The Journal of Heart and Lung Transplantation Volume 26, Number 2S
Conclusions: We conclude that asymptomatic CMV viremia is associated with adverse effects on lung allograft function. This may have important implications for the choice of antiviral prophylaxis in LTX pts. 242 CYTOMEGALOVIRUS REPLICATION IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN PEDIATRIC HEART TRANSPLANT RECIPIENTS J.D. Simmonds,1 M.J. Fenton,1 J.P.J. Halcox,2 N.J. Klein,2 L.M. Ellins,2 C. Storry,2 S. Omeagher,2 L.M. Redmond,2 A.E. Donald,2 C.A. Scott,2 M. Burch,1 1Department of Paediatric Cardiology, Great Ormond Street Hospital, London, United Kingdom; 2Vascular Physiology Department, Institute of Child Health, University College London, London, United Kingdom Purpose: Cytomegalovirus (CMV) can infect endothelial cells. CMV infection is associated with coronary arterial endothelial dysfunction in heart transplant patients and increases risk of post-transplant coronary vasculopathy, particularly in children. It is unknown whether CMV impairs systemic arterial endothelial function in these patients. Methods and Materials: We studied 50 paediatric heart transplant recipients (aged 8 to 17 years, 27 male), separated into two groups: Group 1 (n⫽12, 8 male) - patients with evidence of CMV replication post-transplant (positive CMV polymerase chain reaction [PCR] and/or seroconversion from negative to positive CMV IgG antibody), and Group 2 (n⫽38, 19 male) - those without evidence of viral replication (negative PCR and no change in CMV IgG). Brachial artery endothelial function was assessed by high-resolution ultrasound to determine flow mediated dilatation (FMD), expressed as maximal percentage change in arterial diameter after reactive hyperaemia. Results: FMD was significantly worse in Group 1 than Group 2 (6.64 ⫹/- 1.12% vs. 9.48 ⫹/- 0.79% respectively (mean ⫹/- S.E.); p⬍0.02). This observed difference remained (p⬍0.02) after adjusting for age, gender, time since transplantation, and baseline arterial diameter. Neither donor/recipient CMV status pre-transplantation nor donorrecipient CMV mismatch was associated with FMD. Conclusions: CMV infection is associated with impaired peripheral arterial endothelial function in heart transplant patients. Of note, evidence of active viral replication post-transplantation appears more relevant than pre-transplantation CMV antibody status of donor or recipient. Further studies are needed to determine whether these findings are associated with the clinical extent and progression of graft vasculopathy. 243 META-ANALYSIS OF CMV-HYPERIMMUNE GLOBULIN STUDIES FOR THE PREVENTION OF CMV INFECTION AND DISEASE IN SOLID ORGAN TRANSPLANT RECIPIENTS N. Bonaros,1 A. Kocher,1 B. Mayer,1 G. Laufer,1 1Cardiac Surgery, Innsbruck Medical University, Innsbruck, Austria Purpose: Despite numerous studies comparing CMV-immunoglobulins and antiviral agents the optimal prophylaxis of CMV disease after solid organ transplantation remains debated. We conducted a metaanalysis to study the early and mid-term outcomes of CMV-prophylaxis following solid organ transplantation. Methods and Materials: Medline, EMBASE, and the Cochrane databases were searched and a hand search of bibliographies was conducted. Random effects models were used to calculate pooled risk ratios (RR) and meta-regression was employed to explain study heterogeneity. Stratified analyses were conducted and a Funnel plot was used to assess publication bias.
Abstracts
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Results: Eleven randomized trials (698 patients; median follow-up: 12 months, range: 3-22 months) including 6 randomized trials (302 patients) after kidney transplantation were identified and analyzed separately. The analysis demonstrated a beneficial effect of the prophylactic use of CMVIG on total survival (RR [95% CI]: 0.67 [0.47-0.95]) and prevention of CMV-associated death (RR [95% CI]: 0.45 [0.24-0.84]) in solid organ transplant recipients but not kidney transplant recipients (RR [95% CI]: 0.35 [0.12-1.04]). Analysis of the number of CMV disease revealed a significant benefit solid organ transplant recipients in both analysis groups which received CMVIG as prophylactic therapy (RR [95% CI]: 0.697 [0.57-0.85]. No significant differences were observed in terms of CMV-infections and clinically relevant rejections. Conclusions: CMVIG for CMV-prophylaxis after solid organ transplantation is associated with improved total survival and reduced CMV-associated deaths and CMV-disease. No benefit can be detected in terms of CMV-infections and clinically relevant rejections.
