Pediatric Pediatric Pulmonary Hypertension Research Articles

A single institution anesthetic experience with catheterization of pediatric pulmonary hypertension patients.

Cardiac catheterization remains the gold standard for the diagnosis and management of pediatric pulmonary hypertension (PH). There is lack of consensus regarding optimal anesthetic and airway regimen. This retrospective study describes the anesthetic/airway experience of our single center cohort of pediatric PH patients undergoing catheterization, in which obtaining hemodynamic data during spontaneous breathing is preferential. A total of 448 catheterizations were performed in 232 patients. Of the 379 cases that began with a natural airway, 274 (72%) completed the procedure without an invasive airway, 90 (24%) received a planned invasive airway, and 15 (4%) required an unplanned invasive airway. Median age was 3.4 years (interquartile range [IQR] 0.7-9.7); the majority were either Nice Classification Group 1 (48%) or Group 3 (42%). Vasoactive medications and cardiopulmonary resuscitation were required in 14 (3.7%) and eight (2.1%) cases, respectively; there was one death. Characteristics associated with use of an invasive airway included age <1 year, Group 3, congenital heart disease, trisomy 21, prematurity, bronchopulmonary dysplasia, WHO functional class III/IV, no PH therapy at time of case, preoperative respiratory support, and having had an intervention (p < 0.05). A composite predictor of age <1 year, Group 3, prematurity, and any preoperative respiratory support was significantly associated with unplanned airway escalation (26.7% vs. 6.9%, odds ratio: 4.9, confidence interval: 1.4-17.0). This approach appears safe, with serious adverse event rates similar to previous reports despite the predominant use of natural airways. However, research is needed to further investigate the optimal anesthetic regimen and respiratory support for pediatric PH patients undergoing cardiac catheterization.

Actigraphy methodology in the Kids Mod PAH trial: Physical activity as a functional endpoint in pediatric clinical trials.

Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono- vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open-label, pragmatic trial to compare the safety and efficacy of first-line combination therapy (sildenafil and bosentan) to first-line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America. Investigators will measure participants' physical activity with a research-grade, wrist-worn actigraphy device at multiple time points as an exploratory secondary outcome. Vector magnitude counts per minute and activity intensity will be compared between the treatment arms. By directly and noninvasively measuring physical activity in the ambulatory setting, we aim to identify a novel, simple, inexpensive, and highly reproducible approach for quantitative assessment of exercise tolerance in pediatric PH. These data will increase the field's understanding of the effect of pulmonary vasodilator treatment on daily activity - a quantitative measure of functional status and wellbeing in pediatric PH and a potential primary outcome for future clinical trials in children with cardiopulmonary disorders.

A Canadian, retrospective, multicenter experience with selexipag for a heterogeneous group of pediatric pulmonary hypertension patients.

Selexipag, an oral nonprostanoid prostaglandin receptor agonist, has led to reduced morbidity and mortality in adults with pulmonary arterial hypertension (PAH). While the adult literature has been extrapolated to suggest selexipag as an oral treatment for severe pediatric pulmonary hypertension (PH), longitudinal, multicenter data on the benefits of selexipag in this population are lacking. The purpose of this study is to present a longitudinal, multicentre experience with selexipag in a relatively large cohort of pediatric PH patients and add to the existing selexipag literature. We performed a retrospective, multicenter review describing the clinical outcomes of pediatric PH patients receiving selexipag in addition to standard oral pulmonary vasodilator therapy across three Canadian centers between January 2005 and June 2021. Twenty-four pediatric patients (fifteen female) with a mean age of 9.7 (range 2.0-15.5) years were included. Of this cohort, eighteen (75.0%) were in group 1, one (4.2%) was in group 2, four (16.7%) were in group 3, and one (4.2%) was in group 4. Twenty-two (91.7%) patients were on dual PH therapy after six months. Dosing was targeted to achieve 20-30 mcg/kg/dose orally every twelve hours. Median dose after twelve months was 30 mcg/kg/dose. Twelve months following selexipag initiation, median decreases of 0.2 cm in tricuspid annular plane systolic excursion, 3.5 mmHg in right-ventricular systolic pressure, and 6.1 mmHg in mean pulmonary arterial pressure were observed; none of these changes were statistically significant. Three patients died, one clinically deteriorated and required admission to a pediatric intensive care unit, ten had gastrointestinal symptoms, and three had flushing. Selexipag appears to be a safe and effective adjunctive therapy for pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Additional prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed. Future research should aim to identify subgroups that stand to benefit from the addition of selexipag as well as optimal timing and dosing for the pediatric population.

