Rationale and design of the randomized COmparison of Methods for Pulmonary blood flow Augmentation: Shunt versus Stent (COMPASS) trial: A Pediatric Heart Network study.

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.

Rationale and Design of the Randomized COmparison of Methods for Pulmonary Blood Flow Augmentation: Shunt Versus Stent (COMPASS) Trial: A Pediatric Heart Network Study.

Neonates with congenital heart disease and ductal-dependent pulmonary blood flow (DD-PBF) require early intervention. Historically, this intervention was most often a surgical systemic-to-pulmonary shunt (SPS; eg, 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).

A prospective multicenter feasibility study of a miniaturized implantable continuous flow ventricular assist device in smaller children with heart failure.

Background: There is no FDA-approved left ventricular assist device (LVAD) for smaller children permitting routine hospital discharge. Smaller children supported with LVADs typically remain hospitalized for months awaiting heart transplant-a major burden for families and a challenge for hospitals. We describe the initial outcomes of the Jarvik 2015, a miniaturized implantable continuous flow LVAD, in the NHLBI-funded Pumps for Kids, Infants, and Neonates (PumpKIN) study, for bridge-to-heart transplant.

Asthmatic patients with high serum amyloid A have proinflammatory HDL: Implications for augmented systemic and airway inflammation.

Rationale: Serum amyloid A (SAA) is bound to high-density lipoproteins (HDL) in blood. Although SAA is increased in the blood of patients with asthma, it is not known whether this modifies asthma severity.

Objective: We sought to define the clinical characteristics of patients with asthma who have high SAA levels and assess whether HDL from SAA-high patients with asthma is proinflammatory.

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation.

The Fontan Udenafil Exercise Longitudinal (FUEL) trial showed that treatment with udenafil was associated with improved exercise performance at the ventilatory anaerobic threshold in children with Fontan physiology. However, it is not known how the initiation of phosphodiesterase 5 inhibitor therapy affects heart rate and blood pressure in this population. These data may help inform patient selection and monitoring after the initiation of udenafil therapy.

Unexpected sirolimus-stimulated airway hyperreactivity in lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a multisystem disease affecting primarily women, characterised in the lung by proliferation of LAM cells, abnormal smooth muscle-like cells with dysfunctional tuberous sclerosis complex genes. This dysfunction results in activation of mechanistic target of rapamycin (mTOR), leading to LAM cell proliferation. Sirolimus (rapamycin) is the only United States Food and Drug Administration-approved treatment for pulmonary LAM, resulting in decreased LAM cell growth/size and stabilised lung function [1].

Design of a multi-institutional neurocognitive discovery study in adult congenital heart disease (MINDS-ACHD).

Background: Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD.

Methods: The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD.

The trial to assess chelation therapy 2 (TACT2): Rationale and design.

Background: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design.

Methods: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or NaEDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI).

Height Versus Body Surface Area to Normalize Cardiovascular Measurements in Children Using the Pediatric Heart Network Echocardiographic Z-Score Database.

Normalizing cardiovascular measurements for body size allows for comparison among children of different ages and for distinguishing pathologic changes from normal physiologic growth. Because of growing interest to use height for normalization, the aim of this study was to develop height-based normalization models and compare them to body surface area (BSA)-based normalization for aortic and left ventricular (LV) measurements. The study population consisted of healthy, non-obese children between 2 and 18 years of age enrolled in the Pediatric Heart Network Echo Z-Score Project.

Ultra-Small Lung Cysts Impair Diffusion Without Obstructing Air Flow in Lymphangioleiomyomatosis.

Background: Lymphangioleiomyomatosis (LAM) is a rare lung disease found primarily in women of childbearing age, characterized by the formation of air-filled cysts, which may be associated with reductions in lung function. An experimental, regional ultra-high resolution CT scan identified an additional volume of cysts relative to standard chest CT imaging, which consisted primarily of ultra-small cysts.

Research Question: What is the impact of these ultra-small cysts on the pulmonary function of patients with LAM?

Study Design And Methods: A group of 103 patients with LAM received pulmonary function tests and a CT examination in the same visit.

Pediatric Heart Network Echocardiographic Z Scores: Comparison with Other Published Models.

Background: Different methods have resulted in variable Z scores for echocardiographic measurements. Using the measurements from 3,215 healthy North American children in the Pediatric Heart Network (PHN) echocardiographic Z score database, the authors compared the PHN model with previously published Z score models.

