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Combined prophylaxis of CMV-immune globulin plus ganciclovir versus CMV-immune globulin alone in high risk heart transplant recipients
S156
Abstracts
potent activation through the T cell receptor independent of costimulatory signals from antigen presenting cells, supporting the concept that ICOSmediated events affect later stages of T cell activation. 253 TRANSPLANTATION USING HEARTS FROM PRIMARY PULMONARY HYPERTENSIVE DONORS FOR RECIPIENTS WITH HIGH PULMONARY VASCULAR RESISTANCE E.J. Birks, A. Anyanwu, F. De Robertis, J. Jayakumar, R. Radley Smith, N.R. Banner, M.H. Yacoub, A. Khaghani, Cardiology & Cardiothoracic Surgery, Royal Brompton & Harefield Hospital, Harefield, Middlesex, United Kingdom Transplantation for patients with a high Pulmonary Vascular Resistance (PVR) carries an increased risk of mortality and right heart failure following transplantation. We have performed a total of 131 domino heart transplants since 1987 at our institution. Of these 131 patients, 20 (15.3%) underwent heart transplantation from donors with primary pulmonary hypertension (PPH). Twelve of these 20 (60%) PPH hearts were transplanted into recipients with a PVR ⱖ4. The aim of this study was to describe our experience in these 12 patients with a PVR ⱖ4 who received a conditioned heart from a donor with primary pulmonary hypertension. Ten were males and 2 were female. Mean age was 42.9 (range 13-71) yrs.Transplantation was performed for ischaemic heart disease in 6, dilated cardiomyopathy in 2, congenital heart disease in 3 and valvular heart disease in 1. Mean recipient PVR was 5.3 (range 4-9) Wood units prior to transplantation and mean recipient weight was 70.6kg at transplantation. Mean donor age was 32ys and mean donor weight was 67.3kg. Mean ischaemic time was 85.3 minutes. There was one early death from primary graft dysfunction. Acturial survival was 75% at 1 year and 75% at 5 years. At latest follow up angiography showed coronary disease in only 2 patients. In conclusion donors with primary pulmonary hypertension provide a valuable source of hearts for patients with elevated PVR and provide an alternative to heart-lung transplantation. 254 COMBINED PROPHYLAXIS OF CMV-IMMUNE GLOBULIN PLUS GANCICLOVIR VERSUS CMV-IMMUNE GLOBULIN ALONE IN HIGH RISK HEART TRANSPLANT RECIPIENTS N.E. Bonaros,1 A.A. Kocher,2 M. Ehrlich,2 M. Grimm,2 E. Wolner,2 G. Laufer,1 1Cardiac Surgery, University of Innsbruck, Innsbruck, Austria; 2Cardiothoracic Surgery, University of Vienna, Vienna, Austria Background: Seronegative heart transplant recipients, who receive an allograft from seropositive donors are in higher risk to develop CMVinfection, as well as cardiac allograft vasculopathy and dysfunction. Neither CMV-specific hyperimmune globulin nor ganciclovir as sole CMV-prophylaxis seem to be able to prevent CMV-disease in high-risk patients. We retrospectively evaluated the efficacy of CMV-immune globulin with and without ganciclovir in 207 D⫹/R- heart transplant recipients. Methods: The study population was divided into two groups: Group A (1990-1996): 96 patients, who received CMV immune globulin, as sole CMV prophylaxis and Group B (1997-1999): 111 patients, who received combined CMV prophylaxis. All recipients were subjected to quadruple immunosuppression. The primary endpoint was prevention of CMVassociated death. Secondary endpoints included prevention of CMVdisease and infection, cardiac allograft vasculopathy and overall infection. Results: There was no difference in overall survival between the two groups. 4 patients of the first group died on CMV-Sepsis, whereas no
The Journal of Heart and Lung Transplantation January 2003 CMV-associated death was observed in group B (p ⫽ 0.032). Incidence of CMV-disease was significantly lower in patients who received double CMV-prophylaxis (32.29 vs. 11.71, p ⫽ 0.0003). Although no difference was observed with regard to CMV-infection (53.12 vs. 65.77, p ⫽ NS), cardiac allograft vasculopathy and overall infection rates were significantly higher in the first group (7.29 vs. 0.9, p ⫽ 0.0157 and 70.83 vs. 62.16, p ⫽ 0.03, respectively). Conclusions: Double CMV-prophylaxis consisting of CMV hyperimmune globulin and ganciclovir is able to prevent CMV-death and disease in high-risk patients, after heart transplantation. Therefore the use of a combination regimen is strongly recommended for seronegative recipients of seropositive donors.
