- Email: [email protected]
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The Journal of Heart and Lung Transplantation Volume 25, Number 2S
were transplanted vs. 591 hearts (29.6%) if the donor was HBcAb⫹. From donors under the age of 60 years, and HBcAb⫺, at least one lung was transplanted in 7,789 donors (16.7%) vs. 198 (9.9%) if the donor was HBcAb⫹. There was no significant difference in Kaplan-Meier graft and patient survival curves through 10 years between transplants performed from HBcAb⫺ vs. HBcAb⫹ donors (Figure 1). Conclusion(s): The percentage of donors that are HBcAb⫹ continues to increase in the United States. The utilization of hearts and lungs from HBcAb⫹ donors are lower than HBcAb⫺ donors. However, the overall graft and patient survival for hearts, single lungs and double lungs were similar between HBcAb⫹, and HBcAb⫺ donors. Therefore, donor HBcAb⫹ should not be used as the sole factor in determining suitability of thoracic organs.
205 THE RISK OF PRIMARY ALLOGRAFT FAILURE USING HEARTS FROM OLDER DONORS K. Lietz,1 R. John,2 K. Liao,2 L. Joyce,2 L.W. Miller,1 1 Cardiovascular Division, University of Minnesota, Minneapolis, MN; 2Division of Cardiothoracic Surgery, University of Minnesota, Minneapolis, MN Background: Expansion of donor pool is concerning as it increases the risk of primary graft failure (PGF) in recipients of organs from older donors. Using data obtained from the Scientific Registry of Transplant Recipients we sought to identify donor risk factors associated with PGF in heart transplant (HT) recipients. Methods: The studied population included 25,463 HT recipients btw Jan 1990 and Jan 2003 in the United States. PGF was defined as death within 30 days from HT due to primary, non-specific or other non-rejection related graft failure. Multivariable regression models were employed to derive risk factors for PGF. Results: The average 2.8% incidence of PGF (39% of early deaths) remained unchanged throughout the last decade despite increased use of donors ⬎ 40 yrs from 16.2% of HT recipients in 1990 to 31.2% in 2000 with a slight decline in 2002 to 27.8%. By multivariable analysis risk factors for PGF included: donor age ⬎ 40 yrs (RR⫽1.3)*, donor female gender (RR⫽1.3) **, donor death due to stroke (RR⫽1.6) **, ischemia time ⬎ 4 hrs (RR⫽1.6) ** and graft implantation into the sickest heart failure pts, such as those on ventilatory (RR⫽2.6) ** or circulatory support with IABP (RR⫽1.3) * or LVAD (RR⫽1.4) ** and pts with additional risk factors such as PRA ⬎ 10% (RR⫽1.4) **, retransplant (RR⫽1.6) * and ischemic (RR⫽1.4) ** or congenital cardiomyopathy (RR⫽2.5) **. Conclusion: Cardiac allografts obtained from donors who died of stroke, particularly females, are associated with increased risk of PGF. Since stroke victims are currently the main source of organs from donors ⬎ 40 yrs (65%), avoiding prolonged ischemia time and
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transplantation into the sickest heart failure pts may be an important strategy when considering the use older donor hearts. *P⬍0.05 **P⬍0.001 206 ISCHAEMIA TIME IN CARDIAC TRANSPLANTATION: A UK NATIONAL STUDY J.C. Hussey,1 R.S. Bonser,1 C.J. Rudge,1 N.R. Banner,1 1On behalf of the UK Transplant Cardiothoracic Advisory Group (CTAG), UK Transplant, Bristol, United Kingdom Background: Organ ischaemia time (IT) is an important determinant of outcome after heart transplantation. We examined whether there was any trend in IT or its components in the UK heart transplant service. Methods: Data were obtained from the UK National Transplant Database for 1635 first adult orthotopic heart-only transplants in the UK from 1 April 1995 to 31 March 2004. Patient survival was summarised using the Kaplan-Meier method. Results: The median IT increased from 179 minutes (mins) (IQR: 141–214) in 1995/96 to 213 mins (IQR: 180 –254) in 2003/04 (p⬍0.0001). Most of this increase was due to an increase in median transport time (donor cross-clamp to organ arrival; 1995/96: 95 mins; 2003/04: 120 mins; p⬍0.0001), although implant time (organ arrival to reperfusion) also increased (1995/96: 72 mins; 2003/04: 87 