Pediatric Pulmonary Hypertension Patients 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.

Kiosk 3R-TB-08 - Altered Right and Left Ventricular Hemodynamic Force in Pediatric Pulmonary Hypertension Patients as an Early Indicator of Ventricular Dysfunction

Kiosk 3R-TB-08 - Altered Right and Left Ventricular Hemodynamic Force in Pediatric Pulmonary Hypertension Patients as an Early Indicator of Ventricular Dysfunction

Abstract 15889: An Artificial Intelligence-Derived Pediatric Pulmonary Hypertension Risk Prediction Model From the Pediatric Pulmonary Hypertension Network (PPHNet) Registry

Introduction: Risk prediction is fundamental to guiding pulmonary hypertension (PH) treatment and is a key part of PH guideline based care. Data-driven risk prediction in pediatric PH has been lacking, relying instead on expert opinion. Objective: Use the multi-center Pediatric Pulmonary Hypertension Network (PPHNet) registry to develop a pediatric PH risk model. Methods: Pediatric PH patients (WSPH 1/3) enrolled in the PPHNet were used in this study and randomly split into train (80%) and test cohorts (20%). 176 variables were suitable for analysis including demographics, imaging, hemodynamics, functional/exercise testing, laboratory values, symptoms, and comorbidities. Boruta feature selection with random forest classifier identified variables that predicted the composite outcome of time to death, transplant or reverse Potts shunt. 2 The prediction model was built using an extreme gradient boost classifier with parameter tuning using Bayesian optimization. Model performance was quantified using confusion matrices, calculated sensitivity, specificity, AUC-ROC, and calibration slope. Results: A total of 1232 patients (985 Train, 247 test) were appropriate for inclusion; 134 patients (10.9%) met the composite outcome) with follow-up to 4 years from diagnosis. 37 variables were isolated for the prediction model. The Model performed strongly in the test cohort with an AUROC of 87% (Figure 1A), sensitivity of 85%, and specificity of 77%. Predicted probabilities were stratified into 3 major risk groups based on 1-year risk of event (Figure 1B; low &lt;5%, medium 10-15%, high &gt;15%) with good agreement between predicted and observed outcomes. Conclusions: Using the multicenter PPHNet cohort, we developed a well calibrated 1-year risk prediction model for pediatric groups 1 and 3 PH. This model is uniquely trained on incident and prevalent pediatric patients and could enable accurate identification of high-risk patients in need of aggressive therapy.

Mid-Systolic Notching of the Pulmonary Valve Doppler Signal is Highly Associated with Pulmonary Hypertension.

Mid-systolic notching (MSN) of the pulmonary valve Doppler signal represents a reflected systolic pressure wave from the pulmonary vasculature and is often seen in pulmonary hypertension (PH). We hypothesize that MSN is associated with a higher pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP), and a diagnosis of PH in pediatric patients. This was a retrospective study of patients ≤ 18years who had an echocardiogram obtained ≤ 30days before catheterization for suspected PH. MSN was defined as an indentation in the initial two thirds of the systolic Doppler signal. PH was defined as mPAP > 20mmHg and PVR ≥ 3.0 Wu m2. Subgroups (MSN vs. normal) were compared. Receiver operator characteristic determined a continuous variable's discriminatory ability for a diagnosis of PH. Reproducibility of MSN was assessed. In total, 90 patients (73 with congenital heart disease) were included, of which 36 had MSN and 54 were normal. MSN patients were more likely to have PH, and had significantly higher mPAP, PVR, and lower pulmonary stroke volume. The presence of MSN had good discriminatory ability for PH diagnosis. The presence of MSN had high specificity (96%) for PH, whereas sensitivity was lower (54%). Reproducibility was 100% for MSN. MSN is a simple, highly reproducible echocardiographic metric associated with higher mPAP and PVR. When present, there is a high likelihood a diagnosis of PH confirmed by catheterization. Incorporation of MSN into imaging protocols may be useful. MSN appears worthy of further investigation in pediatric patients with suspected PH.

Factors leading to supranormal cardiac index in pediatric pulmonary hypertension patients treated with parenteral prostanoid therapy.

