- Email: [email protected]
Elevated Cytotoxic T Cells is Associated with Allosensitization of Patients Supported by a Continuous-Flow Left Ventricular Assist Device
S128
Journal of Cardiac Failure Vol. 24 No. 8S August 2018
LV systolic function was defined as an initial LVEF 40% which later improved to 50% consistent with the definition used in the prior UNOS analysis. Results: We found that 23% (38/168) of allocated cardiac allografts from our OPO had transient LV dysfunction with an EF 40% on the initial echocardiogram. This rate was consistent over the years examined. Moreover 55% of donors had an initial echocardiogram with an EF of less than 50%. Comparison of donors with an initial EF 40% to donors with normal LV function on initial examination revealed minimal differences. There was no difference in the average age or sex between the two groups. No differences were found in the dose of vasopressors used either at the time of arrival to the facility or at organ harvest. The average amount of blood transfused was not different between the two groups. Although peak ALT was significantly higher in donors with transient LV dysfunction (402 vs 175 Units/ L), there was no differences found in peak AST, troponin, lactate, or creatinine. Conclusion: We found a markedly higher percentage of cardiac donors with transient LV dysfunction in allografts coming from our OPO facility compared to the UNOS database. The extent to which this reflects increased recognition versus increased organ yield is unknown at this time. These donors did not differ significantly from donors with normal LV function on initial examination. Coupled with prior data that showed equivalent outcomes in donors with recovered LV function, these data suggest that additional efforts to recover cardiac allografts initially found to have LV dysfunction could be an important means of increasing the donor pool and further work is ongoing to understand the most important factors in the recovery process.
340 Elevated Cytotoxic T Cells is Associated with Allosensitization of Patients Supported by a Continuous-Flow Left Ventricular Assist Device Matthew Weiland1, Jennifer Schuitema2, Paula Davidson1, Stefan Jovinge1,2,3, Sangjin Lee2; 1Van Andel Research Institute and Spectrum Health, Grand Rapids, MI; 2 Spectrum Health, Grand Rapids, MI; 3Stanford University, Palo Alto, CA Introduction: Use of CFLVADs as a BTT continues to increase. The mechanisms of host immune system activation following implantation leading to allosensitization complicating transplantation outcomes are not well understood. Hypothesis: We hypothesize that pre-implant cell profiles may predict post-implant allosensitization. Methods: Plasma and PBMC samples were collected before implant (D0), 48 hours post-implant (D2) and 8 days post-implant (D8) in 12 CFLVAD patients. HLA class I and II antibody profiles were obtained pre and post-implant. Calculated panel of reactive antibodies (cPRA) were calculated using the OPTN calculator. Plasma aliquots were randomized and performed in duplicate. Lymphocyte phenotypes were analyzed by multiparameter flow cytometry across 3 randomized panels. Results: Mean age of patients was 53.6§15.3 years, 50% were female and 33% had ischemic cardiomyopathy. Following implant there was a significant increase of Treg cells (CD4+Foxp3+CD25+ 1.07§0.39 p=0.005), T effector cells (CD4+Foxp3¡CD25+ 13.2§2.83 p=0.0007) and B cells (CD3¡CD19+ 7.17§2.93 p=0.032). This was accompanied with a decrease in CD3+ T cells (-10.1§3.69 p=0.019), cytotoxic T cells (CD3+CD8+ -3.28§1.12 p=0.014), and NK cells (CD3¡CD19¡CD56+ -3.86§1.72 p=0.047). Three patients had an increase in cPRA post-implant. All 3 patients had significantly increased cytotoxic T cells compared to patients with no increase (D0 18.4§2.46 vs 7.69§5.79 p=0.013); (D2 15.8§3.12 vs 6.74§3.61 p=0.012); (D8 13.9§3.64 vs 4.83§2.99 p=0.002) (Figure 1). A significant increase in the plasma cytokines IL-6 (D0 79.7 D2 1320 D8 240 p<0.0001), IL-8 (D0 28.0 D2 50.7 D8 28.2 p=0.002), and G-CSF (D0 60.4 D2 559 D8 84.9 p=0.0001) spiked at D2. Conclusion: We show an impaired cellular immunity characterized by an acute rise in Treg, T-effector cells as well as B cells while the tissue aggressive response decreased. IL-6, IL-8 and G-CSF increased significantly post-implant in sensitized patients. Surprisingly, high CD8+ T cells pre-implant were associated with an increased cPRA in our cohort. CD8+ T cells in these patients decreased after implant but remained 2-fold higher than those patients with no increase in cPRA. Higher levels of cytotoxic T cells pre-implant may predict post CFLVAD implant allosensitization. Characterizing preimplant cell profiles may be useful in identifying appropriate CFLVAD recipients.