Methods: Z scores were derived for cardiovascular measurements using four models (PHN, Boston, Italy, and Detroit).

Adapting pharmacological dose-finding designs for early phase behavioral intervention development research.

The use of systematic dose-finding designs to develop behavioral health interventions is lacking. In contrast, drug development research consistently follows a prescribed, regulated, and iterative pathway that begins with empirically establishing optimal drug dose. Adapting dose-finding methodologies from the drug development literature offers several advantages to increasing the feasibility, efficiency, and rigor of this important intervention refining step for behavioral intervention development.

Pregnancy in lymphangioleiomyomatosis: clinical and lung function outcomes in two national cohorts.

Pregnancy in women with lymphangioleiomyomatosis (LAM) has been associated with increased complications and worsening lung function although objective data to advise patients are not available. We assessed lung function and CT scans before and after pregnancy in 16 women with LAM. During the pregnancy, pneumothorax was frequent and mean forced expiratory volume in 1 s (FEV) fell from 77%±19% prepregnancy to 64%±25% predicted and DL from 66±26 to 57±26 (both p<0.

Differential Outcomes With Edetate Disodium-Based Treatment Among Stable Post Anterior vs. Non-Anterior Myocardial Infarction Patients.

Background: The Trial to Assess Chelation Therapy (TACT) found that chelation therapy significantly reduced clinical events in patients with a history of myocardial infarction (MI). The initial report of TACT included the observation of an interaction between edetate disodium infusions and MI location, as well as diabetes. Thus, we examined in greater detail the effect of edetate disodium chelation therapy as a function of MI location and diabetes.

Challenges and lessons learned from the Pediatric Heart Network Normal Echocardiogram Database study.

Background: The Pediatric Heart Network Normal Echocardiogram Database Study had unanticipated challenges. We sought to describe these challenges and lessons learned to improve the design of future studies.

Methods: Challenges were divided into three categories: enrolment, echocardiographic imaging, and protocol violations.

Results of the FUEL Trial.

Background: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking.

Results of a phase 1 multicentre investigation of dexmedetomidine bolus and infusion in corrective infant cardiac surgery.

Background: Dexmedetomidine (DEX) is increasingly used intraoperatively in infants undergoing cardiac surgery. This phase 1 multicentre study sought to: (i) determine the safety of DEX for cardiac surgery with cardiopulmonary bypass; (ii) determine the pharmacokinetics (PK) of DEX; (iii) create a PK model and dosing for steady-state DEX plasma levels; and (iv) validate the PK model and dosing.

Methods: We included 122 neonates and infants (0-180 days) with D-transposition of the great arteries, ventricular septal defect, or tetralogy of Fallot.

Challenges With Left Ventricular Functional Parameters: The Pediatric Heart Network Normal Echocardiogram Database.

Background: The reliability of left ventricular (LV) systolic functional indices calculated from blinded echocardiographic measurements of LV size has not been tested in a large cohort of healthy children. The objective of this study was to estimate interobserver variability in standard measurements of LV size and systolic function in children with normal cardiac anatomy and qualitatively normal function.

Methods: The Pediatric Heart Network Normal Echocardiogram Database collected normal echocardiograms from healthy children ≤18 years old distributed equally by age, gender, and race.

Angiotensin-converting enzyme inhibitors may affect pulmonary function in lymphangioleiomyomatosis.

Introduction: A local renin-angiotensin system exists in the pulmonary nodules of lymphangioleiomyomatosis patients. Sirolimus, the standard treatment for lymphangioleiomyomatosis, stabilizes lung function, but all patients do not respond to or tolerate sirolimus. As renin-angiotensin systems may affect tumor growth and metastasis, we questioned if angiotensin-converting enzyme inhibitors affected lymphangioleiomyomatosis disease progression.

Use of CT Imaging to Quantify Progression and Response to Treatment in Lymphangioleiomyomatosis.

Background: In lymphangioleiomyomatosis (LAM), infiltration of the lungs with smooth muscle-like LAM cells results in cystic destruction and decline in lung function, effects stabilized by sirolimus therapy. LAM lung disease is followed, in part, by high-resolution CT scans. To obtain further information from these scans, we quantified changes in lung parenchyma by analyzing image "texture.