mins; p⫽0.003). Over the period, there was a general decrease in the proportion of ‘domino’ transplants from heart-lung recipients (where the organ is usually used locally) and a 6% increase in the proportion of organs sent to another geographical zone (48% in 2003/04). Median IT also differed between transplant centres (in 1995/96: range of median values 132–197 mins; in 2003/04: range 190 –245 mins). National 30-day patient survival was ⬍150 mins: 92%, 150 –189 mins: 90%, 190 –229 mins: 87% and ⱖ230 mins: 84% (p⫽0.002). Despite the temporal trend in IT, there was no significant change in the 30-day mortality after heart transplantation (p⫽0.5). Conclusions: There has been an increase in IT largely due to increased transport times. However, this has not yet resulted in any increase in post-operative mortality. An Urgent Heart Allocation Scheme commenced in April 1999, and this necessitates organs being transported longer distances to the most urgent patient. The Scheme incorporates a payback system that also results in organ transfers. Differences in IT between centres may reflect geography or transport policies. IT is an important process variable in heart transplantation that should be monitored and controlled. 207 HEART PRESERVATION USING CONTINUOUS EX VIVO PERFUSION IMPROVES VIABILITY AND FUNCTIONAL RECOVERY IN COMPARISON TO COLD STORAGE T. Ozeki,1 M.H. Kwon,1 M.J. Collins,1 J.M. Brassil,2 R.N. Pierson,1 B.P. Griffith,1 R.S. Poston,1 1Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD; 2 Organ Recovery Systems, Inc., Chicago, IL Background: Cold storage (CS) is a proven preservation method for heart transplantion, yet early postoperative graft dysfunction remains prevalent. We hypothesized that continuous perfusion (CP) of the heart during the ex vivo transport period would further improve myocardial viability and function. Methods: Dog hearts underwent CP at 6°C (n⫽10) or CS (n⫽10) for 6 hrs. Hearts biopsies were assayed for ATP, caspase-3, and malonyldialdehyde (MDA) levels at baseline, after preservation, and after Langendorff reperfusion with blood for 60 min to asssess functional
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recovery. Intramyocardial pH was monitored continuously during preservation and reperfusion. Results: After 6 hrs of preservation, CP hearts showed significantly better tissue pH (7.26 vs. 6.39; p⬍0.001) and improved myocardial viability (less caspase-3 and MDA and more ATP stores) than CS hearts (Fig). After Langendorff reperfusion, CP hearts again showed improved viability assays (Fig) and function (peak systolic pressure: 178 vs. 129 mmHg; p⫽0.03, developed pressure: 98.7 vs. 56.1 mmHg; p⫽0.02, LV dP/dt: 1350 vs. 686 mmHg/sec; p⫽0.02, and -dP/dt: -974 vs. -496 mmHg/sec; p⫽0.02) but no difference in LV end-diastolic pressure when compared to CS hearts. While CP created more weight gain during preservation (16.4 vs. 0.8%; p⫽0.02), this difference resolved after blood-reperfusion. Conclusion: Hearts preserved with CP showed significantly improved LV function compared to CS, perhaps related to its benefits against energy depletion, oxidative injury, and apoptosis. Transient edema during CP was not associated with diastolic dysfunction. Clinical studies of CP for conventional donor hearts are indicated.
The Journal of Heart and Lung Transplantation February 2006
regression at each annual angiogram in post-transplant years 2 through 7. Results: By univariable analysis, use of high K solutions were associated with lower incidence of any degree of CAV (figure). After adjusting for variables that are known risk factors for CAV, by multi-variable analysis, high K solutions still conferred a protective effect for development of CAV of any severity (RR 0.5, p⬍0.0001) at 5 years. Conclusion: To date, no large multi-institutional analysis has reported a casual relationship between high K heart transplant preservation and cardiac allograft vascuolpathy. This is the first large retrospective analysis that, contrary to previous literature, suggests that the use of high K preservation solutions for heart procurement may protect against the development of CAV.
