Search

Evaluate the correlation of non-invasive echocardiographic estimates of right ventricular systolic pressure with measurements on cardiac catheterization in children with pulmonary hypertension. Retrospective chart review. Quaternary academic children's hospital. Patients younger than 18 years with a diagnosis of pulmonary hypertension and confirmatory cardiac catheterization from 2015 to 2018. We analyzed the correlation between measures of right ventricular systolic pressure using nonparametric Spearman rho (ρ) with statistical significance set at p < 0.05. Children (N = 111) with biventricular circulation, strictly defined pulmonary hypertension, and adequate tricuspid regurgitation on echocardiogram to estimate right ventricular systolic pressure using the modified Bernoulli equation. Median age and weight were 4.3 years and 14.4 kg. Median right ventricular systolic pressure estimated by tricuspid regurgitant velocity on echocardiography was 55 mmHg (IQR 45-75 mmHg) plus right atrial pressure. On cardiac catheterization, median right ventricular systolic pressure was 57 mmHg (IQR 46-75 mmHg). Echocardiographic estimates of right ventricular systolic pressure were moderately well correlated with right ventricular systolic pressure directly measured on catheterization (ρ = 0.44, 95% CI 0.27-0.6, p < 0.001) with a median difference of 4 mmHg (IQR −10 to 17). Subgroup analysis revealed that echocardiography and catheterization measurements correlated well in children with suprasystemic right ventricular pressure on cardiac catheterization (ρ = 0.75, 95% CI 0.51-0.99, p < 0.001) although catheterization measurements were a median of 26 mmHg (IQR 12-31) higher than echocardiographic estimates in this subgroup. In children with pulmonary hypertension, echocardiographic estimates of right ventricular pressure correlated moderately well with gold standard measurements by cardiac catheterization with stronger correlation in children with suprasystemic right ventricular pressures. This is reassuring for clinicians who must rely on echocardiography for risk stratification before anesthetizing children with pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network. [ABSTRACT FROM AUTHOR]

While care models adapt to the COVID‐19 pandemic with virtual and hybrid visits, clinical factors associated with treatment changes among ambulatory pediatric pulmonary arterial hypertension (PAH) patients are not well characterized. To understand which data critically altered treatment recommendations, we conducted a retrospective review among ambulatory children with Group 1 PAH to determine optimal visit and diagnostic strategies. Changes in management included: unplanned new treatments, dose modifications of vasodilators or diuretics, unscheduled hospitalizations, or changes to activity recommendations, catheterization schedule, or other testing. Factors prompting management changes were classified as symptoms, exam findings, or diagnostic tests. Across 398 ambulatory visits by 48 patients, 38 patients (79%) at 88 visits (22%) required change in management, most commonly in targeted PH medication. Changes were driven by symptoms alone (15%), diagnostic testing alone (47%), exam only (2%), symptoms and exam (2%), combination of testing and symptoms or testing and exam (25%), and other reasons (9%). Patients with World Health Organization functional Class IV (odds ratio [OR] 9.04 vs. Class I, p = 0.014) or Class III (OR 2.08 vs. Class I, p = 0.050) were more likely to undergo change in management. However, among Class I patients, 18% of visits generated changes in management because of test findings. While multiple factors affect management in ambulatory pediatric PH, neither symptoms nor exam was sufficient for identifying patients warranting clinical change in management. Testing accounted for most changes. Thus, in‐person or hybrid surveillance including history, exam, and diagnostic testing remains essential for optimal management of pediatric PAH. [ABSTRACT FROM AUTHOR]

Rationale: Hemodynamic assessments direct care among children with pulmonary hypertension, yet the use of cardiac catheterization is highly variable, which could impact patient care and research. Objectives: We analyzed hemodynamic findings from right heart catheterization (RHC) and left heart catheterization and acute vasodilator testing (AVT) and the safety of catheterization in children with World Symposium on Pulmonary Hypertension (WSPH) group 1 and 3 subtypes in a large multicenter North American cohort. Methods: Of 1,475 children enrolled in the Pediatric Pulmonary Hypertension Network Registry (2014-2020), there were 1,383 group 1 and 3 patients, of whom 671 (48.5%) underwent RHC at diagnosis and were included for analysis. Results: Compared with those without diagnostic RHC, these children were older, less likely to be an infant or preterm, more often female, treated with targeted pulmonary hypertension medications at diagnosis, and had advanced World Health Organization functional class. Catheterization was performed without a difference in complication rates between WSPH groups. Pulmonary capillary wedge pressure was well correlated with left ventricular end-diastolic pressure and left atrial pressures. Results of AVT using three different methods were comparable; positive AVT results were observed in 8.0-11.8% of subjects, did not differ between WSPH groups 1 and 3, and were not associated with freedom from the composite endpoint of lung transplantation or death during follow-up. Conclusions: In a large pediatric pulmonary hypertension cohort, diagnostic RHC with or without left heart catheterization in WSPH group 1 and 3 patients was performed safely at experienced pediatric pulmonary hypertension centers. Hemodynamic differences were noted between group 1 and 3 subjects. Higher mean pulmonary arterial pressure and mean pulmonary arterial pressure/mean systemic arterial pressure ratio were associated with a higher risk of death/transplantation. Findings suggest overall safety and potential value of RHC as a standard diagnostic approach to guide pulmonary hypertension management in children. [ABSTRACT FROM AUTHOR]

