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Value of non invasive tissue doppler derived Tei-index in detection of transplant vasculopathy in pediatric heart transplant recipients
S168
Abstracts
rejection, 2) alternative immunosuppression (IS), and 3) promotion of regression/prevention of graft vasculopathy (CAD). There is little data on the use of sirolimus in the pediatric heart transplant (Tx) population. Purpose: To report our experience with sirolimus in 16 pediatric heart Tx pts. Procedures: Data were obtained by retrospective chart review. Results: There were 9 males and 7 females. Median age at review was 12.3 yr (5.1-18.0yr), and at Tx was 7.5 yr (6mo-18.0yr). Sirolimus was started at median 2.7 yr (1mo– 8.2yr) post-tx and median age 11.2 yr (2.2-18.0yr). At start of sirolimus, 15 pts were on steroids, 9 on tacrolimus (FK)/mycophenolate mofetil (MMF), 5 on FK and 1 on cyclosporine (CYA)/MMF. Average sirolimus dose was 0.25 mg/kg or 7.0 mg/m2, target level 10-12 g/L allowing for decreased calcineurin inhibitor dose. Sirolimus was started for mod-sev CAD (n ⫽ 5, 31%), rejection (n ⫽ 5, 31%), and in 6 pts for combinations of the following: CYA side-effects, FK side-effects, CAD, renal dysfunction and rejection. Six pts who received sirolimus for treatment of rejection (ISHLT 3A) showed improvement (ISHLT 0-1A/B). Three pts received sirolimus due to severely reduced renal function by glomerular filtration rate (GFR); 2 showed improvement at follow-up (GFR 43 and 32 to 67 and 106 ml/min/1.73 m2, respectively) and one pt was transferred prior to follow-up. Side-effects included: abdominal pain (n ⫽ 5, 31%), mouth ulcers (n ⫽ 4, 26%), hyperlipidemia (n ⫽ 3, 19%), anemia/ neutropenia (n ⫽ 2, 12.5%), impaired linear growth (n ⫽ 1, 6%), interstitial lung disease NYD (n ⫽ 1, 6%). Sirolimus was discontinued due to side-effects in 3 pts. Conclusion: In this group of pediatric heart Tx recipients, sirolimus is a valuable adjunct IS agent for management of rejection, renal dysfunction, and calcineurin-inhibitor side-effects. The role of sirolimus in CAD regression and prophylaxis of both primary rejection and CAD remains to be determined.
374 VALUE OF NON INVASIVE TISSUE DOPPLER DERIVED TEIINDEX IN DETECTION OF TRANSPLANT VASCULOPATHY IN PEDIATRIC HEART TRANSPLANT RECIPIENTS H. Abdul-Khaliq,1 M. Abdel-Rhahman,1 S. Schubert,1 H.B. Lehmkuhl,1 E. Wellnhofer,1 P. Ewert,1 N. Hiemann,1 B. Schmitt,1 P.E. Lange,1 R. Hetzer,1 1Deutsches Herzzentrum Berlin, Berlin, Germany Introduction: Transplant vasculopathy (TVP) remains the major cause of graft failure in long term survivors after HTx. Unfortunately, non-invasive methods were found to be insensitive for early diagnosis of TVP. The novel tissue Doppler imaging technique has the potential to provide sensitive information on the ventricular function as reflected by longitudinal contraction. The aim of the study was to evaluate the diagnostic value of tissue derived parameters to detect transplant vasculopathy. Method: Out of 132 pediatric heart transplants recipients in the German Heart Centre Berlin 25 pediatric patients with a median age of 13 years and median period of 5.98 years after heart transplantation, received selective coronary angiography to determine the degree of coronary artery disease (TVP), according to Stanford criteria of Gao et al (1988). Tissue Doppler imaging (TDI) was performed one day before cardiac catheterization and systolic and diastolic myocardial wall motions were analyzed in a 4 chamber and a short axis view. The left ventricular (LV) Tei-index (sum of the isovolumetric contraction and relaxation time divided by the ejection time) was calculated from the TDI-spectral waves and color M-Mode. Results: Seven patients demonstrated lesions of TVP on coronary angiography (28%). The development of TVP correlated significantly with the post transplant period (p ⬍ 0.01). The Tei-index among
The Journal of Heart and Lung Transplantation February 2004
patients with TVP was significantly higher than in patients without TVP (p ⬍ 0.01).The significantly higher Tei- index in the TVP group was due to a significant prolongation of the isovolumetric contraction time (p ⬍ 0.001),indicating a deterioration of the left ventricular systolic function. Conclusions: The non invasive tissue Doppler derived Tei-index may identify pediatric heart transplant recipient with transplant vasculopathy.
