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Background Transthoracic echocardiography is part of the regular follow‐up protocol at most pediatric pulmonary arterial hypertension (PAH) centers. We aimed to develop a comprehensive and simple echocardiographic risk stratification for children with PAH. Methods and Results We included 63 children with PAH and a biventricular cardiac anatomy without relevant shunt lesions (60% female patients; mean age, 9.0 years; 42 idiopathic PAH and 21 associated PAH) undergoing a standardized transthoracic echocardiographic assessment. The prognostic value of echocardiographic parameters was assessed using Cox proportional hazards survival analysis and recursive partitioning for classification tree methods. Over a median follow‐up period of 4.0 years, 17 patients died and 4 underwent lung transplantation. Various echocardiographic parameters were associated with the combined endpoint of death and transplantation on univariate analysis. On further analysis, right atrial area ( z score) and left ventricular diastolic eccentricity index (LVEId) emerged as robust and independent predictors of transplant‐free survival. Considering mortality alone as an end point, a combination of right atrial area, left ventricular diastolic eccentricity index, and tricuspid annular plane systolic excursion were identified as independent predictors of outcome. Based on these parameters, we propose simple risk scores that can be applied at the bedside without computer assistance. CONCLUSIONS Echocardiographic parameters predict prognosis in children with pulmonary hypertension. A combination of widely available parameters including right atrial area, left ventricular eccentricity index, and tricuspid annular plane systolic excursion emerged as risk stratifiers that await external validation but may assist clinicians determining the prognosis of children with PAH.

BACKGROUND: The placement of a pulmonary-to-systemic arterial shunt in children with severe pulmonary hypertension (PH) has been demonstrated, in relatively small studies, to be an effective palliation for their disease.OBJECTIVES: The aim of this study was to expand upon these earlier findings using an international registry for children with PH who have undergone a shunt procedure.METHODS: Retrospective data were obtained from 110 children with PH who underwent a shunt procedure collected from 13 institutions in Europe and the United States.RESULTS: Seventeen children died in-hospital postprocedure (15%). Of the 93 children successfully discharged home, 18 subsequently died or underwent lung transplantation (20%); the mean follow-up was 3.1 years (range: 25 days to 17 years). The overall 1- and 5-year freedom from death or transplant rates were 77% and 58%, respectively, and 92% and 68% for those discharged home, respectively. Children discharged home had significantly improved World Health Organization functional class (P < 0.001), 6-minute walk distances (P = 0.047) and lower brain natriuretic peptide levels (P < 0.001). Postprocedure, 59% of children were weaned completely from their prostacyclin infusion (P < 0.001). Preprocedural risk factors for dying in-hospital postprocedure included intensive care unit admission (hazard ratio [HR]: 3.2; P = 0.02), mechanical ventilation (HR: 8.3; P < 0.001) and extracorporeal membrane oxygenation (HR: 10.7; P < 0.001).CONCLUSIONS: A pulmonary-to-systemic arterial shunt can provide a child with severe PH significant clinical improvement that is both durable and potentially free from continuous prostacyclin infusion. Five-year survival is comparable to children undergoing lung transplantation for PH. Children with severely decompensated disease requiring aggressive intensive care are not good candidates for the shunt procedure.

In children with single ventricle physiology, increased pulmonary vascular resistance may impede surgical progression or result in failing single ventricle physiology. The use of pulmonary vasodilators has been suggested as a potential therapy. However, knowledge on indication, dosage, and effect is limited. A retrospective case notes review of all (n = 36) children with single ventricle physiology, treated with pulmonary vasodilators by the UK Pulmonary Hypertension Service for Children 2004–2017. Therapy was initiated in Stage 1 (n = 12), Glenn (n = 8), or TCPC (n = 16). Treatment indications were high mean pulmonary arterial pressure, cyanosis, reduced exercise tolerance, protein-losing enteropathy, ascites, or plastic bronchitis. Average dose of sildenafil was 2.0 mg/kg/day and bosentan was 3.3 mg/kg/day. 56% had combination therapy. Therapy was associated with a reduction of the mean pulmonary arterial pressure from 19 to 14 mmHg (n = 17, p n = 16, p

