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421 Elevations in Donor Troponin Levels Do Not Predict Worse Outcomes Following Orthotopic Heart Transplant
Abstracts
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superior with less inflammatory reaction in lung grafts preserved with a low-potassium PEG solution compared to the current standard solution. Further experiments to study the “immunocamouflage” properties of PEG based solutions in lungs are warranted. 420 Anaplerotic Substrate Replenishes Tricarboxylic Acid Cycle Intermediates during Machine Perfusion Preservation of Donor Hearts M.L. Cobert,1 M. Peltz,1 M.E. Merritt,2 L.M. West,1 M.E. Jessen.1 1 Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center at Dallas, TX; 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, TX.
echocardiogram, hemodynamics, and inotrope requirements. Although donor troponin (dTn) is commonly measured, previous studies have been variable in demonstrating an association between elevated dTn, typically defined as ⱖ1g/L, and differences in recipient survival. Our goal was to assess the impact of greater elevations in dTn on survival. Methods and Materials: All adult heart transplants performed at our institution from Jan 2003-May 2011 were reviewed and cases where dTn was measured were identified (n⫽566). Patients were divided based on maximum dTn ⱖ3g/L (n⫽81, 14.3%) or ⬍3g/L (n⫽485, 85.7%). We had power ⬎75% to find a 25% difference in hazard ratio. Our primary outcome was post-transplant survival, which was assessed by KaplanMeier analysis. Results: Baseline recipient and donor characteristics were similar. Recipient and Donor Baseline Characteristics
Purpose: Hypothermic perfusion preservation is a promising strategy to extend the cardiac donor ischemic interval. Ongoing metabolism by machine perfused hearts may lead to depletion of intermediates in the tricarboxylic acid (TCA) cycle, the main cellular engine for ATP generation. Anaplerotic substrate replenishes the TCA cycle during normothermia but the ability to support these reactions under hypothermia are not known. The purpose of this study was to determine if an anaplerotic substance can enrich TCA cycle intermediates in the machine perfused heart. Methods and Materials: Rat hearts were perfused for 6 hours at 8⫾2°C with modified UW machine perfusion solution containing increasing concentrations of carbon-13(13C) labeled acetate (2,4,8,16mM) with or without the addition of the anaplerotic substrate propionate (5mM, 13C-labeled). Temperature and MVO2 were measured continuously. After 6 hours perfusion, Magnetic resonance spectroscopy (MRS) was performed on heart extracts to determine enrichment of TCA cycle intermediates. Results: Hearts maintained stable perfusion parameters and MVO2. Lactate/alanine ratios by MRS were low in all groups suggesting primarily oxidative metabolism in perfused hearts. Enrichment of TCA cycle intermediates was reduced in all acetate groups. The addition of propionate resulted in significant increases in enrichment of TCA cylce intermediates. See Table.
Max Tn ⬍3 n RECIPIENT: Age Female CAD Diabetes DONOR: Age Female EF Pressor Inotrope
485
Max Tn ⱖ3
p-value
81
52.1⫾12.8 21.6% 38.4% 24.9%
52.9⫾13.3 25.9% 33.3% 29.6%
0.58 0.37 0.28 0.47
33.7⫾13.0 43.7% 60.6⫾7.5 76.3% 35.9%
32.7⫾12.5 35.8% 58.8⫾8.1 75.3% 38.3%
0.51 0.17 0.06 0.73 0.72
Five-year post-transplant survival between groups was near identical.