255 PREVENTION OF BONE LOSS AFTER CARDIAC TRANSPLANTATION WITH ALENDRONATE OR CALCITRIOL: EFFICACY AND SAFETY S. Maybaum,1 V. Addesso,1 P. Namerow,1 R.B. Staron,1 S.H. Lo,1 M. Zucker,2 S. Pardi,2 D.M. Mancini,1 E. Shane,1 1Medicine, Columbia University, College of Physicians & Surgeons, New York, NY; 2Medicine, Newark-Beth Israel Medical Center, Newark, NJ The first year after cardiac transplantation (CTX) is characterized by high rates of bone loss and vertebral fracture. To prevent this complication of CTX, we conducted a 1-year, double-masked, randomized clinical trial (RCT) evaluating the efficacy and safety of alendronate (ALN; 10 mg QD) and calcitriol (1,25D; 0.25 mg BID). Subjects (n ⫽ 149) were randomized to ALN (n ⫽ 74) or 1,25D (n ⫽ 75), 21⫹/-11 days after CTX. Bone loss was compared between treatment groups and to a nonrandomized group of subjects (CON; n ⫽ 25) who declined to participate in the RCT. All participants received daily calcium (Ca; 1000 mg) and vitamin D (1000 IU) and immunosuppressive therapy. The 3 groups were similar with respect to gender, race, age, renal function, serum/urine Ca. Bone loss (% change from baseline at 1 year ⫹/-S.E.M.) was analyzed by intent-to-treat (ITT) and on a subset that completed the RCT on study drug (Efficacy). Bone loss was minimal in treated groups and did not differ between ALN and 1,25D. Both sustained significantly less bone loss than CON. SITE
ANALYSIS
ALN
1,25D
CON
Lumbar Spine
ITT Efficacy* ITT* Efficacy**
⫺0.8 ⫾ 0.5 ⫹0.3 ⫾ 0.6 ⫺1.5 ⫾ 0.6 ⫺1.3 ⫾ 0.8
⫺1.4 ⫾ 0.6 ⫺0.6 ⫾ 0.8 ⫺1.8 ⫾ 0.8 ⫺0.4 ⫾ 0.8
⫺3.2 ⫾ 0.9 ⫺3.2 ⫾ 0.9 ⫺6.2 ⫾ 0.9 ⫺6.2 ⫾ 0.9
Femoral Neck
*p ⱕ 0.001; **p ⱕ 0.0001 compared to CON.
