- Email: [email protected]
Frailty and Early Mortality after Lung Transplantation: Preliminary Results
Abstracts curves estimated a one-year survival of 75.5% in LVAD vs. 82.3% in HTx patients, which was a non-significant difference (hazard ratio 1.50; 95% confidence interval 0.77-2.94; p¼0.24 for LVAD vs. HTx). Peri-operative mortality at 30 days was 16.3% vs. 11.0%, p¼0.32 in LVAD vs. HTx. LVAD treatment required longer in-hospital stay and an increased number of re-hospitalizations; nevertheless major complications were relatively rare. Transplantation rate at one-year was 8% in our series receiving LVAD therapy. Conclusions: Despite worse preoperative conditions and low transplantation rate, one-year survival is not significantly lower after LVAD than after HTx. Since LVAD is becoming a reliable alternative to HTx at least at medium term, use of LVAD as bridge-totransplantation should be harmonized between centres sharing the same donor pool. 303 The Characteristics and Outcomes of Advanced Heart Failure Patients with Hemodynamic Parameters Predictive of Right Ventricular Failure R.J. Mentz, M.A. Daneshmand, A.D. DeVore, C.A. Milano, J.G. Rogers, C.B. Patel. Duke University Medical Center, Durham, NC. Purpose: Advanced heart failure (HF) patients (pts) with a high central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) ratio are at risk for right ventricular failure (RVF) after left ventricular assist device (LVAD) placement. The incidence of this RVF predictor in ambulatory pts with advanced HF and the associated outcomes are unknown. We investigated the ‘‘RVF biomarker’’ of CVP/PCWPZ 0.63 in ambulatory HF pts. Methods and Materials: We analyzed 188 consecutive INTERMACS 4-5 pts evaluated in the Duke HF Clinic (2005-2010) who had a right heart catheterization and cardiopulmonary exercise test (CPX) within 90-days. Pts were stratified by CVP/PCWP Z or o0.63. Pt characteristics, Seattle HF Model (SHFM) score and outcomes (survival free of LVAD/transplant/death) were evaluated. Results: 51 pts (27%) had a ratio Z0.63. The groups were similar with respect to race, gender, HF etiology, and HF medications (all P40.05). Diuretic dose, ejection fraction and natriuretic peptide levels were similar. There was a trend toward worse CPX variables in pts Z0.63 [peak VO2 10.7 mL/kg/min (8.7-13.6) vs. 11.7 (9.5-14.0), P¼0.12; VE-VCO2 slope 46 (36-50) vs. 39 (34-49), P¼0.056]. Predicted 1 yr survival by SHFM was lower in pts Z0.63 [88% vs. 93%, P¼0.03]. Over a median follow-up of 264 days, observed outcomes were similar between groups (Figure).
S119 304 WITHDRAWN 305 Adaptation over a Wide Range of Donor Graft Lung Size Discrepancies in Living-Donor Lobar Lung Transplantation F. Chen, A. Ohsumi, H. Motoyama, K. Hijiya, T. Kondo, T. Yamada, M. Sato, A. Aoyama, T. Bando, H. Date. Thoracic Surgery, Kyoto University, Kyoto, Japan. Purpose: Unlike deceased donor lung transplantation, ideal size matching between donor and recipient is usually difficult because of the limited population of potential donors in living-donor lobar lung transplantation (LDLLT). As a result, there is a wide range of size discrepancies between donor and recipient in LDLLT. The aim of this study was to evaluate the function of the donor graft lung in the recipient thorax after LDLLT in 12 cases of bilateral LDLLT involving 24 successfully transplanted lower-lobe grafts. Methods and Materials: Pulmonary function tests and threedimensional computed tomography (3D-CT) volumetry were performed perioperatively. Results: Donor graft volume ranged from 40 to 161% of the hemilateral thoracic volume of the recipient. Graft forced vital capacities (FVC) increased over time, reaching 107 ⫾ 38% of preoperatively estimated values at 12 months after LDLLT. Graft volumes also increased over time, reaching 123 ⫾ 39% of the original values at 12 months postoperatively. As for the association between donor graft FVC ratio to the preoperatively estimated value at 12 months after LDLLT and 3D-CT volumetry