Background: Lung transplantation is a therapeutic option for end‐stage pediatric pulmonary hypertension (PH). Right ventricular (RV) recovery post‐lung transplant in children with PH has not been well‐described, and questions persist about the peri‐operative course and post‐transplant cardiac function after lung transplantation in medically refractory PH patients with baseline RV dysfunction. Methods: A single‐center chart review identified patients with childhood PH who subsequently underwent bilateral orthotopic lung transplantation between 2000 and 2020. Twenty‐six patients met criteria; three were excluded due to echocardiograms not available for digital review. RV fractional area change (FAC) and left ventricular eccentricity index (LVEI) were determined prior to transplantation, and at 1, 3, 6, and 12‐month post‐transplantation. Results: Fourteen of 23 patients had baseline RV dysfunction. The median age at transplantation was 16.5 years and 13.9 years for those with and without baseline RV dysfunction, respectively. Of the 14 with baseline RV dysfunction, 12 (86%) were alive 1‐year post‐transplantation. All patients with baseline RV dysfunction had increased RV‐FAC post‐transplantation with normalization of RV‐FAC in 70% at 3 months and 100% of patients by 12‐month post‐transplantation. Duration of ventilation (p =.4), intensive care unit (p =.5), or hospital stay (p =.9) was not associated with pre‐transplant RV function. Conclusions: Among pediatric patients with PH and RV dysfunction, pre‐transplantation RV function was not associated with short‐term outcomes. All patients with baseline RV dysfunction had improvement in RV function, justifying consideration of lung transplantation among pediatric patients with end‐stage PH and RV dysfunction. [ABSTRACT FROM AUTHOR]

• Altitude may exacerbate chronic lung conditions and expose patients to undetected hypoxia. • Most patients with congenital diaphragmatic hernia (CDH) experience significant hypoxia when exposed to simulated altitude and are at risk during air travel. • Patients with CDH should be screened for possible altitude associated hypoxia. • Some patients with CDH may require oxygen supplementation while in flight to ensure safe air travel. Congenital Diaphragmatic Hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension. Many patients receive care in specialty centers requiring air travel upon discharge and for subsequent follow-up care. Premature infants can experience significant hypoxia in flight, but this has not been studied in the CDH population. This report describes our center's experience with simulated altitude testing among CDH patients. In a single center retrospective cohort study, CDH patients who underwent a High Altitude Simulation Test (HAST) from 2006 to 2019 were analyzed. HAST simulates increased altitude by reducing oxygen tension to an FIO2 of 0.15. Patients were tested only when flight was anticipated. Patients requiring oxygen were challenged on their baseline requirement. To pass, patients had to maintain oxygen saturation > 90%, and 94% if diagnosed with pulmonary hypertension. Supplemental oxygen was titrated as needed to achieve this goal. Of twenty patients tested, only six (30%) passed on their first attempt. Ten (50%) eventually passed, after an average of 3.2 additional attempts over 1.8 years. No patient passed initially who utilized ECMO support, diaphragmatic agenesis, or had elevated right ventricular pressure on echocardiogram. All patients achieved the targeted SpO2 with supplemental oxygen. CDH patients experience hypoxia when exposed to the simulated hypobaric nature of air travel and therefore may become hypoxic in flight, requiring oxygen supplementation. Disease severity seems to correlate with risk of in-flight hypoxia. This data suggests that CDH patients should be screened to assess their need for supplemental oxygen to ensure safe air travel. Level 4 case series. [ABSTRACT FROM AUTHOR]