Parenteral prostanoid therapy (PPT) can result in supranormal cardiac index (SCI; >4 L/min/m2) in pediatric pulmonary hypertension (PPH) patients. We evaluated the incidence, hemodynamic factors, and outcomes associated with SCI in PPH. This retrospective cohort study included 22 PPH patients on PPT from 2005 to 2020. Hemodynamic profiles were compared between the baseline and 3-6 month follow-up catheterization in the SCI and non-SCI cohorts. Cox regression analysis examined time to composite adverse outcome (CAO; Potts shunt, lung transplant, or death) controlling for initial disease severity. SCI developed in 17 (77%) patients, of whom 11 (65%) developed SCI within 6 months. The SCI cohort was characterized by significant augmentation of cardiac index (CI) and stroke volume (SV) as well as reductions in systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR). Conversely, the non-SCI cohort had unchanged SV despite a modest rise in CI as well as persistent vasoconstriction. After median follow-up of 4.3 years (range 0.2-13 years), non-SCI patients were at significantly increased risk for the CAO (5/5: three deaths, two Potts shunts) compared withSCI patients (5/17: two deaths, three lung transplants; adjusted hazard ratio 14.0 [95% confidence interval: 2.1-91.3], p < 0.001). A majority of PPH patients developed SCI within 6-12 months of starting PPT and demonstrated lower risk of adverse outcomes compared withnon-SCI patients. These data suggest that change in SVR and SV after 3-6 months of PPT may be early markers of therapeutic response and prognosis.

Safety and tolerability of continuous inhaled iloprost in critically ill pediatric pulmonary hypertension patients: A retrospective case series.

Inhaled iloprost (iILO) has shown efficacy in treating patients with hypoxic lung disease and pulmonary hypertension, inducing selective pulmonary vasodilation and improvement in oxygenation. However, its short elimination half-life of 20-30 min necessitates frequent intermittent dosing (6-9 times per day). Thus, the administration of iILO via continuous nebulization represents an appealing method of drug delivery in the hospital setting. The objectives are: (1) describe our continuous iILO delivery methodology and safety profile in mechanically ventilated pediatric pulmonary hypertension patients; and (2) characterize the initial response of iILO in these pediatric patients currently receiving iNO. Continuous iILO was delivered and well tolerated (median 6 days; range 1-94) via tracheostomy or endotracheal tube using the Aerogen® mesh nebulizer system coupled with a Medfusion® 400 syringe pump. No adverse events or delivery malfunctions were reported. Initiation of iILO resulted in an increase in oxygen saturation from 81.4 ± 8.6 to 90.8 ± 4.1%, p < 0.05. Interestingly, prior iNO therapy for >1 day resulted in a higher response rate to iILO (as defined as a ≥ 4% increase in saturations) compared to those receiving iNO <1 day (85% vs. 50%, p = 0.06). When the use of iILO is considered, continuous delivery represents a safe, less laborious alternative and concurrent treatment with iNO should not be considered a contraindication. However, given the retrospective design and small sample size, this study does not allow the evaluation of the efficacy of continuous iILO on outcomes beyond the initial response. Thus, a prospective study designed to evaluate the efficacy of continuous iILO is necessary.

Associated radiation exposure from medical imaging and excess lifetime risk of developing cancer in pediatric patients with pulmonary hypertension.

Pediatric patients with pulmonary hypertension (PH) receive imaging studies that use ionizing radiation (radiation) such as computed tomography (CT) and cardiac catheterization to guide clinical care. Radiation exposure is associated with increased cancer risk. It is unknown how much radiation pediatric PH patients receive. The objective of this study is to quantify radiation received from imaging and compute associated lifetime cancer risks for pediatric patients with PH. Electronic health records between 2012 and 2022 were reviewed and radiation dose data were extracted. Organ doses were estimated using Monte Carlo modeling. Cancer risks for each patient were calculated from accumulated exposures using National Cancer Institute tools. Two hundred and forty-ninepatients with PH comprised the study cohort; 97% of patients had pulmonary arterial hypertension, PH due to left heart disease, or PH due to chronic lung disease. Mean age at the time of the first imaging study was 2.5 years (standard deviation [SD] = 4.9 years). Patients underwent a mean of 12 studies per patient per year, SD = 32. Most (90%) exams were done in children <5 years of age. Radiation from CT and cardiac catheterization accounted for 88% of the total radiation dose received. Cumulative mean effective dose was 19 mSv per patient (SD = 30). Radiation dose exposure resulted in a mean increased estimated lifetime cancer risk of 7.6% (90% uncertainty interval 3.0%-14.2%) in females and 2.8% (1.2%-5.3%) in males. Careful consideration for the need of radiation-based imaging studies is warranted, especially in the youngest of children.

