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Assessing Performance of Human Donor Hearts Following Donation After Circulatory Death
S104
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
2( 68) Donor and Recipient Renal Dysfunction and Post Cardiac Transplant Graft Survival: Insights Into Reno-Cardiac Interactions O. Laur ,1 M.A. Brisco,2 A.J. Kula,1 S.J. Cheng,1 A.A. Mangi,1 S.G. Coca,1 W.H. Tang,3 J.M. Testani.1 1School of Medicine, Yale University, New Haven, CT; 2Medical Univerisity of South Carolina, Charleston, SC; 3Cleveland Clinic, Cleveland, OH. Purpose: The major mode of death in patients with renal dysfunction (RD) is cardiovascular disease (CVD). Notably, there may be a causal effect of RD given that myocardial necrosis/apoptosis has been seen in animal models of RD. However, RD is also a marker of overall CVD severity. Cardiac transplantation provides an opportunity to study this as hearts are being transplanted in and out of the environment of RD: If irreversible myocardial damage occurs immediately with RD, as seen in animal models of acute kidney injury, transplantation of a heart from a donor with RD should yield reduced graft survival. However, if cardiac damage from RD develops gradually, transplantation of a healthy RD-free donor heart into a recipient with RD should yield an initial low risk period followed by high event rates months to years later. Methods: Adult cardiac allograft recipients in the United Network for Organ Sharing (UNOS) registry were studied (n= 3 5,914). RD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/ min/1.73m2. Results: RD was present in 17.2 % of donors and 39.4% of recipients with an overall worsening in eGFR over time in recipients (p< 0.001). Donor characteristics known to cause or reflect myocardial damage such as ischemic time > 4 hours (adjusted HR 1.2, p< 0.001), age > 50 years (adjusted HR= 1.3, p< 0.001), or ejection fraction ≤ 45% (adjusted HR 1.2, p= 0.03) were associated with reduced graft survival. To the contrary, the risk associated with RD did not follow the heart as transplantation from a donor with RD did not reduce graft survival (adjusted HR= 0.98, p= 0.44). RD-free donor hearts placed into a recipient with RD paradoxically had the highest risk of graft dysfunction in the first 30 post-operative days (Adjusted HR 1.6, p< 0.001). Subsequently, the hazard attributable to recipient RD (adjusted HR 1.2, p< 0.001) did not increase over time (p= 0.8) as would be expected with slow accumulation of myocardial damage from RD. Conclusion: Transplantation of a heart in and out of the environment of RD was not associated with worsened outcomes in a manner consistent with a clinically meaningful direct effect of RD on the myocardium. These data provide additional support that RD primarily serves as a marker rather than a direct cause of CVD.
2( 69) Assessing Performance of Human Donor Hearts Following Donation After Circulatory Death F. Rosenfeldt , R. Ou, S. Marasco, I. Buttfield, J. Woodard, S. Perera, K. Bhagwat, D. McGiffin. Cardiothoracic Surgery, Alfred Hospital, Melbourne, Victoria, Australia. Purpose: We have developed a novel technique of preserving donation after circulatory death (DCD) hearts by perfusion with cold oxygenated crystalloid fluid and a method of assessing the efficacy of preservation using an ex-vivo evaluation rig. We set out to evaluate the postreperfusion performance of perfusion-preserved DCD and brain stem death (BSD) hearts with a view to assessing their potential suitability for transplantation. Methods: Unused human donor hearts from DCD and BSD donors were obtained during organ donation. After cardoplegia each donor heart was perfused for 4 hr with an 8oC oxygenated crystalloid solution at 20 ml/min. The heart was then connected to a blood perfusion rig and a balloon inserted in the left ventricle to record developed (systolic minus diastolic) pressure (DP). Blood perfusate lactate levels were measured. Three DCD and 4 BSD hearts were studied. Potential or transplantation was judged two hours post-reperfusion using DP and lactate. The results for each heart were then compared with the previous conventional clinical assessment of suitability for transplantation based on age and inotrope dosage.
Results: Two DCD hearts (DCD 2,3) and 3 BSD hearts (BSD 1, 2, 4) exhibited good functional recovery on the rig whereas 2 (DCD 1 and BSD 3) did not. All 3 DCD hearts and 1 BSD heart (BSD 1) were associated with low perfusate lactate whereas 3 (BSD 2, 3, 4) were associated with high lactate. Thus DCD 2, 3 and BSD 1 were judged probably transplantable with high DP and low lactate. BSD 3 was judged not suitable for transplantation due to both low DP and high lactate and 2 (BSD 2 & 4) probably unsuitable due to high lactate alone and DCD 1 due to low DP alone (Fig). For the BSD hearts these findings reflected the pre-donation clinical assessment of transplantability. Conclusion: 1. Using an evaluation rig it may be possible to differentiate transplantable from non-transplantable hearts. 2. DCD hearts preserved by continuous cold crystalloid perfusion show promise for clinical transplantation.
