Gloria L. Klein

Atenolol versus Losartan in Children and Young Adults With Marfan's Syndrome

BACKGROUND Aortic-root dissection is the leading cause of death in Marfans syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfans syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS Among children and young adults with Marfans syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).

Physical activity levels in children and adolescents are reduced after the Fontan procedure, independent of exercise capacity, and are associated with lower perceived general health

Objectives: To determine physical activity levels in paediatric patients who underwent the Fontan procedure, and their relationship to functional status and exercise capacity. Study Design: We studied 147 patients (ages 7–18 years) at a median of 8.1 years after Fontan, as part of the Pediatric Heart Network cross-sectional study of Fontan survivors. Assessment included medical history, self-reported physical activity, parent-completed Child Health Questionnaire (CHQ), cardiopulmonary exercise testing and physical activity level measured by accelerometry (MTI Actigraph). Results: Measured time spent in moderate and vigorous activity was markedly below normal at all ages, particularly in females, and was not significantly related to self-reported activity levels, or to maximum Vo2, Vo2 at anaerobic threshold or maximum work rate on exercise testing. Lower measured activity levels were significantly related to lower perceived general health but not to self-esteem, physical functioning, social impact of physical limitations or overall physical or psychosocial health summary scores. Reduced exercise capacity was more strongly related than measured activity levels to lower scores in general health, self-esteem and physical functioning. Conclusions: Physical activity levels are reduced after Fontan, independent of exercise capacity, and are associated with lower perceived general health but not other aspects of functional status.

Delayed diagnosis of Kawasaki disease: what are the risk factors?

OBJECTIVE. Because late diagnosis of Kawasaki disease increases the risk for coronary artery abnormalities, we explored the prevalence of and possible risk factors for delayed diagnosis by using the database of the Pediatric Heart Network trial of corticosteroid treatment for Kawasaki disease. METHODS. We collected sociodemographic and clinical data at presentation for all patients who were treated for presumed Kawasaki disease at 8 centers (7 in the United States, 1 in Canada). Delayed diagnosis was evaluated by total number of illness days to diagnosis and by the percentage of patients who were treated after day 10 of illness. Independent predictors of delayed diagnosis were identified by using multivariate linear and logistic regression. RESULTS. Of the 589 patients who received intravenous immunoglobulin, 27 were treated before screening for the trial and excluded; 562 patients formed the cohort for analysis. Kawasaki disease was diagnosed at 7.9 ± 3.9 days, 92 (16%) cases after day 10. Centers were similar with respect to patient age and gender. Centers differed in the patient percentage with incomplete Kawasaki disease; clinical criteria of cervical adenopathy, oral changes, and conjunctivitis; and distance of residence from the center. Independent predictors of greater number of illness days at diagnosis included center, age of <6 months, incomplete Kawasaki disease, and greater distance from the center. Independent predictors of diagnosis after day 10 were age of <6 months, incomplete Kawasaki disease, and greater distance). Socioeconomic variables had no association with delayed diagnosis. CONCLUSIONS. Even after adjustment for patient factors, illness duration at diagnosis varies by center. These findings underscore the need to maintain a high index of suspicion of Kawasaki disease in the infant who is younger than 6 months and has prolonged fever even with incomplete criteria. Outreach educational programs may be useful in promoting earlier recognition and treatment of Kawasaki disease.

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.

Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy

BACKGROUND The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects. METHODS AND RESULTS Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area-adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection. CONCLUSIONS Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome.

Partial and Transitional Atrioventricular Septal Defect Outcomes

BACKGROUND Surgical and perioperative improvements permit earlier repair of partial and transitional atrioventricular septal defects (AVSD). We sought to describe contemporary outcomes in a multicenter cohort. METHODS We studied 87 patients undergoing primary biventricular repair of partial or transitional AVSD between June 2004 and February 2006 across seven North American centers. One-month and 6-month postoperative data included weight-for-age z-scores, left atrioventricular valve regurgitation (LAVVR) grade, residual shunts, and left ventricular ejection fraction. Paired methods were used to assess 6-month change. RESULTS Median age at surgery was 1.8 years; median weight z-score was -0.88. Median days for ventilation were 1, intensive care 2, and hospitalization 5, all independent of age, with 1 in-hospital death. At 1 month, 27% (16 of 73) had ejection fraction less than 55%; 20% (17 of 87) had significant LAVVR; 2 had residual shunts; 1 each had subaortic stenosis and LAVV stenosis. At 6 months (n = 60), there were no interim deaths, reinterventions, or new development of subaortic or LAVV stenosis. Weight z-score improved by a median 0.4 units (p < 0.001), especially for underweight children less than 18 months old. Left atrioventricular valve regurgitation occurred in 31% (change from baseline, p = 0.13), occurring more frequently in patients repaired at 4 to 7 years (p = 0.01). Three patients had ejection fraction less than 55%, and 1 had a residual atrial shunt. CONCLUSIONS Surgical repair for partial/transitional AVSD is associated with low morbidity and mortality, short hospital stays, and catch-up growth, particularly in underweight children repaired between 3 and 18 months of age. Left atrioventricular valve regurgitation remains the most common residual defect, occurring more frequently in children repaired after 4 years of age.

Functional state following the Fontan procedure

BACKGROUND Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall function. METHODS AND RESULTS We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by averaging the percentile ranks of ventricular ejection fraction, maximal consumption of oxygen, the physical summary score for the Child Health Questionnaire, and a function of brain natriuretic peptide. The mean calculated score was 49.5 plus or minus 17.3, with a range from 3 to 87. After adjustment for time since completion of the circulation, we found that a lower score, and hence worse functional state, was associated with: right ventricular morphology (p less than 0.001), higher ventricular end-diastolic pressure (p equals 0.003) and lower saturations of oxygen (p equals 0.047) prior to completion of the Fontan circulation, lower income for the caregiver (p equals 0.003), and, in subjects without a prior superior cavopulmonary anastomosis, arrhythmias after completion of the circulation (p equals 0.003). The model explained almost one-fifth (18%) of the variation in the calculated scores. The score was not associated with surgical centre, sex, age, weight, fenestration, or the period of stay in hospital after completion of the Fontan circuit. A validation model, using 71 subjects randomly excluded from initial analysis, weakly correlated (R equals 0.17, p equals 0.16) with the score calculated from the dataset. CONCLUSIONS Right ventricular morphology, higher ventricular end-diastolic pressure and lower saturations of oxygen prior to completion of the Fontan circuit, lower income for the provider of care, and arrhythmias after creation of the circuit, are all associated with a worse functional state. Unmeasured factors also influence outcomes.