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ISHLT PGD grade predicts differential mortality following lung transplantation
The Journal of Heart and Lung Transplantation Volume 24, Number 2S
Methods: To project how use of NHBD hearts could increase heart donation, we retrospectively reviewed donor databases from Gift of Life Donor Program (GLDP), our local procurement organization, from 2001–2003. We screened the NHBD population using conservative donor criteria, assuming an acceptable hypoxic/ischemic time (time from withdrawal of care to cross clamp) of 30 min. Results: During the study period there were 894 HBDs, 334 heart transplants, and 119 NHBDs. During this time the number of HBDs increased by 5%, and the NHBD pool increased by 22%. NHBDs were similar to HBDs with respect to gender and ethnicity, but NHBDs were proportionately younger. Of 119 NHBDs, 55 did not meet the age criteria (ⱕ45 yrs), and 20 were eliminated for incomplete data. 20 NHBDs met all cardiac donor criteria. 82 NHBDs were cross-clamped within 30 min of care withdrawal. 14 of 20 NHBDs met cardiac donor criteria and had hypoxic/ischemic times ⱕ30 min. Pro rata estimation for the 20 NHBDs with incomplete data suggested 7 potential additional donors. Conclusion: The annual number of NHBDs increased while that of HBDs remained essentially fixed. NHBDs were demographically similar to HBDs in terms of gender and race but included a relatively greater proportion of younger individuals. If NHBD hearts identified by our criteria could have been transplanted, they would have provided GLDP with 14 to 21 additional hearts in a time interval in which 334 heart transplants were performed. 88 CABG-PATCHED DONOR HEARTS: THE LONG TERM OUTCOME J. Odim,1 H. Laks,1 N.P. Almeda,1 J.K. Patel,1 J.A. Kobashigawa,1 1 Cardiothoracic Surgery, University of California at Los Angeles, Los Angeles, CA Background: Severe shortage in organ donor pools limits the number of patients who are able to undergo transplantation. Acceptance of repairable hearts may expand the donor heart pool. We have had experience with bypass grafts (BPG) to donor hearts (uses of recipient vein grafts, mammary, radial, and donor vein grafts) at the time of transplant, however long-term outcome including graft patency is not known. Methods: We reviewed 22 heart transplant patients between 1992 and 2002 who received a donor heart that necessitated coronary artery bypass surgery (for coronary artery lesions ⱖ50%) at the time of transplantation. Results: The 22 patient group had an average ischemic time of 225.7 ⫾ 66.1 minutes, were 13.6% CMV mismatched (3/22), had an average of 2.0 ⫾ 0.9 vessels bypassed (range of 1– 4 vessels per patient), had an average age of 61.0 ⫾ 12.5 at the time of transplant, were all male, received hearts of donors who were 72.7% (16/22) male with an average age of 53.0 ⫾ 7.8. One, three and five-year survival were 76.2% (16/21) and 70% (14/20), and 57.9% (11/19), respectively. 1 patient transferred, and 2 patients have not reached their 3 and/or 5 year follow-up. The causes of death (n⫽7) included rejection, infection, cardiac, malignancy, and other. Of 16 patients who had 1-year angiograms, only 1 patient had graft closure, with 2 BPGs occluded. Of the 10 patients who had a 5-year angiogram, 3 patients had at least one BPG occluded. BPG patency in these patients was 79% (15/19). Conclusion: The use of bypass donor hearts appears to have acceptable 5-year survival with excellent 5 year BPG patency. 89 FREE RADICAL SCAVENGER MCI-186 AMELIORATES REPERFUSION INJURY IN HEARTS HARVESTED FROM NON-HEART-BEATING-DONORS Y. Kotani,1 K. Ishino,1 S. Osaki,1 O. Honjo,1 T. Suezawa,1 K. Kanki,1 T. Kohmoto,1 S. Sano,1 1Cardiovascular Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
Abstracts
S71
Background: Reperfusion injury is one of the major causes of cardiac dysfunction in heart transplantation from non-heart-beating donors (NHBDs). We evaluated the cardioprotective effect of MCI-186, the free radical scavenger, in porcine model of heart transplantation form NHBDs. Methods: Cardiac arrest was induced by asphyxiation and the hearts were left in situ for 30 minutes. The hearts were harvested and immediately reperfused from the aortic root with leukocyte-depleted blood cardioplegia for the first 20 minutes, followed by the perfusion with oxygenated leukocyte-depleted blood. The hearts were untreated during reperfusion in control group (n⫽6), while MCI-186 (3 mg/kg) was administered from the aortic root for 30 minutes at the beginning of reperfusion in treated group (n⫽6). Orthotopic heart transplantation was then performed. One hour after weaning from CPB, cardiac output (CO), LV Emax , and creatine kinase (CK-MB) were measured. Myocardial injury was assessed by the coronary sinus-aortic differences of malondialdehyde (⌬MDA), heart weight and histopathological examination. Results: The MCI-treated hearts showed better recovery of posttransplant cardiac function than controls (see table). CK-MB and heart weight gain in the treated group were lower than control. ⌬MDA increased at the first 20 minutes of reperfusion in the control group, but it did not change in the treated group. Electron microscopy revealed more severe mitochondrial swelling in the control group. Conclusions: Administration of MCI-186 at initial reperfusion after 30-min global warm ischemia ameliorates early posttransplant dysfunction of hearts harvested from asphyxiated NHBDs.