Multicenter review of a tadalafil suspension formulation for infants and children with pulmonary hypertension: A North American experience.

Phosphodiesterase type 5 (PDE5) inhibitors, with sildenafil the earliest among them, are widely used in the management of pediatric pulmonary arterial hypertension (PAH). Tadalafil is a PDE5 inhibitor with a long half life (16 h), stable pharmacokinetics and pharmacodynamics, and minimal adverse effects. However, the utility of tadalafil suspensions in this setting has not been widely explored due to a lack of clinical experience. We present a multicenter experience that details the safety and tolerability of a tadalafil suspension, either alone or in combination with another vasodilator, for the management of pediatric pulmonary hypertension (PH). This is a retrospective chart review of infants and children at Children's Wisconsin and the Stollery Children's Hospital enrolled in pediatric PH programs between December 2013 and April 2022 managed with a tadalafil suspension. Patients aged six years of age and under who were treated with a tadalafil suspension were included. Demographics, clinical information, echocardiographic and hemodynamic measurements, and laboratory data were collected before and six months after tadalafil initiation. Over the study period, 154 children with a median age of 1.0 (range 0.0-6.9) years were treated with tadalafil therapy. Of these, 39 (25.3%) were in group 1 (PAH), 79 (51.3%) were in group 3 (lung disease), and 33 (21.4%) were in group 5 (pulmonary hypertensive vascular disease). The median initial dose of tadalafil was 1.0 mg/kg once daily. Eleven (7.1%) patients in the cohort were established on tadalafil therapy de novo. The suspension formulation was necessary for 103 (66.9%) patients due to an inability to take enteral tablets and for 49 (31.8%) due to a need for feeding via gastric or jejunal tubes. We observed a statistically significant increase in tricuspid annular plane systolic excursion as well as significant decreases in right-ventricular systolic pressure and NT-proBNP. Tadalafil therapy was well tolerated over the six-month period: at six months, no adverse effects were reported aside from gastrointestinal disturbances by 2 (1.3%) patients. Tadalafil, a long-acting PDE5 inhibitor, when administered in a suspension formulation, has a safe and tolerable adverse effect profile. Following six months of therapy, our cohort showed improvements in clinical parameters, echocardiographic measurements, and laboratory results. Patient compliance was good and adverse effects were rare, minor, and manageable with nonpharmacological means.

Explainable machine learning models for predicting 30-day readmission in pediatric pulmonary hypertension: A multicenter, retrospective study

BackgroundShort-term readmission for pediatric pulmonary hypertension (PH) is associated with a substantial social and personal burden. However, tools to predict individualized readmission risk are lacking. This study aimed to develop machine learning models to predict 30-day unplanned readmission in children with PH.MethodsThis study collected data on pediatric inpatients with PH from the Chongqing Medical University Medical Data Platform from January 2012 to January 2019. Key clinical variables were selected by the least absolute shrinkage and the selection operator. Prediction models were selected from 15 machine learning algorithms with excellent performance, which was evaluated by area under the operating characteristic curve (AUC). The outcome of the predictive model was interpreted by SHapley Additive exPlanations (SHAP).ResultsA total of 5,913 pediatric patients with PH were included in the final cohort. The CatBoost model was selected as the predictive model with the greatest AUC for 0.81 (95% CI: 0.77–0.86), high accuracy for 0.74 (95% CI: 0.72–0.76), sensitivity 0.78 (95% CI: 0.69–0.87), and specificity 0.74 (95% CI: 0.72–0.76). Age, length of stay (LOS), congenital heart surgery, and nonmedical order discharge showed the greatest impact on 30-day readmission in pediatric PH, according to SHAP results.ConclusionsThis study developed a CatBoost model to predict the risk of unplanned 30-day readmission in pediatric patients with PH, which showed more significant performance compared with traditional logistic regression. We found that age, LOS, congenital heart surgery, and nonmedical order discharge were important factors for 30-day readmission in pediatric PH.

