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Coronary ectasia in pediatric heart transplant recipients
The Journal of Heart and Lung Transplantation Volume 22, Number 1S Conclusion: We speculate that causes for mortality in the low IgG group may be complex but recognition of hypogammaglobulinemia identifies a population of patients for whom therapies may contribute to improvement of survival.
182 IMPACT OF DONOR CHARACTERISTICS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS J.M. Lamour, L.J. Addonizio, S. Mital, A. Wiesen, D.T. Hsu, Pediatric Cardiology, Columbia University, New York, NY The impact of donor characteristics on outcome following pediatric heart transplant (HTx) has not been well described.Pediatric HTx donors were characterized and the association of donor variables with HTx outcome was analyzed. Donor sex, age, weight (wt), cause of death, cardiopulmonary arrest (CPA) time, inotropic support (IS), and ventricular function (LVFx) were obtained. Recipient age, wt and post operative course were reviewed, including LVFx and early (⬍ 30 days) and late mortality. HTx was performed in 115 pediatric patients (pts) (56 female, 59 males) between 1/93 and 6/02; mean age was 8.4 ⫾ 11 yrs and mean weight was 36 ⫾ 33 kg. Donor data was available in 106 (92%) pts, 45 female and 61 male; gender mismatch occurred in 46%. Mean donor age was 10.9⫾11.3 yrs (range:1day-48yrs); mean donor/ recipient (D/R) age ratio was 1.4 ⫾1.04 yrs. Mean donor wt was 39.9⫾35.6 kg (r:2.6-170kg) with the mean D/R weight ratio 1.2 ⫾ 0.46 (r:0.48-3.1) Donor death occurred secondary to trauma n⫽51(48%), anoxia n⫽29 (27%), cerebrovascular accident n⫽13 (12%), child abuse n⫽8 (7.5%), brain tumor n⫽3, other n⫽2. CPA occurred in 31 (29%) donors; mean duration was 22⫾10 mins and was significantly associated with anoxic death (p⬍0.01). Shortening fraction ⬍ 28% was present in 4% of donors, none had significant mitral or tricuspid regurgitation. IS was used in 82 donors (77%); 44 (54%) required ⬎ 5 mcg/k/m of dopamine or dobutamine. Post-HTx early mortality was 10.4% (11/106 pts); 3 pts had early graft failure. Mean duration of mechanical ventilation was 4⫾6.3 days and of IS was 5.5⫾4.7 days. LVFx was normal in 76% of pts ⬍ 14 days post-HTx. No donor variable, including IS, CPA, gender mismatch or cause of death was associated with early LV dysfunction or early or late mortality. In conclusion, 77% of pediatric donors required IS and 29% had a prior CPA; 96% had normal LVFx. No donor factor was associated with poor outcome following HTx, further investigation into the use of marginal pediatric donors is warranted.
183 CORONARY ECTASIA IN PEDIATRIC HEART TRANSPLANT RECIPIENTS B.D. Kaufman, D.T. Hsu, J.M. Lamour, L.J. Addonizio, Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY Graft vasculopathy (GV) is a late complication of heart transplantation (HT) often resulting in graft loss. In adult HT recipients, the spectrum of GV lesions ranges from vessel narrowing (pruning) to stenosis and/or occlusion. Surveillance angiography (angio) in our pediatric patients (ped pts) revealed a subgroup with coronary ectasia (CE), significant dilation of one or more coronary arteries without stenosis. Our aim is to describe this unique subgroup of CE pts and compare risk factors and outcomes to pts with stenotic GV. All ped pts transplanted from 1986-2002 with angio evidence of GV were studied. CE was defined as vessel diameter ⬎1.3 times the
Abstracts
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normal adjacent area with no evidence of stenosis. GV pts with CE were compared to those without CE. Angio GV occurred in 26/174 pts (15%) at a mean of 4.4⫾2.8 yrs (range1-9) post HT. Mean age at HT was 8.9⫾5.4 yrs and mean age at GV diagnosis was 13.5⫾5.8 yrs (range1-24). Mean donor age was 13⫾10.6 yrs (range 1-39). Overall mean survival of GV pts was 7.7⫾3.5 yrs (range 1-13). At GV presentation, CE occurred in 7 pts (27%), stenosis in 17 pts (65%), and significant pruning in 2 pts. Pt survival post diagnosis of GV was 3.3⫾1.8 yrs. Comparison including length of followup, noncompliance, rejection with hemodynamic compromise (RHDC), and CMV serology, in pts with and without ectasia revealed: #Pts Yrs f/u CE no CE p value
7 19
4.9 ⫾ 3.9 6.1 ⫾ 2.9 .37
Died Noncompliant RHDC Donor CMV ReHT 0 11 .01
0 12 .01
0 10 .02
6 (86%) 6 (32%) .03
3 5 .64