244 PREDICTIVE VALUE OF PLASMA CMV PCR FOR CMV PNEUMONITIS IN LUNG TRANSPLANT RECIPIENTS J.M. Magill,1 S. Fernandez-Bussy,2 O. Akindipe,2 A.B. Deem,2 E.D. Staples,3 P.A. Drew,1 M.A. Baz,2 1Pathology, University of Florida, Gainesville, FL; 2Medicine, University of Florida, Gainesville, FL; 3Surgery, University of Florida, Gainesville, FL, United Kingdom Purpose: Cytomegalovirus (CMV) is the most common viral infection in lung transplant recipients. Plasma CMV detected by Real Time Polymerase Chain Reaction (PCR) testing was implemented at our center in March 2005. To assess the value of plasma CMV-PCR in predicting CMV pneumonitis, we conducted a retrospective analysis of all patients who had concurrent plasma CMV-PCR testing and CMV Immunohistochemistry (IHC) on transbronchial biopsies between March 1, 2005 and March 26, 2006. Methods and Materials: CMV Immunohistochemistry was performed on 4mm thick tissue using Monoclonal Mouse Anti-Cytomegalovirus. LV-CMV PCR is used for the detection of the Human Cytomegalovirus DNA from the UL123 gene, Exon 4, using plasma. Real Time PCR Taqman assays detect amplified DNA through the use of fluorescent molecules. A Cepheid Smart Cycler II monitors the accumulation of fluorescent signal, as it occurs. All patients who were either CMV seropositive or received CMV seropositive donors were included in this study. Results: 144 transbronchial biopsies from 42 patients had concurrent CMV-IHC and plasma CMV-PCR. The CMV donor/recipient serologies are as follows: 11 d (-)/r (⫹), 13 d (⫹)/r (-), 18 d (⫹)/r (⫹). There were 12 serum CMV-PCR (⫹) samples with 1 corresponding (⫹) biopsy. The remaining 132 plasma samples were (-) and 143 biopsies were (-) (See Table 1). The sensitivity was 100%, specificity ⫽ 92%, positive predictive value ⫽ 8.3%, and negative predictive value ⫽ 100%. During clinical symptoms (decreased FEV1 and/or fever), the sensitivity of plasma CMV-PCR was 10.5%, specificity ⫽ 94%, PPV ⫽ 50% and the NPV ⫽ 64%. Table 1 Plasma CMV-PCR vs. Tissue CMV-IHC Tissue CMV-IHC ⴙ Plasma CMV-PCR Positive Plasma CMV-PCR Negative Total
Tissue CMV-IHC ⴚ
Total
1
11
12 (PPV ⫽ 8.3%)
0
132
132 (NPV ⫽ 100%)
1 (Sensitivity ⫽ 100%)
143 (Specificity ⫽ 92%)
144
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Abstracts
Conclusions: Utilizing plasma negative CMV-PCR to predict CMV pneumonitis in lung transplant patients is superior to clinical symptoms and suggests a high reliability of exclusion of CMV pneumonitis (NPV was 100%). 245 QUALITY OF LIFE AS PERCEIVED BY 8-13 YR OLD HEART TRANSPLANT RECIPIENTS K. Uzark,1 J. Johnston,2 P. Murphy,3 R. Rodriguez,4 C. Nasman,5 J. Slusher,1 1Cincinnati Children’s Hospital, Cincinnati, OH; 2 Loma Linda University Medical Center, Loma Linda, CA; 3St Louis Children’s Hospital, St. Louis, MO; 4Children’s Hospital of New York, New York, NY; 5Cleveland Clinic Foundation, Cleveland, OH Purpose: While overall survival following pediatric heart transplantation (HTx) has steadily improved, little is known about the quality of life (QOL) of HTx survivors. The purpose of this multicenter study was to evaluate QOL, including physical, emotional, social, and school functioning, in pediatric HTx survivors. Methods and Materials: The pediatric quality of life inventory was administered to 63 children 8 to 13 years of age (mean 10.5 years), including 32 males and 31females. Mean time post HTx ranged from 1.1 to 12.9 years (mean 7.9 years). Results: The majority of HTx recipients (⬎ 68%) reported excellent (almost never a problem) physical QOL. In comparison to a normative sample, HTx recipients had significantly lower QOL scores for emotional, social and school functioning (p ⬍.01). One in three (33%) had psychosocial functioning scores which were ⬎ 1 standard deviation below the population sample mean, representing an at-risk status for impaired QOL. HTx recipients were most different from their peers on the dimension of school functioning, including problems with memory and attention. School functioning was significantly correlated with emotional (r⫽0.624, p⬍.01) and social functioning (r⫽0.568, p⬍.01). Psychosocial QOL scores were not significantly correlated with time since HTx (r ⫽ -.014) and did not differ significantly related to gender (male mean ⫽ 72.1 versus female mean ⫽ 70.7) or related to primary immunosuppression (cyclosporine mean ⫽ 72.4 versus tacrolimus mean ⫽ 68.0). Conclusions: While the majority of 8 to 13 yr old children who have undergone HTx report good physical functioning, one in three may be at-risk for significant psychosocial problems. School functioning may impact emotional and social QOL. Comprehensive assessment of QOL, including neuropsychological measures to address educational needs, may facilitate early identification and intervention to promote optimal QOL outcomes in pediatric HTx recipients. 