Unique Pulmonary Hypertension in Young Children: A Case Series Study.

Pediatric pulmonary hypertension (PH) has a similar clinical presentation to the adult disease but is associated with several additional disorders and challenges that require a specific approach for their fulminant course. With improved care for premature infants, various forms of pulmonary vascular disease have been found in children that did not previously exist. Pediatric PH can begin in utero, resulting in pulmonary vascularity growth abnormalities that may persist into adulthood. Here, we retrospectively reviewed several unique pediatric PH cases from 2000 to 2020 at Kaohsiung Medical University Hospital, Taiwan, a tertiary teaching hospital. Their comorbidities varied and included surfactant dysfunction, bronchopulmonary dysplasia, premature closure of the ductus arteriosus, high levels of renin and aldosterone, and Swyer–James–Macleod syndrome. Their clinical profiles, radiological characteristics, echocardiography, pulmonary angiogram, and therapeutic regimens were recorded. Further, because the underlying causes of pediatric PH were complex and markedly different according to age, adult PH classification may not be applicable to pediatric PH in all settings. We also classified these cases using different systems, including the Panama classification and the Sixth World Symposium on PH, and compared their advantages and disadvantages.

Validation of the New Pediatric Pulmonary Hypertension Risk Score by Cardiac Magnetic Resonance Imaging and Speckle Tracking Echocardiography. The European Pediatric Pulmonary Vascular Disease Network (EPPVDN)

<h3>Purpose</h3> The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) developed in 2019 a pediatric pulmonary hypertension (PH) risk score to assess the risk and severity of PH in children and young adults. This prospective observational study seeks to validate the EPPVDN pediatric PH risk score by correlations with suitable and independent variables from cardiac magnetic resonance imaging (CMR) and speckle tracking echocardiography. <h3>Methods</h3> Twenty children with PAH were enrolled into the study (age: 10.8±1.0, range 4.0- 17.6 years). During the same inpatient stay the invasive and non-invasive EPPVDN pediatric PH risk scores were determined and a protocol-driven CMR study was performed. Subsequently, we correlated the risk scores with conventional and strain CMR variables and advanced echocardiographic variables, including strain analysis (speckle-tracking). In addition, we applied the risk score to 9 children with PAH who received add-on selexipag therapy. Before and approximately 6 months after selexipag start the risk score and echocardiographic RV strain were determined and delta-changes of both were correlated. <h3>Results</h3> We observed significant (p<0.001) and strong correlations of conventional CMR (r=0.69-0.88), CMR strain (r=0.71-0.88), advanced echocardiographic (r=0.65-0.88) and echocardiographic strain variables (r=0.67-0.86), with the EPPVDN PHrisk score. The EPPVDN higher risk scores correlated stronger with the CMR-, ECHO-, and CMR-strain variables, when compared to the lower risk scores. In the add-on selexipag cohort, the change in ECHO-derived RV strain correlated most strongly and significantly with the change in the invasive higher risk score (r= -0.72, p<0.004). <h3>Conclusion</h3> We found strong correlations of conventional, outcome-relevant CMR and strain variables (CMR, ECHO) with the EPPVDN pediatric PH risk scores, and thus validated the score via independent methods. The novel EPPVDN pediatric PH risk score will be very useful in routine clinical care, and can now be applied in larger prospective, pharma-interventional PAH studies in children and young adults. According open access online tools for rapid, comprehensive risk assement are in preparation.

Management of Pulmonary Hypertension in the Pediatric Patient.

Pediatric pulmonary hypertension (PH) is a rare disease with historically very high morbidity and mortality. In the past 20years, there has been a growing recognition that pediatric PH, although having similarities to adult PH, is a unique entity with its own particular pathogeneses, presentation, and management. With better understanding and earlier diagnosis of pediatric PH, and as more medications have become available, survival of children with PH has also significantly improved. This article reviews the various forms of PH in childhood, with a focus on both established and investigational therapies that are available for children with PH.

