Linda M. Lambert

Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: comparison with standard cryopreserved allografts.

BACKGROUND Recognition of the immunogenicity of standard cryopreserved allografts has led to the development of new decellularized allografts (CryoValve SG; CryoLife, Inc, Kennesaw, Ga). This preliminary study examined the HLA antibody response to these decellularized allografts and compared it with the response to standard allograft material. METHODS We prospectively measured the frequency of panel-reactive HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR/DQ) alloantibodies in 14 children (age 8.5 +/- 7.9 years) receiving decellularized, cryopreserved allografts, including 6 undergoing allograft patch insertion and 8 with a valved pulmonary allograft. We compared them with 20 historical control subjects (age 1.7 +/- 2.4 years) undergoing implantation of standard cryopreserved allografts, 8 with valves and 12 with allograft patch. All patients had panel-reactive antibody levels measured before and at 1, 3, and 12 months after the operation. HLA class I and class II panel-reactive antibody levels were determined with a sensitive flow cytometry technique. RESULTS We found panel-reactive antibody levels in decellularized allografts to be elevated slightly from preoperative levels for both class I and class II antibodies at 1, 3, and 12 months (P >.05). The panel-reactive antibody level for both class I and class II antibodies were significantly lower for decellularized allografts as compared to standard allografts. Functionally, the allografts were similar with decellularized valved grafts showing a peak echo-determined systolic gradient of 13 +/- 15 mm Hg at 8 +/- 2.6 months postoperatively as compared to a gradient of 24 +/- 18 mm Hg measured 12 +/- 6 months postoperatively in standard allografts (P =.11). CONCLUSIONS Decellularized grafts elicited significantly lower levels of class I and class II HLA antibody formation at 1, 3, and 12 months after implantation than did standard cryopreserved allografts. Early hemodynamic function of decellularized grafts was similar to that of standard cryopreserved allograft valves. Further experience is necessary to determine whether the reduced immunogenicity of decellularized allografts will truly allow tissue ingrowth and improved long-term durability in patients.

Cause, timing, and location of death in the Single Ventricle Reconstruction trial

OBJECTIVES The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths. METHODS There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the timing, location, and other factors for each event. RESULTS The most common cause of death was cardiovascular (42%), followed by unknown cause (24%) and multisystem organ failure (7%). The median age at death for subjects dying during the 12 months was 1.6 months (interquartile range, 0.6 to 3.7 months), with the highest number of deaths occurring during hospitalization related to the Norwood procedure. The most common location of death was at a Single Ventricle Reconstruction trial hospital (74%), followed by home (13%). There were 29 sudden, unexpected deaths (18%), although in retrospect, 12 were preceded by a prodrome. CONCLUSIONS In infants with a single right ventricle undergoing staged repair, the majority of deaths within 12 months of the procedure are due to cardiovascular causes, occur in a hospital, and within the first few months of life. Increased understanding of the circumstances surrounding the deaths of these single ventricle patients may reduce the high mortality rate.

Associated Symptoms in the Ten Days Before Diagnosis of Kawasaki Disease

OBJECTIVE To describe common associated symptoms within the 10 days before diagnosis in subjects enrolled in the Pediatric Heart Networks trial of steroid therapy in Kawasaki disease (KD). STUDY DESIGN Patients with acute KD were enrolled between days 4 and 10 of illness at 8 centers between 2002 and 2004. We defined common associated symptoms as those occurring in >or=10% of patients. Principal clinical criteria for KD were not included in this analysis. RESULTS Among 198 patients, irritability was reported in 98 (50%), vomiting in 88 (44%), decreased food/fluid intake in 73 (37%), cough in 55 (28%), diarrhea in 52 (26%), rhinorrhea in 37 (19%), weakness in 37 (19%), abdominal pain in 35 (18%), and joint pain (arthralgia or arthritis) in 29 (15%). One or more gastrointestinal symptom (vomiting, diarrhea, or abdominal pain) was present in 120 patients (61%) and 69 patients (35%) had >or= 1 respiratory symptom (rhinorrhea or cough). CONCLUSIONS Nonspecific symptoms occur commonly in children with KD. To reduce delays in diagnosis, clinicians should be educated that such symptoms may comprise a significant component in the chief complaint.