2( 70) Influence of Varying Definitions of Primary Graft Dysfunction After Heart Transplantation on Incidence and Risk Factors B.S. Letzen , S. Ghadyani, P. Bonde. Section of Cardiac Surgery, Yale School of Medicine, New Haven, CT. Purpose: There is a plethora of reported definitions of PGD after heart transplantation in the literature. Correspondingly, the accuracy in predicting risk factors and the incidence of PGD is lacking. The aim of this investigation was to determine the influence of varying definitions of PGD on incidence and predicted risk factors. Methods: A nationwide sample of adult heart transplantations from 2002 to 2010 was analyzed using the United Network for Organ Sharing (UNOS) database for definitions of PGD at 2d, 3d, 10d, 30d, 90d as per criteria in literature. We excluded acute rejection, infection, pulmonary hypertension, and surgical issues. Logistic regression was used to identify risk factors for each separate definition. Risk factors common to two or more definitions were used for further multivariate analysis for predictors of 30d mortality. Results: The incidence of PGD for definitions based on varying time frames of graft failure ranged from 1.8% (graft failure time within 2d) to 7.2% (graft failure time within 90d). Predicted risk factors common to two or more definitions included recipient ventilator support, ischemic time > 4h, recipient previous transfusions, recipient total bilirubin > 2 mg/dL, donor age > 40y, and number of previous transplants (p< 0.05). Recipient total bilirubin greater than 2mg/dL showed the greatest risk of 30d mortality [OR 2.08 (1.64 - 2.63), p < 0.01], followed by recipient ventilator support [OR 1.97 (1.34 - 2.91), p < 0.01], ischemic time 4-6h [OR 1.69 (1.36 - 2.09), p < 0.01], and recipient previous transfusions [OR 1.43 (1.16 - 1.75), p = 0.01]. Kaplan-Meier curves showed decrease survival for all of these variables (Figure 1). Conclusion: Individual definitions for PGD result in differing incidences and predicted risk factors. After analyzing multiple definitions, a small set of common risk factors can be elucidated. This provides a framework for moving towards a consensus definition for PGD in heart transplantation.
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
2( 68) Donor and Recipient Renal Dysfunction and Post Cardiac Transplant Graft Survival: Insights Into Reno-Cardiac Interactions O. Laur ,1 M.A. Brisco,2 A.J. Kula,1 S.J. Cheng,1 A.A. Mangi,1 S.G. Coca,1 W.H. Tang,3 J.M. Testani.1 1School of Medicine, Yale University, New Haven, CT; 2Medical Univerisity of South Carolina, Charleston, SC; 3Cleveland Clinic, Cleveland, OH. Purpose: The major mode of death in patients with renal dysfunction (RD) is cardiovascular disease (CVD). Notably, there may be a causal effect of RD given that myocardial necrosis/apoptosis has been seen in animal models of RD. However, RD is also a marker of overall CVD severity. Cardiac transplantation provides an opportunity to study this as hearts are being transplanted in and out of the environment of RD: If irreversible myocardial damage occurs immediately with RD, as seen in animal models of acute kidney injury, transplantation of a heart from a donor with RD should yield reduced graft survival. However, if cardiac damage from RD develops gradually, transplantation of a healthy RD-free donor heart into a recipient with RD should yield an initial low risk period followed by high event rates months to years later. Methods: Adult cardiac allograft recipients in the United Network for Organ Sharing (UNOS) registry were studied (n= 3 5,914). RD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/ min/1.73m2. Results: RD was present in 17.2 % of donors and 39.4% of recipients with an overall worsening in eGFR over time in recipients (p< 0.001). Donor characteristics known to cause or reflect myocardial damage such as ischemic time > 4 hours (adjusted HR 1.2, p< 0.001), age > 50 years (adjusted HR= 1.3, p< 0.001), or ejection fraction ≤ 45% (adjusted HR 1.2, p= 0.03) were associated with reduced graft survival. To the contrary, the risk associated with RD did not follow the heart as transplantation from a donor with RD did not reduce graft survival (adjusted HR= 0.98, p= 0.44). RD-free donor hearts placed into a recipient with RD paradoxically had the highest risk of graft dysfunction in the first 30 post-operative days (Adjusted HR 1.6, p< 0.001). Subsequently, the hazard attributable to recipient RD (adjusted HR 1.2, p< 0.001) did not increase over time (p= 0.8) as would be expected with slow accumulation of myocardial damage from RD. Conclusion: Transplantation of a heart in and out of the environment of RD was not associated with worsened outcomes in a manner consistent with a clinically meaningful direct effect of RD on the myocardium. These data provide additional support that RD primarily serves as a marker rather than a direct cause of CVD.