Safety and tolerability of combination therapy with ambrisentan and tadalafil for the treatment of pulmonary arterial hypertension in children: Real-world experience.

To describe the safety and tolerability of treatment with ambrisentan and tadalafil in pediatric pulmonary hypertension (PH). This retrospective observational two-center study included subjects (≤18 years of age) with PH receiving combination therapy with ambrisentan and tadalafil. Before initiating this therapy, many patients were on other therapies for PH. At baseline, patients either received no therapy or monotherapy with a phosphodiesterase 5 inhibitor (PDE5i) or endothelin receptor antagonist (ERA) (Group A), switched from a different PDE5i and ERA (Group B), or were on prostanoid therapy with or without a PDE5i and/or ERA (Group C and D). Demographics, symptoms, and adverse effects were collected. Pre- and postvalues for exercise capacity, hemodynamics, and biomarkers were compared. There were 43 subjects (26 F, 17 M) ages 4-17.5 years (median 9.3) with World Symposium of PH group 1, 3, and 5. Significant improvements were seen in change scores at follow-up in the entire sample and Group A for 6-min walk distance: +37.0 (6.5-71.0) [p = 0.022], mean pulmonary artery pressure: -6.0 (-14.0 to -3.5) [p = .002], pulmonary vascular resistance: -1.7 (-6.2 to -1.0) [p = .003], NT-proBNP -32.9 (-148.9 to -6.7) [p = .025]. WHO functional class improved in 39.5% and was unchanged in 53.5%; PHrisk scores improved in 16%; were unchanged in 56%; and declined in 14%. Three patients discontinued therapy (two headaches, one peripheral edema). Seven patients were hospitalized for worsening disease (2/7 had a Potts shunt placed, 2/7 had an atrial septostomy). There were no deaths or lung transplantation. Combination therapy with ambrisentan and tadalafil was well-tolerated, with an acceptable safety profile in a select group of children. This therapy was associated with improved exercise capacity and hemodynamics in children who were treatment naïve or on monotherapy with a PH medication before the initiation of ambrisentan and tadalafil. Based on these early data, further study of combination therapy in pediatric PH is warranted.

Building a dedicated pediatric pulmonary hypertension program: A consensus statement from the pediatric pulmonary hypertension network.

Pediatric pulmonary hypertension (PH) is a severe, life‐threatening disease associated with diverse cardiac, pulmonary, and systemic disorders, which generally requires expertise from multiple disciplines for management. Unfortunately, expert centers are limited, often due to inadequate resources or unfamiliarity with needed components for success. The Pediatric Pulmonary Hypertension Network (PPHNet) includes expert centers in North America specifically dedicated to advancing the field of pediatric PH through research and excellent clinical care. PPHNet member sites were queried for valuable program components and these findings were discussed for consensus. Here we provide a collective overview of key elements of an optimal pediatric PH program: team composition, access to services, and commitment to education. It is our intention that this document will assist newer and/or smaller programs identify avenues and resources for growth and provide avenues for collaboration.

Outcomes of COVID-19 infection in pediatric pulmonary hypertension: A single-center experience.

BackgroundThe global COVID‐19 pandemic was particularly concerning for the pediatric pulmonary hypertension (PH) population due to immature immune systems and developmental comorbidities. This study aims to describe a single‐center experience of pediatric PH patients diagnosed with COVID‐19 disease.MethodsA retrospective cohort study of all pediatric patients followed by the PH Center at Texas Children's Hospital diagnosed with COVID‐19 infection from April 2020 to February 2021.ResultsWe identified 23 patients with a median age of 58 months (interquartile range [IQR]: 25–75th, 21–132 months), 48% being Hispanics. Eight patients (35%) required hospitalization; median length of stay was 6 days (IQR: 25–75th, 5–8 days). Only three of these eight patients required increased respiratory support. Targeted PH therapy was escalated in four patients (two in dual and two in triple therapy). There was one mortality in a patient with failing Fontan physiology. Ninety‐one percent of patients have had post‐COVID outpatient follow‐up, median of 101 days (IQR: 25–75th, 50–159 days) from diagnosis. Of the five patients with 6 min walk test (6MWT) data, three (60%) children walked less distance, median of −12 m (IQR: 25–75th, −12 to +49 m) compared to pre‐COVID testing. Postinfection pulmonary function testing (PFT) was notable for decrease in predicted forced vital capacity (FVC; median −6%, range −11% to +6%) and forced expiratory volume in one second (FEV1; median −14%, range −12% to −18%) in 75% of the patients with PFT data.ConclusionIn our institution, COVID‐19 was found more frequently in Hispanics and associated with low mortality.