246 NEURODEVELOPMENTAL OUTCOMES IN PEDIATRIC HEART TRANSPLANT RECIPIENTS K. Uzark,1 J. Slusher,1 D. Beebe,2 R. Spicer,1 1Cardiology, Cincinnati Children’s Hospital, Cincinnati, OH; 2Psychology, Cincinnati Children’s Hospital, Cincinnati, OH Purpose: ISHLT registry data demonstrate that survival following pediatric heart transplantation (PHTx) continues to improve with excellent “functional” status in PHTx survivors, but there are limited data available about neuropsychological outcomes in these children. This study assessed neurodevelopmental outcomes in PHTx recipients. Methods and Materials: Evaluations included standardized measures of intelligence, visual-motor integration (VMI) skills, and adaptive functioning. Patients’ mean scores were compared to the normative mean of 100 ⫾ 15 using single-sample t-tests, and the % of
The Journal of Heart and Lung Transplantation February 2007
patients with “sub-normal” scores (⬍ 85) was compared to the normative base rate of 16%. Results: Routine evaluations were performed in 19 children 12-24 mos (mean 16.2 mos) post HTx/reHTx (n⫽1). One patient diagnosed with autism was excluded. The initial diagnosis was congenital heart disease (CHD) in 7 and dilated cardiomyopathy (CM) in 11. Median age at HTx was 15 mos, range 1mos-8.4 yrs. Patients had a mean overall IQ of 85.8, verbal IQ of 88.5 and nonverbal IQ of 86.4, all in the low-average range but significantly below true normative average (p⬍.001). Eight of 18 (44%) had sub-normal overall IQs, p⬍.005. Children with an initial diagnosis of CHD had lower overall IQ (mean⫽80.3) than children with CM (mean⫽ 89.3). For early expressive language (n⫽11) the mean was 87.3, low average but significantly below norms (p⬍.01), with 45% having low scores, p⬍.005. In contrast, receptive language was normal in the same patients, mean 99.3, with only 18% scoring below 85. The mean score for VMI (n⫽7) was 87.3 (p⬍.05), with 57% below the norm, p⬍.05. On fine motor evaluations (n⫽18), the mean was 82.1 (t⫽5.1, p⬍.001), with 50% obtaining sub-normal scores, p⬍.001. Conclusions: Although many PHTx recipients displayed normal neurodevelopmental functioning, these children are at increased risk for cognitive difficulties, especially related to expressive language, VMI, and fine motor skills. Early identification and intervention are essential to promote optimal neuropsychological outcomes in PHTx recipients. 247 SOCIAL COMPETENCE AFTER PAEDIATRIC TRANSPLANTATION – SHOULD WE BE CONCERNED? J. Wray,1 B.K. Field,1 T. Lunnon-Wood,1 1Cardiothoracic Transplantation, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom Purpose: Although survival rates following paediatric cardiothoracic transplantation are improving, a significant minority of children and adolescents have psychological difficulties at some stage after transplant. Whilst poor social competence has been identified in some patients, the potential role of parental factors in this has not been previously investigated. Methods and Materials: Social competence and behavioural data were collected on 68 children and adolescents (33 girls, 35 boys; mean age: 13.6 years (range: 4.3 - 18.8 years) at a median follow-up of 3 years after cardiothoracic transplantation. Parents and/or children completed the Child Behaviour Checklist, which included items addressing social competence at home and at school and aspects of mood. Teachers also completed the equivalent measure on 45 children. In addition, parents were asked to complete a measure of their own mental health. Results: Thirty-five (51%) children obtained scores in the clinical or borderline range on one or more areas of competence. Almost one third of parents obtained scores indicative of psychological distress and high levels of parental anxiety were significantly correlated with children’s poor social competence scores (r⫽.404; p⫽.006). Teacher ratings of internalising behaviour were also significantly correlated with parental ratings of social competence (p⬍.01). Those children and adolescents who perceived themselves to have more internalising behaviour problems, such as symptoms of anxiety and depression, scored themselves at a lower level (indicating poorer functioning) on the social competence scale. Conclusions: Social competence is an area of concern following successful cardiothoracic transplantation in childhood. The relationship between parental anxiety, patient anxiety/depression and social competence is one which requires further investigation in order that interventions can be targeted to reduce psychological morbidity,