Pediatric Pulmonary Hypertension Research Articles

EXPRESS: Parameters associated with outcome in pediatric patients with congenital heart disease and pulmonary hypertension subjected to combined vasodilator and surgical treatments.

Management of pediatric pulmonary hypertension associated with congenital heart disease (PHT‐CHD) is challenging. Some patients have persistently elevated pulmonary artery pressure (PAP) after cardiac surgery, an undesired condition that is difficult to predict. We investigated the value of clinical, hemodynamic, and histopathological data in predicting the outcome in a prospective cohort. Patients with PHT‐CHD received sildenafil orally pre‐ and postoperatively for six months and then were subjected to a catheter study. Thirty‐three patients were enrolled (age range = 4.6–37.0 months). Pulmonary vascular resistance (PVR) was 4.9 (range = 3.9–7.2) Wood units × m2 (median with IQR). Twenty‐two patients had a ≥ 20% decrease in PVR and pulmonary‐to‐systemic vascular resistance ratio (PVR/SVR) in response to inhaled nitric oxide (NO). The response was directly related to the degree of medial hypertrophy of pulmonary arterioles (P < 0.05) (morphometric analysis, intraoperative lung biopsy). Subsequently, five of the non‐responders had a ≥ 30% increase in pulmonary blood flow in response to sildenafil (3.0 [2.0–4.0] mg/kg/day). Six months after surgery, PAP and PVR were significantly lower (P < 0.001 vs. baseline), even in seven patients with Heath‐Edwards grade III/IV pulmonary vascular lesions (P = 0.018), but still abnormal in 12 individuals (>25 mmHg and >3.0 U × m2, respectively). A preoperative PVR/SVR of ≥24% during NO inhalation and a wall thickness of arteries accompanying respiratory bronchioli of ≥4.7 (Z score) were identified, respectively, as risk and protection factors for abnormal postoperative hemodynamics (hazard ratio [95% CI] = 1.09 [1.01–1.18], P = 0.036; and 0.69 [0.49–0.98], P = 0.040, respectively). Thus, in PHT‐CHD patients receiving oral sildenafil pre‐ and post‐surgical repair of cardiac lesions, mid‐term postoperative outcome is predictable to some extent.

Oral treprostinil use in children: a multicenter, observational experience.

Pulmonary arterial hypertension is a progressive, incurable disease that occurs in adults and children alike. Therapeutic options for children are limited and infrequently described, including newer agents such as treprostinil, an oral prostanoid. Herein, we describe the pooled pediatric experience in 28 patients from four pediatric pulmonary hypertension programs over two years. This descriptive, observational study describes the various methods of initiation of oral treprostinil in both prostanoid-naïve patients and those transitioning from parenteral or inhaled prostanoids. The youngest patient was four years old and the smallest weighed 16 kg. We describe adverse reactions and their management. Most patients in this study (27/28) were able to successfully initiate therapy. However, gastrointestinal adverse reactions were common; half of the patients started on this therapy had discontinued it within the two-year study period.

Racial and Ethnic Differences in Pediatric Pulmonary Hypertension: An Analysis of the Pediatric Pulmonary Hypertension Network Registry

To investigate racial and ethnic differences in pulmonary hypertension subtypes and survival differences in a pediatric population. This was a retrospective analysis of a cohort of patients with pulmonary hypertension (aged ≤18years) enrolled in the Pediatric Pulmonary Hypertension Network registry between 2014 and 2018, comprising patients at eight Pediatric Centers throughout North America (n=1417). Among children diagnosed after the neonatal period, pulmonary arterial hypertension was more prevalent among Asians (OR, 1.83; 95% CI, 1.21-2.79; P=.0045), lung disease-associated pulmonary hypertension among blacks (OR, 2.09; 95% CI, 1.48-2.95; P<.0001), idiopathic pulmonary arterial hypertension among whites (OR, 1.58; 95% CI, 1.06-2.41; P=.0289), and pulmonary veno-occlusive disease among Hispanics (OR, 6.11; 95% CI, 1.34-31.3; P=.0184). Among neonates, persistent pulmonary hypertension of the newborn (OR, 4.07; 95% CI, 1.54-10.0; P=.0029) and bronchopulmonary dysplasia (OR, 8.11; 95% CI, 3.28-19.8; P<.0001) were more prevalent among blacks, and congenital diaphragmatic hernia was more prevalent among whites (OR, 2.29; 95% CI, 1.25-4.18; P=.0070). An increased mortality risk was observed among blacks (HR, 1.99; 95% CI, 1.03-3.84; P=.0396), driven primarily by the heightened mortality risk among those with lung disease-associated pulmonary hypertension (HR, 2.84; 95% CI, 1.15-7.04; P=.0241). We found significant racial variability in the prevalence of pulmonary hypertension subtypes and survival outcomes among children with pulmonary hypertension. Given the substantial burden of this disease, further studies to validate phenotypic differences and to understand the underlying causes of survival disparities between racial and ethnic groups are warranted.