Altitude exposure in pediatric pulmonary hypertension-are we ready for (flight) recommendations?

Patients with congenital heart disease are surviving further into adulthood and want to participate in multiple activities. This includes exposure to high altitude by air travel or recreational activities, such as hiking and skiing. However, at an altitude of about 2,500 m, the barometric environmental pressure is reduced and the partial pressure of inspired oxygen drops from 21% to 15% (hypobaric hypoxia). In physiologic response to high-altitude-related hypoxia, pulmonary vasoconstriction is induced within minutes of exposure followed by compensatory hyperventilation and increased cardiac output. Even in healthy children and adults, desaturation can be profound and lead to a significant rise in pulmonary pressure and resistance. Individuals with already increased pulmonary pressure may be placed at risk during high-altitude exposure, as compensatory mechanisms may be limited. Little is known about the physiological response and risk of developing clinically relevant events on altitude exposure in pediatric pulmonary hypertension (PAH). Current guidelines are, in the absence of clinical studies, mainly based on expert opinion. Today, healthcare professionals are increasingly faced with the question, how best to assess and advise on the safety of individuals with PAH planning air travel or an excursion to mountain areas. To fill the gap, this article summarises the current clinical knowledge on moderate to high altitude exposure in patients with different forms of pediatric PAH.

The Efficacy and Safety of Pulmonary Vasodilators in Pediatric Pulmonary Hypertension (PH): A Systematic Review and Meta-analysis

Background: We performed a meta-analysis to evaluate the efficacy and safety of pulmonary vasodilators in pediatric pulmonary hypertension (PH) patients. Methods: We searched electronic databases including PubMed, EMBASE, and the Cochrane Library up to May 2020, and conducted a subgroup analysis for pulmonary vasodilators or underlying disease. Results: Fifteen studies with 719 pediatric PH patients were included in the meta-analysis. Adverse events did not differ (p = 0.11, I 2 = 15%) between the pulmonary vasodilators group and the control group, neither in the subgroups. In total, compared with the control group treatment, pulmonary vasodilators significantly decreased the mortality (p = 0.002), mean pulmonary artery pressure (mPAP, p = 0.02), and mechanical ventilation duration (p = 0.03), also improved the oxygenation index (OI, p = 0.01). In the persistent pulmonary hypertension of the newborn (PPHN) subgroup, phosphodiesterase type 5 inhibitors (PDE5i) significantly reduced mortality (p = 0.03), OI (p = 0.007) and mechanical ventilation duration (p = 0.004). Administration of endothelin receptor antagonists (ERAs) improved OI (p = 0.04) and mechanical ventilation duration (p < 0.00001) in PPHN. We also found that in the pediatric pulmonary arterial hypertension (PPAH) subgroup, mPAP was pronouncedly declined with ERAs (p = 0.006). Systolic pulmonary artery pressure (sPAP, p < 0.0001) and pulmonary arterial/aortic pressure (PA/AO, p < 0.00001) were significantly relieved with PDE5i, partial pressure of arterial oxygen (PaO2) was improved with prostacyclin in postoperative PH (POPH) subgroup (p = 0.001). Compared with the control group, pulmonary vasodilators could significantly decrease PA/AO pressure (p < 0.00001) and OI (p < 0.00001) in the short-term (duration <7 days) follow-up subgroup, improve mPAP (p = 0.03) and PaO2 (p = 0.01) in the mid-term (7–30 days) follow-up subgroup, also decrease mortality, mPAP (p = 0.0001), PA/AO pressure (p = 0.0007), duration of mechanical ventilation (p = 0.004), and ICU stay (p < 0.00001) in the long-term follow subgroup (>30 days). Conclusion: Pulmonary vasodilators decrease the mortality in pediatric PH patients, improve the respiratory and hemodynamic parameters, reduce the mechanical ventilation duration.