Factors affecting growth in infants with single ventricle physiology: a report from the Pediatric Heart Network Infant Single Ventricle Trial.

OBJECTIVES To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth. STUDY DESIGN Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (z) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC; 5.1 ± 1.8 months, period 1) and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, followed by backward stepwise regression and bootstrapping reliability to inform a final multivariable model. RESULTS Weights were available for 197 of 230 subjects for period 1 and 173 of 197 subjects for period 2. For period 1, greater gestational age, younger age at study enrollment, tube feeding at neonatal hospitalization discharge, and clinical center were associated with a greater negative z (poorer growth) in multivariable modeling (adjusted R(2) = 0.39, P < .001). For period 2, younger age at SCPC and greater daily caloric intake were associated with greater positive z (better growth; R(2) = 0.10, P = .002). CONCLUSIONS Aggressive nutritional support and earlier SCPC are modifiable factors associated with a favorable change in weight-for-age z-score.

Nutrition algorithms for infants with hypoplastic left heart syndrome; birth through the first interstage period.

Failure to thrive is common in infants with hypoplastic left heart syndrome and its variants and those with poor growth may be at risk for worse surgical and neurodevelopmental outcomes. The etiology of growth failure in this population is multifactorial and complex, but may be impacted by nutritional intervention. There are no consensus guidelines outlining best practices for nutritional monitoring and intervention in this group of infants. The Feeding Work Group of the National Pediatric Cardiology Quality Improvement Collaborative performed a literature review and assessment of best nutrition practices from centers participating in the collaborative in order to provide nutritional recommendations and levels of evidence for those caring for infants with single ventricle physiology.

Coarctation repair in neonates and young infants: Is small size or low weight still a risk factor?

OBJECTIVE Previous reports of neonatal coarctation repair demonstrate a high rate of recurrent arch obstruction in small neonates. This study assesses the effect of patient size on reintervention and survival in neonates and infants undergoing repair of simple aortic coarctation. METHODS From 1996 to 2006, 167 neonates and infants younger than 90 days with simple coarctation underwent repair. Median patient age was 16 days (range, 1-85 days). Median patient weight was 3.4 kg (range, 0.8-6.0 kg), with 29 patients weighing less than 2.5 kg. All 167 patients included in the study underwent repair through a left thoracotomy. RESULTS There was 1 early death (1/167, 0.6%). Median follow-up of 4.8 years (range, 0-11.8 years) demonstrated 2 late deaths unrelated to recurrent coarctation. Eighteen patients underwent intervention for recurrent arch obstruction a median of 0.48 years postoperatively (range, 0.14-9.8 years). All were treated with balloon angioplasty and have required no additional intervention. Actuarial freedom from reintervention was 90% at 1 year and 89% at 5 years for infants weighing more than 2.5 kg and 89% at 1 year and 86% at 5 years (P = .31) for infants weighing less than 2.5 kg. There was no difference between survival or reintervention for neonates 30 days of age or younger compared with infants 31 to 90 days of age. Use of polypropylene sutures and female sex did correlate with increased reintervention. CONCLUSIONS Low weight does not affect survival or reintervention rates after coarctation repair in neonates and infants less than 3 months of age. Balloon angioplasty is an effective treatment for recurrent obstruction after coarctation repair in infancy. In the current era, timing of the operation should be based on clinical status.

Clinical performance of decellularized cryopreserved valved allografts compared with standard allografts in the right ventricular outflow tract.