The 3 groups did not differ by immunosuppressive dose, hospitalizations, rejections or GI symptoms. Elevated urine Ca (ⱖ 300 mg/g) and serum Ca (ⱖ 10.4 mg/dl) were more frequent in 1,25D than ALN (p ⫽ 0.04 to 0.001). Subjects randomized to ALN or 1,25D did not sustain significant bone loss, nor did rates of bone loss differ between ALN and 1,25D at any site or time. In contrast, CON subjects sustained significant bone loss. We conclude that both ALN and 1,25D prevent bone loss after CTX. However, the need for monitoring with 1,25D makes ALN a more convenient choice in this setting. 256 TEMPORAL ALTERATION IN B-TYPE NATRIURETIC PEPTIDE EXPRESSION PREDICTS ALLOGRAFT FAILURE IN HEART TRANSPLANTATION
Abstracts
potent activation through the T cell receptor independent of costimulatory signals from antigen presenting cells, supporting the concept that ICOSmediated events affect later stages of T cell activation. 253 TRANSPLANTATION USING HEARTS FROM PRIMARY PULMONARY HYPERTENSIVE DONORS FOR RECIPIENTS WITH HIGH PULMONARY VASCULAR RESISTANCE E.J. Birks, A. Anyanwu, F. De Robertis, J. Jayakumar, R. Radley Smith, N.R. Banner, M.H. Yacoub, A. Khaghani, Cardiology & Cardiothoracic Surgery, Royal Brompton & Harefield Hospital, Harefield, Middlesex, United Kingdom Transplantation for patients with a high Pulmonary Vascular Resistance (PVR) carries an increased risk of mortality and right heart failure following transplantation. We have performed a total of 131 domino heart transplants since 1987 at our institution. Of these 131 patients, 20 (15.3%) underwent heart transplantation from donors with primary pulmonary hypertension (PPH). Twelve of these 20 (60%) PPH hearts were transplanted into recipients with a PVR ⱖ4. The aim of this study was to describe our experience in these 12 patients with a PVR ⱖ4 who received a conditioned heart from a donor with primary pulmonary hypertension. Ten were males and 2 were female. Mean age was 42.9 (range 13-71) yrs.Transplantation was performed for ischaemic heart disease in 6, dilated cardiomyopathy in 2, congenital heart disease in 3 and valvular heart disease in 1. Mean recipient PVR was 5.3 (range 4-9) Wood units prior to transplantation and mean recipient weight was 70.6kg at transplantation. Mean donor age was 32ys and mean donor weight was 67.3kg. Mean ischaemic time was 85.3 minutes. There was one early death from primary graft dysfunction. Acturial survival was 75% at 1 year and 75% at 5 years. At latest follow up angiography showed coronary disease in only 2 patients. In conclusion donors with primary pulmonary hypertension provide a valuable source of hearts for patients with elevated PVR and provide an alternative to heart-lung transplantation. 254 COMBINED PROPHYLAXIS OF CMV-IMMUNE GLOBULIN PLUS GANCICLOVIR VERSUS CMV-IMMUNE GLOBULIN ALONE IN HIGH RISK HEART TRANSPLANT RECIPIENTS N.E. Bonaros,1 A.A. Kocher,2 M. Ehrlich,2 M. Grimm,2 E. Wolner,2 G. Laufer,1 1Cardiac Surgery, University of Innsbruck, Innsbruck, Austria; 2Cardiothoracic Surgery, University of Vienna, Vienna, Austria Background: Seronegative heart transplant recipients, who receive an allograft from seropositive donors are in higher risk to develop CMVinfection, as well as cardiac allograft vasculopathy and dysfunction. Neither CMV-specific hyperimmune globulin nor ganciclovir as sole CMV-prophylaxis seem to be able to prevent CMV-disease in high-risk patients. We retrospectively evaluated the efficacy of CMV-immune globulin with and without ganciclovir in 207 D⫹/R- heart transplant recipients. Methods: The study population was divided into two groups: Group A (1990-1996): 96 patients, who received CMV immune globulin, as sole CMV prophylaxis and Group B (1997-1999): 111 patients, who received combined CMV prophylaxis. All recipients were subjected to quadruple immunosuppression. The primary endpoint was prevention of CMVassociated death. Secondary endpoints included prevention of CMVdisease and infection, cardiac allograft vasculopathy and overall infection. Results: There was no difference in overall survival between the two groups. 4 patients of the first group died on CMV-Sepsis, whereas no
The Journal of Heart and Lung Transplantation January 2003 CMV-associated death was observed in group B (p ⫽ 0.032). Incidence of CMV-disease was significantly lower in patients who received double CMV-prophylaxis (32.29 vs. 11.71, p ⫽ 0.0003). Although no difference was observed with regard to CMV-infection (53.12 vs. 65.77, p ⫽ NS), cardiac allograft vasculopathy and overall infection rates were significantly higher in the first group (7.29 vs. 0.9, p ⫽ 0.0157 and 70.83 vs. 62.16, p ⫽ 0.03, respectively). Conclusions: Double CMV-prophylaxis consisting of CMV hyperimmune globulin and ganciclovir is able to prevent CMV-death and disease in high-risk patients, after heart transplantation. Therefore the use of a combination regimen is strongly recommended for seronegative recipients of seropositive donors.