Introduction:Infants with isolated atrial septal defects are usually minimally symptomatic, and repair is typically performed after infancy. Early repair may be considered if there is high pulmonary blood flow and reduced respiratory reserve or early signs of pulmonary hypertension. Our aim was to review the characteristics and outcomes of a cohort of patients who underwent infant repair at our institute.Methods:The study included 56 infants (28 female, 19 trisomy 21) with isolated atrial septal defect (age: 8 months (1.5–12), weight: 6 kg (2.8–7.5), echo Qp/Qs: 1.9 ± 0.1) who underwent surgical closure (20 fenestrated). Three groups were identified: 1) chronic lung disease and pulmonary hypertension (group A: n = 28%); 2) acutely unwell infants with pulmonary hypertension but no chronic lung disease (group B: n = 20, 36%); and 3) infants with refractory congestive heart failure without either pulmonary hypertension or chronic lung disease (group C: n = 9, 16%).Results:Post-operatively, pulmonary hypertension infants (47/56) showed improvement in tricuspid annular plane systolic excursion z-score (p < 0.001) and right ventricular systolic/diastolic duration ratio (p < 0.05). All ventilator (14.3%) or oxygen-dependent (31.6%) infants could be weaned within 2 weeks after repair. One year later, weight z-score increased in all patients and by +1 in group A, +1.3 in group B and +2 in group C. Over a median follow-up of 1.4 years, three patients died, four patients continued to have pulmonary hypertension evidence and two remained on targeted pulmonary hypertension therapy.Conclusion:Atrial septal defect repair within the first year may improve the clinical status and growth in infants with early signs of pulmonary hypertension or those requiring respiratory support and facilitate respiratory management.

Background The Fontan circulation is a successful operative strategy for abolishing cyanosis and chronic volume overload in patients with congenital heart disease with single ventricle physiology. “Fontan failure” is a major cause of poor quality of life and mortality in these patients. We assessed the number and clinical characteristics of adult patients with Fontan physiology receiving pulmonary arterial hypertension (PAH) therapies across specialist centers in the United Kingdom. Methods and Results We identified all adult patients with a Fontan‐type circulation under active follow‐up in 10 specialist congenital heart disease centers in England and Scotland between 2009 and 2019. Patients taking PAH therapies were matched to untreated patients. A survey of experts was also performed. Of 1538 patients with Fontan followed in specialist centers, only 76 (4.9%) received PAH therapies during follow‐up. The vast majority (90.8%) were treated with a phosphodiesterase‐5 inhibitor. In 33% of patients, PAH therapies were started after surgery or during hospital admission. In the matched cohort, treated patients were more likely to be significantly limited, have ascites, have a history of protein‐losing enteropathy, or receive loop diuretics ( P P =0.01), with no other changes in clinical parameters or safety issues. Conclusions PAH therapies are used in adult patients with Fontan circulation followed in specialist centers, targeting individuals with advanced disease or complications. Follow‐up suggests stabilization of the clinical status after 12 months of therapy.

Background/Introduction Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD) in children and is associated with significant morbidity and mortality. The impact of different phenotypes on management and survival remains unclear. Purpose To examine the clinical features, management and outcomes of paediatric PAH-CHD patients based on the 20-year experience of the UK National Paediatric Pulmonary Hypertension (PH) Service. Methods Consecutive PAH-CHD patients entering the service between January 2001 and January 2021 were included and classified into: Eisenmenger syndrome (ES, group A), PAH related to a significant systemic-pulmonary shunt (group B), PAH with small or co-incidental CHD (group C) and PAH following defect repair (group D). Incident patients (without pre-existing PAH) were included in survival analysis. Results Of the overall PH paediatric cohort of 1104 patients, 819 (74.2%) had co-existing CHD and 354 (32.1%) patients received a diagnosis of PAH-CHD: 57.1% female, median [IQR] 4.6 [1.7–10.9] years. Group D PAH-CHD was the commonest subgroup, accounting for 36%, while the least frequent subtype was group C (14%). Group A and group B PAH-CHD represented 26% and 24%, respectively. Down syndrome was present in over one third (122, 34.5%) of PAH-CHD patients and was more commonly associated with ES (p=0.02). PAH therapy was started in 79.9% of PAH-CHD patients. At the end of follow-up, patients with group C PAH-CHD were more likely to be on combination therapy than any other group (64.6% vs. 28.4%, p The subgroup distribution of PAH-CHD at diagnosis changed from the early (2000–2005) to late (2015–2020) period (Figure 1). The proportion of ES patients decreased from 43.4% to 14.6% of PAH-CHD (p Transplant-free survival in PAH-CHD was 90.9% (95% CI: 87.8–94%) at 1 year, 77.9% (95% CI: 73.1–83.1%) at 5 years, and 74.9% (95% CI: 69.6–80.7%) at 10 years (Figure 2). Group C PAH-CHD had a lower transplant-free survival than the other 3 groups (HR 2.54, 95% CI: 1.51–4.28, p=0.0005). There was no difference in outcome between group A and group D PAH-CHD (HR 1.19, 95% CI: 0.62–2.28, p=0.6). Conclusions Repaired PAH-CHD, not ES, was the most common subtype in this large paediatric cohort. Over time, there were fewer ES patients and more “operable” patients with left-right shunts, suggesting an improvement in early diagnosis and management. Despite widespread use of PAH therapy, PAH-CHD remains a life-limiting disease with the poorest outcomes in PAH with co-incidental CHD. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Constantine received a personal PhD fellowship grant (CHAMPION PhD Fellowship) Figure 1Figure 2