375 PROSPECTIVE FOLLOW-UP OF PANEL REACTIVE ANTIBODIES IN CHILDREN 5-YEARS FOLLOWING IMPLANTATION OF CRYOPRESERVED ALLOGRAFTS D.K. Hooper,1 J.A. Hawkins,2 T.C. Fuller,3 T. Profaizer,3 R.E. Shaddy,1 1Pediatrics, University of Utah, Salt Lake City, UT; 2 Surgery, University of Utah, Salt Lake City, UT; 3Pathology, University of Utah, Salt Lake City, UT Background Circulating HLA panel reactive antibodies (PRA ⬎ 10%) have been independently associated with increased risk of rejection and mortality in patients who undergo cardiac transplantation. Cryopreserved allografts used to repair congenital heart defects induce broadly reactive HLA antibodies in children that persist for an undetermined duration of time. The purpose of this study was to prospectively determine whether circulating HLA antibodies persist in children for 3-8 years after implantation of cryopreserved allograft tissue. Methods and Results We conducted a 3-8 year follow-up (mean 5.6 ⫾ 2 years) of 35 consecutive children previously screened for PRA prior to and following implantation of valved (n ⫽ 22) and non-valved (n ⫽ 13) allografts. Thirteen children are alive and free from allograft replacement; PRA against HLA Class I and Class II antigens was determined using flow cytometry procedures and classified as high reactive (⬎50% PRA), low reactive (11%-50%), or absent (0-10%). Follow-up PRAs in this study were compared to PRAs obtained 3 months following initial allograft implant. In the valved allograft group, HLA Class I PRA was present at follow-up in 5 of 6 children though it had decreased significantly from high to low or from low to absent in 5 of 6 patients (p ⫽ 0.001, Fisher’s exact test). Similarly, in the non-valved allograft group, HLA Class I PRA persisted in 7 of 7 children, though it had decreased from high to low in 6 of 7 children (p ⬍ 0.001). As a group, HLA Class II PRA persisted in 6 of 13 children (46%) but had decreased significantly at follow-up (p ⫽ 0.02). Conclusions The circulating HLA antibodies induced by cryopreserved allograft tissue can persist up to 8 years following implantation. These antibodies decrease over time and can become undetectable in certain patients. Due to the persistence of circulating HLA antibodies, children who have received cryopreserved allografts many years prior to cardiac transplantation may be at greater risk for transplant rejection.
376 LATE OUTCOMES AFTER HEART TRANSPLANTATION IN ADULTS WITH CONGENITAL HEART DISEASE: A MULTIINSTITUTIONAL ANALYSIS B.S. Clemson, J.K. Kirklin, C.E. Canter, D.C. Naftel, J.B. Young, J.A. Hill, R.J. Rodeheffer, B. Radovancevic, S. Faulkner, The Cardiac Transplant Research Database,1 1University of Alabama at Birmingham, Birmingham, AL Background: The long-term outcome of adults with congenital disease (CHD) who undergo cardiac transplantation (CTx) remains uncertain. We examined risk factors for early and late survival after CTx for CHD in a multi-institutional analysis.
Abstracts
rejection, 2) alternative immunosuppression (IS), and 3) promotion of regression/prevention of graft vasculopathy (CAD). There is little data on the use of sirolimus in the pediatric heart transplant (Tx) population. Purpose: To report our experience with sirolimus in 16 pediatric heart Tx pts. Procedures: Data were obtained by retrospective chart review. Results: There were 9 males and 7 females. Median age at review was 12.3 yr (5.1-18.0yr), and at Tx was 7.5 yr (6mo-18.0yr). Sirolimus was started at median 2.7 yr (1mo– 8.2yr) post-tx and median age 11.2 yr (2.2-18.0yr). At start of sirolimus, 15 pts were on steroids, 9 on tacrolimus (FK)/mycophenolate mofetil (MMF), 5 on FK and 1 on cyclosporine (CYA)/MMF. Average sirolimus dose was 0.25 mg/kg or 7.0 mg/m2, target level 10-12 g/L allowing for decreased calcineurin inhibitor dose. Sirolimus was started for mod-sev CAD (n ⫽ 5, 31%), rejection (n ⫽ 5, 31%), and in 6 pts for combinations of the following: CYA side-effects, FK side-effects, CAD, renal dysfunction and rejection. Six pts who received sirolimus for treatment of rejection (ISHLT 3A) showed improvement (ISHLT 0-1A/B). Three pts received sirolimus due to severely reduced renal function by glomerular filtration rate (GFR); 2 showed improvement at follow-up (GFR 43 and 32 to 67 and 106 ml/min/1.73 m2, respectively) and one pt was transferred prior to follow-up. Side-effects included: abdominal pain (n ⫽ 5, 31%), mouth ulcers (n ⫽ 4, 26%), hyperlipidemia (n ⫽ 3, 19%), anemia/ neutropenia (n ⫽ 2, 12.5%), impaired linear growth (n ⫽ 1, 6%), interstitial lung disease NYD (n ⫽ 1, 6%). Sirolimus was discontinued due to side-effects in 3 pts. Conclusion: In this group of pediatric heart Tx recipients, sirolimus is a valuable adjunct IS agent for management of rejection, renal dysfunction, and calcineurin-inhibitor side-effects. The role of sirolimus in CAD regression and prophylaxis of both primary rejection and CAD remains to be determined.
