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End-stage renal failure and kidney transplantation in heart transplant recipients
94
Abstracts
The Journal of Heart and Lung Transplantation January 2002
Results
Recipient Age (yr) Donor Age (yr) Donor Body Weight (kg) D/R Wt Ischaemic Time (min) TPG (mm Hg) 30 day mortality Hospital LOS (days)
HHTx (n ⴝ 13)
OHTx (n ⴝ 91)
P value
55 (51–63) 48 (34–50) 60 (55–70) 0.7 (0.6–0.9) 377 (205–464) 17 (12–22) 2 (15.4%) 22 (11–41)
52 (40–59) 35 (21–46) 75 (66–85) 1.0 (0.9–1.1) 255 (195–346) 8 (5–10) 5 (5.5%) 15 (10.3–21.8)
0.058 0.042 ⬍0.001 ⬍0.001 0.118 ⬍0.001 0.46 0.141
Values given: median (50% confidence limits)
There were two ⬍ 30 day deaths each on day 7, 1 following an “uneventful” cardiac biopsy and 1 from sepsis and multiorgan failure. There were no deaths from primary allograft failure despite the lower D/R Wt, significantly higher TPG’s and the utility of older donors compared to the OHTx group. Four year actuarial survival was 50% for HHTx (3 late deaths in the HHTx from LPD, respiratory failure and sternal wound sepsis) compared to 70% for OHTx. Conclusions: HHTx is a viable option for selected higher risk waiting list patients who might otherwise be denied transplantation. The successful use of often rejected smaller or “marginal” cardiac allografts expands the functional donor pool. 109 LOW AFFINITY FC RECEPTOR (CD32) MEDIATED PLATELET AGGREGATION/ACTIVATION IN VITRO BY ANTITHYMOCYTEGLOBULINE:A POSSIBLE EXPLANATION FOR INDUCTION THERAPY MEDIATED PLATELET DEPLETION IN VIVO H.J. Ankersmit,1 I. Volf,2 G. Roth,1 B. Moser,1 A. Zuckermann,1 A. Kocher,1 B. Schlechta,1 M. Haisjackl,3 G. Wieselthaler,1 M. Grimm,1 G. Boltz-Nitulescu,4 E. Wolner,1 1Department of Cardiothoracic Surgery, Vienna General Hospital, Vienna, Austria; 2Institute of Physiology, University Vienna, Vienna, Austria; 3Department of Anesthesia, Vienna General Hospital, Vienna, Austria; 4Institute of Pathophysiology, University Vienna, Vienna, Austria Background: Anti Thymocyte Globulin is administered in our heart transplant recipient population (2mg/kg) for 4-6 days in addition to initiation of conventional triple therapy (cyclosporine, azathioprine, steroids). This results in our institution to a 89% freedom of rejection (ISHLT II-III) within the first year after heart transplantation in the period 1997-1998 (93 patients who were admitted at the CT ICU). 41% of these patients had to be transfused with packed platelets (range 1-15, average transfusion 2.02 packs) when they reached values less than 30.000. Methods: Packed Platelets were obtained from the blood bank and platelet aggregation was determined by 490-4D four channel aggregometer after addition of ATG, OKT-3 and IL-2 R blocker (daclizumab). FACS analysis was utilized to evaluate CD62P and CD63 markers of platelet activation (ADP and Thrombin activation served as control). Electron microscopy was utilized to demonstrate blebbing after ATG induced activation. Results: ATG,OKT-3 and Il-2 R blocker were exposed to resting platelets in concentrations 10-150 g/cc, only ATG was able to induce aggregation in a dose dependent manner (aggregation threshold value was 10g/cc). Since platelet aggregation is dependent on low affinity receptor engagement (CD32), we coincubated platelets with anti-CD 32 mABs and ATG (10g/cc) an we were able to inhibit aggregation (p⬍0.001). Moreover, ATG
(10g/cc) was also able to increase CD62P/CD63 epitope upregulation (60%, 57%, respectivley), this was reversed by addition of anti-CD32 mABs in a dosedependent fashion. ELMI visualized blebbing, commonly seen in apoptotic cells. Conclusion: ATG, but not OKT3 or IL-2 R blocker are inducing low affinity receptor (CD32) mediated aggregation/activation in vitro and might serve as explanation for platelet depletion in transplant patient after ATG admininstration. 