size matching, there was a significant correlation between these parameters (r2 ¼ 0.31, p ¼ 0.005, Figure 1). In contrast, there was no significant correlation between donor graft volume ratio to the original value at 12 months after LDLLT and 3D-CT volumetry size matching (p ¼ 0.37, Figure 2). Undersized donor grafts expanded more after LDLLT than oversized donor grafts, producing greater FVCs than the preoperatively estimated values. In contrast, oversized donor grafts became inflated to their original size, and the FVCs also approached preoperatively estimated values. Six-minute walk distance dramatically improved at 3 months after LDLLT in both groups, reaching more than 500 m at 12 months postoperatively. Conclusions: In conclusion, we found that donor grafts overinflated or underinflated to the extent that they could maintain their own function in a new recipient environment. 306 Frailty and Early Mortality after Lung Transplantation: Preliminary Results D.J. Lederer, J.R. Sonett, N.A. Philip, M. Larkin, E.R. Peterson, A. Desai, S. Sanyal, L. Shah, H.A. Robbins, K. Raza, G. Reilly, F. D’Ovidio, M. Bacchetta, S.M. Arcasoy. Columbia University Medical Center, New York, NY.
Conclusions: Despite the belief that INTERMACS 4-5 pts may be ‘‘too well’’ for an LVAD, we found that 425% of these pts already displayed a marker for post-LVAD RVF. In pts with a CVP/ PCWPZ0.63, outcomes in the context of contemporary advanced HF therapies were similar vs. pts o0.63 despite worse predicted survival by the SHFM.
Purpose: Our group has hypothesized that the frailty phenotype might help identify those at high risk of early complications after lung transplantation. The prevalence of pre-transplant frailty among transplant recipients and the impact of frailty on outcomes after transplantation is not known. Methods and Materials: We performed an interim analysis of the first 46 consecutive lung transplant recipients Z50 years old enrolled in the Lung Transplant Body Composition (LTBC) study at our center. All LTBC participants undergo a structured frailty assessment during transplant evaluation. Frailty was defined as the presence of Z3 of the following: unintentional weight loss Z 4.5kg, low walking speed, selfreported exhaustion, low activity level, and low grip strength. Wilcoxon rank sum tests, Chi-square tests, Fisher’s exact tests, and log-rank tests were used to compare frail and non-frail participants. Results: The mean (SD) age was 62 (5) yrs, 34% were Z 65 yrs, 44% were female, 13% were African-American, 54% had ILD, 14% had COPD, 2% had CF, 4% were underweight, 13% were obese, the
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median LAS was 42 (IQR 33 to 51), 48% were bilateral, and 11 (24%) were frail. Frail recipients were more frequently African-American (37% vs. 6%, p ¼ 0.02) but were similar with regard to age, gender, BMI, diagnosis, LAS score, PA pressure, and use of cardiopulmonary bypass. There were non-significant trends toward more intraoperative complications (28% vs 6%, p ¼ 0.08), postoperative complications (64% vs 37%, p ¼ 0.17), unplanned returns to the OR (18% vs 6%, p ¼ 0.24), and deaths on the ventilator (18% vs 2%, p ¼ 0.14) among frail vs non-frail recipients, respectively. The 30-day mortality rate was 18% among frail and 0% among non-frail (p ¼ 0.01). Conclusions: The frail phenotype is prevalent among lung transplant recipients over 50 years old at our center and is not associated with diagnosis or LAS score. Our finding of an unadjusted association of frailty with poor outcomes should be interpreted cautiously. These findings merit additional study. 