Introduction Pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is a progressive, life-limiting disease. Areas covered In this paper, we review the classification and pathophysiology of PAH-CHD, including the mechanisms of disease progression and multisystem effects of disease. We evaluate current strategies of risk stratification and the use of biological markers of disease severity, and review principles of management of PAH-CHD. The indications, timing, and the content of advanced heart failure assessment and transplant listing are discussed, along with a review of the types of transplant and other forms of available circulatory support in this group of patients. Finally, the integral role of advance care planning and palliative care is discussed. Expert opinion/commentary All patients with PAH-CHD should be followed up in expert centers, where they can receive appropriate risk assessment, PAH therapy, and supportive care. Referral for transplant assessment should be considered if there continue to be clinical high-risk features, persistent symptoms, or acute heart failure decompensation despite appropriate PAH specific therapy. Expert management of PAH-CHD patients, therefore, requires vigilance for these features, along with a close relationship with local advanced heart failure services and a working knowledge of listing criteria, which may disadvantage congenital heart disease patients.

Background: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 ( BMPR2 ) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene ( EIF2AK4 ) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. Methods: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource–Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. Results: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (K co ; 33% [interquartile range, 30%–35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23–38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. Conclusions: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low K co and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation.

OBJECTIVES: Paediatric pulmonary arterial hypertension (PAH) after neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA) is a clinically recognised entity with an estimated incidence of 0.6%-1.0%. Nevertheless, a clinical characterisation is lacking. We present an international cohort of children with PAH after neonatal ASO for TGA and describe epidemiology and clinical course.METHODS: Data were collected of children with PAH after neonatal ASO (≤6 weeks after birth) for simple TGA without residual shunt defects, identified in four national paediatric PAH networks in Europe and one US referral centre.RESULTS: Twenty-five children were identified between 1989 and 2014. In 17 children (68%), PAH was detected CONCLUSIONS: The occurrence of PAH after ASO for TGA represents a specific association. PAH onset may be early or late after ASO, with similar fatal course from first PAH detection. Mechanisms leading to PAH in this association are unknown, but may include abnormal prenatal pulmonary haemodynamics and/or genetic susceptibility. Routine, lifelong follow-up for children who undergo ASO for TGA should include screening for PAH.

Pulmonary hypertension is a complex and progressive condition that is either idiopathic or heritable, or associated with one or multiple health conditions, with or without congenital or acquired cardiovascular disease. Recent developments have tremendously increased the armamentarium of diagnostic and therapeutic approaches in children and young adults with pulmonary hypertension that is still associated with a high morbidity and mortality. These modalities include non-invasive imaging, pharmacotherapy, interventional and surgical procedures, and supportive measures. The optimal, tailored diagnostic and therapeutic strategies for pulmonary hypertension in the young are rapidly evolving but still face enormous challenges: Healthcare providers need to take the patient’s age, development, disease state, and family concerns into account when initiating advanced diagnostics and treatment. Therefore, there is a need for guidance on core and advanced medical training in paediatric pulmonary hypertension. The Association for European Paediatric and Congenital Cardiology working group “pulmonary hypertension, heart failure and transplantation” has produced this document as an expert consensus statement; however, all recommendations must be considered and applied in the context of the local and national infrastructure and legal regulations.