Metabolism
Group
Lactate/Alanine Ratio
TCA Cycle Enrichment (%)
2mM Acetate 4mM Acetate 8mM Acetate 16mM Acetate 2mM Acetate⫹Propionate 4mM Acetate⫹Propionate 8mM Acetate⫹Propionate 16mM Acetate⫹Propionate
.54⫾.19 .76⫾.18 .54⫾.16 .43⫾.08 .34⫾.05 .37⫾.07 .43⫾.08 .49⫾.24
11⫾8 8⫾3 8⫾3 10⫾5 36⫾5* 33⫾5* 30⫾2† 44⫾20*
Data are mean ⫾ SEM, *-p⬍.05 vs all acetate groups,†-p⬍.05 vs 8mM acetate group
Conclusions: Machine perfusion preservation supports myocardial oxidative metabolism but may deplete TCA cycle intermediates. The addition of anaplerotic substrates reverses this trend and may be important to maintain energy metabolism in the perfused heart. 421 Elevations in Donor Troponin Levels Do Not Predict Worse Outcomes Following Orthotopic Heart Transplant J.A. Yang,1 Y. Naka,1 G. Magda,1 S. Dizon,1 B.P. Shulman,1 T. Horai,1 T. Ota,1 N. Uriel,2 P. Colombo,2 U.P. Jorde,2 P.C. Schulze,2 D. Mancini,2 H. Takayama.1 1Division of Cardiac Surgery, Dept of Surgery, Columbia University Medical Center, New York, NY; 2Division of Cardiology, Dept of Medicine, Columbia University Medical Center, New York, NY. Purpose: Evaluation of a donor heart relies on several factors, including
A similar equivalency in 5-year survival was found when a dTn level of 5g/L or 10g/L was used to dichotomize patients. Conclusions: An elevated maximum dTn value of 3g/L or greater did not predict worse outcomes, and even elevations above 10g/L did not appear to affect survival. Mild to moderate elevations in dTn do not render a donor heart unsafe to transplant, potentially expanding the pool of donor organs considered. 422 Early Clinical Experience Supplementing Celsior Preservation Solution with Pro-Survival Kinase Agents Glyceryl Trinitrate and Erythropoietin Demonstrates Improved Myocardial Recovery Post Cardiac Transplantation G. Kumarasinghe,1,2 A. Iyer,1,2 M. Hicks,1,2 L. Gao,2 A. Doyle,2 A.M. Keogh,1,2 C.S. Hayward,1 E. Kotlyar,1 E. Granger,1 K. Dhital,1 P. Jansz,1 P. Spratt,1 P.S. Macdonald.1,2 1Dept of Heart and Lung Transplantation, St. Vincent’s Hospital, Sydney, NSW, Australia; 2 Cardiac Physiology and Transplantation Laboratory, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia.
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superior with less inflammatory reaction in lung grafts preserved with a low-potassium PEG solution compared to the current standard solution. Further experiments to study the “immunocamouflage” properties of PEG based solutions in lungs are warranted. 420 Anaplerotic Substrate Replenishes Tricarboxylic Acid Cycle Intermediates during Machine Perfusion Preservation of Donor Hearts M.L. Cobert,1 M. Peltz,1 M.E. Merritt,2 L.M. West,1 M.E. Jessen.1 1 Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center at Dallas, TX; 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, TX.
echocardiogram, hemodynamics, and inotrope requirements. Although donor troponin (dTn) is commonly measured, previous studies have been variable in demonstrating an association between elevated dTn, typically defined as ⱖ1g/L, and differences in recipient survival. Our goal was to assess the impact of greater elevations in dTn on survival. Methods and Materials: All adult heart transplants performed at our institution from Jan 2003-May 2011 were reviewed and cases where dTn was measured were identified (n⫽566). Patients were divided based on maximum dTn ⱖ3g/L (n⫽81, 14.3%) or ⬍3g/L (n⫽485, 85.7%). We had power ⬎75% to find a 25% difference in hazard ratio. Our primary outcome was post-transplant survival, which was assessed by KaplanMeier analysis. Results: Baseline recipient and donor characteristics were similar. Recipient and Donor Baseline Characteristics
Purpose: Hypothermic perfusion preservation is a promising strategy to extend the cardiac donor ischemic interval. Ongoing metabolism by machine perfused hearts may lead to depletion of intermediates in the tricarboxylic acid (TCA) cycle, the main cellular engine for ATP generation. Anaplerotic substrate replenishes the TCA cycle during normothermia but the ability to support these reactions under hypothermia are not known. The purpose of this study was to determine if an anaplerotic substance can enrich TCA cycle intermediates in the machine perfused heart. Methods and Materials: Rat hearts were perfused for 6 hours at 8⫾2°C with modified UW machine perfusion solution containing increasing concentrations of carbon-13(13C) labeled acetate (2,4,8,16mM) with or without the addition of the anaplerotic substrate propionate (5mM, 13C-labeled). Temperature and MVO2 were measured continuously. After 6 hours perfusion, Magnetic resonance spectroscopy (MRS) was performed on heart extracts to determine enrichment of TCA cycle intermediates. Results: Hearts maintained stable perfusion parameters and MVO2. Lactate/alanine ratios by MRS were low in all groups suggesting primarily oxidative metabolism in perfused hearts. Enrichment of TCA cycle intermediates was reduced in all acetate groups. The addition of propionate resulted in significant increases in enrichment of TCA cylce intermediates. See Table.