Prevalence of malnutrition in pediatric pulmonary hypertension cohort and role for registered dietitian involvement.

Pediatric pulmonary hypertension (PH) is a serious condition with increased risk for malnutrition due to increased caloric needs and reduced energy intake. This combination of disease and dynamic elements make it particularly challenging to meet expected growth patterns. Pediatric PH patients require close monitoring and individualized nutrition interventions to best meet nutrient needs. The prevalence of malnutrition and effective nutrition interventions in pediatric PH has not been studied. Using our electronic medical record (EMR) patient care dashboard, malnutrition prevalence was assessed by reviewing the active problem list of all active PH patients at our center. A chart review compared patients with diagnosed malnutrition in the EMR to those with malnutrition identified by a registered dietitian (RD) using a standardized tool. Chart reviews also assessed outcomes of RD interventions. 195 patients were identified as active PH patients followed by our PH center during the study period (November 2021 to January 2023). Of these, 5% (10/195) had an ICD-10 code for malnutrition listed in their chart. However, upon further chart review of the remaining 185 patients, 22% (41/185) had malnutrition identified by a RD using Texas Children's Malnutrition Tool, totaling 51/195 (26%) malnourished patients. The PH RD saw 25/51 (49%) patients during PH clinic visits in the study period. At follow up visits (3-4 months after initial assessment), 56% (14/25) patients seen by the PH RD either improved or resolved their malnutrition status by z-score assessment. Malnutrition is present in pediatric PH, although underappreciated and underdiagnosed. Managing malnutrition in pediatric PH requires close monitoring, multidisciplinary involvement, and individualized nutrition recommendations. This is best achieved by a dedicated PH RD who is familiar with the unique needs of this population and available to provide consistent nutritional assessments and interventions to reduce malnutrition in this population.

Failure to tolerate continuous subcutaneous treprostinil in pediatric pulmonary hypertension patients

Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure.

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.

Ventricular global function index is associated with clinical outcomes in pediatric pulmonary hypertension

BackgroundMultiple right ventricular (RV) metrics have prognostic value in pulmonary hypertension (PH). A cardiac magnetic resonance imaging (CMR) derived global ventricular function index (GFI) provided improved prediction of composite adverse outcome (CAO) in adults with atherosclerosis. GFI has not yet been explored in a PH population. We explored the feasibility of GFI as a predictor of CAO in a pediatric PH population. MethodsTwo center retrospective chart review identified pediatric PH patients undergoing CMR from Jan 2005–June 2021. GFI, defined as the ratio of the stroke volume to the sum of mean ventricular cavity and myocardial volume, was calculated for each patient. CAO was defined as death, lung transplant, Potts shunt, or parenteral prostacyclin initiation after CMR. Cox proportional hazards regression was used to estimate associations and assess model performance between CMR parameters and CAO. ResultsThe cohort comprised 89 patients (54% female, 84% World Health Organization (WHO) Group 1; 70% WHO-FC ≤ 2; and 27% on parenteral prostacyclin). Median age at CMR was 12 years (IQR 8.1–17). Twenty-one (24%) patients experienced CAO during median follow up of 1.5 years. CAO cohort had higher indexed RV volumes (end systolic—145 vs 99 mL/m2, p = 0.003; end diastolic—89 vs 46 mL/m2, p = 0.004) and mass (37 vs 24 gm/m2, p = 0.003), but lower ejection fraction (EF) (42 vs 51%, p < 0.001) and GFI (40 vs 52%, p < 0.001). Higher indexed RV volumes (hazard ratios [HR] 1.01, CI 1.01–1.02), lower RV EF (HR 1.09, CI 1.05–1.12) and lower RV GFI (HR 1.09, CI 1.05–1.11) were associated with increased risk of CAO. In survival analysis, patients with RV GFI < 43% demonstrated decreased event-free survival and increased hazard of CAO compared to those with RV GFI ≥ 43%. In multivariable models, inclusion of GFI provided improved prediction of CAO compared to models incorporating ventricular volumes, mass or EF. ConclusionsRV GFI was associated with CAO in this cohort, and inclusion in multivariable models had increased predictive value compared to RVEF. GFI uses readily available CMR data without additional post-processing and may provide additional prognostic value in pediatric PH patients beyond traditional CMR markers.