Detection of Pediatric Pulmonary Arterial Hypertension by School Electrocardiography Mass Screening.

Rationale: To detect pulmonary arterial hypertension (PAH) at any early stage is a promising approach to optimize the outcome. Objectives: To investigate the impact of school ECG-based screening on detecting idiopathic or heritable (I/H)-PAH in the general pediatric population. Methods: This was a nationwide survey of patients with I/H-PAH newly diagnosed at 3 months to 18 years of age in Japan during 2005-2012. Measurements and Main Results: Eighty-seven eligible patients (age range, 1-16 yr) were recruited. Among 68 (78%) patients diagnosed at greater than or equal to 6 years of age (the age of the first ECG-based screening), 28 (41%) were detected by the ECG-based screening (screening group) and 40 (59%) were recognized by their symptoms (n = 37) or coincidental occasions (n = 3; nonscreening group). In the screening group, the proportion of patients in World Health Organization functional class I/II at diagnosis was higher (96% vs. 60%; P < 0.001), plasma brain natriuretic peptide level was lower (149 ± 290 vs. 398 ± 559 pg/ml; P = 0.045), and 6-minute-walk distance was longer (420 ± 109 vs. 327 ± 104 m; P < 0.001) than the nonscreening group, despite similar values in mean pulmonary artery pressure (58 ± 17 vs. 61 ± 17 mm Hg; P = 0.42) and pulmonary vascular resistance index (18 ± 8 vs. 21 ± 11 Wood units ⋅ m2; P = 0.24) between groups. The proportion of patients on intravenous epoprostenol at the final visit was lower in the screening group than the nonscreening group (14% vs. 50; P = 0.004). Conclusions: These findings suggest that the ECG-based screening detects a unique subpopulation of pediatric patients with I/H-PAH that is associated with already established pulmonary hypertension but without obvious right heart failure and warrants investigating the prognostic significance of this system.

Assessment of quality of life in pediatric patients with pulmonary hypertension.

The aim of this study is to evaluate quality of life in four domains (physical, emotional, social, and school) in pediatric patients with pulmonary hypertension (PH) using a validated survey (PedsQL). This is a prospective cohort study of pediatric patients aged 2–18 years with PH. Parents of all children and patients aged 8–18 years with appropriate developmental capacity completed the PedsQL survey in the clinic. Results were compared with published norms for pediatric patients, those with congenital heart disease (CHD) and cancer. Thirty-three children were enrolled yielding 32 parent and 18 patient self-reports: seven patients were aged 2–4 years; three were aged 5–7 years; 11 were aged 8–12 years, and 12 were aged 13–18 years. Twenty-one patients were classified as World Health Organization (WHO) Group I pulmonary arterial hypertension (PAH), 11 WHO Group III PH due to lung disease, and one WHO Group V with segmental PH. Thirteen patients were NYHA functional class (FC) 1, 12 were FC 2, eight were FC 3, and none were FC 4. The PH cohort had significantly lower scores than healthy children in all domains on both parent and self-report. The PH cohort also had significantly lower scores than patients with CHD (parent report: total, physical, social, school; patient self-report: total, physical, school) and cancer (parent report: school; patient self-report: physical, school). Close to 50% of participants reported at risk scores in each domain. The quality of life in pediatric PH patients assessed by PedsQL revealed functional impairment in multiple domains. Administration of the PedsQL during outpatient encounters may provide an easy, reproducible method to assess quality of life and direct referral for interventional services.