307 Using 5-Year Survival Model Does Not Change LAS Estimate of Transplant Benefit M. Valapour,1,2 B. Heubner,1 M. Skeans,1 A. Israni,1 M. Hertz.1,2 1 Minneapolis Medical Research Foundation, Scientific Registry of Transplant Recipients(SRTR), Minneapolis, MN; 2University of Minnesota, Minneapolis, MN. Purpose: The Lung Allocation Score (LAS) has been used since 2005 to rank US lung transplant candidates for access to transplant. A revised LAS (LAS-R) system that will better predict outcomes for the current cohort of transplant patients has been approved and is awaiting implementation. Both the current LAS and LAS-R calculate a candidate’s wait-list mortality risk in the year post-listing and survival likelihood during first year posttransplant. We examined the impact of modifying LAS-R to use a long-term 5-year posttransplant survival model (LAS-R5). Methods and Materials: SRTR standard analysis files were used to estimate posttransplant survival for lung recipients, 5/4/05-9/30/11. We calculated the LAS for all lung-only candidates aged Z 12 years on the waiting list 4/1/2011 using three models: current LAS, LAS-R, and LAS-R5. Using the same variables and parameter estimates for the LAS-R 5-year and 1-year models, we compared C statistics and Hosmer-Lemeshow tests to assess model fit. Results: Boxplots show increased LAS-R for diagnosis group B compared with LAS, but LAS-R5 is similar to LAS-R. C statistics for all models are comparable (LAS ¼ 0.59, LAS-R ¼ 0.61, LAS-R5 ¼ 0.58), suggesting similar survival predictive power. However, the Hosmer-Lemeshow test (P ¼ 0.0214) for the LAS-R5 indicates that observed mortality rates do not match expected event rates in subgroups of the model. Conclusions: Using long-term 5-year survival with the LAS-R covariates does not improve LAS prediction of posttransplant survival likelihood. Possibly, because wait-list mortality risk is given
twice the weight of posttransplant survival in LAS calculation, changes in posttransplant covariates do not significantly impact the LAS. 308 The Impact of Severe Pulmonary Arterial Hypertension on Single Lung Transplantation in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis: An Analysis of the UNOS Database Z.N. Kon, G.J. Bittle, C.F. Evans, P.B. Wehman, B.P. Griffith. University of Maryland School of Medicine, Baltimore, MD. Purpose: Although double lung transplantation may offer a small survival advantage in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), single lung transplantation allows two patients to receive a life-saving intervention with excellent long-term results. However, there remains substantial hesitation to single lung transplantation in patients that also have severe pulmonary arterial hypertension (PAH), and outcomes in this population based on diagnosis have yet to be well described. Methods and Materials: We retrospectively reviewed the United Network of Organ Sharing database for all single lung transplants between 1996 and 2011 performed for COPD or IPF. Demographic data, pre- and post-transplant characteristics, and outcomes were compared for this population based on the presence or absence of severe PAH by right heart catheterization (PASP 450mmHg). The primary outcome analyzed was all-cause mortality. Results: 5,982 patients were identified (COPD, N¼3,580; IPF, N¼2,402). Severe PAH was present in 838 (23%) and 538 (22%) patients with COPD and IPF, respectively. For COPD, survival at 30 days, 1 year and 3 years was 94%, 80% and 60% in patients with severe PAH, and 97%, 85% and 67% without severe PAH (p¼0.264). For IPF, survival at 30 days, 1 year and 3 years was 91%, 70% and 51% in patients with severe PAH, and 95%, 79% and 61% without severe PAH (p¼0.001). Using a Cox proportionalhazards regression, severe PAH was an independent predictor of mortality in patients with IPF (HR¼1.29, po0.001), but not in patients with COPD (HR¼1.06, p¼0.309). Conclusions: In this study, the presence of severe PAH was associated with an increased risk of mortality in patients with IPF, but not COPD. These results suggest that acceptable outcomes for single lung transplantation may be achieved in this population with COPD, but should be considered with caution in patients with IPF. 309 Survival after Lung Transplantation Is Linked with a Genetic Polymorphism in Caveolin-1 E. Vandermeulen,1 D. Ruttens,1 E. Wauters,2 S.E. Verleden,1 