Results after Transplantation
% recovery of CO % recovery of LV Emax CK-MB (IU/L) heart weight gain (%)
Control Group
Treated Group
p
60 ⫾ 10 62 ⫾ 7 741 ⫾ 161 11 ⫾ 1
81 ⫾ 5 82 ⫾ 4 323 ⫾ 56 6⫾2
⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05
90 ISHLT PGD GRADE PREDICTS DIFFERENTIAL MORTALITY FOLLOWING LUNG TRANSPLANTATION J.D. Christie,1,2 V.N. Ahya,1 J.S. Sager,1 A. Pocchetino,3 E. DeMissie,1 L. Zhou,2 R.M. Kotloff,1 1Pulmonary and Critical Care Medicine, University of Pennsylvania, Philadelphia, PA; 2 Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA; 3Thoracic Surgery, University of Pennsylvania, Philadelphia, PA Primary graft dysfunction (PGD) is a severe acute lung injury syndrome following lung transplantation. Recently, an ISHLT working group developed standards for the defining criteria for PGD, with a severity grade specified between zero and three measured at time points up to 72 hours. The purpose of this study was to assess the discriminant validity of the defining criteria by assessing differential mortality among the different grades at the 48 hour and 72 hour time points. We evaluated data from 373 consecutive lung transplants performed at our center. PGD was defined according to ISHLT consensus at 48 and 72 hours. Using 48 hour grade, overall all-cause mortality was significantly different between the groups (p⫽0.005 by log rank test). By 72 hours, there was clearer differentiation of survival functions (p⬍0.001 by log rank test), although there appeared to be some overlap of grades 0 and 1. Using T72 scores, all-cause mortality at thirty days was 36.4% for Grade 3, 11.7% for Grade 2, 6.3% for Grade 1, and 3.5% for grade 0 (chi2 p⬍0.001). We conclude that the ISHLT PGD grade has good discriminant validity for mortality when employed at 48 or 72 hours.
S72
Abstracts
The Journal of Heart and Lung Transplantation February 2005
(10%) and II (7.5%) (p ⫽ 0.03). Overall survival (Figure), mean length of ICU and hospital stay also increased in grade III patients (12 and 25 days) versus grades 0-I (4.5 and 15) and II (5.5 and 17 days) (p ⫽ 0.0001). Conclusions: There is an increased risk of mortality and length of hospital stay associated with grade III PGD. The proposed system can rapidly identify recipients with poor outcomes who may benefit from early aggressive treatment. Refinement of the scoring system may further improve patient risk-stratification.