There was no significant difference in race, sex, sudden death, pre-HT age or diagnosis, donor age, rejection frequency, age at GV, or pt CMV status, between pts with and without CE. Serial angios in 17 pts (mean 4.9 angio/pt range 1-10) revealed progressive GV in 12 pts; including significant stenosis in 3/7 pts who presented with CE. CE is a unique type of GV found in 27% of ped HT pts with GV. Pts presenting with CE may have a better prognosis than those with stenotic GV, however progression can occur. The association of donor CMV with CE requires further study. 184 MYCOPHENOLATE MOFETIL DOSE AND SERUM LEVEL CORRELATION IN YOUNG CARDIAC TRANSPLANT PATIENTS R.J. Gajarski,1 D. Crowley,1 M. Zamberlan,1 K. Lake,3 1Dept of Pediatrics, University of Michigan, C.S. Mott Children’s Hospital, Ann Arbor, MI; 2Dept of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI Background: Increasingly, mycophenolate mofetil (MMF) is replacing azathioprine as a maintenance immunosuppressant, as MMF decreases graft rejection and perhaps coronary intimal proliferation. Few studies have explored the relationship between recommended pediatric drug dosing and success in achieving therapeutic levels. Purpose: To retrospectively investigate the correlation between recommended MMF doses (1200mg/m2/d, max 3000mg/d) and serum trough levels in young orthotopic heart transplant (OHT) patients (pts). Methods: Since October 2001, at the time of endomyocardial biopsy (EMB), trough levels of mycophenolic acid (MPA) and its glucuronide metabolite, (MPAG) were measured by HPLC in pts followed our pediatric OHT service. Assay therapeutic range: MPA 1-3.5 mcg/ml and MPAG 35-100mcg/ml. Corresponding EMB grades and cyclosporine (CyA) levels were recorded when MPA/MPAG levels were obtained. Correlation coefficients were derived between MMF dose and MPA/ MPAG levels. Contingency analysis evaluated the relation between MPA level (ⱕ or ⬎ 1mcg/ml) and EMB grade. Results: Over 10 months, 20 pts had 30 MPA/MPAG levels. At time of levels, mean pt age was 15⫾8.5yrs; interval between OHT date and first MPA/MPAG level 35⫾39 months. Average MMF dose was 1256.7 ⫾ 320.6mg/m2/d, and median MPA and MPAG levels were 1.8⫾5.2 and 49⫾50mcg/ml, respectively. No relationship was found between MMF dose and either MPA (r⫽0.08) or MPAG levels (r⫽0.17). Finally, independent of CyA level (p⫽0.2), EMB grade ⱖ 2 occurred more frequently in pts with MPA levels ⱕ 1.0 (p⫽0.07). Conclusions: In young OHT pts, adherence to MMF pediatric dosing recommendations fails to consistently result in therapeutic HPLC
182 IMPACT OF DONOR CHARACTERISTICS IN PEDIATRIC HEART TRANSPLANT RECIPIENTS J.M. Lamour, L.J. Addonizio, S. Mital, A. Wiesen, D.T. Hsu, Pediatric Cardiology, Columbia University, New York, NY The impact of donor characteristics on outcome following pediatric heart transplant (HTx) has not been well described.Pediatric HTx donors were characterized and the association of donor variables with HTx outcome was analyzed. Donor sex, age, weight (wt), cause of death, cardiopulmonary arrest (CPA) time, inotropic support (IS), and ventricular function (LVFx) were obtained. Recipient age, wt and post operative course were reviewed, including LVFx and early (⬍ 30 days) and late mortality. HTx was performed in 115 pediatric patients (pts) (56 female, 59 males) between 1/93 and 6/02; mean age was 8.4 ⫾ 11 yrs and mean weight was 36 ⫾ 33 kg. Donor data was available in 106 (92%) pts, 45 female and 61 male; gender mismatch occurred in 46%. Mean donor age was 10.9⫾11.3 yrs (range:1day-48yrs); mean donor/ recipient (D/R) age ratio was 1.4 ⫾1.04 yrs. Mean donor wt was 39.9⫾35.6 kg (r:2.6-170kg) with the mean D/R weight ratio 1.2 ⫾ 0.46 (r:0.48-3.1) Donor death occurred secondary to trauma n⫽51(48%), anoxia n⫽29 (27%), cerebrovascular accident n⫽13 (12%), child abuse n⫽8 (7.5%), brain tumor n⫽3, other n⫽2. CPA occurred in 31 (29%) donors; mean duration was 22⫾10 mins and was significantly associated with anoxic death (p⬍0.01). Shortening fraction ⬍ 28% was present in 4% of donors, none had significant mitral or tricuspid regurgitation. IS was used in 82 donors (77%); 44 (54%) required ⬎ 5 mcg/k/m of dopamine or dobutamine. Post-HTx early mortality was 10.4% (11/106 pts); 3 pts had early graft failure. Mean duration of mechanical ventilation was 4⫾6.3 days and of IS was 5.5⫾4.7 days. LVFx was normal in 76% of pts ⬍ 14 days post-HTx. No donor variable, including IS, CPA, gender mismatch or cause of death was associated with early LV dysfunction or early or late mortality. In conclusion, 77% of pediatric donors required IS and 29% had a prior CPA; 96% had normal LVFx. No donor factor was associated with poor outcome following HTx, further investigation into the use of marginal pediatric donors is warranted.