Background— Chronic thromboembolic pulmonary hypertension results from incomplete resolution of pulmonary emboli. Pulmonary endarterectomy (PEA) is potentially curative, but residual pulmonary hypertension following surgery is common and its impact on long-term outcome is poorly understood. We wanted to identify factors correlated with poor long-term outcome after surgery and specifically define clinically relevant residual pulmonary hypertension post-PEA. Methods and Results— Eight hundred eighty consecutive patients (mean age, 57 years) underwent PEA for chronic thromboembolic pulmonary hypertension. Patients routinely underwent detailed reassessment with right heart catheterization and noninvasive testing at 3 to 6 months and annually thereafter with discharge if they were clinically stable at 3 to 5 years and did not require pulmonary vasodilator therapy. Cox regressions were used for survival (time-to-event) analyses. Overall survival was 86%, 84%, 79%, and 72% at 1, 3, 5, and 10 years for the whole cohort and 91% and 90% at 1 and 3 years for the recent half of the cohort. The majority of patient deaths after the perioperative period were not attributable to right ventricular failure (chronic thromboembolic pulmonary hypertension). At reassessment, a mean pulmonary artery pressure of ≥30 mm Hg correlated with the initiation of pulmonary vasodilator therapy post-PEA. A mean pulmonary artery pressure of ≥38 mm Hg and pulmonary vascular resistance ≥425 dynes·s −1 ·cm −5 at reassessment correlated with worse long-term survival. Conclusions— Our data confirm excellent long-term survival and maintenance of good functional status post-PEA. Hemodynamic assessment 3 to 6 months and 12 months post-PEA allows stratification of patients at higher risk of dying of chronic thromboembolic pulmonary hypertension and identifies a level of residual pulmonary hypertension that may guide the long-term management of patients postsurgery.

BackgroundCardiopulmonary exercise testing helps prognosticate and guide treatment in adults with pulmonary hypertension. Concerns regarding its feasibility and safety limit its use in children with pulmonary hypertension. We aimed to assess the feasibility and safety of cardiopulmonary exercise testing in a large paediatric pulmonary hypertension cohort.MethodsWe reviewed all consecutive cardiopulmonary exercise tests performed between March, 2004 and November, 2013. The exclusion criteria were as follows: height 2 saturation.ResultsA total of 98 children underwent 167 cardiopulmonary exercise tests. The median age was 14 years (inter-quartile range 10–15 years). Peak oxygen uptake was 20.4±7.3 ml/kg/minute, corresponding to 51.8±18.3% of the predicted value. Peak respiratory quotient was 1.08±0.16. All the tests except two were maximal, being terminated prematurely for clinical reasons. Baseline Oxygen saturation was 93.3±8.8% and was 81.2±19.5% at peak exercise. A drop in arterial O2 saturation >20% was observed in 23.5% of the patients. Moreover, five patients (3.0%) experienced dizziness, one requiring termination of cardiopulmonary exercise testing; five children (3.0%) experienced chest pain, with early cardiopulmonary exercise test termination in one patient. No significant arrhythmias or electrocardiogram changes were observed.ConclusionExercise testing in non-severely symptomatic children with pulmonary hypertension is safe and practical, and can be performed in a large number of children with pulmonary hypertension in a controlled environment with an experienced team. Side-effects were not serious and were resolved promptly with test termination.

Background—Conventional cardiopulmonary exercise testing can objectively measure exercise intolerance but cannot provide comprehensive evaluation of physiology. This requires additional assessment of cardiac output and arteriovenous oxygen content difference. We developed magnetic resonance (MR)–augmented cardiopulmonary exercise testing to achieve this goal and assessed children with right heart disease.Methods and Results—Healthy controls (n=10) and children with pulmonary arterial hypertension (PAH; n=10) and repaired tetralogy of Fallot (n=10) underwent MR-augmented cardiopulmonary exercise testing. All exercises were performed on an MR-compatible ergometer, and oxygen uptake was continuously acquired using a modified metabolic cart. Simultaneous cardiac output was measured using a real-time MR flow sequence and combined with oxygen uptake to calculate arteriovenous oxygen content difference. Peak oxygen uptake was significantly lower in the PAH group (12.6±1.31 mL/kg per minute;P=0.01) and trended toward lower in the tetralogy of Fallot group (13.5±1.29 mL/kg per minute;P=0.06) compared with controls (16.7±1.37 mL/kg per minute). Although tetralogy of Fallot patients had the largest increase in cardiac output, they had lower resting (3±1.2 L/min per m2) and peak (5.3±1.2 L/min per m2) values compared with controls (resting 4.3±1.2 L/min per m2and peak 6.6±1.2 L/min per m2) and PAH patients (resting 4.5±1.1 L/min per m2and peak 5.9±1.1 L/min per m2). Both the PAH and tetralogy of Fallot patients had blunted exercise–induced increases in arteriovenous oxygen content difference. However, only the PAH patients had significantly reduced peak values (6.9±1.3 mlO2/100 mL) compared with controls (8.4±1.4 mlO2/100 mL;P=0.005).Conclusions—MR-augmented cardiopulmonary exercise testing is feasible in both healthy children and children with cardiac disease. Using this novel technique, we have demonstrated abnormal exercise patterns in oxygen uptake, cardiac output, and arteriovenous oxygen content difference.