Disclosure: John Brassil is an employee of Organ Recovery Systems, Inc. 208
209
EFFECTS OF HIGH-POTASSIUM HEART TRANSPLANT PRESERVATION SOLUTIONS ON THE DEVELOPMENT OF CARDIAC ALLOGRAFT VASCULOPATHY: A MULTIINSTITUTIONAL INVESTIGATION N. Moazami,1 R.N. Brown,2 J.K. Kirklin,2 K. Aaronson,3 A.B. VanBakel,4 N. Lewis,5 D.S. Feldman,6 R.N. Oren,7 J. Krull,1 1 Washington University in St. Louis, St. Louis, MO; 2The University of Alabama at Birmingham, Birmingham, AL; 3 University of Michigan Medical Center, Ann Arbor, MI; 4Medical University of South Carolina, Charleston, SC; 5Veterans Affairs Medical Center, Richmond, VA; 6Ohio State University, Columbus, OH; 7University of Iowa Hospitals and Clinics, Iowa City, IA
DONOR HEART SELECTION: THE OUTCOME OF “UNACCEPTABLE” DONORS N.H. Khasati,1 A. Machaal,1 N. Yonan,1 1Transplant Unit/ Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, United Kingdom
Background: The pathophysiology of transplant cardiac allograft vasculopathy (CAV) may be partly due to endothelial cell injury initiated during procurement and preservation of donor graft. High potassium (K) solutions have been implicated in the development of CAV. We performed a retrospective multicenter evaluation to determine if there was a relationship between high potassium preservation solutions and CAV. Methods: Between January 1990 and December 2002, 6872 patients at 30 institutions were transplanted with follow-up at December 2004. Data on K content of solution used for donor heart preservation was avaliable for 6316 patients. CAV was evaluated by annual angiography and stratified as none, mild, moderate, or severe. The degree of CAV was predicted using multi-variable ordinal logistic
Background: The decline in the number of donor hearts has led to an increasing interest in the use of previously unacceptable organs. In the UK, if one centre declines a donor heart on medical grounds it may be offered to other centres. This study aimed to evaluate the outcome of hearts considered medically unsuitable for transplantation by one centre in the UK, that were then used in other centres. Methods: From April 1998 to March 2003, 93 donor hearts (Group A) were transplanted in the UK, after being considered medically unsuitable for transplantation by other centres. During the same period 723 hearts (Group B) were transplanted in the UK using donors not previously rejected. Data on the donors and recipients was obtained from the UK National Transplant Database. Comparative analysis on the two groups was performed. Results: The characteristics of recipients were similar in both groups. The main reasons for refusal of hearts are listed in Table 1. There was no significant difference in the 30-day mortality (13.6 % in group A versus 12.9 in group B), ICU and hospital stay (2.3⫾ 2.9 and 25.3⫾15.7 in group A and 4.1⫾8.5 and 26.0 ⫾ 17.6 in group B respectively) between the two groups. The 5-year survival was similar in the two groups (Log Rank test p ⬍ 0.30) (fig.1).
were transplanted vs. 591 hearts (29.6%) if the donor was HBcAb⫹. From donors under the age of 60 years, and HBcAb⫺, at least one lung was transplanted in 7,789 donors (16.7%) vs. 198 (9.9%) if the donor was HBcAb⫹. There was no significant difference in Kaplan-Meier graft and patient survival curves through 10 years between transplants performed from HBcAb⫺ vs. HBcAb⫹ donors (Figure 1). Conclusion(s): The percentage of donors that are HBcAb⫹ continues to increase in the United States. The utilization of hearts and lungs from HBcAb⫹ donors are lower than HBcAb⫺ donors. However, the overall graft and patient survival for hearts, single lungs and double lungs were similar between HBcAb⫹, and HBcAb⫺ donors. Therefore, donor HBcAb⫹ should not be used as the sole factor in determining suitability of thoracic organs.
205 THE RISK OF PRIMARY ALLOGRAFT FAILURE USING HEARTS FROM OLDER DONORS K. Lietz,1 R. John,2 K. Liao,2 L. Joyce,2 L.W. Miller,1 1 Cardiovascular Division, University of Minnesota, Minneapolis, MN; 2Division of Cardiothoracic Surgery, University of Minnesota, Minneapolis, MN Background: Expansion of donor pool is concerning as it increases the risk of primary graft failure (PGF) in recipients of organs from older donors. Using data obtained from the Scientific Registry of Transplant Recipients we sought to identify donor risk factors associated with PGF in heart transplant (HT) recipients. Methods: The studied population included 25,463 HT recipients btw Jan 1990 and Jan 2003 in the United States. PGF was defined as death within 30 days from HT due to primary, non-specific or other non-rejection related graft failure. Multivariable regression models were employed to derive risk factors for PGF. Results: The average 2.8% incidence of PGF (39% of early deaths) remained unchanged throughout the last decade despite increased use of donors ⬎ 40 yrs from 16.2% of HT recipients in 1990 to 31.2% in 2000 with a slight decline in 2002 to 27.8%. By multivariable analysis risk factors for PGF included: donor age ⬎ 40 yrs (RR⫽1.3)*, donor female gender (RR⫽1.3) **, donor death due to stroke (RR⫽1.6) **, ischemia time ⬎ 4 hrs (RR⫽1.6) ** and graft implantation into the sickest heart failure pts, such as those on ventilatory (RR⫽2.6) ** or circulatory support with IABP (RR⫽1.3) * or LVAD (RR⫽1.4) ** and pts with additional risk factors such as PRA ⬎ 10% (RR⫽1.4) **, retransplant (RR⫽1.6) * and ischemic (RR⫽1.4) ** or congenital cardiomyopathy (RR⫽2.5) **. Conclusion: Cardiac allografts obtained from donors who died of stroke, particularly females, are associated with increased risk of PGF. Since stroke victims are currently the main source of organs from donors ⬎ 40 yrs (65%), avoiding prolonged ischemia time and