92
91 VALIDATION OF THE PROPOSED ISHLT GRADING SYSTEM FOR PRIMARY GRAFT DYSFUNCTION FOLLOWING LUNG TRANSPLANTATION M.E. Prekker,1 D.S. Nath,1 A.C. Johnson,1 A.R. Walker,1 M.I. Hertz,2 P.S. Dahlberg,1 1Cardiovascular and Thoracic Surgery, University of Minnesota, Minneapolis, MN; 2Medicine, University of Minnesota, Minneapolis, MN Introduction: Primary graft dysfunction (PGD) is a frequent early complication of lung transplantation. A grading system has been proposed by the ISHLT for PGD based on arterial oxygenation to fraction of inspired oxygen (P/F) ratios at ICU arrival (T0), 24 hours (T24), and 48 hours (T48) post-transplantation. Our objective was to determine if this PGD grading system is predictive of short-term outcomes. Methods: We reviewed donor and recipient medical records for 369 consecutive lung transplants performed between 1992 and 2003. Grade 0-I recipients had P/F ratios ⬎ 300, grade II 299 –200, and grade III ⬍200. Results: During the study period 237 single (SLT), and 132 bilateral single (BSL) lung transplants were performed. The incidence of severe PGD (grade III) was 25% at T0, 5.4% at T24, and 14% at T48. Grouping recipients by the lowest P/F ratio recorded within 48 (T0-48) hours yielded evenly distributed groups: 130 grade 0-I (35%), 107 grade II (29%), and 132 grade III (35%). Grade III T0-48 recipients had an increased 90 day mortality (18%) versus recipients in grades 0-I
PULMONARY MICROCIRCULATION AFTER CLINICAL LUNG TRANSPLANTATION: IN VIVO INTRAVITALMICROSCOPY M. Kamler,1 V. Milekhin,1 I. Aleksic,1 U. Herold,1 R. Ragette,2 H. Jakob,1 1Thoracic- and Cardiovascular Surgery, West German Heart Center Essen, University Hospital Essen, Essen, Germany; 2 Pneumology, Ruhrlandklinik, University Hospital Essen, Essen, Germany Introduction: Transplant failure due to ischemia/reperfusion injury is one of the major risks during solid organ transplantation. Responsible for the so called no reflow phenomenon is a severed microcirculation. It was the aim of our study to analyze the microcirculation of human transplanted lungs during the early phase of reperfusion. Methods: The pulmonary microcirculation was assessed by direct intraoperative intravital microscopy from the surface of a transplanted lung. Images were obtained at timepoint (1) - 15 min (2) – 30 min (3) – 45 min (4) – 60 min after reperfusion with the help of a orthogonal polarization spectral (OPS) imaging system (Cytoscan™) and processed computer assisted. Results: Lungs of eight patients after lung transplantations were studied. 15 min after reperfusion capillaries on the lung surface were only minimally perfused. After 30 min we found initialization of the microcirculatory blood flow, with red blood cell (RBC) velocity reaching 119,6 ⫾ 46,7 m/s (mean ⫾ SD) up to 290,4 ⫾ 78,9 m/s (p⬍0.05) 60 min after reperfusion. Functional capillary density (FCD) increased from 0.7 ⫾ 0.5 to 8.1 ⫾ 4.1 m/m2 (p⬍0.05). Conclusion: Our study describes the microcirculation of human lungs in the early phase after transplantation for the first time. We demonstrated a significant delay of the reperfusion process in the microcirculation compared to the macrocirculation in large vessels after organ reperfusion. Weather or not OPS imaging is a reliable instrument to detect early pathological events after lung transplantation shall be further evaluated.
Methods: To project how use of NHBD hearts could increase heart donation, we retrospectively reviewed donor databases from Gift of Life Donor Program (GLDP), our local procurement organization, from 2001–2003. We screened the NHBD population using conservative donor criteria, assuming an acceptable hypoxic/ischemic time (time from withdrawal of care to cross clamp) of 30 min. Results: During the study period there were 894 HBDs, 334 heart transplants, and 119 NHBDs. During this time the number of HBDs increased by 5%, and the NHBD pool increased by 22%. NHBDs were similar to HBDs with respect to gender and ethnicity, but NHBDs were proportionately younger. Of 119 NHBDs, 55 did not meet the age criteria (ⱕ45 yrs), and 20 were eliminated for incomplete data. 20 NHBDs met all cardiac donor criteria. 82 NHBDs were cross-clamped within 30 min of care withdrawal. 14 of 20 NHBDs met cardiac donor criteria and had hypoxic/ischemic times ⱕ30 min. Pro rata estimation for the 20 NHBDs with incomplete data suggested 7 potential additional donors. Conclusion: The annual number of NHBDs increased while that of HBDs remained essentially fixed. NHBDs were demographically similar to HBDs in terms of gender and race but included a relatively greater proportion of younger individuals. If NHBD hearts identified by our criteria could have been transplanted, they would have provided GLDP with 14 to 21 additional hearts in a time interval in which 334 heart transplants were performed. 