Figure 1. ROC Curve for PAPi < 1 and Severe RVF.
Introduction: The pulmonary artery pulsatility index (PAPi) is an emerging hemodynamic marker correlated with severe post-LVAD RVF in single-center cohort studies. We set out to examine if this is generalizable in a multi-institutional analysis. Hypothesis: The preoperative PAPi correlates with RVF as defined by new INTERMACS criteria (INTERMACS-RVF), severe RVF, and death at 1-year. Methods: We performed a dual-center retrospective study of 404 patients from Ohio and New York who received a continuous-flow durable LVAD and had a pre-operative PAPi measurement. The PAPi was defined as: [(PA systolic - PA diastolic) RA pressure]. Severe RVF was defined as meeting criteria for clinical RVF and having inotropes > 14 days after implant, inotropes re-started 14 days after implant, RVAD placement during implant admission, and death from RVF during implant admission. A multivariate analysis of predictors of post-LVAD severe RVF was conducted. A survival analysis was performed to examine pre-operative PAPi as a predictor of 1-year mortality. Results: In our cohort of 404 patients, 84 (21%) had severe RVF. Multivariable logistic regression for severe RVF (controlling for age, INTERMACS level, creatinine, and gender) showed that creatinine > 1.5 (OR 2.24, p=0.002, 95% CI [1.43-4.42]) and total bilirubin > 2.5 (OR 2.87, p=0.004, 95% CI [1.39-5.93]) significantly increased the odds of severe RVF, and a PAPi < 1 (OR 1.93, p=0.071, 95% CI [0.95-3.94]) was nearly significant. The multivariable model for INTERMACS-RVF (controlling for age, INTERMACS level, creatinine, and gender) found that a PAPi < 1 (OR 2.2, p=0.018, 95% CI [1.15-4.24]) doubled the odds of RVF. The ROC curves for PAPi < 1 and severe RVF (c-statistic=0.69, Figure 1) and INTERMACSRVF (c-statistic=0.63) were similar. With respect to survival, the final multivariable model (controlling for age, gender, and ethnicity) showed a PAPi < 1 was nearly a significant independent predictor of 1-year mortality (HR 1.76, p=0.054, 95% CI [0.99-3.13]). Conclusion: PAPi < 1 significantly increases the odds of INTERMACS-RVF and was associated with severe RVF. To our knowledge, this is the first time that the PAPi has been validated in a multi-institutional retrospective LVAD cohort study and shown to predict death at 1-year.
342 Impact of Body Mass Index on Device Measured Diagnostic Sensor Measurements in Ambulatory Heart Failure Patients John Boehmer1, George Mark2, Gezheng Wen3, Pramod Thakur3, Gabor Zoltan Duray4; 1Penn State Hershey Medical Center, Hershey, PA; 2Cooper University Hospital, Camden, NJ; 3Boston Scientific, St. Paul, MN; 4Medical Center, Hungarian Defense Forces, Budapest, Hungary
341 A Multi-Institutional Retrospective Cohort Study of the Pulmonary Artery Pulsatility Index’s Ability to Predict post-LVAD Implant Right Ventricular Failure and 1-Year Mortality Salil Kumar1, Sakima A. Smith2,3, Mohamed H. Derbala2,3, Daniel Pinkhas2,3, Bryan Lee2,3, Joshua S. Josephs1, Sandhya Murthy1, Snehal Patel1, Omar Saeed1, J. Julia Shin1, Stephen Forest1, Daniel J. Goldstein1, Ulrich P. Jorde1, Daniel B. Sims1; 1Montefiore Medical Center, New York, NY; 2The Ohio State University Wexner Medical Center, Columbus, OH; 3The Ohio State University College of Medicine, Columbus, OH
Background: Previous studies have reported the link between obesity and the development and progression of Heart Failure. A multi-sensor algorithm based on sensor data of an implanted device was recently shown to detect impending worsening HF events with high sensitivity. The objective of this analysis was to characterize the relationship between sensor measurements and body mass index (BMI) of HF patients. Methods: The MultiSENSE trial enrolled 900 patients implanted with a COGNIS CRT-D and followed them up to 1 year. Device software was modified to permit collection of chronic diagnostic sensor data including heart sounds, respiration, thoracic impedance, heart rate and activity. Sensor data were combined into a multi-sensor alert algorithm (HeartLogicTM). Patients (N=892) were classified into four categories of BMI: Underweight/Normal (BMI<25 kg/m2, N=193), Overweight (25 kg/m2 BMI<30 kg/m2, N=285), Obesity I (30 kg/m2 BMI<35 kg/m2,
Journal of Cardiac Failure Vol. 24 No. 8S August 2018