Background— There are very few validated prognostic markers in pediatric pulmonary hypertension. Cardiac MRI is a useful, noninvasive method for determining prognosis in adults. The present study is the first to assess its prognostic value in children. Methods and Results— A total of 100 children with pulmonary hypertension (median, 10.4 years; range, 0.5–17.6 years) were evaluated (idiopathic, n=60; repaired congenital heart disease, n=22; miscellaneous, n=18). In all patients, ventricular volumes and great vessel flow were measured. Volumetric data were obtained using retrospectively gated cine imaging (n=37) or real-time imaging (n=63), depending on the patient’s ability to hold his or her breath. During a median follow-up of 1.9 years, 11 patients died and 3 received lung transplantation. Of the cardiac MR parameters measured, right ventricular ejection fraction and left ventricular stroke volume index were most strongly predictive of survival on univariate analysis (2.6- and 2.5-fold increase in mortality for every 1-SD decrease, respectively; P Conclusions— Cardiac MR measures correlate with clinical status and prognosis in children with pulmonary hypertension. Cardiac MR is feasible and may be useful in clinical decision making in pediatric pulmonary hypertension.

The European Paediatric Pulmonary Vascular Disease (PVD) Network is a registered, non-profit organisation that strives to define and develop effective, innovative diagnostic methods and treatment options in all forms of paediatric pulmonary hypertensive vascular disease, including specific forms such as pulmonary arterial hypertension (PAH)-congenital heart disease, pulmonary hypertension (PH) associated with bronchopulmonary dysplasia, persistent PH of the newborn, and related cardiac dysfunction. Methods The writing group members conducted searches of the PubMed/MEDLINE bibliographic database (1990–2015) and held five face-to-face meetings with votings. Clinical trials, guidelines, and reviews limited to paediatric data were searched using the terms ‘pulmonary hypertension’ and 5–10 other keywords, as outlined in the other nine articles of this special issue. Class of recommendation (COR) and level of evidence (LOE) were assigned based on European Society of Cardiology/American Heart Association definitions and on paediatric data only, or on adult studies that included >10% children. Results A total of 9 original consensus articles with graded recommendations (COR/LOE) were developed, and are summarised here. The topics included diagnosis/monitoring, genetics/biomarker, cardiac catheterisation, echocardiography, cardiac magnetic resonance/chest CT, associated forms of PH, intensive care unit/ventricular assist device/lung transplantation, and treatment of paediatric PAH. Conclusions The multipaper expert consensus statement of the European Paediatric PVD Network provides a specific, comprehensive, detailed but practical framework for the optimal clinical care of children with PH.

Background The function of the right and left ventricles is intimately related through a shared septum and pericardium. Therefore, right ventricular (RV) disease in pulmonary hypertension (PH) can result in abnormal left ventricular (LV) myocardial mechanics. To assess this, we implemented novel cardiovascular magnetic resonance (CMR) tissue phase mapping (TPM) to assess radial, longitudinal and tangential LV myocardial velocities in patients with PH. Methods Respiratory self-gated TPM was performed using a rotating golden-angle spiral acquisition with retrospective cardiac gating. TPM of a mid ventricular slice was acquired in 40 PH patients and 20 age- and sex-matched healthy controls. Endocardial and epicardial LV borders were manually defined, and myocardial velocities calculated using in-house software. Patients without proximal CTEPH (chronic thromboembolic PH) and not receiving intravenous prostacyclin therapy (n = 34) were followed up until the primary outcome of disease progression (death, transplantation, or progression to intravenous therapy) or the end of the study. Physicians who determined disease progression were blinded to CMR data. Conventional ventricular volumetric indices and novel TPM metrics were analyzed for prediction of 6-min walk distance (6MWD) and disease progression. Results Peak longitudinal (p