Abstracts
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transplantation into the sickest heart failure pts may be an important strategy when considering the use older donor hearts. *P⬍0.05 **P⬍0.001 206 ISCHAEMIA TIME IN CARDIAC TRANSPLANTATION: A UK NATIONAL STUDY J.C. Hussey,1 R.S. Bonser,1 C.J. Rudge,1 N.R. Banner,1 1On behalf of the UK Transplant Cardiothoracic Advisory Group (CTAG), UK Transplant, Bristol, United Kingdom Background: Organ ischaemia time (IT) is an important determinant of outcome after heart transplantation. We examined whether there was any trend in IT or its components in the UK heart transplant service. Methods: Data were obtained from the UK National Transplant Database for 1635 first adult orthotopic heart-only transplants in the UK from 1 April 1995 to 31 March 2004. Patient survival was summarised using the Kaplan-Meier method. Results: The median IT increased from 179 minutes (mins) (IQR: 141–214) in 1995/96 to 213 mins (IQR: 180 –254) in 2003/04 (p⬍0.0001). Most of this increase was due to an increase in median transport time (donor cross-clamp to organ arrival; 1995/96: 95 mins; 2003/04: 120 mins; p⬍0.0001), although implant time (organ arrival to reperfusion) also increased (1995/96: 72 mins; 2003/04: 87 mins; p⫽0.003). Over the period, there was a general decrease in the proportion of ‘domino’ transplants from heart-lung recipients (where the organ is usually used locally) and a 6% increase in the proportion of organs sent to another geographical zone (48% in 2003/04). Median IT also differed between transplant centres (in 1995/96: range of median values 132–197 mins; in 2003/04: range 190 –245 mins). National 30-day patient survival was ⬍150 mins: 92%, 150 –189 mins: 90%, 190 –229 mins: 87% and ⱖ230 mins: 84% (p⫽0.002). Despite the temporal trend in IT, there was no significant change in the 30-day mortality after heart transplantation (p⫽0.5). Conclusions: There has been an increase in IT largely due to increased transport times. However, this has not yet resulted in any increase in post-operative mortality. An Urgent Heart Allocation Scheme commenced in April 1999, and this necessitates organs being transported longer distances to the most urgent patient. The Scheme incorporates a payback system that also results in organ transfers. Differences in IT between centres may reflect geography or transport policies. IT is an important process variable in heart transplantation that should be monitored and controlled. 207 HEART PRESERVATION USING CONTINUOUS EX VIVO PERFUSION IMPROVES VIABILITY AND FUNCTIONAL RECOVERY IN COMPARISON TO COLD STORAGE T. Ozeki,1 M.H. Kwon,1 M.J. Collins,1 J.M. Brassil,2 R.N. Pierson,1 B.P. Griffith,1 R.S. Poston,1 1Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD; 2 Organ Recovery Systems, Inc., Chicago, IL Background: Cold storage (CS) is a proven preservation method for heart transplantion, yet early postoperative graft dysfunction remains prevalent. We hypothesized that continuous perfusion (CP) of the heart during the ex vivo transport period would further improve myocardial viability and function. Methods: Dog hearts underwent CP at 6°C (n⫽10) or CS (n⫽10) for 6 hrs. Hearts biopsies were assayed for ATP, caspase-3, and malonyldialdehyde (MDA) levels at baseline, after preservation, and after Langendorff reperfusion with blood for 60 min to asssess functional
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recovery. Intramyocardial pH was monitored continuously during preservation and reperfusion. Results: After 6 hrs of preservation, CP hearts showed significantly better tissue pH (7.26 vs. 6.39; p⬍0.001) and improved myocardial viability (less caspase-3 and MDA and more ATP stores) than CS hearts (Fig). After Langendorff reperfusion, CP hearts again showed improved viability assays (Fig) and function (peak systolic pressure: 178 vs. 129 mmHg; p⫽0.03, developed pressure: 98.7 vs. 56.1 mmHg; p⫽0.02, LV dP/dt: 1350 vs. 686 mmHg/sec; p⫽0.02, and -dP/dt: -974 vs. -496 mmHg/sec; p⫽0.02) but no difference in LV end-diastolic pressure when compared to CS hearts. While CP created more weight gain during preservation (16.4 vs. 0.8%; p⫽0.02), this difference resolved after blood-reperfusion. Conclusion: Hearts preserved with CP showed significantly improved LV function compared to CS, perhaps related to its benefits against energy depletion, oxidative injury, and apoptosis. Transient edema during CP was not associated with diastolic dysfunction. Clinical studies of CP for conventional donor hearts are indicated.