The already high rates of anxiety and depression among healthy children have increased further since the COVID-19 pandemic began in early 2020. Prepandemic data suggest children with chronic disease were already experiencing increased rates of anxiety and depression as compared to their healthy peers. There is currently a paucity of literature on the prevalence of anxiety and depression in patients with pediatric pulmonary hypertension. In addition, there are no practice recommendations regarding mental health screening in this population. We evaluated provider perception of mental health screening at 14 pediatric pulmonary hypertension care centers across the United States and Canada using a cross-sectional survey. Thirty-seven providers from 14 pediatric pulmonary hypertension centers in North America completed the survey. Health care providers caring for pediatric pulmonary hypertension patients perceive their patient cohort to frequently experience anxiety and depression. In addition, these providers believe that their patients would benefit from formalized, and routine, assessment of anxiety and depression with referral to mental health services as appropriate. This highlights the need to better understand the prevalence of anxiety and depression in pediatric pulmonary hypertension patients and to establish formal mental health screening practices within pediatric pulmonary hypertension care centers. [ABSTRACT FROM AUTHOR]

The authors discuss a study from the Great Ormand Street Hospital for Children (GOSH) provides a unique window into the nature of pediatric pulmonary hypertension (PH) by characterizing the longitudinal outcomes of incident cases from throughout the United Kingdom (UK). Topics include strengths and limitations of the study, importance of registries as applied to current standards for disease characterization, and the need for more effective classification systems for children.

Background Pulmonary hypertension is a rare, life-threatening disease with limited therapeutic options and no definitive cure. Continuous intravenous prostacyclin therapy is indicated for treatment of severe disease. These medications have a narrow therapeutic index and a brief half-life; therefore, administration errors can be lethal. Objective To reduce medication errors through an inpatient program to improve, standardize, and disseminate continuous intravenous prostacyclin therapy practice guidelines. Methods Data were collected from the electronic safety reporting system of a single hospital to determine the number and types of continuous intravenous prostacyclin therapy errors that were reported over an 8-year period. A clinical database and hospital pharmacy records were used to determine the number of days on which hospitalized pediatric patients received the therapy. Interventions A nursing-directed quality improvement initiative to enhance the safety of continuous intravenous prostacyclin therapy for pediatric patients was begun in January 2009. Efforts to improve safety fell into 4 domains: policy, process, education, and hospital-wide safety initiatives. Results The number of therapy errors per 1000 patient days fell from 19.28 in 2009 to 5.95 in 2016. Chi-square analysis was used to compare the result for 2009 with that for each subsequent year, with P values of.66,.35,.16,.09,.03,.12, and.25 found for 2010 through 2016, respectively. Conclusions The trend in reduction of continuous intravenous prostacyclin therapy errors suggests that proactive processes to standardize its administration, emphasizing both policy and education, reduce medication errors and increase patient safety. [ABSTRACT FROM AUTHOR]

Atrial septal defects (ASDs) are common congenital heart defects in children and adults. Pulmonary arterial hypertension (PAH) is found in subsets of both pediatric and adult patients with atrial defects under varied clinical contexts. The pulmonary hypertension specialist is often faced with questions surrounding timing and method of defect closure, which may have significant impact on procedural and long-term morbidity and survival. This review highlights important differences in management between children and adults with ASDs associated with PAH, highlighting indications for closure, operability, types of closure, and long-term outcomes. [ABSTRACT FROM AUTHOR]

An abstract of the article "Quality of Life and Parental Adjustment in Pediatric Pulmonary Hypertension" by Mary P. Mullen and colleagues is presented.

Misra MV, Mullen MP, Vargas SO, Kim HB, Boyer D. Bilateral lung transplant for hereditary hemorrhagic telangiectasia in a pediatric patient. Abstract: HHT is an autosomal dominant vascular dysplasia, in which abnormalities of endothelial cells cause patients to develop mucocutaneous telangiectasias, and AVMs of the pulmonary, hepatic, and cerebral circulations. Pulmonary AVMs occur in more than 20% of patients with HHT, and presentation varies from simple diffuse telangiectasias to large complex structures. Surgical management is usually indicated for large pulmonary AVMs. Treatment options for pulmonary AVMs include therapeutic embolization, segmental or lobar resection of the affected lung, and less commonly lung transplantation. Here we report the first successful case of a bilateral lung transplant for a four-yr-old girl with HHT. [ABSTRACT FROM AUTHOR]

The article explores the causes and treatment of idiopathic and heritable pulmonary arterial hypertension (PAH) in children. It offers information about idiopathic PAH including the prevalence of the disease as well as genetic causes. It also offers information regarding hereditary hemorrhagic telangiectasia (HHT) which is linked with mucocutaneous telangiectasias, recurrent epistaxis, and large vessel arteriovenous malformations.