374 VALUE OF NON INVASIVE TISSUE DOPPLER DERIVED TEIINDEX IN DETECTION OF TRANSPLANT VASCULOPATHY IN PEDIATRIC HEART TRANSPLANT RECIPIENTS H. Abdul-Khaliq,1 M. Abdel-Rhahman,1 S. Schubert,1 H.B. Lehmkuhl,1 E. Wellnhofer,1 P. Ewert,1 N. Hiemann,1 B. Schmitt,1 P.E. Lange,1 R. Hetzer,1 1Deutsches Herzzentrum Berlin, Berlin, Germany Introduction: Transplant vasculopathy (TVP) remains the major cause of graft failure in long term survivors after HTx. Unfortunately, non-invasive methods were found to be insensitive for early diagnosis of TVP. The novel tissue Doppler imaging technique has the potential to provide sensitive information on the ventricular function as reflected by longitudinal contraction. The aim of the study was to evaluate the diagnostic value of tissue derived parameters to detect transplant vasculopathy. Method: Out of 132 pediatric heart transplants recipients in the German Heart Centre Berlin 25 pediatric patients with a median age of 13 years and median period of 5.98 years after heart transplantation, received selective coronary angiography to determine the degree of coronary artery disease (TVP), according to Stanford criteria of Gao et al (1988). Tissue Doppler imaging (TDI) was performed one day before cardiac catheterization and systolic and diastolic myocardial wall motions were analyzed in a 4 chamber and a short axis view. The left ventricular (LV) Tei-index (sum of the isovolumetric contraction and relaxation time divided by the ejection time) was calculated from the TDI-spectral waves and color M-Mode. Results: Seven patients demonstrated lesions of TVP on coronary angiography (28%). The development of TVP correlated significantly with the post transplant period (p ⬍ 0.01). The Tei-index among
The Journal of Heart and Lung Transplantation February 2004
patients with TVP was significantly higher than in patients without TVP (p ⬍ 0.01).The significantly higher Tei- index in the TVP group was due to a significant prolongation of the isovolumetric contraction time (p ⬍ 0.001),indicating a deterioration of the left ventricular systolic function. Conclusions: The non invasive tissue Doppler derived Tei-index may identify pediatric heart transplant recipient with transplant vasculopathy.
375 PROSPECTIVE FOLLOW-UP OF PANEL REACTIVE ANTIBODIES IN CHILDREN 5-YEARS FOLLOWING IMPLANTATION OF CRYOPRESERVED ALLOGRAFTS D.K. Hooper,1 J.A. Hawkins,2 T.C. Fuller,3 T. Profaizer,3 R.E. Shaddy,1 1Pediatrics, University of Utah, Salt Lake City, UT; 2 Surgery, University of Utah, Salt Lake City, UT; 3Pathology, University of Utah, Salt Lake City, UT Background Circulating HLA panel reactive antibodies (PRA ⬎ 10%) have been independently associated with increased risk of rejection and mortality in patients who undergo cardiac transplantation. Cryopreserved allografts used to repair congenital heart defects induce broadly reactive HLA antibodies in children that persist for an undetermined duration of time. The purpose of this study was to prospectively determine whether circulating HLA antibodies persist in children for 3-8 years after implantation of cryopreserved allograft tissue. Methods and Results We conducted a 3-8 year follow-up (mean 5.6 ⫾ 2 years) of 35 consecutive children previously screened for PRA prior to and following implantation of valved (n ⫽ 22) and non-valved (n ⫽ 13) allografts. Thirteen children are alive and free from allograft replacement; PRA against HLA Class I and Class II antigens was determined using flow cytometry procedures and classified as high reactive (⬎50% PRA), low reactive (11%-50%), or absent (0-10%). Follow-up PRAs in this study were compared to PRAs obtained 3 months following initial allograft implant. In the valved allograft group, HLA Class I PRA was present at follow-up in 5 of 6 children though it had decreased significantly from high to low or from low to absent in 5 of 6 patients (p ⫽ 0.001, Fisher’s exact test). Similarly, in the non-valved allograft group, HLA Class I PRA persisted in 7 of 7 children, though it had decreased from high to low in 6 of 7 children (p ⬍ 0.001). As a group, HLA Class II PRA persisted in 6 of 13 children (46%) but had decreased significantly at follow-up (p ⫽ 0.02). Conclusions The circulating HLA antibodies induced by cryopreserved allograft tissue can persist up to 8 years following implantation. These antibodies decrease over time and can become undetectable in certain patients. Due to the persistence of circulating HLA antibodies, children who have received cryopreserved allografts many years prior to cardiac transplantation may be at greater risk for transplant rejection.
376 LATE OUTCOMES AFTER HEART TRANSPLANTATION IN ADULTS WITH CONGENITAL HEART DISEASE: A MULTIINSTITUTIONAL ANALYSIS B.S. Clemson, J.K. Kirklin, C.E. Canter, D.C. Naftel, J.B. Young, J.A. Hill, R.J. Rodeheffer, B. Radovancevic, S. Faulkner, The Cardiac Transplant Research Database,1 1University of Alabama at Birmingham, Birmingham, AL Background: The long-term outcome of adults with congenital disease (CHD) who undergo cardiac transplantation (CTx) remains uncertain. We examined risk factors for early and late survival after CTx for CHD in a multi-institutional analysis.