255 PREVENTION OF BONE LOSS AFTER CARDIAC TRANSPLANTATION WITH ALENDRONATE OR CALCITRIOL: EFFICACY AND SAFETY S. Maybaum,1 V. Addesso,1 P. Namerow,1 R.B. Staron,1 S.H. Lo,1 M. Zucker,2 S. Pardi,2 D.M. Mancini,1 E. Shane,1 1Medicine, Columbia University, College of Physicians & Surgeons, New York, NY; 2Medicine, Newark-Beth Israel Medical Center, Newark, NJ The first year after cardiac transplantation (CTX) is characterized by high rates of bone loss and vertebral fracture. To prevent this complication of CTX, we conducted a 1-year, double-masked, randomized clinical trial (RCT) evaluating the efficacy and safety of alendronate (ALN; 10 mg QD) and calcitriol (1,25D; 0.25 mg BID). Subjects (n ⫽ 149) were randomized to ALN (n ⫽ 74) or 1,25D (n ⫽ 75), 21⫹/-11 days after CTX. Bone loss was compared between treatment groups and to a nonrandomized group of subjects (CON; n ⫽ 25) who declined to participate in the RCT. All participants received daily calcium (Ca; 1000 mg) and vitamin D (1000 IU) and immunosuppressive therapy. The 3 groups were similar with respect to gender, race, age, renal function, serum/urine Ca. Bone loss (% change from baseline at 1 year ⫹/-S.E.M.) was analyzed by intent-to-treat (ITT) and on a subset that completed the RCT on study drug (Efficacy). Bone loss was minimal in treated groups and did not differ between ALN and 1,25D. Both sustained significantly less bone loss than CON. SITE
ANALYSIS
ALN
1,25D
CON
Lumbar Spine
ITT Efficacy* ITT* Efficacy**
⫺0.8 ⫾ 0.5 ⫹0.3 ⫾ 0.6 ⫺1.5 ⫾ 0.6 ⫺1.3 ⫾ 0.8
⫺1.4 ⫾ 0.6 ⫺0.6 ⫾ 0.8 ⫺1.8 ⫾ 0.8 ⫺0.4 ⫾ 0.8
⫺3.2 ⫾ 0.9 ⫺3.2 ⫾ 0.9 ⫺6.2 ⫾ 0.9 ⫺6.2 ⫾ 0.9
Femoral Neck
*p ⱕ 0.001; **p ⱕ 0.0001 compared to CON.
The 3 groups did not differ by immunosuppressive dose, hospitalizations, rejections or GI symptoms. Elevated urine Ca (ⱖ 300 mg/g) and serum Ca (ⱖ 10.4 mg/dl) were more frequent in 1,25D than ALN (p ⫽ 0.04 to 0.001). Subjects randomized to ALN or 1,25D did not sustain significant bone loss, nor did rates of bone loss differ between ALN and 1,25D at any site or time. In contrast, CON subjects sustained significant bone loss. We conclude that both ALN and 1,25D prevent bone loss after CTX. However, the need for monitoring with 1,25D makes ALN a more convenient choice in this setting. 256 TEMPORAL ALTERATION IN B-TYPE NATRIURETIC PEPTIDE EXPRESSION PREDICTS ALLOGRAFT FAILURE IN HEART TRANSPLANTATION