Abstract: Bronchopulmonary dysplasia (BPD), the chronic lung disease that follows oxygen and ventilator therapy of premature neonates, is characterized by significant cardiac and pulmonary sequelae. Since its original description in the late ''60s, poor outcome in BPD has been strongly associated with late pulmonary hypertension (PH). Despite progressive improvements in the care of preterm infants, PH still remains a significant cause of late morbidity and mortality in premature infants. More recently, experimental and clinical studies have shown that lung vascular growth is abnormal in infants with BPD, which may contribute to abnormalities of lung airspace structure, alters gas exchange with respiratory infections and exercise, and further increases the risk for developing PH. Current data are limited with regards to many fundamental aspects of pulmonary vascular disease and PH in infants with BPD, including: basic mechanisms that alter lung vascular growth and development after premature birth and may contribute to the pathogenesis of PH; the prevalence and natural history of PH in infants with BPD; approaches to screen and diagnose PH in this group; and effective therapies for the prevention and treatment of PH in infants with BPD. This article discusses recent observations and recommendations in the clinical approach to PH in BPD and highlights current gaps in our knowledge. [Copyright &y& Elsevier]

Objectives: To compare registry and electronic health record (EHR) data mining approaches for cohort ascertainment in patients with pediatric pulmonary hypertension (PH) in an effort to overcome some of the limitations of registry enrollment alone in identifying patients with particular disease phenotypes.Study Design: This study was a single-center retrospective analysis of EHR and registry data at Boston Children's Hospital. The local Informatics for Integrating Biology and the Bedside (i2b2) data warehouse was queried for billing codes, prescriptions, and narrative data related to pediatric PH. Computable phenotype algorithms were developed by fitting penalized logistic regression models to a physician-annotated training set. Algorithms were applied to a candidate patient cohort, and performance was evaluated using a separate set of 136 records and 179 registry patients. We compared clinical and demographic characteristics of patients identified by computable phenotype and the registry.Results: The computable phenotype had an area under the receiver operating characteristics curve of 90% (95% CI, 85%-95%), a positive predictive value of 85% (95% CI, 77%-93%), and identified 413 patients (an additional 231%) with pediatric PH who were not enrolled in the registry. Patients identified by the computable phenotype were clinically distinct from registry patients, with a greater prevalence of diagnoses related to perinatal distress and left heart disease.Conclusions: Mining of EHRs using computable phenotypes identified a large cohort of patients not recruited using a classic registry. Fusion of EHR and registry data can improve cohort ascertainment for the study of rare diseases.Trial Registration: ClinicalTrials.gov: NCT02249923. [ABSTRACT FROM AUTHOR]

Abstract: Pulmonary venous hypertension may be caused by increased pressure anywhere between the intraparenchymal pulmonary veins and the left ventricle. Pulmonary venous hypertension has different causes in children compared with adults. In adults the most common cause of pulmonary venous hypertension is left ventricular diastolic disease. In children, congenital heart diseases, acquired and congenital cardiomyopathies are the usual causes of pulmonary venous hypertension. There are three important mechanisms in the pathophysiology of pulmonary venous hypertension. Firstly there is a passive rise in pulmonary artery pressure as down stream pressure increases to maintain left sided preload and cardiac output. In this situation the transpulmonary gradient (<10 mmHg) and pulmonary vascular resistance index are low (<2.5–5 WU m2) and the pulmonary artery diastolic pressure is similar to the left atrial, or in the absence of pulmonary vein or mitral valve pathology, the left ventricular end diastolic pressure. Secondly there is reflex vasoconstriction of the pulmonary arteries or veins or both and the diastolic pulmonary artery pressure will be higher than the pulmonary vein, left atrial or left ventricular end diastolic pressure depending on the site of the left sided pressure increase. The transpulmonary gradient will be >10 mmHg and pulmonary vascular resistance index >2.5–5 WU m2. These patients respond to a cautious pulmonary vasodilator challenge with a decrease in both transpulmonary gradient and pulmonary vascular resistance index but with a variable increase in pulmonary venous pressure. Thirdly, there may be fixed pulmonary artery or vein obstruction. Quite often a combination of all three mechanisms (passive, reflex vasoconstriction and fixed) conspire to increase pulmonary artery pressure. Outside of restrictive cardiomyopathies, severe pulmonary hypertension due to isolated left ventricular diastolic disease is not prominent in young children. However, it seems likely that with the emergence of childhood obesity, insulin resistance, systemic hypertension, survivors of left sided congenital heart disease and organ transplantation that diastolic heart disease will assume more prominence in pediatrics. In general the pulmonary hypertension regresses if the left sided obstruction or dysfunction can be addressed adequately. [Copyright &y& Elsevier]