PH Professional Network: The Benefits and Challenges in Delivering Telehealth in Pediatric Pulmonary Hypertension

PH Professional Network: The Benefits and Challenges in Delivering Telehealth in Pediatric Pulmonary Hypertension

Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy

The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) investigated the safety and efficacy of add-on selexipag, an oral prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH) in adults, in the largest, exploratory pediatric cohort to date. This is a prospective observational study of 15 consecutive children with PAH, treated with oral add-on selexipag at 3 centers. Most patients underwent cardiac catheterizations at baseline and median of 8 months follow-up. All patients had clinical, echocardiographic, and N-terminal pro b-type natriuretic peptide studies, including the EPPVDN pediatric pulmonary hypertension (PH) risk score. There was no death during the use of selexipag. Two of 15 patients ultimately underwent lung transplantation. One patient with heritable PAH died on intravenous treprostinil (off selexipag). The mean right atrial pressure, the ratio of pulmonary arterial pressure (PAP) to systemic arterial pressure (SAP) (mean PAP/mean SAP, diastolic PAP/diastolic SAP: -17%), and transpulmonary pressure gradients (TPG) (mean TPG: -17%; p < 0.01; diastolic TPG: -6 mmHg; p < 0.05) were improved after the therapy (n = 10). Selexipag therapy was associated with a better right ventricular systolic function (tricuspid annular plane systolic excursion: +14.5%; p < 0.01) and functional class. Improvement was seen in non-invasive and combined invasive/non-invasive PH risk scores (lower risk: +18%-22%, higher risk: -35%-37%; p < 0.05). Overall, the efficacy of selexipag was variable, often with a better response in less sick patients. Oral selexipag use in children with PAH is well tolerated and safe when closely monitored. Add-on selexipag therapy improved several outcome-relevant variables in about 50% of patients and prevented disease progression in additional 27% of patients. The novel EPPVDN pediatric PH risk score indicated these drug effects properly, can be useful in clinical follow-up, and should be validated in larger prospective studies.

The role of a multidisciplinary team in a pediatric pulmonary hypertension center.

The multidisciplinary team in a pediatric pulmonary hypertension (PH) center can improve the delivery of care to the PH patient by helping them address the different challenges that correlate to a PH diagnosis. Currently, there are a limited number of accredited pediatric PH centers nationwide, and many healthcare facilities have little experience managing patients with this complex and rare disease. Patients with PH may see providers from multiple medical specialties, inherit a high-cost burden from their PH medications, and have little community backing due to unfamiliarity of the disease. The multidisciplinary team can embrace these challenges. Through the delineation of tasks and roles within the composition of the team, patients can experience the support, resources, and care they need. The composition of the team can vary from center to center, but it may include an attending physician, advanced practice provider, nurse, dietitian, physiologists, respiratory therapists, social workers, research coordinators, and subspecialty collaboration including cardiology, pulmonology, genetics, psychology, and palliative care. When composing a multidisciplinary team, consider the heterogeneity of the patient population being served. Look at the resources available and overall community familiarity with PH. It is important to know the center's limits and refer to an expert PH center as necessary. The goal for every patient with pulmonary hypertension is to maximize their quality of life and outcomes, and the use of the multidisciplinary team is one approach to reaching this goal.

Pediatric Pulmonary Hypertension on the World Stage: Do We Need Separate Neonatal Guidelines?

Pediatric Pulmonary Hypertension on the World Stage: Do We Need Separate Neonatal Guidelines?

