(558). Higher Rate of Hospitalizations for Infection and Cancer Than. Rejection in Low Risk Heart Transplant Patients Followed by Gene. Expression Profiling.
S208
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
However, the influence of BMI on results of heart transplant in LVAD-BTT pts is unclear. We analyzed a contemporary cohort of LVAD-BTT candidates undergoing OHT to determine influence of BMI on early and late survival. Methods: Patients (n= 2200) with an LVAD undergoing heart transplant between 2009 -2014 were stratified into four categories according to their BMI at listing. Adjusted Cox proportional hazards analysis was performed to determine difference in survival between groups. Results: In the five-year study period, normal (26%), overweight (37%), moderately obese (26%), and severely obese (9.6%) underwent heart transplant. Severely obese category patients were more often younger (mean 49 vs 53 yrs), diabetic (38% vs 17%), African Americans (35% vs 20%) and had dilated cardiomyopathy (47% vs 36%). Severely obese recipients were transplanted more as status 1A (46% vs 37%) with longer status 1A time (median 39 vs 28 days). While post-transplant mortality was comparable (4.2 vs 2.7%; p = 0.38). One-year survival was 92 % and 87% in the normal and severely obese categories (p 60 years old) and BMI (> 30 kg/m2) have been associated with increased mortality after heart transplantation. We explored the relationship between these recipient variables and indices of coronary microvascular health in the early post-transplant period. Methods: In the Angiotensin Converting Enzyme Inhibition and Cardiac Allograft Vasculopathy Trial, fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were measured at 4-6 weeks and 1-year post-transplant in 48 recipients. We explored the relationship between these indices and recipient age and BMI. Results: Increased recipient age and BMI prior to transplant were significantly associated with an increase in IMR at 1-year after transplant, p= 0.0031 and p= 0.05 respectively. Recipient age did not show any correlation with FFR (p= 0.66) or CFR (p= 0.52) at 1-year. Similarly, recipient BMI prior to transplant did not have any association with FFR (p= 0.61) or CFR (P= 0.78) at 1-year after transplant. Conclusion: Increased age and BMI of the recipient were associated with microcirculatory remodeling, as shown by an increase in IMR at 1-year after transplant. However, age and BMI did not show any association with modifications in the functionality of the vessels, as there was no association with FFR and CFR measurements. Further investigation should be made into how various recipient risk factors contribute to microcirculatory modification of the donated heart following transplant.
5( 57) Clinical Implication of Non-Complement-Binding De Novo DonorSpecific Anti-HLA Antibodies in Heart Transplant Recipients: Do We Really Have to Care All the DSA Positive Patients? T. Sato ,1 O. Seguchi,1 Y. Kanaumi,2 M. Yanase,1 N. Okada,1 K. Kuroda,1 E. Hisamatsu,1 H. Sunami,1 S. Nakajima,1 H. Hata,3 T. Fujita,3 H. Ishibashi-Ueda,4 N. Fukushima,1 J. Kobayashi,3 T. Nakatani.1 1Transplantation, National Cardiovascular Center, Osaka, Japan; 2Transfusion Medicine, National Cardiovascular Center, Osaka, Japan; 3Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan; 4Pathology, National Cardiovascular Center, Osaka, Japan. Purpose: The development of de novo human leukocyte antigen (HLA) donor specific antibodies (DSA), detected by both cytotoxic or solid phase assays, was considered the major risk factor for cardiac graft failure in heart transplantation.However, it was shown that not all patients with persistent production of DSA suffered loss of their allografts. The ability to activate complement may be an important factor differentiating clinically relevant DSA from non- relevant DSA. Recently, a C1q-binding assay (C1qScreen; One Lambda, Inc. Canoga Park, CA) has been developed to identify complement-fixing HLA antibodies with high sensitivity and specificity.The aim of this study was to investigate the association between C1q-binding ability of HLA-DSA and the clinical outcomes post-transplant to identify clinically significant de novo DSA in heart transplantation. Methods: We enrolled 64 consecutive patients who received heart transplant between May 1999 and January 2015 in our institute. Sixty of 64 patients (93.7%) were screened for the presence of circulating DSA using Luminex Single Antigen Flow Bead assays between June 2014 and August 2015, and patients with post-transplant DSA with mean fluorescence intensity (MFI) > 500 were selected to assess C1q fixation by C1q-binding assays. The clinical outcomes were compared with the results. Results: Of 60 patients, twelve patients were considered as DSA positive (MFI> 500, range 698-5952, class 1: 75% class 2: 17%, class1+2:8%). All of these patients were identified as C1q negative. As the results, we divided all patients into two groups; group DSA+, C1q- (n= 12) and group DSA(n= 48). Rejection episodes, development of cardiac graft vasculopathy, cardiac function (EF, BNP), cardiac event-free survival and overall mortality were not statistically different between the two groups. Conclusion: Patients producing C1q-negative DSA had good graft survival, which was comparable to that of DSA negative patients. Adding the assessment of the complement-binding capacity of DSA might redefine the traditional risk stratification of de novo DSA positive patients. 