Neonates with congenital heart disease (CHD) and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; e.g., Blalock-Thomas-Taussig shunt). However, over the past two decades an alternative to SPS has emerged in the form of transcatheter ductal artery stenting (DAS). While many reports have indicated safety and durability of the DAS approach, few studies compare outcomes between DAS and SPS. The reports that do exist are comprised primarily of small-cohort single-center reviews. Two multicenter retrospective studies suggest that DAS is associated with similar or superior survival compared to SPS. These studies offer the best evidence to-date, and yet both have important limitations. The authors describe herein the rationale and design of the COMPASS (COmparison of Methods for Pulmonary blood flow Augmentation: Shunt vs. Stent) Trial (NCT05268094, IDE G210212). The COMPASS Trial aims to randomize 236 neonates with DD-PBF to either DAS or SPS across approximately 27 pediatric centers in North America. The goal of this trial is to compare important clinical outcomes between DAS and SPS over the first year of life in a cohort of neonates balanced by randomization to assess whether one method of palliation demonstrates therapeutic superiority.
In fiscally challenging times, scientists must seek creative strategies and leverage existing resources to advance research.This review describes programmes supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) to promote research in paediatric cardiology and congenital heart disease (CHD).An understanding of NHLBI-supported research programmes will help investigators identify opportunities to collaborate with existing systems and use scientific results from existing efforts to catalyse future research in CHD.
A 3-month-old boy is brought to the emergency department for a persistent cough and difficulty breathing. He was born at 34 weeks' gestation after preterm labor and a complete course of maternal betamethasone. His mother had diet-controlled gestational diabetes. A maternal first cousin died of an unspecified cause in early infancy. His birthweight was 2,717 g. He required brief continuous positive air pressure therapy, but he weaned to room air within 24 hours. His NICU course was prolonged due to hypotonia and poor oral motor coordination. Results of brain magnetic resonance imaging, 2 metabolic screens, and Prader-Willi gene testing were normal. His swallow study demonstrated poor coordination, without aspiration. After 7 weeks, he was discharged home on bolus nasogastric feeds. He is tolerating the nasogastric feeds, with normal wet diapers. There are no sick contacts.On examination, he is afebrile, normotensive, fully saturated, tachypneic, and in mild distress. He weighs 5,500 g, with a length of 24 in (60 cm) and a head circumference measuring 15 in (39 cm) (age adjusted to the 80th, 90th, and 40th percentiles, respectively). He is nondysmorphic, with a soft fontanelle. He has moderate intercostal retractions with transmitted upper airway sounds. Cardiac auscultation reveals a regular rate and rhythm with a soft systolic ejection murmur with no gallops. He has normal capillary refill and strong femoral pulses. The abdomen is soft and without hepatosplenomegaly. Neurologic examination reveals diffuse hypotonia, severe head lag, and 1+ reflexes.Laboratory examination reveals a normal complete blood cell count and complete metabolic panel, with a markedly elevated serum creatine kinase level. A chest radiograph reveals mild atelectasis with moderate cardiomegaly (Fig 1). An electrocardiogram demonstrates a shortened PR interval and biventricular hypertrophy with giant QRS complexes (Fig 2). An echocardiogram shows severe concentric hypertrophic cardiomyopathy with normal function (Fig 3). Subsequent enzyme testing reveals the diagnosis.Blood testing was positive for low enzyme activity for lysosomal acid maltase, also known as acid α-1,4-glucosidase (GAA), consistent with the diagnosis of infantile-onset Pompe disease. Additional discussions with the family revealed that a first-degree cousin died of an enzyme deficiency, later found to be Pompe disease. The family agreed to begin enzyme replacement therapy (ERT) with the hope that it will improve his poor prognosis. After 3 months of treatment, there have been slow clinical improvements, with continued reliance on nasogastric feeds.Pompe disease, also known as glycogen storage disease type II, is an inborn error of glycogen metabolism related to a deficiency of GAA. Deficiency of this enzyme results in accumulation of glycogen in lysosomes and the cytoplasm, leading to tissue destruction. Pompe disease is a rare autosomal recessive disorder estimated to occur in the infantile form in 1 in 138,000, and 1 in 57,000 for the juvenile and adult presentation. The infantile-onset form has a higher incidence in African Americans and in individuals from southern China and Taiwan, with later-onset disease having a higher incidence in the Netherlands. More than 200 mutations have been reported in the gene encoding GAA located on chromosome 17.The classic infantile form of Pompe disease presents in the first few months after birth with respiratory distress secondary to cardiac insufficiency, muscle