Phenotype characterisation ofTBX4mutation and deletion carriers with neonatal and paediatric pulmonary hypertension

Rare variants in the T-box transcription factor 4 gene (TBX4) have recently been recognised as an emerging cause of paediatric pulmonary hypertension (PH). Their pathophysiology and contribution to persistent pulmonary hypertension in neonates (PPHN) are unknown. We sought to define the spectrum of clinical manifestations and histopathology associated with TBX4 variants in neonates and children with PH.We assessed clinical data and lung tissue in 19 children with PH, including PPHN, carrying TBX4 rare variants identified by next-generation sequencing and copy number variation arrays.Variants included six 17q23 deletions encompassing the entire TBX4 locus and neighbouring genes, and 12 likely damaging mutations. 10 infants presented with neonatal hypoxic respiratory failure and PPHN, and were subsequently discharged home. PH was diagnosed later in infancy or childhood. Three children died and two required lung transplantation. Associated anomalies included patent ductus arteriosus, septal defects, foot anomalies and developmental disability, the latter with a higher prevalence in deletion carriers. Histology in seven infants showed abnormal distal lung development and pulmonary hypertensive remodelling.TBX4 mutations and 17q23 deletions underlie a new form of developmental lung disease manifesting with severe, often biphasic PH at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies.

Right Ventricular Myocardial Stiffness and Relaxation Components by Kinematic Model-Based Transtricuspid Flow Analysis in Children and Adolescents with Pulmonary Arterial Hypertension

We hypothesized that the kinematic model-based parameters obtained from the transtricuspid E-wave would be useful for evaluating the right ventricular diastolic property in pediatric pulmonary arterial hypertension (PAH) patients. The model was parametrized by stiffness/elastic recoil k, relaxation/damping c and load x. These parameters were determined as the solution of m⋅d2x/dt2 + c⋅dx/dt + kx = 0, which is based on the theory that the E-wave contour is determined by the interplay of stiffness/restoring force, damping/relaxation force and load. The PAH group had a significantly higher k and c compared with the control group (182.5 ± 72.4 g/s vs. 135.7 ± 49.5 g/s2, p = 0.0232, and 21.9 ± 6.5 g/s vs. 10.6 ± 5.2 g/s, p <0.0001, respectively). These results indicate that in the PAH group, the right ventricle had higher stiffness/elastic recoil and inferior cross-bridge relaxation. The present findings indicate the feasibility and utility of using kinematic model parameters to assess right ventricular diastolic function.

Right ventricular-vascular coupling ratio in pediatric pulmonary arterial hypertension: A comparison between cardiac magnetic resonance and right heart catheterization measurements

BackgroundIn pulmonary arterial hypertension (PAH), right ventricular (RV) failure is the main cause of mortality. Non-invasive estimation of ventricular-vascular coupling ratio (VVCR), describing contractile response to afterload, could be a valuable tool for monitoring clinical course in children with PAH. This study aimed to test two hypotheses: VVCR by cardiac magnetic resonance (VVCRCMR) correlates with conventional VVCR by right heart catheterization (VVCRRHC) and both correlate with disease severity. Methods and resultsTwenty-seven patients diagnosed with idiopathic and associated PAH without post-tricuspid shunt, who underwent RHC and CMR within 17 days at two specialized centers for pediatric PAH were retrospectively studied. Clinical functional status and hemodynamic data were collected. Median age at time of MRI was 14.3 years (IQR: 11.1–16.8), median PVRi 7.6 WU × m2 (IQR: 4.1–12.2), median mPAP 40 mm Hg (IQR: 28–55) and median WHO-FC 2 (IQR: 2–3). VVCRCMR, defined as stroke volume/end-systolic volume ratio was compared to VVCRRHC by single-beat pressure method using correlation and Bland-Altman plots. VVCRCMR and VVCRRHC showed a strong correlation (r = 0.83, p < 0.001). VVCRCMR and VVCRRHC both correlated with clinical measures of disease severity (pulmonary vascular resistance index [PVRi], mean pulmonary artery pressure [mPAP], mean right atrial pressure [mRAP], and World Health Organization functional class [WHO-FC]; all p ≤ 0.02). ConclusionsNon-invasively measured VVCRCMR is feasible in pediatric PAH and comparable to invasively assessed VVCRRHC. Both correlate with functional and hemodynamic measures of disease severity. The role of VVCR assessed by CMR and RHC in clinical decision-making and follow-up in pediatric PAH warrants further clinical investigation.