88 CABG-PATCHED DONOR HEARTS: THE LONG TERM OUTCOME J. Odim,1 H. Laks,1 N.P. Almeda,1 J.K. Patel,1 J.A. Kobashigawa,1 1 Cardiothoracic Surgery, University of California at Los Angeles, Los Angeles, CA Background: Severe shortage in organ donor pools limits the number of patients who are able to undergo transplantation. Acceptance of repairable hearts may expand the donor heart pool. We have had experience with bypass grafts (BPG) to donor hearts (uses of recipient vein grafts, mammary, radial, and donor vein grafts) at the time of transplant, however long-term outcome including graft patency is not known. Methods: We reviewed 22 heart transplant patients between 1992 and 2002 who received a donor heart that necessitated coronary artery bypass surgery (for coronary artery lesions ⱖ50%) at the time of transplantation. Results: The 22 patient group had an average ischemic time of 225.7 ⫾ 66.1 minutes, were 13.6% CMV mismatched (3/22), had an average of 2.0 ⫾ 0.9 vessels bypassed (range of 1– 4 vessels per patient), had an average age of 61.0 ⫾ 12.5 at the time of transplant, were all male, received hearts of donors who were 72.7% (16/22) male with an average age of 53.0 ⫾ 7.8. One, three and five-year survival were 76.2% (16/21) and 70% (14/20), and 57.9% (11/19), respectively. 1 patient transferred, and 2 patients have not reached their 3 and/or 5 year follow-up. The causes of death (n⫽7) included rejection, infection, cardiac, malignancy, and other. Of 16 patients who had 1-year angiograms, only 1 patient had graft closure, with 2 BPGs occluded. Of the 10 patients who had a 5-year angiogram, 3 patients had at least one BPG occluded. BPG patency in these patients was 79% (15/19). Conclusion: The use of bypass donor hearts appears to have acceptable 5-year survival with excellent 5 year BPG patency. 89 FREE RADICAL SCAVENGER MCI-186 AMELIORATES REPERFUSION INJURY IN HEARTS HARVESTED FROM NON-HEART-BEATING-DONORS Y. Kotani,1 K. Ishino,1 S. Osaki,1 O. Honjo,1 T. Suezawa,1 K. Kanki,1 T. Kohmoto,1 S. Sano,1 1Cardiovascular Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
Abstracts
S71
Background: Reperfusion injury is one of the major causes of cardiac dysfunction in heart transplantation from non-heart-beating donors (NHBDs). We evaluated the cardioprotective effect of MCI-186, the free radical scavenger, in porcine model of heart transplantation form NHBDs. Methods: Cardiac arrest was induced by asphyxiation and the hearts were left in situ for 30 minutes. The hearts were harvested and immediately reperfused from the aortic root with leukocyte-depleted blood cardioplegia for the first 20 minutes, followed by the perfusion with oxygenated leukocyte-depleted blood. The hearts were untreated during reperfusion in control group (n⫽6), while MCI-186 (3 mg/kg) was administered from the aortic root for 30 minutes at the beginning of reperfusion in treated group (n⫽6). Orthotopic heart transplantation was then performed. One hour after weaning from CPB, cardiac output (CO), LV Emax , and creatine kinase (CK-MB) were measured. Myocardial injury was assessed by the coronary sinus-aortic differences of malondialdehyde (⌬MDA), heart weight and histopathological examination. Results: The MCI-treated hearts showed better recovery of posttransplant cardiac function than controls (see table). CK-MB and heart weight gain in the treated group were lower than control. ⌬MDA increased at the first 20 minutes of reperfusion in the control group, but it did not change in the treated group. Electron microscopy revealed more severe mitochondrial swelling in the control group. Conclusions: Administration of MCI-186 at initial reperfusion after 30-min global warm ischemia ameliorates early posttransplant dysfunction of hearts harvested from asphyxiated NHBDs.
Results after Transplantation
% recovery of CO % recovery of LV Emax CK-MB (IU/L) heart weight gain (%)
Control Group
Treated Group
p
60 ⫾ 10 62 ⫾ 7 741 ⫾ 161 11 ⫾ 1
81 ⫾ 5 82 ⫾ 4 323 ⫾ 56 6⫾2
⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05
90 ISHLT PGD GRADE PREDICTS DIFFERENTIAL MORTALITY FOLLOWING LUNG TRANSPLANTATION J.D. Christie,1,2 V.N. Ahya,1 J.S. Sager,1 A. Pocchetino,3 E. DeMissie,1 L. Zhou,2 R.M. Kotloff,1 1Pulmonary and Critical Care Medicine, University of Pennsylvania, Philadelphia, PA; 2 Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA; 3Thoracic Surgery, University of Pennsylvania, Philadelphia, PA Primary graft dysfunction (PGD) is a severe acute lung injury syndrome following lung transplantation. Recently, an ISHLT working group developed standards for the defining criteria for PGD, with a severity grade specified between zero and three measured at time points up to 72 hours. The purpose of this study was to assess the discriminant validity of the defining criteria by assessing differential mortality among the different grades at the 48 hour and 72 hour time points. We evaluated data from 373 consecutive lung transplants performed at our center. PGD was defined according to ISHLT consensus at 48 and 72 hours. Using 48 hour grade, overall all-cause mortality was significantly different between the groups (p⫽0.005 by log rank test). By 72 hours, there was clearer differentiation of survival functions (p⬍0.001 by log rank test), although there appeared to be some overlap of grades 0 and 1. Using T72 scores, all-cause mortality at thirty days was 36.4% for Grade 3, 11.7% for Grade 2, 6.3% for Grade 1, and 3.5% for grade 0 (chi2 p⬍0.001). We conclude that the ISHLT PGD grade has good discriminant validity for mortality when employed at 48 or 72 hours.
