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77: Donor-Specific Antibodies Correlate with Rejection in Heart Transplant Patients
S92
Abstracts
76 Obesity Confers Protection from Cardiac Allograft Vasculopathy? A. Ankrom1, J. Patel1, E. Shao1, S. Carr1, M. Kawano1, M. Kittleson1, K. Kiyosaki1, J. Moriguchi, A. Ardehali2, J. Kobashigawa1 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2David Geffen School of Medicine at UCLA, Los Angeles, CA Purpose: There is conflicting evidence on the role of obesity in the development of cardiac allograft vasculopathy (CAV) post heart transplant. Some studies indicate that obesity with body mass index (BMI) ⬎ 30 kg/m2 is associated with an increased incidence of cardiac allograft vasculopathy (CAV) but other studies have not confirmed this observation. The purpose of this single center observational study was to examine the impact of obesity on the development of CAV. Methods and Materials: Between 1994 and 2008, 75 pts who underwent heart transplant were obese, defined as a pre-transplant BMI ⱖ30 kg/m2 . These patients were compared with 714 nonobese patients with BMI ⬍30 kg/m2. Outcomes for a high obesity group, defined as BMI ⬎ 33 kg/m2 (N ⫽ 19), were also assessed. Outcomes included 5-year survival, 5-year CAV (angiographic stenosis -⬎ 30%), 5-year non-fatal major adverse cardiac events (NF-MACE; myocardial infarction, heart failure, percutaneous intervention, stroke, peripheral vascular disease), and 1-year treated rejection. Results: The incidence of diabetes was comparable between the obese and nonobese patients(31.3% vs. 21.5%, p⫽NS). 5-year survival and NF-MACE were similar between obese and nonobese patients (74.7% vs. 77.9%, p⫽0.48 and 89.3% vs. 93.0%, p⫽0.19, respectively). First-year any-treated rejection was also similar between the two groups (90.7% vs. 90.2%, p⫽0.93). However, freedom from CAV was significantly higher in the obese group compared to the nonobese group (90.7% vs. 77.3%, p⫽0.015). The high obesity group yielded similar results: patients with BMI ⬎ 33 kg/m2 had greater freedom from CAV compared to controls (100.0% vs. 78.1%, p⫽0.037). Conclusions: Obese patients with BMI ⬎30 kg/m2 have less CAV five years after heart transplantation with comparable survival to nonobese patients. Freedom from CAV is also an apparent benefit of highly obese patients (BMI ⱖ 33 kg/m2). The mechanism of the basis of this observation requires further investigation. 77 Donor-Specific Antibodies Correlate with Rejection in Heart Transplant Patients N. Patel, B. Pavlovic-Surjancev, J. Sinacore, B. Susskind, N. Neuswanger, T. Dasari, A. Heroux Loyola University Medical Center, Maywood, IL Purpose: Antibodies (abs) against Human Leukocyte Antigens (HLA) in heart transplant (HTx) patients (pts) are associated with poor outcome. Panel Reactive Abs (PRA) are nonspecific abs against class I and class II HLA. Luminex technology detects and quantifies abs against donor HLA-Donor Specific Ab (DSA). Experience with DSA in HTx pts is limited. We tested correlation of DSA with episodes of suspected rejection in HTx pts with elevated PRA. Methods and Materials: Patients with HTx done between 1984 and 2008 who had PRA drawn between Mar 06 and Sep 08 were included. PRA was done either related or unrelated to episode of rejection. Rejection was based on clinical suspicion or echocardiographic criteria. PRA blood samples were further tested for DSA, based on the clinician’s decision. To reduce bias that could occur with analysis of multiple samples from one pt, we included only one sample per pt, with highest PRA % (either class I or class II). Pts were divided in two groups: PRA ⱖ 10% (High) and PRA ⬍10% (Low). Low level DSA was defined as ⬍100,000 Molecules of Equivalent Soluble Fluorescence units (MESF).