A. Vaneylen,1 J. Somers,1 D.E. Van Raemdonck,1 D. Lambrechts,2 G.M. Verleden,1 R. Vos,1 T.S. Nawrot,3,4 B.M. Vanaudenaerde.1 1The Leuven Lung Transplant Group, Katholieke Universiteit Leuven, Leuven, Belgium; 2Laboratory of Translational Genetics, Katholieke Universiteit Leuven, Vesalius Research Center, Leuven, Belgium; 3Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; 4 Department of Public Health, Katholieke Universiteit Leuven, Leuven, Belgium. Purpose: Caveolin 1 (Cav-1) is a structural protein of the cell membrane invaginations, important in tissue homeostasis. Expression of Cav-1 is involved in pulmonary inflammation and fibrosis. Therefore we investigated in our lung transplant cohort the influence of Cav-1 polymorphism on acute and chronic rejection, respiratory infection rate and survival after lung transplantation. Methods and Materials: Recipient DNA from blood or explant lung tissue was collected and investigated for the Cav-1 (rs3807989) polymorphism by iPLEX technology on a MassARRAY and paralleled with patient information available in our database regarding the mentioned outcome parameters. Results: Of all 568 LTx patients, Cav-1 SNP (rs3807989) was successfully determined in 503 patients of which 92 had the AA genotype (18.3%), 234 had the AG genotype (46.5%) and 177 had the GG genotype (35.2%). The A allele (AAþAG) was linked with a
S119 304 WITHDRAWN 305 Adaptation over a Wide Range of Donor Graft Lung Size Discrepancies in Living-Donor Lobar Lung Transplantation F. Chen, A. Ohsumi, H. Motoyama, K. Hijiya, T. Kondo, T. Yamada, M. Sato, A. Aoyama, T. Bando, H. Date. Thoracic Surgery, Kyoto University, Kyoto, Japan. Purpose: Unlike deceased donor lung transplantation, ideal size matching between donor and recipient is usually difficult because of the limited population of potential donors in living-donor lobar lung transplantation (LDLLT). As a result, there is a wide range of size discrepancies between donor and recipient in LDLLT. The aim of this study was to evaluate the function of the donor graft lung in the recipient thorax after LDLLT in 12 cases of bilateral LDLLT involving 24 successfully transplanted lower-lobe grafts. Methods and Materials: Pulmonary function tests and threedimensional computed tomography (3D-CT) volumetry were performed perioperatively. Results: Donor graft volume ranged from 40 to 161% of the hemilateral thoracic volume of the recipient. Graft forced vital capacities (FVC) increased over time, reaching 107 ⫾ 38% of preoperatively estimated values at 12 months after LDLLT. Graft volumes also increased over time, reaching 123 ⫾ 39% of the original values at 12 months postoperatively. As for the association between donor graft FVC ratio to the preoperatively estimated value at 12 months after LDLLT and 3D-CT volumetry size matching, there was a significant correlation between these parameters (r2 ¼ 0.31, p ¼ 0.005, Figure 1). In contrast, there was no significant correlation between donor graft volume ratio to the original value at 12 months after LDLLT and 3D-CT volumetry size matching (p ¼ 0.37, Figure 2). Undersized donor grafts expanded more after LDLLT than oversized donor grafts, producing greater FVCs than the preoperatively estimated values. In contrast, oversized donor grafts became inflated to their original size, and the FVCs also approached preoperatively estimated values. Six-minute walk distance dramatically improved at 3 months after LDLLT in both groups, reaching more than 500 m at 12 months postoperatively. Conclusions: In conclusion, we found that donor grafts overinflated or underinflated to the extent that they could maintain their own function in a new recipient environment. 306 Frailty and Early Mortality after Lung Transplantation: Preliminary Results D.J. Lederer, J.R. Sonett, N.A. Philip, M. Larkin, E.R. Peterson, A. Desai, S. Sanyal, L. Shah, H.A. Robbins, K. Raza, G. Reilly, F. D’Ovidio, M. Bacchetta, S.M. Arcasoy. Columbia University Medical Center, New York, NY.