The Journal of Heart and Lung Transplantation February 2006
regression at each annual angiogram in post-transplant years 2 through 7. Results: By univariable analysis, use of high K solutions were associated with lower incidence of any degree of CAV (figure). After adjusting for variables that are known risk factors for CAV, by multi-variable analysis, high K solutions still conferred a protective effect for development of CAV of any severity (RR 0.5, p⬍0.0001) at 5 years. Conclusion: To date, no large multi-institutional analysis has reported a casual relationship between high K heart transplant preservation and cardiac allograft vascuolpathy. This is the first large retrospective analysis that, contrary to previous literature, suggests that the use of high K preservation solutions for heart procurement may protect against the development of CAV.
Disclosure: John Brassil is an employee of Organ Recovery Systems, Inc. 208
209
EFFECTS OF HIGH-POTASSIUM HEART TRANSPLANT PRESERVATION SOLUTIONS ON THE DEVELOPMENT OF CARDIAC ALLOGRAFT VASCULOPATHY: A MULTIINSTITUTIONAL INVESTIGATION N. Moazami,1 R.N. Brown,2 J.K. Kirklin,2 K. Aaronson,3 A.B. VanBakel,4 N. Lewis,5 D.S. Feldman,6 R.N. Oren,7 J. Krull,1 1 Washington University in St. Louis, St. Louis, MO; 2The University of Alabama at Birmingham, Birmingham, AL; 3 University of Michigan Medical Center, Ann Arbor, MI; 4Medical University of South Carolina, Charleston, SC; 5Veterans Affairs Medical Center, Richmond, VA; 6Ohio State University, Columbus, OH; 7University of Iowa Hospitals and Clinics, Iowa City, IA
DONOR HEART SELECTION: THE OUTCOME OF “UNACCEPTABLE” DONORS N.H. Khasati,1 A. Machaal,1 N. Yonan,1 1Transplant Unit/ Cardiothoracic Surgery, Wythenshawe Hospital, Manchester, United Kingdom
Background: The pathophysiology of transplant cardiac allograft vasculopathy (CAV) may be partly due to endothelial cell injury initiated during procurement and preservation of donor graft. High potassium (K) solutions have been implicated in the development of CAV. We performed a retrospective multicenter evaluation to determine if there was a relationship between high potassium preservation solutions and CAV. Methods: Between January 1990 and December 2002, 6872 patients at 30 institutions were transplanted with follow-up at December 2004. Data on K content of solution used for donor heart preservation was avaliable for 6316 patients. CAV was evaluated by annual angiography and stratified as none, mild, moderate, or severe. The degree of CAV was predicted using multi-variable ordinal logistic
Background: The decline in the number of donor hearts has led to an increasing interest in the use of previously unacceptable organs. In the UK, if one centre declines a donor heart on medical grounds it may be offered to other centres. This study aimed to evaluate the outcome of hearts considered medically unsuitable for transplantation by one centre in the UK, that were then used in other centres. Methods: From April 1998 to March 2003, 93 donor hearts (Group A) were transplanted in the UK, after being considered medically unsuitable for transplantation by other centres. During the same period 723 hearts (Group B) were transplanted in the UK using donors not previously rejected. Data on the donors and recipients was obtained from the UK National Transplant Database. Comparative analysis on the two groups was performed. Results: The characteristics of recipients were similar in both groups. The main reasons for refusal of hearts are listed in Table 1. There was no significant difference in the 30-day mortality (13.6 % in group A versus 12.9 in group B), ICU and hospital stay (2.3⫾ 2.9 and 25.3⫾15.7 in group A and 4.1⫾8.5 and 26.0 ⫾ 17.6 in group B respectively) between the two groups. The 5-year survival was similar in the two groups (Log Rank test p ⬍ 0.30) (fig.1).