Childhood pulmonary hypertension (PH) is a heterogenous disease associated with considerable morbidity and mortality. Invasive assessment of haemodynamics is crucial for accurate diagnosis and guidance of medical therapy. However, adequate imaging is increasingly important in children with PH to evaluate the right heart and the pulmonary vasculature. Cardiac MR (CMR) and computed tomography (CT) represent important non-invasive imaging modalities that may enable comprehensive assessment of right ventricular (RV) function and pulmonary haemodynamics. Here, we present graded consensus recommendations for the evaluation of children with PH by CMR and CT. The article provides a structured approach for the use of CMR and CT imaging, emphasises non-invasive variables of RV function, myocardial tissue and afterload parameters that may be useful for initial diagnosis and monitoring. Furthermore, assessment of pulmonary perfusion and characterisation of the lung parenchyma provides structural information about processes that may cause or be due to PH.

Background: Pathological pulmonary wave reflections (WR) are a potential hemodynamic biomarker for pulmonary hypertension (PH). WR can be quantified using wave intensity analysis (WIA), typically utilizing simultaneous invasive pressure and velocity measurements. In this study we reformulated WIA to use CMR area and flow to measure reflections non-invasively. We hypothesized that this method could detect differences in WR in PH patients compared to healthy controls and could also differentiate certain PH subtypes. Methods: 20 patients with PH (35% CTEPH), mean age 54years (75% female) and 10 healthy controls, 47years (60% female) were recruited. Branch pulmonary artery (PA) flow volume (Q) and area curves (A) were used to measure wave intensity ( dI ), defined as, dI =[[Unable to Display Character: ∆]]Ax[[Unable to Display Character: ∆]]Q and dI ± =± c /4 [[[Unable to Display Character: ∆]]A± [[Unable to Display Character: ∆]]Q/ c ] 2 , where c =wave-speed. Data were acquired using a retrospectively gated, respiratory navigated, golden-angle, 10.5ms temporal resolution, phase-contrast MR sequence. All patients also underwent right heart cardiac catheterization for pressure and vascular resistance (PVR) measurement, median interval 6 days (IQR 2-11days). The presence of proximal clot in CTEPH patients was determined from contemporaneous CT/angiographic data. Results: A backwards-travelling compression wave (BCW) was present in both left and right PAs of all PH patients, but was absent in all controls ( p =6e -8 ). A backwards-travelling expansion/suction wave was present in the 19/20 branch PAs of controls, and only 4/40 PAs in patients ( p < 0.0001). The area under the BCW was associated with a sensitivity of 100% (95% CI 63-100%) and specificity of 91% (95% CI 75-98%) for the presence of clot in the proximal pulmonary arteries of patients with CTEPH. Conclusions: Noninvasive pulmonary WIA accurately delineates pulmonary vascular health and disease. The main findings of this study were: i) There was a significant difference in WIA metrics between patients and controls, in particular, the presence of a BCW was specifically associated with the presence of PH; and ii) The magnitude of the BCW area showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the non-invasive assessment of PH.

Background— This study assesses the relationship between septal curvature and mean pulmonary artery pressure and indexed pulmonary vascular resistance in children with pulmonary hypertension. We hypothesized that septal curvature could be used to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics. Methods and Results— Fifty patients with a median age of 6.7 years (range, 0.45–16.5 years) underwent combined cardiac catheterization and cardiovascular magnetic resonance. The majority had idiopathic pulmonary arterial hypertension (n=30); the remaining patients had pulmonary hypertension associated with repaired congenital heart disease (n=17) or lung disease (n=3). Mean pulmonary artery pressure and pulmonary vascular resistance were acquired at baseline and during vasodilation. Septal curvature was measured using real-time cardiovascular magnetic resonance. There was a strong correlation between mean pulmonary artery pressure and SC min at baseline and during vasodilator testing ( r =–0.81 and –0.85, respectively; P r =–0.88 and –0.87, respectively; P r =0.58 and –0.74; P SC min values of 0.523, 0.551, and 0.568. If the middle value of 0.551 is taken as a cutoff, the approximate sensitivity would be 67% and the specificity would be 93%. Conclusions— Septal curvature metrics are able to estimate right ventricular afterload and track acute changes in pulmonary hemodynamics during vasodilator testing. This suggests that septal curvature could be used for continuing assessment of load in pulmonary hypertension.

