510: Quality of life and psychological functioning in paediatric patients at 1 year post lung transplant – a single centre experience

510: Quality of life and psychological functioning in paediatric patients at 1 year post lung transplant – a single centre experience

The Journal of Heart and Lung Transplantation Volume 26, Number 2S Abstracts Dr. Rossano is a cardiology fellow and his salary is partially supporte...

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The Journal of Heart and Lung Transplantation Volume 26, Number 2S

Abstracts

Dr. Rossano is a cardiology fellow and his salary is partially supported by Scios; Scios. 508 CARDIAC STRUCTURE AND FUNCTION IN LONG-TERM PEDIATRIC HEART TRANSPLANT SURVIVORS A. Kulikowska,1 S.E. Boslaugh,1 S. Foerster,1 C.H. Gumbiner,2 K.E. Ward,3 C. Ong Simon,4 M. Kimberling,5 S.K. Gandhi,6 C.E. Huddleston,6 C.E. Canter,1 1Department of Pediatrics, St Louis Children’s Hospital, St. Louis, MO; 2Department of Pediatrics, Children’s Hospital of Omaha, Omaha, NE; 3Department of Pediatrics, The Children’s Hospital at Univ. of Oklahoma, Oklahoma City, OK; 4Department of Pediatrics, Chilren’s Mercy Hospitals and Clinics, Kansas City, MO; 5Department of Pediatrics, The Children’s Hospital at Saint Francis, Tulsa, OK; 6Department of Surgery, St Louis Children’s Hospital, St. Louis, MO Purpose: Abnormalities of cardiac structure and function, especially restrictive hemodynamics, have been reported in pediatric heart transplant recipients, but there is scant data in long-term survivors. Methods and Materials: We analyzed resting right atrial (RAP), pulmonary artery (PAP), and left ventricular end-diastolic (LVEDP) pressures and echocardiographic shortening fraction (SF), left ventricular end-diastolic dimension (LVEDD), LV posterior wall thickness (LVPWT), and septal thickness (ST) at 5 yr (N⫽68) and 10 yr (N⫽33) after transplant in the absence of active rejection and moderate-severe coronary disease. Echocardiographic dimensions were converted to age and sex appropriate z scores. A mean RA pressure ⬎ 9 mm Hg and LVEDP ⬎ 12 mm Hg were defined as abnormal. Results: The table displays the data stratified by age at transplant. Rejection frequency (p⫽0.002), hemodynamically compromising rejections (p⫽0.001), and presence of angiographic coronary disease at 5 years after transplant (p⫽0.002) were significantly related to LVEDP 10 yr after transplant. Race, sex, diagnosis, graft ischemic time, history of primary graft failure, treated hypertension had no significant associations. Conclusions: Long-term survivors demonstrate normal echocardiographic measurements late after transplant. Rejection history and mild transplant coronary disease are associated with elevation of LV enddiastolic pressures. Infant heart transplant recipients demonstrate better preservation of normal cardiac filling pressures than older recipients late after transplant.

SF% 10 yr (5 yr) LVEDD 10 yr (5 yr) LVPWT 10 yr (5 yr) ST 10 yr (5 yr) Mean RAp 5 yr Mean RAp 10 yr Mean MPA pressure 5 yr Mean MPA pressure 10 yr LVEDP 5 yr LVEDP 10 yr

Transplant at <1 yr

Transplant at >1 yr

p

37 (35) ⫺0.2 (0.2) ⫺0.4 (⫺0.4) ⫺0.8 (⫺0.7) 4.5 4.4 16.0 15.3 8.8 7.8

37 (37) ⫺1.1 (⫺1.3) ⫺0.6 (⫺0.8) ⫺0.9 (⫺0.8) 5.4 10.6 15.3 18.9 10.0 14.1

ns ns ns ns ns ⬍0.001 ns 0.03 ns ⬍0.001

509 THE PREDICTIVE VALUE OF DONOR SPECIFIC ANTIBODY RESPONSES IN PEDIATRIC HEART RECIPIENTS: A PILOT STUDY R.J. Boucek, Jr.,1 D. Yung,1 K. Nelson,2 P. Hopkins,1 L. Permut,3 G. Cohen,3 1Pediatrics, U of Wash/Seattle Children’s Hospital, Seattle, WA; 2Puget Sound Blood Center, Seattle, WA; 3Surgery, U of Wash, Seattle, WA