Conclusions: Despite the belief that INTERMACS 4-5 pts may be ‘‘too well’’ for an LVAD, we found that 425% of these pts already displayed a marker for post-LVAD RVF. In pts with a CVP/ PCWPZ0.63, outcomes in the context of contemporary advanced HF therapies were similar vs. pts o0.63 despite worse predicted survival by the SHFM.
Purpose: Our group has hypothesized that the frailty phenotype might help identify those at high risk of early complications after lung transplantation. The prevalence of pre-transplant frailty among transplant recipients and the impact of frailty on outcomes after transplantation is not known. Methods and Materials: We performed an interim analysis of the first 46 consecutive lung transplant recipients Z50 years old enrolled in the Lung Transplant Body Composition (LTBC) study at our center. All LTBC participants undergo a structured frailty assessment during transplant evaluation. Frailty was defined as the presence of Z3 of the following: unintentional weight loss Z 4.5kg, low walking speed, selfreported exhaustion, low activity level, and low grip strength. Wilcoxon rank sum tests, Chi-square tests, Fisher’s exact tests, and log-rank tests were used to compare frail and non-frail participants. Results: The mean (SD) age was 62 (5) yrs, 34% were Z 65 yrs, 44% were female, 13% were African-American, 54% had ILD, 14% had COPD, 2% had CF, 4% were underweight, 13% were obese, the
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median LAS was 42 (IQR 33 to 51), 48% were bilateral, and 11 (24%) were frail. Frail recipients were more frequently African-American (37% vs. 6%, p ¼ 0.02) but were similar with regard to age, gender, BMI, diagnosis, LAS score, PA pressure, and use of cardiopulmonary bypass. There were non-significant trends toward more intraoperative complications (28% vs 6%, p ¼ 0.08), postoperative complications (64% vs 37%, p ¼ 0.17), unplanned returns to the OR (18% vs 6%, p ¼ 0.24), and deaths on the ventilator (18% vs 2%, p ¼ 0.14) among frail vs non-frail recipients, respectively. The 30-day mortality rate was 18% among frail and 0% among non-frail (p ¼ 0.01). Conclusions: The frail phenotype is prevalent among lung transplant recipients over 50 years old at our center and is not associated with diagnosis or LAS score. Our finding of an unadjusted association of frailty with poor outcomes should be interpreted cautiously. These findings merit additional study. 307 Using 5-Year Survival Model Does Not Change LAS Estimate of Transplant Benefit M. Valapour,1,2 B. Heubner,1 M. Skeans,1 A. Israni,1 M. Hertz.1,2 1 Minneapolis Medical Research Foundation, Scientific Registry of Transplant Recipients(SRTR), Minneapolis, MN; 2University of Minnesota, Minneapolis, MN. Purpose: The Lung Allocation Score (LAS) has been used since 2005 to rank US lung transplant candidates for access to transplant. A revised LAS (LAS-R) system that will better predict outcomes for the current cohort of transplant patients has been approved and is awaiting implementation. Both the current LAS and LAS-R calculate a candidate’s wait-list mortality risk in the year post-listing and survival likelihood during first year posttransplant. We examined the impact of modifying LAS-R to use a long-term 5-year posttransplant survival model (LAS-R5). Methods and Materials: SRTR standard analysis files were used to estimate posttransplant survival for lung recipients, 5/4/05-9/30/11. We calculated the LAS for all lung-only candidates aged Z 12 years on the waiting list 4/1/2011 using three models: current LAS, LAS-R, and LAS-R5. Using the same variables and parameter estimates for the LAS-R 5-year and 1-year models, we compared C statistics and Hosmer-Lemeshow tests to assess model fit. Results: Boxplots show increased LAS-R for diagnosis group B compared with LAS, but LAS-R5 is similar to LAS-R. C statistics for all models are comparable (LAS ¼ 0.59, LAS-R ¼ 0.61, LAS-R5 ¼ 0.58), suggesting similar survival predictive power. However, the Hosmer-Lemeshow test (P ¼ 0.0214) for the LAS-R5 indicates that observed mortality rates do not match expected event rates in subgroups of the model. Conclusions: Using long-term 5-year survival with the LAS-R covariates does not improve LAS prediction of posttransplant survival likelihood. Possibly, because wait-list mortality risk is given