Max Tn ⬍3 n RECIPIENT: Age Female CAD Diabetes DONOR: Age Female EF Pressor Inotrope
485
Max Tn ⱖ3
p-value
81
52.1⫾12.8 21.6% 38.4% 24.9%
52.9⫾13.3 25.9% 33.3% 29.6%
0.58 0.37 0.28 0.47
33.7⫾13.0 43.7% 60.6⫾7.5 76.3% 35.9%
32.7⫾12.5 35.8% 58.8⫾8.1 75.3% 38.3%
0.51 0.17 0.06 0.73 0.72
Five-year post-transplant survival between groups was near identical.
Metabolism
Group
Lactate/Alanine Ratio
TCA Cycle Enrichment (%)
2mM Acetate 4mM Acetate 8mM Acetate 16mM Acetate 2mM Acetate⫹Propionate 4mM Acetate⫹Propionate 8mM Acetate⫹Propionate 16mM Acetate⫹Propionate
.54⫾.19 .76⫾.18 .54⫾.16 .43⫾.08 .34⫾.05 .37⫾.07 .43⫾.08 .49⫾.24
11⫾8 8⫾3 8⫾3 10⫾5 36⫾5* 33⫾5* 30⫾2† 44⫾20*
Data are mean ⫾ SEM, *-p⬍.05 vs all acetate groups,†-p⬍.05 vs 8mM acetate group
Conclusions: Machine perfusion preservation supports myocardial oxidative metabolism but may deplete TCA cycle intermediates. The addition of anaplerotic substrates reverses this trend and may be important to maintain energy metabolism in the perfused heart. 421 Elevations in Donor Troponin Levels Do Not Predict Worse Outcomes Following Orthotopic Heart Transplant J.A. Yang,1 Y. Naka,1 G. Magda,1 S. Dizon,1 B.P. Shulman,1 T. Horai,1 T. Ota,1 N. Uriel,2 P. Colombo,2 U.P. Jorde,2 P.C. Schulze,2 D. Mancini,2 H. Takayama.1 1Division of Cardiac Surgery, Dept of Surgery, Columbia University Medical Center, New York, NY; 2Division of Cardiology, Dept of Medicine, Columbia University Medical Center, New York, NY. Purpose: Evaluation of a donor heart relies on several factors, including
A similar equivalency in 5-year survival was found when a dTn level of 5g/L or 10g/L was used to dichotomize patients. Conclusions: An elevated maximum dTn value of 3g/L or greater did not predict worse outcomes, and even elevations above 10g/L did not appear to affect survival. Mild to moderate elevations in dTn do not render a donor heart unsafe to transplant, potentially expanding the pool of donor organs considered. 422 Early Clinical Experience Supplementing Celsior Preservation Solution with Pro-Survival Kinase Agents Glyceryl Trinitrate and Erythropoietin Demonstrates Improved Myocardial Recovery Post Cardiac Transplantation G. Kumarasinghe,1,2 A. Iyer,1,2 M. Hicks,1,2 L. Gao,2 A. Doyle,2 A.M. Keogh,1,2 C.S. Hayward,1 E. Kotlyar,1 E. Granger,1 K. Dhital,1 P. Jansz,1 P. Spratt,1 P.S. Macdonald.1,2 1Dept of Heart and Lung Transplantation, St. Vincent’s Hospital, Sydney, NSW, Australia; 2 Cardiac Physiology and Transplantation Laboratory, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia.