- Email: [email protected]
Reduced PF4 and C6orf25 Gene Copies Prior to LVAD in Patients with Thromboembolic Events
S94
The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
neopterin tertile demonstrated poorer overall survival (% survival at 12 months for the highest tertile vs combined low and intermediate tertiles = 76.3% vs 87.8%, p= 0.006). Similarly, survival free from RV failure was worse in the highest neopterin tertile (12 month= 61.9% vs 84.7%, p= 0.005, Figure). No significant difference was evident by sIL-2R tertiles either in overall survival or survival free from RV failure. Conclusion: Elevated neopterin levels prior to LVAD implantation were associated with worse survival. Increased cellular immune activation evident in end-stage heart failure impacts outcomes, and neopterin levels may assist risk stratification prior to LVAD implantation.
2( 27) Improved Survival After Lung Transplantation for Adults Requiring Pre-Operative Invasive Mechanical Ventilation: A National Cohort Study B.C. Hamilton ,1 G.R. Dincheva,2 J.A. Golden,3 S.R. Hays,3 L.E. Leard,3 R. Shah,3 M.E. Kleinhenz,3 T. Deuse,2 B. Trinh,2 M. Brzenzinski,4 M.A. Matthay,5 J.P. Singer,3 J. Kukreja.2 1Department of Surgery, UCSF, San Francisco, CA; 2Department of Surgery, Division of Cardiothoracic Surgery, UCSF, San Francisco, CA; 3Department of Medicine, Pulmonary and Critical Care, UCSF, San Francisco, CA; 4Department of Anesthesia, UCSF, San Francisco, CA; 5Department of Medicine and Anesthesia, Cardiovascular Research Institute, UCSF, San Francisco, CA.
2( 26) Reduced PF4 and C6orf25 Gene Copies Prior to LVAD in Patients with Thromboembolic Events G.H. Kim ,1 G. Sayer,1 D. Rodgers,1 R. Woodward,2 P. Arnold,2 N. Sarswat,1 J. Grinstein,1 S. Kalantari,1 S. Adatya,1 J. Yee,2 T. Ota,1 V. Jeevanandam,1 N. Uriel.1 1University of Chicago, Chicago, IL; 2CareDx, Inc, Brisbane, CA. Purpose: Antiplatelet therapy plays a key role in the management of left ventricular assist devices (LVAD). Currently, functional assays for platelet reactivity are not utilized and uniform anti-platelet protocols are used instead of an individualized approach. This study aims to evaluate changes in platelet gene expression before and after LVAD implantation. Methods: Peripheral blood mononuclear cells were collected prospectively prior to LVAD implantation and at 1 and 6 months after implant using the AlloMap kit. Gene copy number of individual gene components was calculated using quantitative PCR. Platelet activity was assessed using VonWillebrand Factor (VWF) antigen, Ristocetin cofactor assay and VWF multimers. Gene expression pre- and post-LVAD implantation was compared using paired t-tests. Results: 30 consecutive LVAD patients were enrolled (Age 57 +/- 13 years, 77% male) and divided into those who experienced thromboembolic events (TE) defined as LVAD thrombosis requiring device exchange and embolic CVA and compared to those who did not (NoTE) after LVAD implantation. The copy numbers of two genes implicated in platelet aggregation were reduced, indicative of increased platelet activation, prior to LVAD implant in the TE group compared to the NoTE group: PF4 (14,062 +/- 2524 vs 24,641 +/- 2738; p= 0.0258) and C6orf25 (8240 +/- 1634 vs 13209 +/- 1524; p= 0.0574) (Figure 1). 96% of all the patients had reduced high weight multimers post-LVAD compared to 6% at baseline (p< 0.001). VWF Ristocetin Cofactor was also reduced compared to baseline (149 +/- 62 vs 222 +/- 83, p= 0.001). Conclusion: Reduction in the gene copies of PF4 and C6orf25 is suggestive of platelet activation prior to LVAD and may be associated with thromboembolic events. Measurement of patient-specific platelet gene expression may guide a personalized approach to antiplatelet therapy in LVAD patients.
Purpose: Early survival after lung transplantation has improved in the last decade as a result of advances in recipient and donor management. Subsets of transplant candidates, such as those who are mechanically ventilated (MV), are known to be at higher risk for early post-transplant mortality. We evaluated whether post-transplant survival in MV recipients has improved. Methods: Using a national registry, we compared adults on MV at the time of donor offer who underwent lung or heart-lung transplantation from May 4th, 2010 to March 28th, 2014 (late group) to those undergoing transplantation from May 4th, 2005 to May 3rd, 2010 (early group). Odds of death at 6, 12, and 14 months post-transplant were evaluated using multivariate logistic regression, adjusting for known risk factors in lung transplantation. Mortality rate was also stratified by diagnostic category. To address missing covariate data, we used 50-fold multiple imputation. Results: A total of 412 MV recipients underwent lung transplantation in the early period, and 453 in the late period. Recipients in the late group had lower serum creatinine at time of organ matching (0.7 vs. 0.8 mg/dl, p< 0.001) and higher lung allocation score (75 vs. 66, p= 0.013) than recipients in the early group. In the first 6, 12, and 14 months post-transplant, recipients from the late group had nearly 2-fold lower odds of death than recipients in the early group. This survival advantage was suggested across diagnostic categories although we had the most power to detect this association in recipients with fibrotic lung disease (n= 523). Conclusion: While MV recipients remain a high-risk group, survival in this specific patient population has improved in the more contemporary period and appears to benefit recipients across diagnostic categories.