Meaningful and feasible composite clinical worsening definitions in paediatric pulmonary arterial hypertension: An analysis of the TOPP registry

BackgroundComposite clinical worsening (cCW) outcomes might allow measurement of disease progression in paediatric pulmonary arterial hypertension (PAH). This TOPP registry analysis investigated three cCW outcomes and their predictive strength for lung transplantation/death. MethodsPatients ≤17 years with idiopathic/familial PAH or PAH-associated congenital heart disease diagnosed ≤3 months before enrolment were included. cCW outcomes included the following variables at enrolment and/or follow-up: all-cause death, PAH-related hospitalisation, lung transplantation, atrial septostomy (cCW1, 2 and 3), WHO FC deterioration, intravenous/subcutaneous prostanoids initiation, syncope (cCW2,3) and occurrence/worsening of ≥2 PAH symptoms (cCW3). The predictive value of CW (excluding transplantation and death) to transplantation or death was assessed. Predictive values of each cCW for lung transplantation/death were analysed by Cox proportional hazards models. ResultsFrom 255 patients, first-event rate/100 person-years (95% CI) were cCW1: 23.1(19.3,27.6), cCW2: 43.6(37.6,50.6), and cCW3: 46.3(40.0,53.7) with PAH-related hospitalisation as the most frequent first event in each. The cCW definitions comprised from endpoints (excluding transplantation and death), were associated with higher risk [hazard ratio (95% CI)] for lung transplantation/death [4.23(2.27,7.91), 3.25(1.65,6.39), 2.74(1.41,5.34), respectively]; individual parameters with higher risks were WHO FC deterioration [3.49(1.47,8.29)], PAH-related hospitalisation [2.62(1.32,5.20)] and occurrence/worsening of ≥2 PAH symptoms [2.13(1.02,4.45)]. ConclusionsThese data support the use of cCW outcomes in paediatric PAH research. WHO FC deterioration, PAH-related hospitalisation, occurrence/worsening of ≥2 PAH symptoms may be important for risk assessment during clinical management.

Survival in Paediatric Pulmonary Arterial Hypertension

Survival in Paediatric Pulmonary Arterial Hypertension

Structural and Biomechanical Adaptations of Right Ventricular Remodeling-In Pulmonary Arterial Hypertension-Reduces Left Ventricular Rotation During Contraction: A Computational Study.

Pulmonary hypertension (PH) is a degenerative disease characterized by progressively increased right ventricular (RV) afterload that leads to ultimate functional decline. Recent observational studies have documented a decrease in left ventricular (LV) torsion during ejection, with preserved LV ejection fraction (EF) in pediatric and adult PH patients. The objective of this study was to develop a computational model of the biventricular heart and use it to evaluate changes in LV torsion mechanics in response to mechanical, structural, and hemodynamic changes in the RV free wall. The heart model revealed that LV torsion and apical rotation were decreased when increasing RV mechanical rigidity and during re-orientation of RV myocardial fibers, both of which have been demonstrated in PH. Furthermore, structural changes to the RV appear to have a notable impact on RV EF, but little influence on LV EF. Finally, RV pressure overload exponentially increased LV myocardial stress. The computational results found in this study are consistent with clinical observations in adult and pediatric PH patients, which reveal a decrease in LV torsion with preserved LV EF. Furthermore, discovered causes of decreased LV torsion are consistent with RV structural adaptations seen in PH rodent studies, which might also explain suspected stress-induced changes in LV myocardial gene and protein expression.

New guidelines for home oxygen therapy in children

New guidelines for home oxygen therapy in children

THREE DIMENSIONAL RIGHT VENTRICULAR STRAIN IN PEDIATRIC PULMONARY HYPERTENSION

Right ventricular (RV) function is important in pediatric pulmonary arterial hypertension (PAH) evaluation. Three-dimensional echocardiography (3DE) RV deformation becomes progressively worse and affects survival in adult PAH. 3DE RV deformation has not been studied in pediatric PH. We compared 3DE

Bronchopulmonary dysplasia-associated pulmonary hypertension

Chronic respiratory sequelae are a major health problem in surviving premature infants. Despite immense improvement in the care of premature infants, the rate of bronchopulmonary dysplasia (BPD) and pulmonary morbidities have remained the same or even slightly increased over the past decades. BPD results from the impairment of lung development following premature birth, and the resultant dysregulated pulmonary vasculature leads to chronic pulmonary hypertension (PH). It is seen more commonly in the setting of moderate to severe BPD. A high index of suspicion is necessary to diagnose PH in BPD. Diagnosis is most commonly done by echocardiogram, but cardiac catheterization may be required to delineate the cardiac structure, cardio-pulmonary vasculature and myocardial function. Once the diagnosis is made, a multidisciplinary approach for management of these patients is suggested, aiming to optimize management of BPD and use of various pulmonary vasodilators. The various therapeutic agents available help reduce pulmonary vascular resistance by acting on the nitric oxide (NO), prostacyclin and/or endothelin pathways. Serial echocardiograms and measurement of biomarkers are used to evaluate the response to therapy. Currently there is not much evidence to support optimal management approaches, but the recent guidelines published by the Pediatric Pulmonary Hypertension Network (PPHNet) provide practical recommendations for screening and management of these infants.

