Reduced pulmonary arterial compliance predicts poor short-term outcome in children with pulmonary arterial hypertension independent of pulmonary vascular resistance.

Background And Study Aim: Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease with pulmonary vascular remodelling leading to an increased pulmonary vascular resistance (PVRi) and decreased pulmonary arterial compliance (PACi). It is debated whether PACi provides prognostic information additional to PVRi and whether the relationship between PVRi and PACi, expressed as their product resistance-compliance-time (RC-time), is constant. The aim of this study is to investigate the relationship between PVRi and PACi and to determine the prognostic value of PACi in addition to PVRi in newly diagnosed children with idiopathic or heritable pulmonary arterial hypertension (IPAH/HPAH).

Impact of Persistent Pulmonary Hypertension of the Newborn in Neonates with Dextro-transposition of the Great Arteries.

Objectives: This study aimed to assess the impact of persistent pulmonary hypertension of the newborn (PPHN) on perioperative morbidity and mortality in patients with dextro-transposition of the great arteries. Secondarily, we evaluated the association between postoperative outcomes and intraoperative variables including the duration of cardiopulmonary bypass, cerebral oxygen desaturation, and hypotension.

Design: Retrospective observational study.

Pulmonary arterial hypertension associated with pulmonary arteriovenous malformations and pulmonary veno-occlusive disease: A devastating combination.

We describe a case of an adolescent male with the rare combination of pulmonary arterial hypertension (PAH) and pulmonary arteriovenous malformations (PAVM's) without confirmed hereditary hemorrhagic telangiectasia (HHT). The patient showed clinical deterioration on standard vasodilator therapy, leading us to question our initial diagnosis. Post-mortem evaluation confirmed the presence of pulmonary veno-occlusive disease of which no conclusive signs were recognized at diagnostic work-up.

Parenteral Prostanoids in Pediatric Pulmonary Arterial Hypertension: Start Early, Dose High, Combine.

There are currently no data supporting specific dosing and weaning strategies for parenteral prostanoid therapy in children with pulmonary arterial hypertension (PAH). To describe the clinical practice of intravenous (IV) or subcutaneous (SC) prostanoid therapy in pediatric PAH and identify dosing strategies associated with favorable outcome. From an international multicenter cohort of 275 children with PAH, 98 patients who received IV/SC prostanoid therapy were retrospectively analyzed.

Hypoxic/ischemic hits predispose to necrotizing enterocolitis in (near) term infants with congenital heart disease: a case control study.

Background: Necrotizing enterocolitis (NEC) is a devastating disease that is relatively frequently diagnosed in term infants with congenital heart disease (CHD), compared with term infants without CHD, in whom NEC is rare. The exact pathogenesis of NEC in term infants with CHD is unknown, but it is hypothesized that ischemia of the intestines plays a pivotal role. We aimed to explore whether (near) term CHD infants, who develop NEC, exhibit more clinical signs of hypoxia/ischemia and low body perfusion directly after birth and during the first 48 hours after admission to the neonatal intensive care unit, when compared with (near) term CHD infants who did not develop NEC.

Upfront triple combination therapy in severe paediatric pulmonary arterial hypertension.

Treatment strategies in paediatric pulmonary arterial hypertension (PAH) have evolved over the last years, but survival is still poor. Recently, in adults with severe PAH, upfront triple combination therapy (uTCT) from diagnosis has been reported to show significant clinical improvement and excellent long-term outcome. This retrospective, observational study aimed to assess the efficacy of uTCT in paediatric PAH.

Cerebrovascular Autoregulation in Preterm Infants During and After Surgical Ligation of the Ductus Arteriosus, a Comparison Between Two Surgical Approaches.

During ligation of the ductus arteriosus, cerebrovascular autoregulation (CAR) may deteriorate. It is unknown whether different surgical approaches affect changes in CAR differently. The objective of this study was to compare the potential change in CAR in preterm infants during and after ligation comparing two surgical approaches: sternotomy and posterolateral thoracotomy.

Fate of pulmonary hypertension associated with bronchopulmonary dysplasia beyond 36 weeks postmenstrual age.

Objective: To determine the survival and evolution of pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) in extremely premature born infants beyond 36 weeks postmenstrual age (PMA).