110 CONTRIBUTION OF IMPAIRED LEFT VENTRICULAR FUNCTION TO EXERCISE INTOLERANCE IN HEART TRANSPLANT RECIPIENTS M. Dandel, R. Ewert, M. Hummel, R. Meyer, J. Mueller, R. Hetzer, Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany Background: We assessed the left ventricular (LV) function and exercise tolerance in non-rejecting heart recipients, in connection with post-transplant time, amount of interstitial fibrosis and presence of transplant coronary artery disease (TxCAD). Methods: Echocardiographic analysis of LV function (M-mode, 2D, flow Doppler and tissue Doppler) was performed in 120 patients (post-transplant time: 3 months -13 years), prior to exercise testing, cardiac catheterization and endomyocardial biopsy. Echocardiographic parameters were tested for relationships with histological, angiographical and exercise findings. Results: Exercise intolerance (low peak VO2) was found in 117 patients (97.5%). Even without TxCAD, peak VO2 reached only 73.8 ⫾9.2% of predicted values. The elevated LV end-diastolic pressure [LVEDP] (11.8 ⫾5.9 mmHg) and reduced transmitral pressure half-time [PHT] (42.3 ⫾9.9 ms) suggest that without TxCAD, exercise intolerance was mainly related to diastolic dysfunction. All TxCAD patients showed exercise intolerance, which was highest in the angiographic TxCAD group. In these patients, the LV ejection fraction (LVEF), although lower than without TxCAD (p ⫽0.0011), was in the normal range (62.8 ⫾11.5%). The high LVEDP (14.8 ⫾5.6 mmHg) and short PHT (30.1 ⫾ 8.7 ms) in these patients were indicative of a mainly diastolic dysfunction. The significantly reduced systolic wall motion peak velocities in both angiographic TxCAD and TxCAD, visible only by intracoronary ultrasound, suggest also the contribution of systolic dysfunction to exercise intolerance. Impaired diastolic function and exercise intolerance also appeared to be related to interstitial fibrosis. Patients with diffuse perivascular and interstitial fibrosis showed shorter PHT, higher LVEDP, and more altered exercise parameters than those with minimal or reduced fibrosis (p ⬍0.001). Patients with TxCAD showed reduced chronotropic responses to exercise (p ⬍0.01). Conclusions: The LV diastolic dysfunction, closely related to interstitial fibrosis, is a major cause of post-transplant exercise intolerance. TxCAD impairs exercise capacity mainly by aggravating pre-existent diastolic dysfunction and reduced chronotropic response to exercise. 111 END-STAGE RENAL FAILURE AND KIDNEY TRANSPLANTATION IN HEART TRANSPLANT RECIPIENTS M.C.Y. Chan, B. Cantin, H.A. Valantine, S.A. Hunt, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA
The Journal of Heart and Lung Transplantation Volume 21, Number 1
Abstracts
95
Background: Renal dysfunction is common in heart transplant (HTX) recipients due to pre-existing renal impairment and cyclosporine use. A subset will develop end-stage renal failure (ESRF). It is unclear what factors predict ESRF, and what the long-term outcome is after kidney transplantation (KTX) in these patients. Methods: We identified HTX patients in our center who subsequently underwent KTX. We then compared them to those who did not develop ESRF (control group). We also reviewed the outcome following KTX. Results: From May 1974 to May 2000, 877 patients underwent HTX at our center, of which 19 (2.2%) underwent interval KTX. Of the 19 KTX patients, all but 2 had CSA nephrotoxicity. Time from HTX to ESRF was 81⫾39 months, time from ESRF to KTX was 13⫾11 months, and duration of follow-up after KTX was 66⫾54 months. The creatinine levels just before KTX, at 6-month post-KTX, and at 2 yr post-KTX were 8.1⫾2.7, 1.6⫾0.6, and 1.7⫾1.2 mg/dL respectively.
Blood transfusion may affect outcomes after transplantation of some organs, but data are limited for heart transplantation (HT). 241 consecutive HTs from one center were reviewed to identify: (1) factors predicting use of blood products during and after HT, and (2) the effect of transfusion on survival and rejection. 68 perioperative variables were tested including: recipient age, weight, ABO group, creatinine, Hgb, PT, aPTT, platelet count; use of ASA, warfarin, or heparin; etiology of CHF; prior sternotomy; pre-op VAD; UNOS status; cardiopulmonary bypass and aortic clamp times; and use of inotropes, aminocaproic acid or aprotinin. Data were incomplete for 7 patients. 175 patients received at least one unit of PRBC, FFP, platelets, or cryoprecipitate (Group 1); 59 received none (Group 2). Groups were compared by Fisher’s Exact test for discreet variables and Student’s T-test for continuous variables. Variables differing at p⬍.05 were entered into a multivariate logistic regression model. 3 independent predictors of transfusion were found (see table).