Feature extraction for phenotyping from semantic and knowledge resources.

Phenotyping algorithms can efficiently and accurately identify patients with a specific disease phenotype and construct electronic health records (EHR)-based cohorts for subsequent clinical or genomic studies. Previous studies have introduced unsupervised EHR-based feature selection methods that yielded algorithms with high accuracy. However, those selection methods still require expert intervention to tweak the parameter settings according to the EHR data distribution for each phenotype. To further accelerate the development of phenotyping algorithms, we propose a fully automated and robust unsupervised feature selection method that leverages only publicly available medical knowledge sources, instead of EHR data. SEmantics-Driven Feature Extraction (SEDFE) collects medical concepts from online knowledge sources as candidate features and gives them vector-form distributional semantic representations derived with neural word embedding and the Unified Medical Language System Metathesaurus. A number of features that are semantically closest and that sufficiently characterize the target phenotype are determined by a linear decomposition criterion and are selected for the final classification algorithm. SEDFE was compared with the EHR-based SAFE algorithm and domain experts on feature selection for the classification of five phenotypes including coronary artery disease, rheumatoid arthritis, Crohn's disease, ulcerative colitis, and pediatric pulmonary arterial hypertension using both supervised and unsupervised approaches. Algorithms yielded by SEDFE achieved comparable accuracy to those yielded by SAFE and expert-curated features. SEDFE is also robust to the input semantic vectors. SEDFE attains satisfying performance in unsupervised feature selection for EHR phenotyping. Both fully automated and EHR-independent, this method promises efficiency and accuracy in developing algorithms for high-throughput phenotyping.

Normal Pediatric Values of the Subcostal Tricuspid Annular Plane Systolic Excursion (S-TAPSE) and Its Value in Pediatric Pulmonary Hypertension

BackgroundThe clinical value of determination of right ventricular (RV) function in adults using echocardiographic determination of the subcostal tricuspid annular plane systolic excursion (S-TAPSE) has previously been reported. We aim to provide representative, normal reference values for S-TAPSE in the pediatric age group. Moreover, validation of abnormal S-TAPSE values in children with impaired RV function, such as pulmonary hypertension (PH), is intended. MethodsWe propose a prospective echocardiographic study in 658 healthy children and in 27 children with PH (age: 1 day to 18 years; BSA 0.2-2.0 m2). We correlated the effects of body surface area (BSA) on S-TAPSE values of our healthy subjects and children with PH. S-TAPSE values were compared with apically derived TAPSE values. ResultsS-TAPSE values ranged from a mean of 0.65 ± 0.16 cm in healthy neonates to 1.79 ± 0.33 cm in 18-year-old healthy adolescents. S-TAPSE values increased with increasing age (P = 0.841, P < 0.001), body weight (P = 0.852, P < 0.001), body length (P = 0.846, P < 0.001), and BSA (P = 0.851, P < 0.001) in a nonlinear way in our healthy patients group. No difference in healthy male and female patients could be observed. In our 27 patients with PH (age range: 0.6 to 15.7 years) the median BSA specific S-TAPSE z-score ranged from –3.24 to 1.10, depending on restraint of RV function. ConclusionThe provided S-TAPSE normal reference values and z-scores may assist to identify children with impaired RV function. Abnormal S-TAPSE values will help to identify impaired RV function in pediatric patients with PH.

Evaluation and Monitoring of Pulmonary Hypertension in Neonates With Congenital Diaphragmatic Hernia.