Design: A single-centre retrospective cohort study from a university hospital.

Patients: Extremely preterm (gestational age <30 weeks and/or birth weight <1000 g) infants, born between 2012 and 2017, in the University Medical Center Groningen with confirmed PH at/beyond 36 weeks PMA.

Serial Measurements of N-Terminal Pro-B-Type Natriuretic Peptide Serum Level for Monitoring Pulmonary Arterial Hypertension in Children.

Objective: To assess the association between serially measured N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels and disease severity in children with pulmonary arterial hypertension (PAH), and to assess its predictive value for death or (heart-)lung transplantation.

Study Design: This was a longitudinal cohort study of the Dutch National Network for Pediatric Pulmonary Hypertension conducted between 2003 and 2017. Data on NT-proBNP and disease severity markers (World Health Organization Functional Class [WHO-FC], 6-minute walking distance [6MWD], and tricuspid annular plane systolic excursion [TAPSE]) were collected every 3 to 6 months from 82 children with PAH.

Cerebral and Renal Oxygen Saturation Are Not Compromised in the Presence of Retrograde Blood Flow in either the Ascending or Descending Aorta in Term or Near-Term Infants with Left-Sided Obstructive Lesions.

Background: In infants with left-sided obstructive lesions (LSOL), the presence of retrograde blood flow in either the ascending or descending aorta may lead to diminished cerebral and renal blood flow, respectively.

Objectives: Our aim was to compare cerebral and renal tissue oxygen saturation (rSO2) between infants with LSOL with antegrade and retrograde blood flow in the ascending aorta and with and without diastolic backflow in the descending aorta.

Methods: Based on 2 echocardiograms, the study group was categorized according to the direction of blood flow in the ascending and descending aorta.

Physical Activity in Pediatric Pulmonary Arterial Hypertension Measured by Accelerometry. A Candidate Clinical Endpoint.

Rationale: The development of evidence-based treatment guidelines for pediatric pulmonary arterial hypertension (PAH) is hampered by lack of pediatric clinical trials. Trial design is hampered by lack of a feasible clinical endpoint in this population.

Objectives: To evaluate the use of accelerometry for measuring physical activity (PA) in pediatric PAH and to investigate its correlation with clinical disease severity markers.

Clinical classification in pediatric pulmonary arterial hypertension associated with congenital heart disease.

Congenital heart disease (CHD) is a frequent cause of pediatric pulmonary arterial hypertension (PAH), with diverse etiology and outcome. We aimed to describe phenotypic heterogeneity in pediatric PAH associated with CHD (PAH-CHD), assess the applicability of the Nice CHD classification, and explore whether this classification accurately reflects patient/disease characteristics and survival. All children with CHD from a contemporary cohort of consecutive pediatric PAH patients followed in three major referral centers (Denver, New York, the Netherlands) were characterized and classified on the basis of the latest proposed clinical classification for PAH-CHD (World Symposium on Pulmonary Hypertension, Nice, 2013).

Multisite Tissue Oxygenation Monitoring Indicates Organ-Specific Flow Distribution and Oxygen Delivery Related to Low Cardiac Output in Preterm Infants With Clinical Sepsis.

Objectives: Cardiac output may be compromised in preterm infants with sepsis. Whether low cardiac output is associated with low tissue oxygen supply in these patients is unclear. The aim of the current study was to assess the association between cardiac output, assessed by echocardiography, and tissue oxygenation, measured with multisite near-infrared spectroscopy, in a cohort of preterm infants with clinical sepsis.

A Hemodynamically Significant Patent Ductus Arteriosus Does Not Affect Cerebral or Renal Tissue Oxygenation in Preterm Infants.

Background: Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidity. To determine whether the PDA is hemodynamically significant (HSDA), several echocardiographic parameters have been suggested, including retrograde diastolic blood flow in the descending aorta (Dao).

Objective: To assess the impact of an HSDA, including retrograde diastolic flow in the Dao, on regional tissue oxygen saturation (rSO2) and extraction measured by near-infrared spectroscopy (NIRS).

Six-minute walking distance and decrease in oxygen saturation during the six-minute walk test in pediatric pulmonary arterial hypertension.