12 Months after HTX
KTX (n ⴝ 18)
Control (n ⴝ 482)
p
Variable
Transfused
Not Transfused
Odds Ratio
P value
Creatinine (mg/dl) Sytolic Pressure (mm Hg) Diastolic Pressure (mm Hg) Cyclosporine dose (mg/kg/day)
1.9 ⫾ 0.6 145 ⫾ 13 98 ⫾ 11 6.4 ⫾ 5.4
1.6 ⫾ 0.6 133 ⫾ 18 89 ⫾ 13 5.3 ⫾ 4.2
0.0298 0.0099 0.0083 0.28
95% Confidence Interval
Preoperative aPTT Preoperative Hgb Use of Epinephrine
35.1 ⫾ 0.8 sec 12.0 ⫾ 0.2 g/dL 40.6%
30.7 ⫾ 0.7 sec 13.2 ⫾ 0.2 g/dL 15.3%
1.066 0.771 3.789
1.008–1.128 0.625–0.951 1.347–10.655
⬍0.03 ⬍0.02 ⬍0.02
One year after HTX, patients who subsequently required KTX had higher blood pressure and creatinine levels. The number of treated cardiac rejections episodes was 0.8⫾0.4/year/patient before KTX and 0.01⫾0.06/year/patient after KTX(p⬍0.0001). The 1-year survival after KTX was 84% and the 5-year survival was 66%.
Conclusion: Higher serum creatinine, systolic and diastolic blood pressure 1 year post-HTX may be associated with higher risk of developing ESRF later on, therefore control of these factors is important. For those who develop ESRF, interval KTX has a favorable outcome and is a reasonable alternative to chronic dialysis.
112 DO HEART TRANSPLANT RECIPIENTS THAT AVOID BLOOD TRANSFUSION FARE BETTER? T.T. Hamilton, J.A. Quin, L.M. Huber, D.M. Meyer, M.A. Wait, J.M. DiMaio, W.S. Ring, M.E. Jessen, Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
Long term survival (figure 1) and freedom from acute rejection (figure 2) were not affected by blood products. These data suggest that perioperative factors can help predict the need for transfusion after HT, but transfusion per se does not influence these major outcomes.
Abstracts
The Journal of Heart and Lung Transplantation January 2002
Results
Recipient Age (yr) Donor Age (yr) Donor Body Weight (kg) D/R Wt Ischaemic Time (min) TPG (mm Hg) 30 day mortality Hospital LOS (days)
HHTx (n ⴝ 13)
OHTx (n ⴝ 91)
P value
55 (51–63) 48 (34–50) 60 (55–70) 0.7 (0.6–0.9) 377 (205–464) 17 (12–22) 2 (15.4%) 22 (11–41)
52 (40–59) 35 (21–46) 75 (66–85) 1.0 (0.9–1.1) 255 (195–346) 8 (5–10) 5 (5.5%) 15 (10.3–21.8)
0.058 0.042 ⬍0.001 ⬍0.001 0.118 ⬍0.001 0.46 0.141
Values given: median (50% confidence limits)
There were two ⬍ 30 day deaths each on day 7, 1 following an “uneventful” cardiac biopsy and 1 from sepsis and multiorgan failure. There were no deaths from primary allograft failure despite the lower D/R Wt, significantly higher TPG’s and the utility of older donors compared to the OHTx group. Four year actuarial survival was 50% for HHTx (3 late deaths in the HHTx from LPD, respiratory failure and sternal wound sepsis) compared to 70% for OHTx. Conclusions: HHTx is a viable option for selected higher risk waiting list patients who might otherwise be denied transplantation. The successful use of often rejected smaller or “marginal” cardiac allografts expands the functional donor pool. 109 LOW AFFINITY FC RECEPTOR (CD32) MEDIATED PLATELET AGGREGATION/ACTIVATION IN VITRO BY ANTITHYMOCYTEGLOBULINE:A POSSIBLE EXPLANATION FOR INDUCTION THERAPY MEDIATED PLATELET DEPLETION IN VIVO H.J. Ankersmit,1 I. Volf,2 G. Roth,1 B. Moser,1 A. Zuckermann,1 A. Kocher,1 B. Schlechta,1 M. Haisjackl,3 G. Wieselthaler,1 M. Grimm,1 G. Boltz-Nitulescu,4 E. Wolner,1 1Department of Cardiothoracic Surgery, Vienna General Hospital, Vienna, Austria; 2Institute of Physiology, University Vienna, Vienna, Austria; 3Department of Anesthesia, Vienna General Hospital, Vienna, Austria; 4Institute of Pathophysiology, University Vienna, Vienna, Austria Background: Anti Thymocyte Globulin is administered in our heart transplant recipient population (2mg/kg) for 4-6 days in addition to initiation of conventional triple therapy (cyclosporine, azathioprine, steroids). This results in our institution to a 89% freedom of rejection (ISHLT II-III) within the first year after heart transplantation in the period 1997-1998 (93 patients who were admitted at the CT ICU). 