This review aims to describe the assessment of pulmonary hypertension and ventricular function in neonates with congenital diaphragmatic hernia and the long-term follow-up of their pulmonary vascular disease. In 2015, the pediatric pulmonary hypertension guidelines from the American Heart Association and American Thoracic Society suggested class I level of evidence B guidelines for routine evaluation of patients with congenital diaphragmatic hernia, including longitudinal care in an interdisciplinary pulmonary hypertension program and following the recommendations offered for all children with pulmonary hypertension. Congenital diaphragmatic hernia causes compression of the lungs during critical stages of fetal development and results in lung hypoplasia. As a result, there is abnormal development of pulmonary vasculature that leads to post-natal pulmonary hypertension and increased afterload to the right ventricle. Left ventricular filling is affected by decreased pre-load and mechanical compression by abdominal content leading to decreased systemic perfusion. Persistent pulmonary hypertension after surgical repair of congenital diaphragmatic hernia is associated with increased mortality. Assessment and monitoring of pulmonary hypertension and ventricular function in this population of neonates is crucial to determine response to medical treatment, the need for extracorporeal membrane oxygenation, and the timing of surgical repair.

Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management.

Paediatric pulmonary arterial hypertension (PAH) shares common features of 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 the care of children with PAH, as presented by the Paediatric Task Force of the 6th World Symposium on Pulmonary Hypertension. We provide updates of the current definition, epidemiology, classification, diagnostics and treatment of paediatric PAH, and identify critical knowledge gaps. Several features of paediatric PAH including the prominence of neonatal PAH, especially in pre-term infants with developmental lung diseases, and novel genetic causes of paediatric PAH are highlighted. The use of cardiac catheterisation as a diagnostic modality and haemodynamic definitions of PAH, including acute vasoreactivity, are addressed. Updates are provided on issues related to utility of the previous classification system to reflect paediatric-specific aetiologies and approaches to medical and interventional management of PAH, including the Potts shunt. Although a lack of clinical trial data for the use of PAH-targeted therapy persists, emerging data are improving the identification of appropriate targets for goal-oriented therapy in children. Such data will likely improve future clinical trial design to enhance outcomes in paediatric PAH.

A Bayesian Network Approach to Disease Subtype Discovery.

Human diseases are historically categorized into groups based on the specific organ or tissue affected. Over the past two decades, advances in high-throughput genomic and proteomic technologies have generated substantial evidence demonstrating that many diseases are in fact markedly heterogeneous, comprising multiple clinically and molecularly distinct subtypes that simply share an anatomical location. Here, a Bayesian network analysis is applied to study comorbidity patterns that define disease subtypes in pediatric pulmonary hypertension. The analysis relearned established subtypes, thus validating the approach, and identified rare subtypes that are difficult to discern through clinical observations, providing impetus for deeper investigation of the disease subtypes that will enrich current disease classifications. Further advances linking disease subtypes to therapeutic response, disease outcomes, as well as the molecular profiles of individual subtypes will provide impetus for the development of more effective and targeted therapies.

Right Ventricular-Arterial Coupling Ratio Derived From 3-Dimensional Echocardiography Predicts Outcomes in Pediatric Pulmonary Hypertension.

Right ventricular (RV) function is an important determinant of outcomes in pulmonary hypertension (PH). RV-arterial coupling ratio using stroke volume (SV) to end-systolic volume (ESV) has been shown to be an independent predictor of outcome in adults with PH. SV/ESV has not been used in pediatrics to predict outcomes. We compared SV/ESV between pediatric patients with PH, controls, and among groups based on disease severity. We correlated SV/ESV to RV strain and evaluated SV/ESV as a predictor of outcomes in pediatric PH. One hundred and twenty-five children with PH (8 years [3-12 years]) underwent 3-dimensional echocardiography from 2014 to 2017 and compared with 65 controls (9 years [7-13 years]). Offline analysis generated 3-dimensional end-diastolic volume, ESV, SV, and free-wall RV longitudinal strain. SV/ESV ratios were compared between patients with PH, controls, and disease severity. Correlations between SV/ESV to free-wall RV longitudinal strain were assessed using general linear mixed models. Cox proportional hazards analysis assessed the predictive ability of SV/ESV. Patients with PH had lower SV/ESV compared with controls (0.88±0.18 versus 1.24±0.23; P<0.0001). There were significant associations between SV/ESV to free-wall RV longitudinal strain (r=-0.53; P<0.001). SV/ESV emerged as a strong predictor of adverse clinical event (hazard ratio [CI], 0.52 [0.38-0.69] per 0.1 increase in SV/ESV; P<0.0001). SV/ESV as a volume estimate of RV-arterial coupling ratio correlates with RV strain and is a strong predictor of adverse clinical events in pediatric PH.