183 CORONARY ECTASIA IN PEDIATRIC HEART TRANSPLANT RECIPIENTS B.D. Kaufman, D.T. Hsu, J.M. Lamour, L.J. Addonizio, Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY Graft vasculopathy (GV) is a late complication of heart transplantation (HT) often resulting in graft loss. In adult HT recipients, the spectrum of GV lesions ranges from vessel narrowing (pruning) to stenosis and/or occlusion. Surveillance angiography (angio) in our pediatric patients (ped pts) revealed a subgroup with coronary ectasia (CE), significant dilation of one or more coronary arteries without stenosis. Our aim is to describe this unique subgroup of CE pts and compare risk factors and outcomes to pts with stenotic GV. All ped pts transplanted from 1986-2002 with angio evidence of GV were studied. CE was defined as vessel diameter ⬎1.3 times the
Abstracts
S133
normal adjacent area with no evidence of stenosis. GV pts with CE were compared to those without CE. Angio GV occurred in 26/174 pts (15%) at a mean of 4.4⫾2.8 yrs (range1-9) post HT. Mean age at HT was 8.9⫾5.4 yrs and mean age at GV diagnosis was 13.5⫾5.8 yrs (range1-24). Mean donor age was 13⫾10.6 yrs (range 1-39). Overall mean survival of GV pts was 7.7⫾3.5 yrs (range 1-13). At GV presentation, CE occurred in 7 pts (27%), stenosis in 17 pts (65%), and significant pruning in 2 pts. Pt survival post diagnosis of GV was 3.3⫾1.8 yrs. Comparison including length of followup, noncompliance, rejection with hemodynamic compromise (RHDC), and CMV serology, in pts with and without ectasia revealed: #Pts Yrs f/u CE no CE p value
7 19
4.9 ⫾ 3.9 6.1 ⫾ 2.9 .37
Died Noncompliant RHDC Donor CMV ReHT 0 11 .01
0 12 .01
0 10 .02
6 (86%) 6 (32%) .03
3 5 .64
There was no significant difference in race, sex, sudden death, pre-HT age or diagnosis, donor age, rejection frequency, age at GV, or pt CMV status, between pts with and without CE. Serial angios in 17 pts (mean 4.9 angio/pt range 1-10) revealed progressive GV in 12 pts; including significant stenosis in 3/7 pts who presented with CE. CE is a unique type of GV found in 27% of ped HT pts with GV. Pts presenting with CE may have a better prognosis than those with stenotic GV, however progression can occur. The association of donor CMV with CE requires further study. 184 MYCOPHENOLATE MOFETIL DOSE AND SERUM LEVEL CORRELATION IN YOUNG CARDIAC TRANSPLANT PATIENTS R.J. Gajarski,1 D. Crowley,1 M. Zamberlan,1 K. Lake,3 1Dept of Pediatrics, University of Michigan, C.S. Mott Children’s Hospital, Ann Arbor, MI; 2Dept of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI Background: Increasingly, mycophenolate mofetil (MMF) is replacing azathioprine as a maintenance immunosuppressant, as MMF decreases graft rejection and perhaps coronary intimal proliferation. Few studies have explored the relationship between recommended pediatric drug dosing and success in achieving therapeutic levels. Purpose: To retrospectively investigate the correlation between recommended MMF doses (1200mg/m2/d, max 3000mg/d) and serum trough levels in young orthotopic heart transplant (OHT) patients (pts). Methods: Since October 2001, at the time of endomyocardial biopsy (EMB), trough levels of mycophenolic acid (MPA) and its glucuronide metabolite, (MPAG) were measured by HPLC in pts followed our pediatric OHT service. Assay therapeutic range: MPA 1-3.5 mcg/ml and MPAG 35-100mcg/ml. Corresponding EMB grades and cyclosporine (CyA) levels were recorded when MPA/MPAG levels were obtained. Correlation coefficients were derived between MMF dose and MPA/ MPAG levels. Contingency analysis evaluated the relation between MPA level (ⱕ or ⬎ 1mcg/ml) and EMB grade. Results: Over 10 months, 20 pts had 30 MPA/MPAG levels. At time of levels, mean pt age was 15⫾8.5yrs; interval between OHT date and first MPA/MPAG level 35⫾39 months. Average MMF dose was 1256.7 ⫾ 320.6mg/m2/d, and median MPA and MPAG levels were 1.8⫾5.2 and 49⫾50mcg/ml, respectively. No relationship was found between MMF dose and either MPA (r⫽0.08) or MPAG levels (r⫽0.17). Finally, independent of CyA level (p⫽0.2), EMB grade ⱖ 2 occurred more frequently in pts with MPA levels ⱕ 1.0 (p⫽0.07). Conclusions: In young OHT pts, adherence to MMF pediatric dosing recommendations fails to consistently result in therapeutic HPLC