How Is Pulmonary Hypertension Characterised and Treated in Children With Trisomy 21? Observations From the TOPP Registry (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension).

Pulmonary hypertension is common in children with Trisomy 21, frequently with multifactorial aetiologies. Registry data provide better understanding of disease development, diagnostic workup and treatment patterns in children with Trisomy 21. TOPP (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) is a centre-based, comprehensive registry.

SUL-150 Limits Vascular Remodeling and Ventricular Failure in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH.

Enhancing Drug Development for Paediatric Pulmonary Hypertension-An Integrative Perspective.

As with adult pulmonary hypertension (PH), high morbidity and mortality persist with diverse types of paediatric PH. Despite major advances in pharmacologic therapies based on extensive studies in adult PH, few drugs have been comprehensively studied in neonates, infants, and children, leaving current paediatric PH care largely dependent on small observational studies and extrapolation of evidence from adult clinical trials. Challenges in developing successful clinical trials in children include the need to define distinct disease phenotypes with well-characterised natural history and outcomes, the lack of established age- and disease-specific study endpoints, small and heterogeneous paediatric populations, and the common off-label use of PH-targeted drug therapies without regulatory approval.

Predicting pulmonary hemodynamics in pediatric pulmonary arterial hypertension using cardiac magnetic resonance imaging and machine learning: an exploratory pilot study.

Purpose: Pulmonary arterial hypertension (PAH) significantly affects the pulmonary vasculature, requiring accurate estimation of mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRi). Although cardiac catheterization is the gold standard for these measurements, it poses risks, especially in children. This pilot study explored how machine learning (ML) can predict pulmonary hemodynamics from non-invasive cardiac magnetic resonance (CMR) cine images in pediatric PAH patients.

Hemodynamic profiling of patients with a Fontan circulation using pulmonary pressure/flow relations during dobutamine stress and pulmonary vasodilation testing.

The hemodynamics of Fontan pathophysiology and the effects of pulmonary vasodilator therapy are insufficiently understood. The aim was to evaluate hemodynamic responses to dobutamine-induced stress and the effect of concomitant acute pulmonary vasodilation (APV) testing in patients with a Fontan circulation to identify hemodynamic phenotypes. Sixteen adult patients undergoing cardiac catheterization for clinical indication were included.

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).

Heart failure in patients with a systemic right ventricle: A multicentre study with long-term follow-up.

Aims: Adult patients with transposition of the great arteries (TGA) and an systemic right ventricle (sRV) are at risk for heart failure (HF). In this study, we investigated risk factors for HF hospitalization and developed a novel risk stratification tool to optimize risk prediction for clinical practice.

Methods And Results: In this international multicentre study, 522 patients with TGA and an sRV, without history of HF hospitalization, were followed retrospectively for a median of 17.

Physical Activity Measured by Hip-Anchored Accelerometry in Pediatric Pulmonary Hypertension: Association With Disease Severity and Estimation of Minimal Important Differences.

Background: Pediatric pulmonary hypertension (PH) is a severe incurable disease with a poor prognosis. In pediatric PH, trial design is hampered by the absence of age-appropriate trial end points. This study evaluated physical activity (PA) measured by hip-anchored accelerometry as a potential trial end point in pediatric PH.

Age- and sex-specific reference percentile curves for accelerometry-measured physical activity in healthy European children and adolescents.

Unlabelled: Physical activity measured by accelerometry (PA-accelerometry) is used as an indicator of physical capacity in chronic diseases. Currently, only fragmented age ranges of reference percentile curves are available for European children and adolescents. This study aimed to provide age- and sex-specific percentiles for physical activity measured by hip-worn accelerometry derived throughout the full age range of European children and adolescents.

The Pulmonary Artery Pulsatility Index Provides No Additional Prognostic Information in Pediatric Pulmonary Arterial Hypertension.

Background/objectives: The pulmonary artery pulsatility index (PAPi, calculated as (SPAP - DPAP)/mRAP) has been suggested as a measure of right ventricular-vascular coupling (RVVC) and as a prognostic parameter in cardiovascular conditions, particularly right ventricular failure. This retrospective study investigated the relationship between the PAPi and its components with disease severity parameters, the RVVC, and clinical outcomes in children with pulmonary arterial hypertension (PAH).

Methods: We analyzed data from 111 children from the Dutch National Registry with PAH.