41% of these patients had to be transfused with packed platelets (range 1-15, average transfusion 2.02 packs) when they reached values less than 30.000. Methods: Packed Platelets were obtained from the blood bank and platelet aggregation was determined by 490-4D four channel aggregometer after addition of ATG, OKT-3 and IL-2 R blocker (daclizumab). FACS analysis was utilized to evaluate CD62P and CD63 markers of platelet activation (ADP and Thrombin activation served as control). Electron microscopy was utilized to demonstrate blebbing after ATG induced activation. Results: ATG,OKT-3 and Il-2 R blocker were exposed to resting platelets in concentrations 10-150 g/cc, only ATG was able to induce aggregation in a dose dependent manner (aggregation threshold value was 10g/cc). Since platelet aggregation is dependent on low affinity receptor engagement (CD32), we coincubated platelets with anti-CD 32 mABs and ATG (10g/cc) an we were able to inhibit aggregation (p⬍0.001). Moreover, ATG
(10g/cc) was also able to increase CD62P/CD63 epitope upregulation (60%, 57%, respectivley), this was reversed by addition of anti-CD32 mABs in a dosedependent fashion. ELMI visualized blebbing, commonly seen in apoptotic cells. Conclusion: ATG, but not OKT3 or IL-2 R blocker are inducing low affinity receptor (CD32) mediated aggregation/activation in vitro and might serve as explanation for platelet depletion in transplant patient after ATG admininstration. 110 CONTRIBUTION OF IMPAIRED LEFT VENTRICULAR FUNCTION TO EXERCISE INTOLERANCE IN HEART TRANSPLANT RECIPIENTS M. Dandel, R. Ewert, M. Hummel, R. Meyer, J. Mueller, R. Hetzer, Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany Background: We assessed the left ventricular (LV) function and exercise tolerance in non-rejecting heart recipients, in connection with post-transplant time, amount of interstitial fibrosis and presence of transplant coronary artery disease (TxCAD). Methods: Echocardiographic analysis of LV function (M-mode, 2D, flow Doppler and tissue Doppler) was performed in 120 patients (post-transplant time: 3 months -13 years), prior to exercise testing, cardiac catheterization and endomyocardial biopsy. Echocardiographic parameters were tested for relationships with histological, angiographical and exercise findings. Results: Exercise intolerance (low peak VO2) was found in 117 patients (97.5%). Even without TxCAD, peak VO2 reached only 73.8 ⫾9.2% of predicted values. The elevated LV end-diastolic pressure [LVEDP] (11.8 ⫾5.9 mmHg) and reduced transmitral pressure half-time [PHT] (42.3 ⫾9.9 ms) suggest that without TxCAD, exercise intolerance was mainly related to diastolic dysfunction. All TxCAD patients showed exercise intolerance, which was highest in the angiographic TxCAD group. In these patients, the LV ejection fraction (LVEF), although lower than without TxCAD (p ⫽0.0011), was in the normal range (62.8 ⫾11.5%). The high LVEDP (14.8 ⫾5.6 mmHg) and short PHT (30.1 ⫾ 8.7 ms) in these patients were indicative of a mainly diastolic dysfunction. The significantly reduced systolic wall motion peak velocities in both angiographic TxCAD and TxCAD, visible only by intracoronary ultrasound, suggest also the contribution of systolic dysfunction to exercise intolerance. Impaired diastolic function and exercise intolerance also appeared to be related to interstitial fibrosis. Patients with diffuse perivascular and interstitial fibrosis showed shorter PHT, higher LVEDP, and more altered exercise parameters than those with minimal or reduced fibrosis (p ⬍0.001). Patients with TxCAD showed reduced chronotropic responses to exercise (p ⬍0.01). Conclusions: The LV diastolic dysfunction, closely related to interstitial fibrosis, is a major cause of post-transplant exercise intolerance. TxCAD impairs exercise capacity mainly by aggravating pre-existent diastolic dysfunction and reduced chronotropic response to exercise. 111 END-STAGE RENAL FAILURE AND KIDNEY TRANSPLANTATION IN HEART TRANSPLANT RECIPIENTS M.C.Y. Chan, B. Cantin, H.A. Valantine, S.A. Hunt, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA
The Journal of Heart and Lung Transplantation Volume 21, Number 1
Abstracts
95
Background: Renal dysfunction is common in heart transplant (HTX) recipients due to pre-existing renal impairment and cyclosporine use. A subset will develop end-stage renal failure (ESRF). It is unclear what factors predict ESRF, and what the long-term outcome is after kidney transplantation (KTX) in these patients. Methods: We identified HTX patients in our center who subsequently underwent KTX. We then compared them to those who did not develop ESRF (control group). We also reviewed the outcome following KTX. Results: From May 1974 to May 2000, 877 patients underwent HTX at our center, of which 19 (2.2%) underwent interval KTX. Of the 19 KTX patients, all but 2 had CSA nephrotoxicity. Time from HTX to ESRF was 81⫾39 months, time from ESRF to KTX was 13⫾11 months, and duration of follow-up after KTX was 66⫾54 months. The creatinine levels just before KTX, at 6-month post-KTX, and at 2 yr post-KTX were 8.1⫾2.7, 1.6⫾0.6, and 1.7⫾1.2 mg/dL respectively.
Blood transfusion may affect outcomes after transplantation of some organs, but data are limited for heart transplantation (HT). 241 consecutive HTs from one center were reviewed to identify: (1) factors predicting use of blood products during and after HT, and (2) the effect of transfusion on survival and rejection. 68 perioperative variables were tested including: recipient age, weight, ABO group, creatinine, Hgb, PT, aPTT, platelet count; use of ASA, warfarin, or heparin; etiology of CHF; prior sternotomy; pre-op VAD; UNOS status; cardiopulmonary bypass and aortic clamp times; and use of inotropes, aminocaproic acid or aprotinin. Data were incomplete for 7 patients. 175 patients received at least one unit of PRBC, FFP, platelets, or cryoprecipitate (Group 1); 59 received none (Group 2). Groups were compared by Fisher’s Exact test for discreet variables and Student’s T-test for continuous variables. Variables differing at p⬍.05 were entered into a multivariate logistic regression model. 3 independent predictors of transfusion were found (see table).
12 Months after HTX
KTX (n ⴝ 18)
Control (n ⴝ 482)
p
Variable
Transfused
Not Transfused
Odds Ratio
P value
Creatinine (mg/dl) Sytolic Pressure (mm Hg) Diastolic Pressure (mm Hg) Cyclosporine dose (mg/kg/day)
1.9 ⫾ 0.6 145 ⫾ 13 98 ⫾ 11 6.4 ⫾ 5.4
1.6 ⫾ 0.6 133 ⫾ 18 89 ⫾ 13 5.3 ⫾ 4.2
0.0298 0.0099 0.0083 0.28
95% Confidence Interval
Preoperative aPTT Preoperative Hgb Use of Epinephrine
35.1 ⫾ 0.8 sec 12.0 ⫾ 0.2 g/dL 40.6%
30.7 ⫾ 0.7 sec 13.2 ⫾ 0.2 g/dL 15.3%
1.066 0.771 3.789
1.008–1.128 0.625–0.951 1.347–10.655
⬍0.03 ⬍0.02 ⬍0.02
One year after HTX, patients who subsequently required KTX had higher blood pressure and creatinine levels. The number of treated cardiac rejections episodes was 0.8⫾0.4/year/patient before KTX and 0.01⫾0.06/year/patient after KTX(p⬍0.0001). The 1-year survival after KTX was 84% and the 5-year survival was 66%.
Conclusion: Higher serum creatinine, systolic and diastolic blood pressure 1 year post-HTX may be associated with higher risk of developing ESRF later on, therefore control of these factors is important. For those who develop ESRF, interval KTX has a favorable outcome and is a reasonable alternative to chronic dialysis.
112 DO HEART TRANSPLANT RECIPIENTS THAT AVOID BLOOD TRANSFUSION FARE BETTER? T.T. Hamilton, J.A. Quin, L.M. Huber, D.M. Meyer, M.A. Wait, J.M. DiMaio, W.S. Ring, M.E. Jessen, Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX
Long term survival (figure 1) and freedom from acute rejection (figure 2) were not affected by blood products. These data suggest that perioperative factors can help predict the need for transfusion after HT, but transfusion per se does not influence these major outcomes.