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Purpose: Recent advances allow quantitative determination of donorspecific antibody (DSA)responses following cardiac transplantation (HT). The freqency and significance of positive DSA in pediatric HT recipients has not been defined. Methods and Materials: We report DSA responses surveyed in 26 pediatric recipients ⬍ 6 months post-HT(“early” ; n⫽11; median days post-HT⫽46) or ⬎ 6 months post-HT (“late”; n⫽15; median years post-HT⫽2.9) post-HT between 8/05 and 9/06. Significance of a positive DSA, defined as detectable antibody titer to at least one donor antigen, was assessed as follows: vascular C4d complement deposition; graft histopathology with biopsy-derived ISHLT pathology scores; and/or graft function indexed by quantitative echocardiography (ECHO-A score) and B-type naturetic peptide (BNP). Results: DSA was positive in: 20 of 69 determinations; 12/46 (26%) of the early determinations; and 8/22 (35 %) of the late determinations. Two recipients with PRA⬎10 % pre-HT were both DSA positive in 5/10 (50%) determinations in the first 40 days post-HT, despite prophylactic plasmaphoresis and cyclophosphamide, and became negative by 2 months post-HT. When performed within 24 hrs of endomyocardial biopsy, positive DSA was associated with: C4d deposition in 4/6 determinations (p⫽ NS by Fischer’s Exact test); ISHLT score ⱖ 3 in 0/6 determinations (p⫽NS). Positive DSA was associated with: BNP ⬎ 150 in 11/20 determinations (p⫽NS); or with ECHO-A score ⬎ 4 in 4/17 determinations (p⫽NS). Of note, the positive predictive value of a positive DSA for humoral/vascular rejection (⫹C4d) was 67% whereas for cellular rejection, indexed by ISHLT score ⱖ 3 and/or ECHO-A score ⬎ 4, was 0 and 24% respectively. Conclusions: This pilot analysis of DSA determinations in pediatric recipients over 1 year supports prospective analyses of scheduled testing focused on the potential of DSA surveillance to predict humoral rejection, particularly in high risk pediatric recipients, and to identify immunosuppressive strategies that target anti-donor B cell responses. 510 QUALITY OF LIFE AND PSYCHOLOGICAL FUNCTIONING IN PAEDIATRIC PATIENTS AT 1 YEAR POST LUNG TRANSPLANT – A SINGLE CENTRE EXPERIENCE T. Lunnon-Wood,1 B.K. Field,1 J. Wray,1 P. Aurora,1 1Dept of Cardiothoracic Transplantation, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom Purpose: Paediatric lung transplantation is becoming a preferred treatment option for end stage lung and respiratory diseases. Although improvements in physical parameters are reported at 1 year posttransplant (tx), there is little information on the psychological outcomes at this time. Methods and Materials: Between 2002 and 2005, 23 children and adolescents (15 females, 8 males) underwent successful lung transplantation (10 heart-lung, 12 bilateral lung and 1 single lung). Pre-tx diagnoses included CF (n ⫽17), IPAH (n⫽4), Restrictive Cardiomyopathy (n⫽1) and Bronchiolitis Obliterans (n⫽1). Mean age at tx was 12.7 yrs (range 5.0-17.0 yrs). A semi-structured interview was completed at patients’ first annual review; covering physical and psychosocial topics. Results: There were no deaths in the first year post tx. At one year, 8 patients (35%) had ongoing medical complications; recurrent infections (n⫽3), PTLD (n⫽2), airway problems(n⫽1), recurrent nausea and vomiting (n⫽1) and impaired cardiac function (n⫽1). A total of 9 patients (39%) reported significant psychological difficulties including adjustment, body image, low mood, anxiety and social integration difficulties; 5 of these 9 patients were those who also had ongoing medical complications. Despite this, 14 patients (61%) were attending school full-time and were participating in physical education classes. Ten parents noted difficulties with their own adjustment and loss of