The Journal of Heart and Lung Transplantation February 2009
Results: Among 140 pts, 42 pts had PRA ⱖ10% (30%) and 98 pts had PRA ⬍10% (70%). High PRA group: Among 42 pts, 17 had rejection (42%). 79% of pts with rejection had positive (pos) DSA. 25 pts did not have rejection. 21% of pts without rejection had pos DSA (all had low level). Low PRA group: Among 98 pts, 8 had rejection (8%). 17% of pts with rejection had pos DSA. 90 pts did not have rejection. 17% of pts without rejection had pos DSA (2 had low level). There were more rejection episodes in high PRA group (n⫽17) compared to low PRA Group (n⫽8) (p⬍0.05). Association of rejection and pos DSA was significant in high PRA group by Pearson Chi-square test (OR⫽13.4, p⬍0.05). Conclusions: Pts with PRAⱖ10% had more episode of rejection. Majority of pts hospitalized for suspected rejection (68%) had high-level positive DSA (52%) or cross-reactive ab to donor-specific ag (16%). There were more graft related deaths in pts with PRAⱖ10% and pos DSA. 78 Magnetic Resonance Imaging Correlates with Transcript Gene Expression in Cardiac Allograft Biopsies I. Paterson, B. Sis, D. Kim, J. Ezekowitz, J. Burton, W. Tymchak, M. Mengel, T. Mueller, P. Halloran University of Alberta, Edmonton, AB, Canada Purpose: T2 weighted imaging on magnetic resonance imaging (MRI) has been shown to predict ISHLT grading of allograft rejection. We sought to determine if MRI measures also correlated with transcript gene expression in cardiac allografts undergoing biopsy. Methods and Materials: Consecutive patients undergoing clinically indicated or routine biopsy were enrolled after obtaining informed consent. Biopsy specimens were analyzed with the Affymetrix microarray in addition to standard histopathologic analysis according to ISHLT 2005 rejection grading. A conventional cardiac MRI that included an assessment of left ventricular function and mass was performed within 24 hours of biopsy. A HASTE (dark blood) sequence with a variable echo time was used to quantify myocardial T2. Post-processing was performed by a reader blinded to the results of histology and gene expression. Results: 7 endomyocardial biopsies from 6 patients (4 male) were obtained. Mean patient age 59 ⫹/6 years and mean time from transplant 120⫹/-90days. ISHLT grade rejection was 0R in 2, 1R in 4 and 2R in 1 and 1 patient was suspected as having clinical rejection. MRI revealed a mean left ventricular (LV) EF of 60⫹/-9%, mean LV mass of 185⫹/-61g and a mean T2 of 57⫹/-5ms. No MRI measures correlated with histologic rejection (all p values were non-significant). Comparison between MRI measures and allograft gene expression revealed a significant correlation between myocardial T2 and inflammatory transcripts (cytotoxic T-cell and macrophage expression), R⫽ 0.86, P⬍0.05. Gene transcripts for myocardial injury and function also correlated with T2 on MRI, R⫽ 0.92 p⬍0.05, and, R⫽ -0.86 p⬍0.05, respectively. Similar correlations were also found for LV wall thickness and transcript gene expression. Conclusions: These preliminary results suggest that MRI measures of cardiac allograft rejection correlate well with transcript gene expression. However, in contrast to previous published reports, MRI seems less predictive of histopathology. 79 Implementation of Molecular Diagnostic Testing in the Early (2-6 Months) Post-Transplant Period T.M. Rowe1, A. Hicks2, H.J. Eisen3, J. Patel4, S.R. Hankins3 1 Hahnemann University Hospital, Philadelphia, PA; 2Drexel University College of Medicine, Philadelphia, PA; 3Drexel University College of Medicine, Philadelphia, PA; 4Drexel University, Philadelphia, PA
Abstracts
76 Obesity Confers Protection from Cardiac Allograft Vasculopathy? A. Ankrom1, J. Patel1, E. Shao1, S. Carr1, M. Kawano1, M. Kittleson1, K. Kiyosaki1, J. Moriguchi, A. Ardehali2, J. Kobashigawa1 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2David Geffen School of Medicine at UCLA, Los Angeles, CA Purpose: There is conflicting evidence on the role of obesity in the development of cardiac allograft vasculopathy (CAV) post heart transplant. Some studies indicate that obesity with body mass index (BMI) ⬎ 30 kg/m2 is associated with an increased incidence of cardiac allograft vasculopathy (CAV) but other studies have not confirmed this observation. The purpose of this single center observational study was to examine the impact of obesity on the development of CAV. Methods and Materials: Between 1994 and 2008, 75 pts who underwent heart transplant were obese, defined as a pre-transplant BMI ⱖ30 kg/m2 . These patients were compared with 714 nonobese patients with BMI ⬍30 kg/m2. Outcomes for a high obesity group, defined as BMI ⬎ 33 kg/m2 (N ⫽ 19), were also assessed. Outcomes included 5-year survival, 5-year CAV (angiographic stenosis -⬎ 30%), 5-year non-fatal major adverse cardiac events (NF-MACE; myocardial infarction, heart failure, percutaneous intervention, stroke, peripheral vascular disease), and 1-year treated rejection. Results: The incidence of diabetes was comparable between the obese and nonobese patients(31.3% vs. 21.5%, p⫽NS). 5-year survival and NF-MACE were similar between obese and nonobese patients (74.7% vs. 77.9%, p⫽0.48 and 89.3% vs. 93.0%, p⫽0.19, respectively). First-year any-treated rejection was also similar between the two groups (90.7% vs. 90.2%, p⫽0.93). However, freedom from CAV was significantly higher in the obese group compared to the nonobese group (90.7% vs. 77.3%, p⫽0.015). The high obesity group yielded similar results: patients with BMI ⬎ 33 kg/m2 had greater freedom from CAV compared to controls (100.0% vs. 78.1%, p⫽0.037). Conclusions: Obese patients with BMI ⬎30 kg/m2 have less CAV five years after heart transplantation with comparable survival to nonobese patients. Freedom from CAV is also an apparent benefit of highly obese patients (BMI ⱖ 33 kg/m2). The mechanism of the basis of this observation requires further investigation. 77 Donor-Specific Antibodies Correlate with Rejection in Heart Transplant Patients N. Patel, B. Pavlovic-Surjancev, J. Sinacore, B. Susskind, N. Neuswanger, T. Dasari, A. Heroux Loyola University Medical Center, Maywood, IL Purpose: Antibodies (abs) against Human Leukocyte Antigens (HLA) in heart transplant (HTx) patients (pts) are associated with poor outcome. Panel Reactive Abs (PRA) are nonspecific abs against class I and class II HLA. Luminex technology detects and quantifies abs against donor HLA-Donor Specific Ab (DSA). Experience with DSA in HTx pts is limited. We tested correlation of DSA with episodes of suspected rejection in HTx pts with elevated PRA. Methods and Materials: Patients with HTx done between 1984 and 2008 who had PRA drawn between Mar 06 and Sep 08 were included. PRA was done either related or unrelated to episode of rejection. Rejection was based on clinical suspicion or echocardiographic criteria. PRA blood samples were further tested for DSA, based on the clinician’s decision. To reduce bias that could occur with analysis of multiple samples from one pt, we included only one sample per pt, with highest PRA % (either class I or class II). Pts were divided in two groups: PRA ⱖ 10% (High) and PRA ⬍10% (Low). Low level DSA was defined as ⬍100,000 Molecules of Equivalent Soluble Fluorescence units (MESF).