Tricuspid annular plane systolic excursion (TAPSE) in pediatric pulmonary hypertension: Integrating right ventricular ejection efficiency (RVEe) into advanced multi-parametric imaging

The tricuspid annular plane systolic excursion (TAPSE) has evolved into one of the major echocardiographic indicators of systolic right ventricular (RV) longitudinal function in pediatric pulmonary hypertension (PH). Current RV function research in children with PH focusses on multi-parametric approaches that include TAPSE. The RV ejection efficiency (RVEe) is one of the new variables that reflects the relationship of TAPSE divided by the indexed pulmonary vascular resistance (PVRi) measured by cardiac catheterization. Here, we investigated not only RVEe, but also the ratio of TAPSE divided by pulmonary systolic arterial pressure (PASP; TAPSE/PASP ratio), and a possible association of these indices with NYHA functional class (FC) or the modified ROSS score in 42 children with PH. Both, the RVEe (TAPSE/PVRi) and the TAPSE/PASP ratio were inversely related to NYHA FC and the modified ROSS score in the pediatric PH compared. Compared to TAPSE as single measure, in both multiparametric variables (RVEe, TAPSE/PASP) more pronounced differences in subjects with different NYHA FC/modified ROSS score values were observed. Taken together, the RVEe (TAPSE/PVRi) and TAPSE/PASP ratio distinguish between NYHA FC/modified ROSS score compared to the single echocardiographic variable TAPSE, highlighting the usefulness of a multiparametric approach.

Genotypes and Phenotypes: Making Progress Toward a Precision Medicine Approach in Pediatric Pulmonary Hypertension

Pediatric pulmonary hypertension (PH) is a heterogeneous disease that includes etiologies related to growth and development that are unique to children. Recent pediatric registry studies have characterized diverse phenotypes even within recognized PH subtypes, including PH associated with congenital heart disease and developmental lung disease. Advances in genetics are resulting in increased understanding of the genetic basis for PH, with recent discoveries such as TBX4 mutations specific for pediatric-onset pulmonary arterial hypertension (PAH) and SOX17 related to congenital heart disease–associated PAH. In addition to potential genetic underpinnings, PAH risk and clinical presentation in children with congenital heart disease may vary by cardiac condition, such as single-ventricle physiology or transposition of the great arteries. Growth and development of the pulmonary vasculature likely plays a role in all pediatric PH, which is highlighted by the disruption of normal lung growth in patients with PH related to prematurity and developmental lung disease. These diverse pediatric genotypes and phenotypes underscore a need for an individualized approach to diagnose and treat the complex pediatric PH population. Magnetic resonance imaging (MRI) is increasingly being used to improve clinical characterization of PH in children, with recent identification of specific MRI biomarkers associated with PH severity and outcomes. While much progress has been made, additional understanding of the important genetic causes and developmental concepts in pediatric PH is needed to develop a precision medicine approach to diagnosis and treatment of children with PH.

Central line replacement following infection does not improve reinfection rates in pediatric pulmonary hypertension patients receiving intravenous prostanoid therapy.

Treatment of pediatric pulmonary hypertension (PH) with IV prostanoids has greatly improved outcomes but requires a central line, posing inherent infection risk. This study examines the types of infections, infection rates, and importantly the effect of line management strategies on reinfection in children receiving IV prostanoids for PH. This study is a retrospective review of all pediatric PH patients receiving intravenous epoprostenol (EPO) or treprostinil (TRE) at one academic tertiary care center between 2000 and 2014. No patients declined participation in the study or were otherwise excluded. Infectious complications were characterized by organism(s), infection rates, time to next infection, and line management decisions (salvage vs. replace). Of the 40 patients followed, 13 sustained 38 infections involving 49 pathogens, with a predominance of gram-positive (GP) organisms (n = 35). The pooled infection rate was 1.06 per 1000 prostanoid days with no difference between EPO and TRE. No significant difference in reinfection rate was observed when comparing line salvage to replacement, regardless of organism type. Both overall and organism-type comparisons suggest longer time between line infections following line salvage compared with line replacement (732 vs. 410 days overall; 793 vs. 363 days for GP; 611 vs. 581 days for gram-negative [GN]; P > 0.05 for all comparisons). Central line replacement following blood stream infections in pediatric PH patients does not improve subsequent infection rates or time to next infection, and may lead to unnecessary risks associated with line replacement, including potential loss of vascular access. A revised approach to central line infections in pediatric PH is proposed.