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Abstracts

role, though all patients and parents reported good or excellent quality of life at 1 year post-tx. Conclusions: All patients were alive at 1 year post-tx and reported good quality of life with improved physical parameters including participation in activities and attending school. However, a number of children, adolescents and parents report difficulties adjusting to life post-tx. Evaluation at 1 year enables identification of areas of psychological difficulty, which will allow interventions to be targeted to reduce morbidity and further enhance psychological well-being, and maximise quality of life. 511 ASSOCIATIONS BETWEEN MARKERS OF INFLAMMATORY ACTIVATION AND HEART FAILURE IN CHILDREN C. Ratnasamy,1 D.D. Kinnamon,1 S.E. Lipshultz,1 P.G. Rusconi,1 1 Pediatrics, Miller School of Medicine University of Miami, Miami, FL Purpose: We hypothesized that blood markers of neuroendocrine and inflammatory activation are associated with symptom severity and echocardiographic measurements in children with heart failure (HF). In adults HF is associated with the activation of neuroendocrine and inflammatory pathways. Similar associations have not been studied in children. Methods and Materials: Children with HF secondary to dilated cardiomyopathy (DCM) (n ⫽ 15) and repaired congenital heart defects (n ⫽ 4) were divided into three groups by symptom severity. Measurements were taken of echocardiographically determined left ventricular ejection fraction (LVEF) and shortening fraction (LVSF), indexed left ventricular end-systolic (LVSDz) and end-diastolic (LVDDz) diameters, blood levels of N-terminal-prohormone brain natriuretic peptide (NTproBNP), high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-alpha (TNF-alpha), and soluble tumor necrosis factor receptor II (sTNF-RII). Results: NT-proBNP and hsCRP were significantly increased in children with severe symptoms (P ⱕ 0.003). NT-proBNP was inversely related to LVEF and LVSF (P ⱕ 0.05) and directly related to LVSDz (P ⱕ 0.008). HsCRP was inversely associated with LVSF and directly associated with NT-proBNP (P ⱕ 0.03). TNF-alpha was inversely associated with LVSF (P ⫽ 0.03) and directly associated with LVSDz (P ⱕ 0.05) and NT-proBNP (P ⱕ 0.05). sTNF-RII was inversely associated with LVSF (P ⫽ 0.008) and LVEF (P ⫽ 0.03) and directly associated with LVSDz (P ⫽ 0.04) and NT-proBNP (P ⫽ 0.05) in children with DCM. Conclusions: In children with HF, neuroendocrine and inflammatory mediators are activated in proportion to the severity of symptoms and are associated with echocardiographic measurements, as well as with each other. Further studies may determine whether these markers can be used to indicate the severity of HF, to predict morbidity and mortality and to assess the response to medications. It will be important to know if anti-inflammatory therapy directed toward those patients with increased inflammatory mediators is beneficial. 512 DOBUTAMINE STRESS ECHOCARDIOGRAPHY FOR THE ASSESSMENT OF CORONARY ARTERY DISEASE IN PAEDIATRIC HEART TRANSPLANT RECIPIENTS A.I. Dipchand,1 W. Bharat,1 C. Manlhiot,1 M. Safi,1 N. Lobach,1 B.W. McCrindle,1 1Cardiology, Hospital for Sick Children, Toronto, ON, Canada Purpose: Transplant coronary artery disease (CAD) is the leading cause of graft loss beyond 1 year post-heart transplant (HTx). Diagnosis can be

The Journal of Heart and Lung Transplantation February 2007

challenging and angiography (ANG) is the gold standard. The purpose of this study was to relate dobutamine stress echocardiography (DSE) results to ANG for the diagnosis of CAD. Methods and Materials: Prospective annual DSE and ANG at a single centre in all HTx patients. Changes in serial measures were sought using general estimating equations for longitudinal serial data. Results: There were 102 HTx patients (54 males). Prospective DSEs starting in 1999 on patients Tx from 1989-2006. Median age at Tx was 17 mo. Initial DSE at median of 10 months post-Tx. There was a high correlation between an abn DSE and ANG (p⫽0.002). The probability of an abn DSE or ANG increased more in the first 4 yrs post-Tx, with a slower increase in risk after. There was an increased probability of an abnormal DSE with increasing grade of CAD as assessed by ANG (p⬍0.001). No patient with normal DSEs ⬍4 y post-Tx developed an abn DSE in follow-up. Factors associated with an abn DSE included older age at Tx (p⫽0.05), higher grade of rejection (p⫽0.01), and older age at DSE (p⫽0.01). DSE result was not related to lipid or homocysteine levels, or to steroid use. Conclusions: The probability of an abn DSE result increases with increasing ANG grade of CAD, and thus DSE may be used for initial screening for CAD with ANG reserved for confirmation and grading. The greatest increase in probability of an abn DSE is in the first 4 years post-Tx, with patients Tx at an older age and those with a greater history of rejection at increased risk over time. These high risk patients require increased surveillance for CAD.

513 HEART RATE RECOVERY FROM MAXIMAL EXERCISE IN CHILDREN ONE-YEAR AFTER HEART TRANSPLANTATION – EFFECT OF AUTONOMIC DENERVATION T.P. Singh,1 J. Rhodes,1 H.J. Bastardi,1 E.D. Blume,1 1Cardiology, Children’s Hospital, Boston, MA Purpose: Peak heart rate (HR) during exercise is modulated by cardiac and circulating adrenergic response. One-minute HR recovery on exercise-cessation is predominantly determined by vagal reactivation. We hypothesized that children undergoing exercise testing 1-year after heart transplant will have lower HR increase with exercise and slower HR recovery compared to controls due to autonomic denervation of their hearts. Methods and Materials: We assessed HR response during and HR recovery following a maximal treadmill exercise test (Bruce protocol) in 35 children (age 13.3⫾2.8 years) 0.98⫾ 0.17 years after heart transplant (TX group) and in 2 age-matched control groups - 32 post-operative Fontan patients (age 12.8⫾2.9 years) and 35 healthy children (age 13⫾2.9 years).