twice the weight of posttransplant survival in LAS calculation, changes in posttransplant covariates do not significantly impact the LAS. 308 The Impact of Severe Pulmonary Arterial Hypertension on Single Lung Transplantation in Patients with Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis: An Analysis of the UNOS Database Z.N. Kon, G.J. Bittle, C.F. Evans, P.B. Wehman, B.P. Griffith. University of Maryland School of Medicine, Baltimore, MD. Purpose: Although double lung transplantation may offer a small survival advantage in chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), single lung transplantation allows two patients to receive a life-saving intervention with excellent long-term results. However, there remains substantial hesitation to single lung transplantation in patients that also have severe pulmonary arterial hypertension (PAH), and outcomes in this population based on diagnosis have yet to be well described. Methods and Materials: We retrospectively reviewed the United Network of Organ Sharing database for all single lung transplants between 1996 and 2011 performed for COPD or IPF. Demographic data, pre- and post-transplant characteristics, and outcomes were compared for this population based on the presence or absence of severe PAH by right heart catheterization (PASP 450mmHg). The primary outcome analyzed was all-cause mortality. Results: 5,982 patients were identified (COPD, N¼3,580; IPF, N¼2,402). Severe PAH was present in 838 (23%) and 538 (22%) patients with COPD and IPF, respectively. For COPD, survival at 30 days, 1 year and 3 years was 94%, 80% and 60% in patients with severe PAH, and 97%, 85% and 67% without severe PAH (p¼0.264). For IPF, survival at 30 days, 1 year and 3 years was 91%, 70% and 51% in patients with severe PAH, and 95%, 79% and 61% without severe PAH (p¼0.001). Using a Cox proportionalhazards regression, severe PAH was an independent predictor of mortality in patients with IPF (HR¼1.29, po0.001), but not in patients with COPD (HR¼1.06, p¼0.309). Conclusions: In this study, the presence of severe PAH was associated with an increased risk of mortality in patients with IPF, but not COPD. These results suggest that acceptable outcomes for single lung transplantation may be achieved in this population with COPD, but should be considered with caution in patients with IPF. 309 Survival after Lung Transplantation Is Linked with a Genetic Polymorphism in Caveolin-1 E. Vandermeulen,1 D. Ruttens,1 E. Wauters,2 S.E. Verleden,1 A. Vaneylen,1 J. Somers,1 D.E. Van Raemdonck,1 D. Lambrechts,2 G.M. Verleden,1 R. Vos,1 T.S. Nawrot,3,4 B.M. Vanaudenaerde.1 1The Leuven Lung Transplant Group, Katholieke Universiteit Leuven, Leuven, Belgium; 2Laboratory of Translational Genetics, Katholieke Universiteit Leuven, Vesalius Research Center, Leuven, Belgium; 3Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium; 4 Department of Public Health, Katholieke Universiteit Leuven, Leuven, Belgium. Purpose: Caveolin 1 (Cav-1) is a structural protein of the cell membrane invaginations, important in tissue homeostasis. Expression of Cav-1 is involved in pulmonary inflammation and fibrosis. Therefore we investigated in our lung transplant cohort the influence of Cav-1 polymorphism on acute and chronic rejection, respiratory infection rate and survival after lung transplantation. Methods and Materials: Recipient DNA from blood or explant lung tissue was collected and investigated for the Cav-1 (rs3807989) polymorphism by iPLEX technology on a MassARRAY and paralleled with patient information available in our database regarding the mentioned outcome parameters. Results: Of all 568 LTx patients, Cav-1 SNP (rs3807989) was successfully determined in 503 patients of which 92 had the AA genotype (18.3%), 234 had the AG genotype (46.5%) and 177 had the GG genotype (35.2%). The A allele (AAþAG) was linked with a