-
Ronald V Lacro,
Lin T Guey,
Harry C Dietz,
Gail D Pearson,
Anji T Yetman,
Bruce D Gelb,
Bart L Loeys,
D Woodrow Benson,
Timothy J Bradley,
Julie De Backer, [......],
Jami C Levine,
Mark B Lewin,
Larry W Markham,
Stephen M Paridon,
Mary Ella Pierpont, Elizabeth Radojewski,
Elif Seda Selamet Tierney,
Angela M Sharkey,
Stephanie Burns Wechsler,
Lynn Mahony
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
American heart journal 05/2013; 165(5):828-835.e3. · 4.65 Impact Factor
-
Steven D Colan,
Girish Shirali,
Renee Margossian,
Dianne Gallagher,
Karen Altmann,
Charles Canter,
Shan Chen,
Fraser Golding, Elizabeth Radojewski,
Michael Camitta,
Michael Carboni,
Jack Rychik,
Mario Stylianou,
Lloyd Y Tani,
Elif Seda Selamet Tierney,
Yanli Wang,
Lynn A Sleeper
[show abstract]
[hide abstract]
ABSTRACT: Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers.
Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles to enable assessment of intraobserver and interobserver variability. The impacts of beat averaging (BA), observer type (local vs core), and variable type (areas, calculations, dimensions, slopes, time intervals, and velocities) on measurement reproducibility were studied. The outcome measure was percentage error (100 × difference/mean).
Of 173 enrolled subjects, 131 met criteria for dilated cardiomyopathy. BA, variable type and observer type all influenced percentage error (P < .0001). Core interobserver percentage error (medians, 11.4%, 10.2%, and 9.3% for BA using one, two, and three beats, respectively) was approximately twice the intraobserver percentage error (medians, 6.3%, 4.9%, and 4.2% for BA using one, two, and three beats, respectively). Slopes and calculated variables exhibited high percentage error despite BA. Chamber dimensions, areas, velocities, and time intervals exhibited low percentage error.
This comprehensive evaluation of quantitative echocardiographic methods will provide a valuable resource for the design of future pediatric studies. BA and a single core lab observer improve the reproducibility of echocardiographic measurements in children with dilated cardiomyopathy. Certain measurements are highly reproducible, while others, despite BA, are poorly reproducible.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 06/2012; 25(8):842-854.e6. · 2.98 Impact Factor
-
Andrew M Atz,
Thomas G Travison,
Brian W McCrindle,
Lynn Mahony,
Michael Quartermain,
Richard V Williams,
Roger E Breitbart,
Minmin Lu, Elizabeth Radojewski,
Renee Margossian,
Wesley Covitz,
Welton M Gersony
[show abstract]
[hide abstract]
ABSTRACT: This study was undertaken to determine the effects of creating a systemic-to-pulmonary venous atrial-level communication (fenestration) at the time of the Fontan procedure on late outcomes.
Fenestrations are frequently performed during Fontan procedures, but late consequences are not well described.
Patient characteristics were compared between those with and without surgical fenestration among 536 subjects (mean age 11.9 years) enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study. The status of the fenestration and the association of a currently patent fenestration with health status and measures of ventricular performance were investigated.
Fenestration was performed in 361 patients (67%), and frequency differed by year and center (p < 0.001 for each). After adjustment for center, age at Fontan, year of Fontan, and prior superior cavopulmonary surgery, the fenestrated group had shorter length of Fontan hospital stay. At the time of cross-sectional testing 8 ± 3 years after Fontan, the fenestration remained open in 19% of subjects. Among those with confirmed fenestration closure, 59% were by catheter intervention and 1% by surgical intervention, and 40% had apparent spontaneous closure. Compared with those without evidence of a fenestration, subjects with a current fenestration were taking more medications (p = 0.02) and had lower resting oxygen saturation (median 89% vs. 95%, p < 0.001). Functional health status, exercise performance, echocardiographic variables, prevalence of post-Fontan stroke or thrombosis, and growth did not differ by current fenestration status.
Surgical fenestration is associated with well-demonstrated early post-operative benefits. This cross-sectional study found few associations between a persistent fenestration and deleterious later outcomes.