Background Paediatric pulmonary hypertension is often difficult to assess non-invasively. Early detection and treatment of mild disease in high-risk populations e.g. pulmonary disease is associated with improved outcome. In such cases, echocardiographic measurement of tricuspid regurgitation is unreliable for estimation of right heart pressure. Cardiac MR imaging offers an alternative, using deformation of the interventricular septum to assess the pressure differential between the ventricles. In this study, we hypothesised that this technique offers a useful tool for both detection of pulmonary hypertension and assessment of those with established disease. Methods Septal curvature ratio (SCR) at peak systole was analysed in twenty normal controls and twelve patients with diagnosed pulmonary hypertension. All patients underwent a joint cardiac catheterisation and MR procedure. Their pulmonary vascular resistance (PVR) was calculated using phase contrast measures and simultaneous pulmonary arterial (PAP) and capillary wedge pressures. SCR was measured at papillary muscle level in the mid ventricle from kt-SENSE short axis images, using regions of interest applied to the epicardial surfaces of the left ventricular free wall and right ventricular septal wall. [Fig 1] Pearson correlation coefficients of PVR and PAP with SCR were calculated. Sensitivity and specificity of the method were assessed using SCR measures from the control population. Results In PH patients, the median SCR was -0.05 (range: -0.390.35). PVR was strongly negatively correlated with SCR (r=-0.81, P=

To develop a non-invasive method of assessing disease severity in pulmonary hypertension by quantifying the overall degree of vascular pruning using fractal geometry.A retrospective analysis of ECG-gated CT pulmonary angiograms.A single national referral centre for the investigation and treatment of children with pulmonary hypertension.Consecutive CT pulmonary angiograms in children and young adults (mean age 10.3 years, range 0.7-19.1) with pulmonary arterial hypertension assessed between January 2007 and April 2009.The fractal dimension (FD) of skeletonised CT pulmonary angiograms was calculated using the box counting method. The FD was compared with pulmonary vascular resistance, the percentage of predicted 6-min walk distance, WHO functional class and survival.Diagnostic plots confirmed that the pulmonary artery angiograms were all fractal. The FD correlated negatively with the pulmonary vascular resistance index (r=-0.55, p=0.01, n=21) and with WHO functional class (p0.01, n=31) while it correlated positively with the percentage of predicted 6-min walk distance (r=0.43, p=0.04, n=24). A lower FD was associated with poorer survival (HR 5.6; 95% CI 1.2 to 25; p=0.027) for every SD reduction in FD.The FD derived from CT can be used to quantify vascular changes in pulmonary hypertension. This non-invasive technique may be useful in monitoring disease progression and response to therapy.

Objective To clarify the clinical characteristics and epidemiology of idiopathic pulmonary arterial hypertension (IPAH) in childhood, a rare condition with a bad prognosis, poorly documented in children. Also, to describe the long-term outcome. Design A retrospective study of 7 years9 experience. Setting UK Service for Pulmonary Hypertension in Children based at a tertiary referral centre. Patients 64 children. Interventions Patients were initially treated with prostanoids (n=15), bosentan (n=23), sildenafil (n=9), combination therapy (n=11) or calcium channel antagonists (n=6). Main outcome measures WHO functional class, distance walked in 6 minutes, escalation of therapy, survival, transplant-free survival. Results Incidence of IPAH was 0.48 cases per million children per year and the prevalence was 2.1 cases per million. 31% presented with syncope. Oedema was rare. During the first year of follow-up WHO functional class and 6-minute walk distance improved significantly. Survival at 1, 3 and 5 years was 89%, 84% and 75%, respectively; while transplant-free survival was 89% 76% and 57%, respectively. Factors predicting worse survival were WHO functional class (HR 2.4, p=0.04) and poor height and weight z-score (p Conclusions We showed, for the first time, that the incidence of IPAH is lower in children than adults and that the clinical features can be different. Most children present with clinical evidence of advanced disease and clinical status at presentation is predictive of outcome. This 7-year experience confirms the significant improvement in survival over historical controls.