LV systolic function was defined as an initial LVEF 40% which later improved to 50% consistent with the definition used in the prior UNOS analysis. Results: We found that 23% (38/168) of allocated cardiac allografts from our OPO had transient LV dysfunction with an EF 40% on the initial echocardiogram. This rate was consistent over the years examined. Moreover 55% of donors had an initial echocardiogram with an EF of less than 50%. Comparison of donors with an initial EF 40% to donors with normal LV function on initial examination revealed minimal differences. There was no difference in the average age or sex between the two groups. No differences were found in the dose of vasopressors used either at the time of arrival to the facility or at organ harvest. The average amount of blood transfused was not different between the two groups. Although peak ALT was significantly higher in donors with transient LV dysfunction (402 vs 175 Units/ L), there was no differences found in peak AST, troponin, lactate, or creatinine. Conclusion: We found a markedly higher percentage of cardiac donors with transient LV dysfunction in allografts coming from our OPO facility compared to the UNOS database. The extent to which this reflects increased recognition versus increased organ yield is unknown at this time. These donors did not differ significantly from donors with normal LV function on initial examination. Coupled with prior data that showed equivalent outcomes in donors with recovered LV function, these data suggest that additional efforts to recover cardiac allografts initially found to have LV dysfunction could be an important means of increasing the donor pool and further work is ongoing to understand the most important factors in the recovery process.
340 Elevated Cytotoxic T Cells is Associated with Allosensitization of Patients Supported by a Continuous-Flow Left Ventricular Assist Device Matthew Weiland1, Jennifer Schuitema2, Paula Davidson1, Stefan Jovinge1,2,3, Sangjin Lee2; 1Van Andel Research Institute and Spectrum Health, Grand Rapids, MI; 2 Spectrum Health, Grand Rapids, MI; 3Stanford University, Palo Alto, CA Introduction: Use of CFLVADs as a BTT continues to increase. The mechanisms of host immune system activation following implantation leading to allosensitization complicating transplantation outcomes are not well understood. Hypothesis: We hypothesize that pre-implant cell profiles may predict post-implant allosensitization. Methods: Plasma and PBMC samples were collected before implant (D0), 48 hours post-implant (D2) and 8 days post-implant (D8) in 12 CFLVAD patients. HLA class I and II antibody profiles were obtained pre and post-implant. Calculated panel of reactive antibodies (cPRA) were calculated using the OPTN calculator. Plasma aliquots were randomized and performed in duplicate. Lymphocyte phenotypes were analyzed by multiparameter flow cytometry across 3 randomized panels. Results: Mean age of patients was 53.6§15.3 years, 50% were female and 33% had ischemic cardiomyopathy. Following implant there was a significant increase of Treg cells (CD4+Foxp3+CD25+ 1.07§0.39 p=0.005), T effector cells (CD4+Foxp3¡CD25+ 13.2§2.83 p=0.0007) and B cells (CD3¡CD19+ 7.17§2.93 p=0.032). This was accompanied with a decrease in CD3+ T cells (-10.1§3.69 p=0.019), cytotoxic T cells (CD3+CD8+ -3.28§1.12 p=0.014), and NK cells (CD3¡CD19¡CD56+ -3.86§1.72 p=0.047). Three patients had an increase in cPRA post-implant. All 3 patients had significantly increased cytotoxic T cells compared to patients with no increase (D0 18.4§2.46 vs 7.69§5.79 p=0.013); (D2 15.8§3.12 vs 6.74§3.61 p=0.012); (D8 13.9§3.64 vs 4.83§2.99 p=0.002) (Figure 1). A significant increase in the plasma cytokines IL-6 (D0 79.7 D2 1320 D8 240 p<0.0001), IL-8 (D0 28.0 D2 50.7 D8 28.2 p=0.002), and G-CSF (D0 60.4 D2 559 D8 84.9 p=0.0001) spiked at D2. Conclusion: We show an impaired cellular immunity characterized by an acute rise in Treg, T-effector cells as well as B cells while the tissue aggressive response decreased. IL-6, IL-8 and G-CSF increased significantly post-implant in sensitized patients. Surprisingly, high CD8+ T cells pre-implant were associated with an increased cPRA in our cohort. CD8+ T cells in these patients decreased after implant but remained 2-fold higher than those patients with no increase in cPRA. Higher levels of cytotoxic T cells pre-implant may predict post CFLVAD implant allosensitization. Characterizing preimplant cell profiles may be useful in identifying appropriate CFLVAD recipients.