weakness, feeding difficulty, and failure to thrive. Their hypertrophic cardiomyopathy is concentric, involving the muscle of the interventricular septum and free walls due to diffuse accumulation of glycogen in cardiac muscle, as opposed to the hypertrophic cardiomyopathy in infants of diabetic mothers, which predominantly involves the interventricular septum. Infants with Pompe disease may have hepatomegaly related to heart failure and can have macroglossia. Without treatment, death will result in the first 1 to 2 years after birth because of progressive cardiorespiratory failure.Late-onset Pompe disease can present at any age, depending on the level of enzyme activity. Skeletal muscle is primarily affected, so children may present with delayed gross motor skills and progressive limb-girdle weakness. Diaphragm weakness commonly develops with late-onset disease, with disordered breathing occurring with sleep. Respiratory failure and death can occur as early as the second or third decade of life, but it can be seen later if progressive weakness has an adult onset. Cardiomegaly is not usually associated with late-onset Pompe disease.Infants with cardiomegaly and hypotonia should undergo an evaluation for Pompe disease. An electrocardiogram will classically show a short PR interval and biventricular hypertrophy as evidenced by giant QRS complexes in all leads. The echocardiogram will often demonstrate concentric hypertrophic cardiomyopathy. Late-onset disease will have normal cardiac findings, with abnormal electromyographic findings.All forms of Pompe disease typically include an elevated serum creatine kinase level, with decreased leukocyte acid maltase activity. α-Glucosidase enzyme activity can easily be measured in white blood cells on dried blood spots, fibroblasts, or muscle tissue. There is a possible role for future newborn screening initiatives, given the ease of sample testing and the ability of early ERT to reduce the morbidity and mortality associated with the infantile form of the disease. Muscle biopsy reveals glycogen stores in lysosomes, with free glycogen in the cytoplasm and a secondary vacuolar myopathy.In 2006, ERT with the recombinant human acid maltase alglucosidase alfa (Lumizyme®; Genzyme Corp, Cambridge, MA) was approved by the Food and Drug Administration (FDA) for Pompe disease. Treatment response seems to be affected by cross-reactive immunologic material (CRIM) status. The CRIM-negative patients (ie, those lacking residual GAA expression) have a higher risk of death or mechanical ventilation because their high antibody titers to alglucosidase alfa interfere with treatment response.Approximately 75% of patients with the infantile form will die by age 1 year, with almost 85% requiring ventilator support if untreated. Patients studied on ERT for 3 years had up to a 95% reduction in risk of death, a 90% reduction in risk of mechanical ventilation, and improved or stabilized cardiomyopathy, with improved motor skills. Also, ERT has been shown to have benefit with the adult-onset form, as patients experience improved motor skills and respiratory function. In addition, juvenile and adult patients can benefit from a diet high in protein and low in carbohydrates.The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, National Heart, Lung, and Blood Institute, or the United States Government. Dr. Cunningham is a military service member, and Dr. Burns is an employee of the US government. This work was prepared as part of our official duties. Title 17, USC, §105 provides that ‘Copyright protection under this title is not available for any work of the U.S. Government.’ Title 17, USC, §101 defines a US government work as a work prepared by a military service member or employee of the US government as part of that person's official duties.
Abstract Objective We sought to analyse the variation in the incidence of patent ductus arteriosus over three recent time points and characterise ductal ligation practices in preterm infants in the United States, adjusting for demographic and morbidity factors. Methods Using the Kids’ Inpatient Database from 2003, 2006, and 2009, we identified infants born at ⩽32 weeks of gestation with International Classification of Diseases, Ninth Revision diagnosis of patent ductus arteriosus and ligation code. We examined patient and hospital characteristics and identified patient and hospital variables associated with ligation. Results Of 182,610 preterm births, 30,714 discharges included a patent ductus arteriosus diagnosis. The rate of patent ductus arteriosus diagnosis increased from 14% in 2003 to 21% in 2009 (p<0.001). A total of 4181 ligations were performed, with an overall ligation rate of 14%. Ligation rate in infants born at ⩽28 weeks of gestation was 20% overall, increasing from 18% in 2003 to 21% in 2009 (p<0.001). The ligation rate varied by state (4–28%), and ligation was associated with earlier gestational age, associated diagnoses, hospital type, teaching hospital status, and region (p<0.001). Conclusion The rates of patent ductus arteriosus diagnosis and ligation have increased in the recent years. Variation exists in the practice of patent ductus arteriosus ligation and is influenced by patient and non-patient factors.