2( 69) Assessing Performance of Human Donor Hearts Following Donation After Circulatory Death F. Rosenfeldt , R. Ou, S. Marasco, I. Buttfield, J. Woodard, S. Perera, K. Bhagwat, D. McGiffin. Cardiothoracic Surgery, Alfred Hospital, Melbourne, Victoria, Australia. Purpose: We have developed a novel technique of preserving donation after circulatory death (DCD) hearts by perfusion with cold oxygenated crystalloid fluid and a method of assessing the efficacy of preservation using an ex-vivo evaluation rig. We set out to evaluate the postreperfusion performance of perfusion-preserved DCD and brain stem death (BSD) hearts with a view to assessing their potential suitability for transplantation. Methods: Unused human donor hearts from DCD and BSD donors were obtained during organ donation. After cardoplegia each donor heart was perfused for 4 hr with an 8oC oxygenated crystalloid solution at 20 ml/min. The heart was then connected to a blood perfusion rig and a balloon inserted in the left ventricle to record developed (systolic minus diastolic) pressure (DP). Blood perfusate lactate levels were measured. Three DCD and 4 BSD hearts were studied. Potential or transplantation was judged two hours post-reperfusion using DP and lactate. The results for each heart were then compared with the previous conventional clinical assessment of suitability for transplantation based on age and inotrope dosage.
Results: Two DCD hearts (DCD 2,3) and 3 BSD hearts (BSD 1, 2, 4) exhibited good functional recovery on the rig whereas 2 (DCD 1 and BSD 3) did not. All 3 DCD hearts and 1 BSD heart (BSD 1) were associated with low perfusate lactate whereas 3 (BSD 2, 3, 4) were associated with high lactate. Thus DCD 2, 3 and BSD 1 were judged probably transplantable with high DP and low lactate. BSD 3 was judged not suitable for transplantation due to both low DP and high lactate and 2 (BSD 2 & 4) probably unsuitable due to high lactate alone and DCD 1 due to low DP alone (Fig). For the BSD hearts these findings reflected the pre-donation clinical assessment of transplantability. Conclusion: 1. Using an evaluation rig it may be possible to differentiate transplantable from non-transplantable hearts. 2. DCD hearts preserved by continuous cold crystalloid perfusion show promise for clinical transplantation.
2( 70) Influence of Varying Definitions of Primary Graft Dysfunction After Heart Transplantation on Incidence and Risk Factors B.S. Letzen , S. Ghadyani, P. Bonde. Section of Cardiac Surgery, Yale School of Medicine, New Haven, CT. Purpose: There is a plethora of reported definitions of PGD after heart transplantation in the literature. Correspondingly, the accuracy in predicting risk factors and the incidence of PGD is lacking. The aim of this investigation was to determine the influence of varying definitions of PGD on incidence and predicted risk factors. Methods: A nationwide sample of adult heart transplantations from 2002 to 2010 was analyzed using the United Network for Organ Sharing (UNOS) database for definitions of PGD at 2d, 3d, 10d, 30d, 90d as per criteria in literature. We excluded acute rejection, infection, pulmonary hypertension, and surgical issues. Logistic regression was used to identify risk factors for each separate definition. Risk factors common to two or more definitions were used for further multivariate analysis for predictors of 30d mortality. Results: The incidence of PGD for definitions based on varying time frames of graft failure ranged from 1.8% (graft failure time within 2d) to 7.2% (graft failure time within 90d). Predicted risk factors common to two or more definitions included recipient ventilator support, ischemic time > 4h, recipient previous transfusions, recipient total bilirubin > 2 mg/dL, donor age > 40y, and number of previous transplants (p< 0.05). Recipient total bilirubin greater than 2mg/dL showed the greatest risk of 30d mortality [OR 2.08 (1.64 - 2.63), p < 0.01], followed by recipient ventilator support [OR 1.97 (1.34 - 2.91), p < 0.01], ischemic time 4-6h [OR 1.69 (1.36 - 2.09), p < 0.01], and recipient previous transfusions [OR 1.43 (1.16 - 1.75), p = 0.01]. Kaplan-Meier curves showed decrease survival for all of these variables (Figure 1). Conclusion: Individual definitions for PGD result in differing incidences and predicted risk factors. After analyzing multiple definitions, a small set of common risk factors can be elucidated. This provides a framework for moving towards a consensus definition for PGD in heart transplantation.