Embracing the challenges of neonatal and paediatric pulmonary hypertension.

Paediatric pulmonary arterial hypertension (PAH) shares common features with adult disease, but is associated with several additional disorders and challenges that require unique approaches. This article discusses recent advances, ongoing challenges and distinct approaches for caring for infants and children with PAH, as presented by the paediatric task force of the 7th World Symposium on Pulmonary Hypertension. We provide updates on diagnosing, classifying, risk-stratifying and treating paediatric pulmonary hypertension (PH) and identify critical knowledge gaps.

Cardiac output drop reflects circulatory attrition after Fontan completion: serial cardiac magnetic resonance study.

Aims: Cardiac magnetic resonance (CMR) imaging is a main diagnostic tool in the follow-up of Fontan patients. However, the value of serial CMR for the evaluation of Fontan attrition is unknown. The aim of this prospective study of serial CMR is to describe the analysis of time-dependent evolution of blood flow distribution, ventricular volumes, and function in patients after Fontan completion.

Prognostic Value of Serial Risk Stratification in Adult and Pediatric Pulmonary Arterial Hypertension: A Systematic Review.

Background: In pulmonary arterial hypertension, it is recommended to base therapeutic decisions on risk stratification. This systematic review aims to report the prognostic value of serial risk stratification in adult and pediatric pulmonary arterial hypertension and to explore the usability of serial risk stratification as treatment target.

Methods And Results: Electronic databases PubMed, Embase, and Web of Science were searched up to January 30, 2023, using terms associated with pulmonary arterial hypertension, pediatric pulmonary hypertension, and risk stratification.

Iron deficiency in patients with a Fontan circulation and its impact on exercise capacity.

Background: Iron deficiency (ID) has been reported in patients with congenital heart disease. There is, however, a scarcity of data on its prevalence in patients with a Fontan circulation. The aim of this study is to investigate the prevalence of ID in Fontan patients and to investigate the association between ID and exercise capacity in this population.

Long-term safety and tolerability of ambrisentan treatment for pediatric patients with pulmonary arterial hypertension: An open-label extension study.

This open-label, extension study assessed long-term safety, tolerability, and efficacy of ambrisentan in a pediatric population (age 8- < 18 years) with pulmonary arterial hypertension (PAH). Following completion of a 6-month, randomized study, participants entered the long-term extension at individualized ambrisentan dosages (2.5/5/7.

Intraoperative transit-time flow measurement of caval veins before and after bidirectional cavopulmonary anastomosis.

Background: Haemodynamic changes in caval venous flow distribution occurring during bidirectional cavopulmonary anastomosis operation are still largely unknown.

Methods: Transit time flow measurements were performed in 15 cavopulmonary anastomosis operations. Superior and inferior caval vein flows were measured before and after the cavopulmonary anastomosis.

Muscle strength is reduced in children with pulmonary arterial hypertension.

Muscle strength is decreased in adults with pulmonary arterial hypertension (PAH). We aim to investigate muscle strength in children with PAH in relation to a cohort of healthy children, and investigate correlations with disease severity markers. This prospective study included children with PAH aged 4-18 years, who visited the Dutch National Referral Center for Pulmonary Hypertension in Childhood between October 2015 and March 2016.

Decreased Muscle Strength in Children With Repaired Tetralogy of Fallot: Relation With Exercise Capacity.

Background The aim of this study is to describe muscle strength in pediatric patients with repaired tetralogy of Fallot compared with healthy peers and to analyze the correlation between muscle strength and peak oxygen uptake, exercise capacity (mL/min). Methods and Results A prospective, cross-sectional study was carried out in the University Medical Center Groningen between March 2016 and December 2019, which included 8 -to-19-year-old patients with repaired tetralogy of Fallot. Exclusion criteria comprised the following: Down syndrome, unstable pulmonary disease and severe scoliosis affecting pulmonary function, neuromuscular disease, and mental or physical limitations that prohibit the execution of the functional tests.

Cardiac Magnetic Resonance Derived Left Ventricular Eccentricity Index and Right Ventricular Mass Measurements Predict Outcome in Children with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, affecting RV remodeling and RV performance, a major determinant of outcome in PAH-patients. In children with PAH, treatment strategy is guided by risk stratification where noninvasive prognosticators are highly needed. The prognostic value of RV characteristics derived by cardiac magnetic resonance (CMR) has been scarcely studied in pediatric PAH.