Safety and Efficacy of Sildenafil for Group 2 Pulmonary Hypertension in Left Heart Failure.

Pulmonary hypertension (PH) is a multifactorial, progressive disease with poor outcomes. Group 2 PH is defined by pulmonary vascular disease with elevated pulmonary capillary wedge pressure including both left-sided obstructive lesions and diastolic heart failure (HF). Sildenafil was historically discouraged in this population as pulmonary vasodilation can lead to pulmonary edema. However, evidence suggests that sildenafil can help to treat the precapillary component of PH. This is a single center, retrospective pilot study of pediatric PH patients with left-sided HF who were treated with sildenafil for ≥ 4 weeks. HF patients without mechanical support (HF group) and HF patients with a left ventricular assist device (HF-VAD) were analyzed. The exploratory analysis described the safety and side effects of the drug. Echocardiographic parameters were compared before and after sildenafil treatment in a paired analysis. The changes in medical therapy during treatment, mechanical support, and mortality was reported; 19/22 patients tolerated sildenafil. Pulmonary edema in two patients resolved upon discontinuation of sildenafil. In the HF group, both the right atrial volume and right ventricular diastolic area decreased, and the tricuspid regurgitation (TR) S/D ratio decreased after therapy (p = 0.02). Across both the groups, four patients weaned off milrinone and seven weaned off inhaled nitric oxide. Of the thirteen HF patients, four received a transplant, and all of the nine HF-VAD patients received a transplant. Sildenafil can be safely used in carefully selected patients with HF and mixed pre/postcapillary PH with judicious titration and inpatient surveillance, with patients showing improvements in echocardiographic parameters.

A North American, single-center experience implanting fenestrated atrial devices and atrial flow regulators into a heterogeneous group of pediatric pulmonary hypertension patients.

The clinical deterioration commonly experienced by pediatric patients with pulmonary arterial hypertension (PAH) has motivated a shift in the treatment of pulmonary hypertension (PH) through innovations in surgical salvage interventions. The Occlutech fenestrated atrial septal defect (FASD) Occluder and the atrial flow regulator (AFR), which provides a protective, atrial-level shunt during hypertensive crises, have found an important role in treating pediatric patients with PAH. Other groups of pediatric patients with PH may also benefit from a similar protective physiology. The primary aim of this work is to present a single center's experience with AFR and FASD devices for managing a heterogeneous group of pediatric PH patients. A secondary goal is to identify hemodynamic changes and complications following device implantation. We performed a retrospective review of all pediatric PH patients who, after being found suitable, either successfully or unsuccessfully received an FASD or AFR device between January 2015 and December 2021 at the Stollery Children's Hospital in Edmonton, Canada. Fourteen patients (eight female) with a median age of 4.6 (range 0.3-17.9) years and a median body mass index of 15.1 (Q1 = 13.8, Q3 = 16.8) kg/m2 underwent device implantation: five received FASDs, eight received AFRs, and one was ultimately unable to receive an implant due to thrombosed iliac vessels and required surgical intervention. Of the fourteen patients, seven were in group 1 (PAH), one was in group 3 (lung disease), and six were in group 5 (primarily pulmonary hypertension vascular disease) under the World Symposium PH classification. All patients were on mono-, dual-, or triple-drug PH therapy. Device stabilization was not possible for two patients, who then required a repeat catheterization. Of the group 1 patients, three AFR and three FASD implants were successful, while one FASD implant was unsuccessful due to thrombosed vessels. At a six-month clinical assessment, all group 1 patients had patent devices and improved WHO FCs. This work presents a single center's experience with AFR and FASD implants in a heterogeneous group of fourteen pediatric patients with severe PH. This treatment strategy is novel in the pediatric population and so this work provides momentum for future studies of interventional cardiac catheterization procedures for pediatric patients with PH. Further collaborations are required to develop criteria to identify ideal pediatric candidates and optimally time interventions in order to maximize the benefits of this treatment.