Figure 1. ROC Curve for PAPi < 1 and Severe RVF.
Introduction: The pulmonary artery pulsatility index (PAPi) is an emerging hemodynamic marker correlated with severe post-LVAD RVF in single-center cohort studies. We set out to examine if this is generalizable in a multi-institutional analysis. Hypothesis: The preoperative PAPi correlates with RVF as defined by new INTERMACS criteria (INTERMACS-RVF), severe RVF, and death at 1-year. Methods: We performed a dual-center retrospective study of 404 patients from Ohio and New York who received a continuous-flow durable LVAD and had a pre-operative PAPi measurement. The PAPi was defined as: [(PA systolic - PA diastolic) RA pressure]. Severe RVF was defined as meeting criteria for clinical RVF and having inotropes > 14 days after implant, inotropes re-started 14 days after implant, RVAD placement during implant admission, and death from RVF during implant admission. A multivariate analysis of predictors of post-LVAD severe RVF was conducted. A survival analysis was performed to examine pre-operative PAPi as a predictor of 1-year mortality. Results: In our cohort of 404 patients, 84 (21%) had severe RVF. Multivariable logistic regression for severe RVF (controlling for age, INTERMACS level, creatinine, and gender) showed that creatinine > 1.5 (OR 2.24, p=0.002, 95% CI [1.43-4.42]) and total bilirubin > 2.5 (OR 2.87, p=0.004, 95% CI [1.39-5.93]) significantly increased the odds of severe RVF, and a PAPi < 1 (OR 1.93, p=0.071, 95% CI [0.95-3.94]) was nearly significant. The multivariable model for INTERMACS-RVF (controlling for age, INTERMACS level, creatinine, and gender) found that a PAPi < 1 (OR 2.2, p=0.018, 95% CI [1.15-4.24]) doubled the odds of RVF. The ROC curves for PAPi < 1 and severe RVF (c-statistic=0.69, Figure 1) and INTERMACSRVF (c-statistic=0.63) were similar. With respect to survival, the final multivariable model (controlling for age, gender, and ethnicity) showed a PAPi < 1 was nearly a significant independent predictor of 1-year mortality (HR 1.76, p=0.054, 95% CI [0.99-3.13]). Conclusion: PAPi < 1 significantly increases the odds of INTERMACS-RVF and was associated with severe RVF. To our knowledge, this is the first time that the PAPi has been validated in a multi-institutional retrospective LVAD cohort study and shown to predict death at 1-year.
342 Impact of Body Mass Index on Device Measured Diagnostic Sensor Measurements in Ambulatory Heart Failure Patients John Boehmer1, George Mark2, Gezheng Wen3, Pramod Thakur3, Gabor Zoltan Duray4; 1Penn State Hershey Medical Center, Hershey, PA; 2Cooper University Hospital, Camden, NJ; 3Boston Scientific, St. Paul, MN; 4Medical Center, Hungarian Defense Forces, Budapest, Hungary
341 A Multi-Institutional Retrospective Cohort Study of the Pulmonary Artery Pulsatility Index’s Ability to Predict post-LVAD Implant Right Ventricular Failure and 1-Year Mortality Salil Kumar1, Sakima A. Smith2,3, Mohamed H. Derbala2,3, Daniel Pinkhas2,3, Bryan Lee2,3, Joshua S. Josephs1, Sandhya Murthy1, Snehal Patel1, Omar Saeed1, J. Julia Shin1, Stephen Forest1, Daniel J. Goldstein1, Ulrich P. Jorde1, Daniel B. Sims1; 1Montefiore Medical Center, New York, NY; 2The Ohio State University Wexner Medical Center, Columbus, OH; 3The Ohio State University College of Medicine, Columbus, OH
Background: Previous studies have reported the link between obesity and the development and progression of Heart Failure. A multi-sensor algorithm based on sensor data of an implanted device was recently shown to detect impending worsening HF events with high sensitivity. The objective of this analysis was to characterize the relationship between sensor measurements and body mass index (BMI) of HF patients. Methods: The MultiSENSE trial enrolled 900 patients implanted with a COGNIS CRT-D and followed them up to 1 year. Device software was modified to permit collection of chronic diagnostic sensor data including heart sounds, respiration, thoracic impedance, heart rate and activity. Sensor data were combined into a multi-sensor alert algorithm (HeartLogicTM). Patients (N=892) were classified into four categories of BMI: Underweight/Normal (BMI<25 kg/m2, N=193), Overweight (25 kg/m2 BMI<30 kg/m2, N=285), Obesity I (30 kg/m2 BMI<35 kg/m2,