BACKGROUND Although decellularized cryopreserved valved allografts (DCAs) have reduced immunogenicity, proof of clinical superiority over standard cryopreserved allografts (SCAs) is lacking. To assess functional results and durability, we studied a group of patients with DCAs implanted between 2000 and 2005 and compared them with a similar group with SCAs. METHODS From July 2000 until January 2005, 47 patients underwent insertion of a DCA between the right ventricle and pulmonary arteries. The DCA patients were compared with 47 age-matched and diagnosis-matched controls receiving SCAs. All patients received pulmonary allografts and were matched for valve position (orthotopic versus heterotopic). We analyzed each group for survival, reoperation, reintervention (surgical or catheter-based), stenosis, and regurgitation. RESULTS There were no differences between groups with respect to weight, age, valve size, or survival. Actuarial freedom from reintervention at 8 years was 79% for DCAs as compared with 63% for SCAs (p = 0.31, log-rank). Echocardiogram in the DCA group (median 66 months) showed a slightly lower median peak gradient of 16 mm Hg (range, 0 to 82 mm Hg) as compared with 22 mm Hg (range, 0 to 63) in the SCA group (median 61 months, p = 0.051, Wilcoxon). However, when conduits 18 mm or less in diameter were compared, DCA patients had a median peak gradient of 10 mm Hg (range, 0 to 43) compared with 25 mm Hg in SCAs (range, 0 to 55 mm Hg, p = 0.03). There were no differences in the degree of allograft insufficiency in either group. CONCLUSIONS Decellularized cryopreserved valved allografts have a nonsignificant trend toward lower peak valve gradient and reintervention in comparison with SCAs. Small valve sizes (18 mm or less) show a slight but significant improvement in peak gradient, but no advantage in valve insufficiency. These findings and a significantly higher cost (>

Anthropometric Measures After Fontan Procedure: Implications for Suboptimal Functional Outcome

3,000) make further direct comparisons necessary before widespread use of DCAs can be justified.

Effects of homograft blood type and anatomic type on stenosis, regurgitation and calcium in homografts in the pulmonary position.

BACKGROUND Abnormal height and adiposity are observed after the Fontan operation. These abnormalities may be associated with worse functional outcome. METHODS We analyzed data from the National Heart, Lung, and Blood Institute Pediatric Heart Network cross-sectional study of Fontan patients. Groups were defined by height (z-score<-1.5 or≥-1.5) and body mass index (body mass index [BMI] z-score<-1.5 or -1.5 to 1.5 or≥1.5). Associations of anthropometric measures with measurements from clinical testing (exercise, echocardiography, magnetic resonance imaging) were determined adjusting for demographics, anatomy, and pre-Fontan status. Relationships between anthropometric measures and functional health status (FHS) were assessed using the Child Health Questionnaire. RESULTS Mean age of the cohort (n=544) was 11.9±3.4 years. Lower height-z patients (n=124, 23%) were more likely to have pre-Fontan atrioventricular valve regurgitation (P=.029), as well as orthopedic and developmental problems (both P<.001). Lower height-z patients also had lower physical and psychosocial FHS summary scores (both P<.01). Higher BMI-z patients (n=45, 8%) and lower BMI-z patients (n=53, 10%) did not have worse FHS compared to midrange BMI-z patients (n=446, 82%). However, higher BMI-z patients had higher ventricular mass-to-volume ratio (P=.03) and lower % predicted maximum work (P=.004) compared to midrange and lower BMI-z patients. CONCLUSIONS Abnormal anthropometry is common in Fontan patients. Shorter stature is associated with poorer FHS and non-cardiac problems. Increased adiposity is associated with more ventricular hypertrophy and poorer exercise performance, which may have significant long-term implications in this at-risk population.

Factors associated with neurodevelopment for children with single ventricle lesions.

The use of both aortic and pulmonary homografts in the pulmonary position for treatment of right ventricular or pulmonary outflow tract obstruction has gained widespread popularity.1–3 Although this homograft tissue presents a potential allogeneic stimulus to the recipient, little is known about the effects of blood-type (ABO) compatibility or incompatibility on homograft function.4 This study retrospectively reviews the outcome of homografts in the pulmonary position in 39 consecutive children who had placement of an aortic or pulmonary homograft in the pulmonary position for treatment of pulmonary outflow tract obstruction.