S72
Abstracts
The Journal of Heart and Lung Transplantation February 2005
(10%) and II (7.5%) (p ⫽ 0.03). Overall survival (Figure), mean length of ICU and hospital stay also increased in grade III patients (12 and 25 days) versus grades 0-I (4.5 and 15) and II (5.5 and 17 days) (p ⫽ 0.0001). Conclusions: There is an increased risk of mortality and length of hospital stay associated with grade III PGD. The proposed system can rapidly identify recipients with poor outcomes who may benefit from early aggressive treatment. Refinement of the scoring system may further improve patient risk-stratification.
92
91 VALIDATION OF THE PROPOSED ISHLT GRADING SYSTEM FOR PRIMARY GRAFT DYSFUNCTION FOLLOWING LUNG TRANSPLANTATION M.E. Prekker,1 D.S. Nath,1 A.C. Johnson,1 A.R. Walker,1 M.I. Hertz,2 P.S. Dahlberg,1 1Cardiovascular and Thoracic Surgery, University of Minnesota, Minneapolis, MN; 2Medicine, University of Minnesota, Minneapolis, MN Introduction: Primary graft dysfunction (PGD) is a frequent early complication of lung transplantation. A grading system has been proposed by the ISHLT for PGD based on arterial oxygenation to fraction of inspired oxygen (P/F) ratios at ICU arrival (T0), 24 hours (T24), and 48 hours (T48) post-transplantation. Our objective was to determine if this PGD grading system is predictive of short-term outcomes. Methods: We reviewed donor and recipient medical records for 369 consecutive lung transplants performed between 1992 and 2003. Grade 0-I recipients had P/F ratios ⬎ 300, grade II 299 –200, and grade III ⬍200. Results: During the study period 237 single (SLT), and 132 bilateral single (BSL) lung transplants were performed. The incidence of severe PGD (grade III) was 25% at T0, 5.4% at T24, and 14% at T48. Grouping recipients by the lowest P/F ratio recorded within 48 (T0-48) hours yielded evenly distributed groups: 130 grade 0-I (35%), 107 grade II (29%), and 132 grade III (35%). Grade III T0-48 recipients had an increased 90 day mortality (18%) versus recipients in grades 0-I
PULMONARY MICROCIRCULATION AFTER CLINICAL LUNG TRANSPLANTATION: IN VIVO INTRAVITALMICROSCOPY M. Kamler,1 V. Milekhin,1 I. Aleksic,1 U. Herold,1 R. Ragette,2 H. Jakob,1 1Thoracic- and Cardiovascular Surgery, West German Heart Center Essen, University Hospital Essen, Essen, Germany; 2 Pneumology, Ruhrlandklinik, University Hospital Essen, Essen, Germany Introduction: Transplant failure due to ischemia/reperfusion injury is one of the major risks during solid organ transplantation. Responsible for the so called no reflow phenomenon is a severed microcirculation. It was the aim of our study to analyze the microcirculation of human transplanted lungs during the early phase of reperfusion. Methods: The pulmonary microcirculation was assessed by direct intraoperative intravital microscopy from the surface of a transplanted lung. Images were obtained at timepoint (1) - 15 min (2) – 30 min (3) – 45 min (4) – 60 min after reperfusion with the help of a orthogonal polarization spectral (OPS) imaging system (Cytoscan™) and processed computer assisted. Results: Lungs of eight patients after lung transplantations were studied. 15 min after reperfusion capillaries on the lung surface were only minimally perfused. After 30 min we found initialization of the microcirculatory blood flow, with red blood cell (RBC) velocity reaching 119,6 ⫾ 46,7 m/s (mean ⫾ SD) up to 290,4 ⫾ 78,9 m/s (p⬍0.05) 60 min after reperfusion. Functional capillary density (FCD) increased from 0.7 ⫾ 0.5 to 8.1 ⫾ 4.1 m/m2 (p⬍0.05). Conclusion: Our study describes the microcirculation of human lungs in the early phase after transplantation for the first time. We demonstrated a significant delay of the reperfusion process in the microcirculation compared to the macrocirculation in large vessels after organ reperfusion. Weather or not OPS imaging is a reliable instrument to detect early pathological events after lung transplantation shall be further evaluated.