The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
neopterin tertile demonstrated poorer overall survival (% survival at 12 months for the highest tertile vs combined low and intermediate tertiles = 76.3% vs 87.8%, p= 0.006). Similarly, survival free from RV failure was worse in the highest neopterin tertile (12 month= 61.9% vs 84.7%, p= 0.005, Figure). No significant difference was evident by sIL-2R tertiles either in overall survival or survival free from RV failure. Conclusion: Elevated neopterin levels prior to LVAD implantation were associated with worse survival. Increased cellular immune activation evident in end-stage heart failure impacts outcomes, and neopterin levels may assist risk stratification prior to LVAD implantation.
2( 27) Improved Survival After Lung Transplantation for Adults Requiring Pre-Operative Invasive Mechanical Ventilation: A National Cohort Study B.C. Hamilton ,1 G.R. Dincheva,2 J.A. Golden,3 S.R. Hays,3 L.E. Leard,3 R. Shah,3 M.E. Kleinhenz,3 T. Deuse,2 B. Trinh,2 M. Brzenzinski,4 M.A. Matthay,5 J.P. Singer,3 J. Kukreja.2 1Department of Surgery, UCSF, San Francisco, CA; 2Department of Surgery, Division of Cardiothoracic Surgery, UCSF, San Francisco, CA; 3Department of Medicine, Pulmonary and Critical Care, UCSF, San Francisco, CA; 4Department of Anesthesia, UCSF, San Francisco, CA; 5Department of Medicine and Anesthesia, Cardiovascular Research Institute, UCSF, San Francisco, CA.
2( 26) Reduced PF4 and C6orf25 Gene Copies Prior to LVAD in Patients with Thromboembolic Events G.H. Kim ,1 G. Sayer,1 D. Rodgers,1 R. Woodward,2 P. Arnold,2 N. Sarswat,1 J. Grinstein,1 S. Kalantari,1 S. Adatya,1 J. Yee,2 T. Ota,1 V. Jeevanandam,1 N. Uriel.1 1University of Chicago, Chicago, IL; 2CareDx, Inc, Brisbane, CA. Purpose: Antiplatelet therapy plays a key role in the management of left ventricular assist devices (LVAD). Currently, functional assays for platelet reactivity are not utilized and uniform anti-platelet protocols are used instead of an individualized approach. This study aims to evaluate changes in platelet gene expression before and after LVAD implantation. Methods: Peripheral blood mononuclear cells were collected prospectively prior to LVAD implantation and at 1 and 6 months after implant using the AlloMap kit. Gene copy number of individual gene components was calculated using quantitative PCR. Platelet activity was assessed using VonWillebrand Factor (VWF) antigen, Ristocetin cofactor assay and VWF multimers. Gene expression pre- and post-LVAD implantation was compared using paired t-tests. Results: 30 consecutive LVAD patients were enrolled (Age 57 +/- 13 years, 77% male) and divided into those who experienced thromboembolic events (TE) defined as LVAD thrombosis requiring device exchange and embolic CVA and compared to those who did not (NoTE) after LVAD implantation. The copy numbers of two genes implicated in platelet aggregation were reduced, indicative of increased platelet activation, prior to LVAD implant in the TE group compared to the NoTE group: PF4 (14,062 +/- 2524 vs 24,641 +/- 2738; p= 0.0258) and C6orf25 (8240 +/- 1634 vs 13209 +/- 1524; p= 0.0574) (Figure 1). 96% of all the patients had reduced high weight multimers post-LVAD compared to 6% at baseline (p< 0.001). VWF Ristocetin Cofactor was also reduced compared to baseline (149 +/- 62 vs 222 +/- 83, p= 0.001). Conclusion: Reduction in the gene copies of PF4 and C6orf25 is suggestive of platelet activation prior to LVAD and may be associated with thromboembolic events. Measurement of patient-specific platelet gene expression may guide a personalized approach to antiplatelet therapy in LVAD patients.
Purpose: Early survival after lung transplantation has improved in the last decade as a result of advances in recipient and donor management. Subsets of transplant candidates, such as those who are mechanically ventilated (MV), are known to be at higher risk for early post-transplant mortality. We evaluated whether post-transplant survival in MV recipients has improved. Methods: Using a national registry, we compared adults on MV at the time of donor offer who underwent lung or heart-lung transplantation from May 4th, 2010 to March 28th, 2014 (late group) to those undergoing transplantation from May 4th, 2005 to May 3rd, 2010 (early group). Odds of death at 6, 12, and 14 months post-transplant were evaluated using multivariate logistic regression, adjusting for known risk factors in lung transplantation. Mortality rate was also stratified by diagnostic category. To address missing covariate data, we used 50-fold multiple imputation. Results: A total of 412 MV recipients underwent lung transplantation in the early period, and 453 in the late period. Recipients in the late group had lower serum creatinine at time of organ matching (0.7 vs. 0.8 mg/dl, p< 0.001) and higher lung allocation score (75 vs. 66, p= 0.013) than recipients in the early group. In the first 6, 12, and 14 months post-transplant, recipients from the late group had nearly 2-fold lower odds of death than recipients in the early group. This survival advantage was suggested across diagnostic categories although we had the most power to detect this association in recipients with fibrotic lung disease (n= 523). Conclusion: While MV recipients remain a high-risk group, survival in this specific patient population has improved in the more contemporary period and appears to benefit recipients across diagnostic categories.