Journal of the American College of Cardiology 06/2011; 57(24):2437-43. · 14.16 Impact Factor
-
Lisa Virzi,
Victoria Pemberton,
Richard G Ohye,
Sarah Tabbutt,
Minmin Lu,
Teresa C Atz,
Teresa Barnard,
Carolyn Dunbar-Masterson,
Nancy S Ghanayem,
Jeffrey P Jacobs,
Linda M Lambert,
Alan Lewis,
Nancy Pike,
Christian Pizarro, Elizabeth Radojewski,
David Teitel,
Mingfen Xu,
Gail D Pearson
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this analysis was to evaluate a novel strategy for reporting adverse events in the Pediatric Heart Network's randomized surgical trial of systemic-pulmonary artery shunt versus right ventricle-pulmonary artery conduit in infants with hypoplastic left heart syndrome. The strategy was developed to align the reporting process with the needs of a surgical trial while maintaining participant safety.
Adverse event reporting was analyzed for 2 groups of study subjects: those randomized to a trial arm during a period in which a standard adverse event reporting system was used (period 1) and those randomized after institution of a system that focused serious adverse event reporting on 6 sentinel events (period 2). The analysis encompassed the period from randomization (Norwood surgery) to hospital discharge from stage II surgery. Adverse event rates were compared using a Poisson regression model for the number of events per subject.
From period 1 to period 2, the rate of serious adverse events requiring expedited reporting decreased as expected (0.42 vs 0.14/subject/month of follow-up; P < .001). Subjects with a serious (sentinel) adverse event in period 2 had a significantly higher rate of death and cardiac transplantation.
The new adverse event reporting system successfully targeted subjects at highest risk, while decreasing the administrative burden associated with adverse event reports. This methodology may be of benefit in trials evaluating surgical or device-based interventions and in critically ill populations where many common clinical events would qualify as serious adverse events in the context of a drug trial.
The Journal of thoracic and cardiovascular surgery 03/2011; 142(3):531-7. · 3.41 Impact Factor
-
Jennifer S Li,
Steven D Colan,
Lynn A Sleeper,
Jane W Newburger,
Victoria L Pemberton,
Andrew M Atz,
Meryl S Cohen,
Fraser Golding,
Gloria L Klein,
Ronald V Lacro, Elizabeth Radojewski,
Marc E Richmond,
L Luann Minich
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Mitral regurgitation is the most common indication for reoperation in children following repair of atrioventricular septal defect (AVSD). We hypothesized that angiotensin-converting enzyme inhibitor therapy would decrease the severity of mitral regurgitation and limit left ventricular volume overload in children following AVSD repair. METHODS: The Pediatric Heart Network designed a placebo-controlled randomized trial of enalapril in this population. The primary aim was to test the effect of enalapril on the change in left ventricular end-diastolic dimension body surface area-adjusted z score. Before the launch of the trial, a feasibility study was performed to estimate the number of patients with at least moderate mitral regurgitation following AVSD repair. TRIAL EXPERIENCE: Seventeen months after the start of the study, 349 patients were screened, 8 were trial eligible, and only 5 were enrolled. The study was subsequently terminated because of low patient accrual. Several factors led to the problems with patient accrual, including (1) the use of criteria to assess disease severity in the feasibility study that were not identical to those used in the trial, (2) failure to achieve equipoise for the study among clinicians and referring physicians, (3) reliance on methodology developed in adult populations with different disease mechanisms, and (4) absence of adequate data to define the natural history of the disease process under study. Progress in the treatment of children with cardiovascular disease will depend on the future of multicenter collaborative clinical trials. The lessons learned from this study may contribute to improvements in this research.
American heart journal 02/2011; 161(2):233-40. · 4.65 Impact Factor
-
Linda M Lambert,
L LuAnn Minich,
Jane W Newburger,
Minmin Lu,
Victoria L Pemberton,
Ellen A McGrath,
Andrew M Atz,
Mingfen Xu, Elizabeth Radojewski,
Darlene Servedio,
Brian W McCrindle
[show abstract]
[hide abstract]
ABSTRACT: We sought to compare perceptions of functional health status between children who had undergone a Fontan procedure and their parents.
Fontan procedure survivors 10 to 18 years of age were included in the study if the child completed the Child Health Questionnaire (CHQ) and the parent completed the parent form to assess the child's functional health status. Comparisons were made between raw domain scores for the parent- and child-completed CHQs.
Between March 2003 and April 2004, 1078 Fontan survivors were screened. Of the 546 eligible and consented patients, 354 were 10-18 years of age and 328 parent/child pairs completed the CHQs. Parents reported significantly lower scores (worse functioning) for their children than the children reported for themselves in the domains of physical functioning (P < .01), impact on school or activities from emotional and behavioral problems (P < .01), impact on school or activities from physical health issues (P < .01), general behavior (P < .01), mental health (P < .01), self-esteem (P < .01), and general health perceptions (P < .01). No significant differences were noted for the domains of bodily pain, family cohesiveness, or family activities. For the physical functioning domain, factors contributing to lower scores for parent versus child reports included pulmonary artery anomalies and fenestration at the time of the Fontan operation. Lower parent-reported scores also were associated with more noncardiac health problems in the child.