Objective: To investigate the prognostic value of the 6-minute walking distance (6-MWD), transcutaneous saturation (tcSO2) and heart rate (HR) obtained during the 6-minute walk test (6-MWT) in pediatric pulmonary arterial hypertension (PAH).

Methods: This was an observational study with forty-seven pediatric PAH patients, aged ≥7 years, and diagnosed and followed at the national referral center for pediatric PAH in the Netherlands. All patients performed a comprehensive 6-minute walk test (6-MWT), which measures 6-MWD and tcSO2 and HR before ("baseline"), during ("exercise") and 5 min after ("recovery") the walk test.

Clinical Worsening as Composite Study End Point in Pediatric Pulmonary Arterial Hypertension.

Background: Clinical worsening (CW), an increasingly used composite end point in adult pulmonary arterial hypertension (PAH), has not yet been evaluated in pediatric PAH. This study aims to evaluate the usefulness of CW in pediatric PAH by assessing the event incidence and prognostic value of each separate component of CW and of the composite CW end point.

Methods: Seventy pediatric patients with PAH from the Dutch National Network for Pediatric Pulmonary Hypertension, who started PAH-targeted therapy between January 2000 and January 2014, were included in the study and underwent standardized follow-up.

Echocardiography in pediatric pulmonary arterial hypertension: early study on assessing disease severity and predicting outcome.

Background: The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH.

Methods And Results: Forty-three consecutive children (median age, 8.

Identification of treatment goals in paediatric pulmonary arterial hypertension.

To be able to design goal-oriented treatment strategies in paediatric pulmonary arterial hypertension (PAH), we aimed to identify treatment goals by investigating the prognostic value of treatment-induced changes in noninvasive predictors of transplant-free survival. 66 consecutive, treatment-naïve paediatric PAH patients in the Dutch National Network for Paediatric Pulmonary Hypertension who started taking PAH-targeted drugs between January 2000 and April 2013 underwent prospective, standardised follow-up. Clinical, biochemical and echocardiographic measures were longitudinally collected at treatment initiation and follow-up, and their respective predictive values for transplant-free survival were assessed.

Survival differences in pediatric pulmonary arterial hypertension: clues to a better understanding of outcome and optimal treatment strategies.

Objectives: In order to describe survival and treatment strategies in pediatric pulmonary arterial hypertension (PAH) in the current era of PAH-targeted drugs and to identify predictors of outcome, we studied uniformly defined contemporary patient cohorts at 3 major referral centers for pediatric PAH (New York [NY], Denver, and the Netherlands [NL]).

Background: In pediatric PAH, discrepancies exist in reported survival rates between North American and European patient cohorts, and robust data for long-term treatment effects are lacking.

Methods: According to uniform inclusion criteria, 275 recently diagnosed consecutive pediatric PAH patients who visited the 3 referral centers between 2000 and 2010 were included.

Sildenafil add-on therapy in paediatric pulmonary arterial hypertension, experiences of a national referral centre.

Objective: In paediatric pulmonary arterial hypertension (PAH), the effectiveness of add-on combination PAH-therapy has not yet been systematically studied. The purpose of this study was to determine the effect of sildenafil add-on therapy in paediatric PAH patients treated with bosentan.

Methods: In this observational study within a national paediatric patient cohort, follow-up data of 24 consecutive paediatric PAH patients initially treated with bosentan monotherapy and prospectively followed at the Dutch national referral centre for paediatric PAH in 2007-2013, were reviewed.

Frequency and prognostic significance of hemoptysis in pediatric pulmonary arterial hypertension.

Data concerning the prevalence, risk factors, and prognostic significance of hemoptysis in pediatric pulmonary arterial hypertension (PAH) are scarce. A Dutch national cohort of 74 children with either idiopathic or heritable PAH (IPAH/HPAH, n = 43) or PAH associated with congenital heart disease (PAH-CHD, n = 31) were followed from 1993 to 2012. During a median follow-up of 3.

TBX4 mutations (small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension.

Background: Childhood-onset pulmonary arterial hypertension (PAH) is rare and differs from adult-onset disease in clinical presentation, with often unexplained mental retardation and dysmorphic features (MR/DF). Mutations in the major PAH gene, BMPR2, were reported to cause PAH in only 10-16% of childhood-onset patients. We aimed to identify more genes associated with childhood-onset PAH.