort, late ACR and AMR episodes are observed. The majority of late ACR episodes are not associated with HDC and are not predicted by traditional risk factors. Further work is needed to clarify the risk factors and clinical significance of late rejection. 130 Does a Sternal Sparring Surgical Approach in Lung Transplantation Improve Postoperative Respiratory Function? B. Sareyyupoglu, C. Bermudez, J.K. Bhama, N. Shigemura, T. Ota, K. Minakata, H. Shayan, A. Bansal, K. Fujimoto, K. Turhan, P. Bonde, J. Thacker, M.-H.T. Nguyen, Y. Toyoda. University of Pittsburgh Medical Center, Pittsburgh. Purpose: We aimed to evaluate the effect of a sternal sparring surgical approach on respiratory function after lung transplantation (LTx). Methods and Materials: Between January 2006 and December 2009, 320 consecutive patients underwent double LTx. Bilateral anteroaxillary approach was applied to 193 patients (group A) and clamshell approach to 127 (group B). Groups were compared peri-operatively.
129 Incidence and Predictors of Late Rejection after Cardiac Transplantation M.X. Pham,1,2 H. Wolters,3 D.A. Baran,4 R.C. Starling,5 J.J. Teuteberg,6 A.G. Kfoury,7 M.C. Deng,8 T.P. Capolla,9 A. Kao,10 A.S. Anderson,11 W.G. Cotts,12 G.A. Ewald,13 R.C. Bogaev,14 K. Shahzad,8 J.P. Yee,3 H.A. Valantine.2 1VA Palo Alto Health Care System, Palo Alto; 2 Stanford University Medical Center, Stanford; 3XDx, Brisbane; 4 Newark Beth Israel Medical Center, Newark; 5Cleveland Clinic, Cleveland; 6University of Pittsburgh Medical Center, Pittsburgh; 7 Intermountain Medical Center and Intermountain Healthcare, Salt Lake City; 8Columbia University Medical Center, New York; 9Hospital of the University of Pennsylvania, Philadelphia; 10Mid America Heart Institute, St. Luke’s Hospital, Kansas City; 11University of Chicago Medical Center, Chicago; 12Northwestern University, Chicago; 13 Washington University School of Medicine, St. Louis; 14Texas Heart Institute, Houston. Purpose: The risk of rejection after the first year post-transplant (late rejection) is thought to be low in the current era of immunosuppression. We sought to determine the incidence of biopsy-proven acute cellular rejection (ACR) and antibody-mediated rejection (AMR) in this period and to assess whether traditional risk factors can predict late rejection episodes. Methods and Materials: The IMAGE study enrolled 602 heart transplant recipients who were at low risk for rejection and compared endomyocardial biopsy (EMB) vs gene-expression profiling (GEP) for rejection monitoring. Patients were followed for a median of 19 months. We analyzed locally scored biopsy results from 564 patients who were ⱖ12 months posttransplant during the study. We defined rejection as either ACR of ISHLT Grade ⱕ2R or AMR of ISHLT Grade AMR1 in the presence of HDC. HDC required an LVEFⱕ30%, a proportional LVEF decrease of ⱖ25%, a CI⬍2.0 L/min/m2, or the use of inotropic drugs. Using published data, we pre-defined rejection risk factors as age ⬍35, African-American race, BMI ⬎35, or ⱖ2 rejections in the first year. Results: A total of 44/564 patients (7.8%) experienced late rejection at a median of 26 months (range 14-62) post-transplant. ACR was reported in 22 patients (7.7%) in the EMB arm and in 13 patients (4.6%) in the GEP arm. HDC was present in 11 patients (2%). AMR occurred in 5 patients (1.8%) in the EMB arm and in 10 patients (3.6%) in the GEP arm. Patients with late rejection were younger compared to non-rejectors (mean age 47 vs 55, P⬍0.01), but there were no significant differences in gender, CMV status, pre-transplant VAD use, induction therapy use, BMI, or number of
Results: Sixty-seven percent of patients were extubated in less than 48 hours in Group A vs. 39% in Group B (p⬍0.001), while 36% in group B required prolonged intubation (⬎5 days) vs. 15% in group A (p⬍0.001). At six-months post LTx, for Group A vs. Group B, FVC was 73% vs 67% (p⫽0.025), FEV1 was 84% vs. 77% (p⫽0.013), and FEF25-75% was 105 vs. 91% (p⫽0.022). There was no significant difference in graft survival between surgical approaches.