Parents' perceptions of the functional health status of their children after the Fontan procedure were worse than the children's perceptions.
PEDIATRICS 10/2009; 124(5):e942-9. · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Studies have suggested that patients who have undergone the Fontan procedure experience lower functional health status and diminished exercise capacity compared with other children.
To compare the functional health status of Fontan patients with and without siblings, assess whether there are any differences between Fontan patients and their siblings, and determine associated factors.
A cross-sectional, single-centre, observational study was performed on Fontan patients 10 to 20 years of age, and their sibling closest in age, followed in a tertiary pediatric hospital. Functional health status was measured by the Child Health Questionnaire Child Form and the Pediatric Quality of Life Inventory.
A total of 68 patients and 38 siblings were enrolled. Patients with siblings scored significantly lower on numerous domains of physical functional status than those without siblings. Compared with their matched siblings, Fontan patients reported significantly lower scores in all domains of the Pediatric Quality of Life Inventory and on physical (but not psychosocial) domains of the Child Health Questionnaire Child Form. Factors associated with increased patient-sibling differences included younger patient age, female sex, intracardiac lateral tunnel Fontan connection and lower ejection fraction at the time of study enrollment.
Adolescents with Fontan physiology reported a lower functional health status in physical domains than their siblings, but had similar status in psychosocial domains. Having a sibling was associated with lower reported functional health status, suggesting an important effect of self-perceived physical limitations over true limitations.
The Canadian journal of cardiology 09/2009; 25(9):e294-300. · 3.36 Impact Factor
-
Annette L Baker,
Minmin Lu,
L LuAnn Minich,
Andrew M Atz,
Gloria L Klein,
Rosalind Korsin,
Linda Lambert,
Jennifer S Li,
Wilbert Mason, Elizabeth Radojewski,
Victoria L Vetter,
Jane W Newburger
[show abstract]
[hide abstract]
ABSTRACT: To describe common associated symptoms within the 10 days before diagnosis in subjects enrolled in the Pediatric Heart Network's trial of steroid therapy in Kawasaki disease (KD).
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.
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).
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.
The Journal of pediatrics 12/2008; 154(4):592-595.e2. · 4.02 Impact Factor
-
Ronald V Lacro,
Harry C Dietz,
Lisa M Wruck,
Timothy J Bradley,
Steven D Colan,
Richard B Devereux,
Gloria L Klein,
Jennifer S Li,
L LuAnn Minich,
Stephen M Paridon,
Gail D Pearson,
Beth F Printz,
Reed E Pyeritz, Elizabeth Radojewski,
Mary J Roman,
J Philip Saul,
Mario P Stylianou,
Lynn Mahony
[show abstract]
[hide abstract]
ABSTRACT: Cardiovascular disease, including aortic root dilation, dissection, and rupture, is the leading cause of mortality in patients with Marfan syndrome (MFS). The maximal aortic root diameter at the sinuses of Valsalva is considered the best predictor of adverse cardiovascular outcome. Although advances in therapy have improved life expectancy, affected individuals continue to suffer cardiovascular morbidity and mortality. Recent studies in an FBN1-targeted mouse model of MFS with aortic disease similar to that seen in humans showed that treatment with losartan normalized aortic root growth and aortic wall architecture.
The Pediatric Heart Network designed a randomized clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in subjects with MFS receiving atenolol or losartan. Individuals 6 months to 25 years of age with a body surface area-adjusted aortic root z score >3.0 will be eligible for inclusion. The primary aim is to compare the effect of atenolol therapy with that of losartan therapy on the rate of aortic root growth over 3 years. Secondary end points include progression of aortic regurgitation; incidence of aortic dissection, aortic root surgery, and death; progression of mitral regurgitation; left ventricular size and function; echocardiographically derived measures of central aortic stiffness; skeletal and somatic growth; and incidence of adverse drug reactions.
This randomized trial should make a substantial contribution to the management of individuals with MFS and expand our understanding of the mechanisms responsible for the aortic manifestations of this disorder.
American heart journal 10/2007; 154(4):624-31. · 4.65 Impact Factor