5( 58) Higher Rate of Hospitalizations for Infection and Cancer Than Rejection in Low Risk Heart Transplant Patients Followed by Gene Expression Profiling J.J. Teuteberg ,1 M.A. Shullo,1 P.J. Berman,2 N. Haglund,3 M.A. Wigger,3 G.A. Ewald.4 1University of Pittsburgh, Pittsburgh, PA; 2Tampa General Hospital, Tampa, FL; 3Vanderbilt University, Nashville, TN; 4Washington University, St. Louis, MO. Purpose: The Outcomes AlloMap® Registry (OAR) is a registry for heart transplant patients (HTX) being managed with gene-expression profiling (GEP) allowing insights into the real-world long-term outcomes of patients managed with GEP. Methods: Between 4/2013 and 10/2016, 596 HTX from 20 United States centers who underwent GEP testing as part of standard of care rejection surveillance were enrolled in this prospective, observational, ongoing registry. Study data were collected using a secure, web-based, electronic data capture system. Results: In all, 73% (427) male and 27% (157) female underwent 2171 clinical surveillance visits. The median time of visits was 10 months post transplant (6-18, 25-75% quartile). Baseline demographics were: 74% white, 18% black. CMV serology was D+/R+ (34%), D-/R+ (25%), D-/R- (22%), D+/R- (19%). Of 947 endomyocardial biopsies performed, only 2% were locally graded as acute cellular rejections (ACR) ≥ 2R (Table). At the time of ≥ 2R ACR, the median GEP score was higher [32 (29-37)] compared to the median GEP without rejection [29 (25-33)], P= 0.009. Interval hospitalization
Abstracts S209 was reported in 182 cases (42 infections, 4 ACR, 2 AMR, 2 graft dysfunction and 132 “other reasons”). 7 deaths and 2 cardiac re-transplantations were reported and 19 patients were diagnosed with cancer. In patients who were hospitalized for infections, the median GEP score was higher [32 (26-35)] than the median of GEP without hospitalization for infections [29 (24-32)], P= 0.028. Conclusion: Patients in the OAR have a higher incidence of hospitalization for infections and new diagnoses of cancer than ACR. The association between higher GEP scores and infections was unexpected and is under further investigation. Number of visits with ≥ 2R acute cellular rejections Interval post-transplant
2R
3R
Total number of study visits
2-6 months, n 7-12 months, n 13-36 months, n > 36 months, n Total, n
6 7 3 0 16
1 1 1 0 3
562 807 658 144 2171
5( 59) Evaluation of Left Ventricular Myocardial Mechanics in Heart Transplant Recipients Using Three-Dimensional Speckle Tracking Echocardiography A. Assabiny , A. Kovacs, A. Kosztin, B.F. Farkas, M. Tokodi, B. Sax, B. Merkely. Heart and Vascular Center, Semmelweis University, Budapest, Hungary. Purpose: Speckle-tracking echocardiography is a novel imaging technique to describe myocardial deformation. Derived parameters have been proven to be useful in the early detection of myocardial dysfunction in several cardiac pathologies. Current echocardiographical parameters are not sensitive enough to predict rejection in cardiac transplant recipients. Deformation imaging may possibly allow identification of subclinical dysfunction associated with allograft rejection. In order to gain insight into deformation characteristics of allograft rejection, we first aimed to evaluate complex 3D deformation of the left ventricle in patients after cardiac transplant (HTX) and compare them to healthy volunteers. Methods: Twenty-four HTX patients (mean age 54±14 years, with a median of 366 days after HTX) were enrolled and compared to 17 age- and gender matched healthy volunteers. Patients with acute allograft rejection were excluded (latest endomyocardial biopsy ISHLT Grade 0R). Beyond standard echocardiographic protocol, we acquired 3D datasets from apical view using multi-beat reconstruction from 4 or 6 cardiac cycles. Using a dedicated software for left ventricular (LV) quantification (4D LV-Function 3) ejection fraction (EF) was measured. Global longitudinal (GLS) and circumferential (GCS) strain were quantified by 3D speckle tracking analysis. Systolic dyssynchrony index (SDI) derived from 16 subvolumes of the LV was also assessed. Results: According to the 3D measurements EF was similar in the two groups (HTX vs control: 62±8 vs 64±4 %). GCS did not differ between groups (GCS: -30±7 vs -31±4 %) but GLS was significantly decreased in HTX patients compared to controls (-18±4 vs -21±1%, p