The Journal of Heart and Lung Transplantation February 2009
Results: Among 140 pts, 42 pts had PRA ⱖ10% (30%) and 98 pts had PRA ⬍10% (70%). High PRA group: Among 42 pts, 17 had rejection (42%). 79% of pts with rejection had positive (pos) DSA. 25 pts did not have rejection. 21% of pts without rejection had pos DSA (all had low level). Low PRA group: Among 98 pts, 8 had rejection (8%). 17% of pts with rejection had pos DSA. 90 pts did not have rejection. 17% of pts without rejection had pos DSA (2 had low level). There were more rejection episodes in high PRA group (n⫽17) compared to low PRA Group (n⫽8) (p⬍0.05). Association of rejection and pos DSA was significant in high PRA group by Pearson Chi-square test (OR⫽13.4, p⬍0.05). Conclusions: Pts with PRAⱖ10% had more episode of rejection. Majority of pts hospitalized for suspected rejection (68%) had high-level positive DSA (52%) or cross-reactive ab to donor-specific ag (16%). There were more graft related deaths in pts with PRAⱖ10% and pos DSA. 78 Magnetic Resonance Imaging Correlates with Transcript Gene Expression in Cardiac Allograft Biopsies I. Paterson, B. Sis, D. Kim, J. Ezekowitz, J. Burton, W. Tymchak, M. Mengel, T. Mueller, P. Halloran University of Alberta, Edmonton, AB, Canada Purpose: T2 weighted imaging on magnetic resonance imaging (MRI) has been shown to predict ISHLT grading of allograft rejection. We sought to determine if MRI measures also correlated with transcript gene expression in cardiac allografts undergoing biopsy. Methods and Materials: Consecutive patients undergoing clinically indicated or routine biopsy were enrolled after obtaining informed consent. Biopsy specimens were analyzed with the Affymetrix microarray in addition to standard histopathologic analysis according to ISHLT 2005 rejection grading. A conventional cardiac MRI that included an assessment of left ventricular function and mass was performed within 24 hours of biopsy. A HASTE (dark blood) sequence with a variable echo time was used to quantify myocardial T2. Post-processing was performed by a reader blinded to the results of histology and gene expression. Results: 7 endomyocardial biopsies from 6 patients (4 male) were obtained. Mean patient age 59 ⫹/6 years and mean time from transplant 120⫹/-90days. ISHLT grade rejection was 0R in 2, 1R in 4 and 2R in 1 and 1 patient was suspected as having clinical rejection. MRI revealed a mean left ventricular (LV) EF of 60⫹/-9%, mean LV mass of 185⫹/-61g and a mean T2 of 57⫹/-5ms. No MRI measures correlated with histologic rejection (all p values were non-significant). Comparison between MRI measures and allograft gene expression revealed a significant correlation between myocardial T2 and inflammatory transcripts (cytotoxic T-cell and macrophage expression), R⫽ 0.86, P⬍0.05. Gene transcripts for myocardial injury and function also correlated with T2 on MRI, R⫽ 0.92 p⬍0.05, and, R⫽ -0.86 p⬍0.05, respectively. Similar correlations were also found for LV wall thickness and transcript gene expression. Conclusions: These preliminary results suggest that MRI measures of cardiac allograft rejection correlate well with transcript gene expression. However, in contrast to previous published reports, MRI seems less predictive of histopathology. 79 Implementation of Molecular Diagnostic Testing in the Early (2-6 Months) Post-Transplant Period T.M. Rowe1, A. Hicks2, H.J. Eisen3, J. Patel4, S.R. Hankins3 1 Hahnemann University Hospital, Philadelphia, PA; 2Drexel University College of Medicine, Philadelphia, PA; 3Drexel University College of Medicine, Philadelphia, PA; 4Drexel University, Philadelphia, PA