Conclusions: A sternal sparring approach for double LTX reduces the duration of mechanical ventilator support in the early postoperative period,
Abstracts results in shorter hospitalization, and affords improved respiratory function at short term follow up. 131 The Role of Open Lung Biopsy in Lung-Transplant Recipients: Does the Establishment of Restrictive Allograft Syndrome (RAS) Change Practice? M. Sato, T.K. Waddell, D.M. Hwang, C. Chaparro, L.G. Singer, M.A. Hutcheon, S. Keshavjee. The Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada. Purpose: Open lung biopsy (Bx) can cause significant morbidity. Restrictive allograft syndrome (RAS) is a novel form of chronic lung allograft dysfunction with characteristic interstitial inflammation and fibrosis. The purpose of the study is to review indications and outcomes of open Bx in the light of the clinical diagnosis of RAS. Methods and Materials: Patients who received bilateral lung or heart lung transplantation (Tx) from 1996 to 2010 were reviewed focusing on indications, complications, and outcomes of open lung Bx. Results: Among 560 patients, 33 underwent open Bx. 14 Bx were indicated secondary to early post-Tx complications (n⫽13) and esophageal cancer resection (n⫽1). Open Bx was primarily indicated for nodular lesions (n⫽4), early inexplicable graft dysfunction after Tx (n⫽2), and late graft dysfunction (respiratory exacerbation or failure inexplicable by rejection, infection, or typical BOS; n⫽13). All the nodular lesions reached diagnosis (2 PTLD, 1 abscess, 1 organized infarction) without complications. In contrast, all the Bx indicated for graft dysfunction revealed diffuse alveolar damage (DAD) without infection or rejection that explains the condition. As such, the Bx finding did not change patient management. Prolonged airleak or chest tube placement ⬎2 weeks was common among those who had late graft dysfunction (8/13 cases). Increased oxygen requirement or prolonged mechanical ventilation was documented in 5 cases. Applying the diagnostic criteria for RAS (decline in both FEV1⬍80% and total lung capacity (TLC) ⬍90% of baselines), 10/13 cases with late graft dysfunction were attributed to RAS; the other 3 showed radiographic characteristics of RAS although patients’ conditions limited access to TLC measurement to confirm the diagnosis. Conclusions: Open Bx was not useful in cases of respiratory failure clinically associated with RAS and was associated with high incidence of complications. Clinical diagnosis of RAS is likely to reduce open Bx in lung transplant recipients with graft dysfunction. 132
S51 CMV disease, relatively minor CMV antigenemia (⬍10/100,000 cells) was observed around the time of RAS onset in 3 mismatched patients and 9 non-mismatched patients. Despite successful treatment for CMV antigenemia in these cases, the disease condition of RAS progressed. Within the RAS group, “purely restrictive RAS” that did not accompany a decline in FEV1/ FVC ⬍80% of baseline (i.e. without obstructive component) showed an even higher ratio of primary CMV mismatch (12/27, 44%). Conclusions: CMV mismatch has significant association with RAS, particularly the purely restrictive form. Subclinical CMV infection may be an important contributing factor to RAS. 133 The Impact of Vaccination on Allosensitization in Candidates on the Lung Transplant Wait List G. Smith,1 J. Chu,1 L. Danziger-Isakov,2 R. Avery,2 D. Van Duin,2 E. Poggio,2 L. Klingman,2 M. Budev,2 K. McCurry,2 M. Askar.2 1 Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH; 2Cleveland Clinic, Cleveland, OH. Purpose: Although it is generally accepted that lung transplant recipients should receive a number of vaccines, the impact of vaccination on pretransplant allosenstitization remains unclear. In this study we investigate the changes in PRA%. Methods and Materials: We retrospectively correlated the changes in HLA antibody screening and identification results with vaccination dates in 209 prospective lung transplant recipient on the waitlist at our institute. These patients had a mean age of 55 yrs (range: 1 month - 75 yrs) and included 144 males, 64 females, 176 Caucasians, 11 AFAM, 21 others/unknown race. PRA% was based on flow PRA screening beads. Results: Twenty three out of 209 patients (11%) showed ⬎20% PRA increase, of those 11 (48%) were non-sensitized pre-vaccination (PRA ⬎ 10%). Only one patient showed increase in class II antibodies only while the remaining 22 patients showed increase in class I antibodies only. Distribution of these 23 patients based on the vaccine type and the prevaccination allosentization status is shown in the figure. The PRA% returned to base line in 9 of the 23 patients (39%) and that took 113 days on the average (range 16-247). Conclusions: Our results suggest that vaccination may be associated with increases in the allosensitization particularly class I HLA antibodies in prospective lung transplant recipients. A significant proportion of patients who show this increase maintain high levels of allosensitization. It appears that this association is not influenced by the pre-vaccination allosensitization or the type of the vaccine. The potential implications of these findings on the length of time to transplant and overall transplant outcomes warrant further studies.
Cytomegalovirus Primary Mismatch Increases the Risk of Restrictive Allograft Syndrome after Lung Transplantation M. Sato, S. Husain, T.K. Waddell, C. Chaparro, L.G. Singer, M.A. Hutcheon, S. Keshavjee. The Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada. Purpose: We have recently identified restrictive allograft syndrome (RAS), a novel form of chronic lung allograft dysfunction (CLAD) after lung transplantation characterized by restrictive physiology and peripheral lung inflammation/fibrosis. However, the cause of RAS is totally unknown. Since cytomegalovirus (CMV) is known to have immunomodulatory and profibrotic properties, we hypothesized that CMV infection contributes to the pathogenesis of RAS after lung transplantation. Methods and Materials: Donor-recipient CMV status and phenotypes of CLAD were examined among patients who received bilateral lung transplantation from January 1996 to March 2010 and survived more than 3 months (n⫽518). Among patients with CLAD (FEV1⬍80% baseline), RAS was defined by an irreversible decline in total lung capacity ⬍90% of baseline. BOS was defined by CLAD without RAS. A chi-square test was used to compare among groups. Results: The phenotypes of BOS, RAS and no CLAD were observed in 151, 48, 319 patients, respectively by the end of observation (September, 2010). CMV donor(⫹) recipient(⫺) mismatch was observed more frequently in the RAS group (14/48(29%) vs. BOS, 22/151(15%), no CLAD, 57/319(18%); P ⫽ 0.009). Although none of these RAS patients showed clinically evident
134 The Phenotype of Chronic Lung Allograft Dysfunction (CLAD) Determines Survival R. Vos,1 G.M. Verleden,1 S.E. Verleden,2 S. De Vleeschauwer,2 D. Van Raemdonck,1 L.J. Dupont,1 B. Vanaudenaerde.2 1Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium; 2Lab of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium. Purpose: CLAD remains the most important cause of late mortality after lung transplantation (LTx). Our aim was to investigate several clinical,