A canadian retrospective multicenter experience with selexipag in a heterogeneous group of pediatric pulmonary hypertension patients

Abstract Funding Acknowledgements Type of funding sources: None. Background The introduction of the oral prostanoid selexipag for treating severe adult pulmonary arterial hypertension (PH) has contributed to reduced rates of death and secondary complications in PAH. Pediatric physicians have extrapolated from the adult literature to utilize this medication to treat severe pediatric pulmonary hypertension. However, longitudinal, multicenter data on the therapeutic benefits of selexipag for pediatric patients is lacking. Materials and Methods We performed a retrospective review describing the clinical outcomes of pediatric PH patients receiving selexipag for pulmonary hypertension (PH) therapy in addition to standard pulmonary vasodilator therapy across three North American pediatric PH centers between January 2005 and June 2021. Results Across three Canadian centers, 24 patients (15 female) with a mean age at diagnosis of 5.4 (0.9) years were included. Of this cohort, 19 (79.2%) had group 1 PAH, 4 (16.7%) had group 3 PH, and 1 (4.2%) had group 4 PH. Genetic syndromes were noted in 7 (29.2%) patients. Dosing was targeted to achieve 20–30 mcg/kg/dose orally every 12 hours; the mean dosage after 12 months was 31.2 (10.3) mcg/kg/dose. Twelve months following selexipag initiation, a median increase of 71.5 m (p = 0.44) in six-minute walk test distance was observed together with median decreases of 0.2 cm (p = 0.17) in tricuspid annular plane systolic excursion, 3.5 mmHg (p = 0.95) in right ventricle systolic pressure, and 6.1 mmHg (p = 0.09) in mean pulmonary artery pressure. 2 patients (8.3%) died, 1 (4.2%) was referred for a heart transplant, and 1 (4.2%) received an atrial flow regulator. One patient (4.2%) required admission to a pediatric intensive care unit during their treatment course this was related to profound desaturation, six (25.0%) had gastrointestinal symptoms, and two (8.3%) had facial flushing. Conclusion Selexipag appears to be a beneficial adjunctive therapy for selected pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Further prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed.

Subcutaneous use of treprostinil in pediatric pulmonary hypertension patients: A report of three cases.

Treprostinil was approved by the United States Food and Drug Administration for use in the treatment of pulmonary arterial hypertension in 2002. Intravenous or subcutaneous treprostinil is used in pulmonary arterial hypertension patients in the functional classes of II-IV to alleviate exercise-related symptoms, or in cases where epoprostenol treatment should be reduced due to side effects. In this article, we describe three pediatric cases of pulmonary arterial hypertension in whom subcutaneous treprostinil was used.

Respiratory Microbiome Profile of Pediatric Pulmonary Hypertension Patients Associated With Congenital Heart Disease.

Pulmonary hypertension (PH) associated with congenital heart disease (CHD) is the most common type of PH in pediatric patients. The airway microbiome profile in CHD-PH patients remains rarely studied. A total of 158 children were recruited for collection of oropharyngeal swabs to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of respiratory microbiome, to establish a correlation between these bacterial groups and echocardiography indicators in CHD-PH patients. Bacterial α- and β-diversity of the airway microbiome indicated a significantly lower richness in the CHD-PH group and compositional differences associated with the specific taxa and their relative abundances in the upper respiratory tract. Principal coordinate analysis showed that the pharynx microbiota composition in the CHD-PH group varied from that in the CHD or control group. The linear discriminant analysis effect size also highlighted an increased presence of Streptococcus and Rothia in pediatric CHD-PH patients. Comparison of microbial composition between pediatric and adult PH patients showed significant differences and separation of microbiota. The correlation between bacterial abundance and transthoracic echocardiography indexes in CHD-associated PH indicated that different groups of microbiomes may be related to different PH grades. In summary, our study reported the systematic definition and divergent profile of the upper respiratory tract microbiota in pediatric PH patients, CHD and reference subjects, as well as between pediatric and adult PH patients.

Prognostic value of longitudinal vasoreactivity in pediatric pulmonary hypertension.

Upon diagnosis of pulmonary hypertension in pediatrics, standard practice often involves acute vasoreactivity testing (AVT) in the cardiac catheterization laboratory. However, the importance of repeated AVT testing in a given patient thereafter remains unclear. This study sought to describe serial AVT results in pediatric patients and understand the prognostic significance of longitudinal AVT results in pediatric pulmonary hypertension. A retrospective chart review was performed for pediatric pulmonary hypertension patients diagnosed between 2008 and 2021. Patients were included if they had two or more catheterizations with AVT. The study cohorts were patients who were AVT negative upon initial catheterization then AVT positive at any subsequent catheterization (AVT-/+) compared to those were AVT negative upon initial and all subsequent catheterizations (AVT-/-). A positive AVT was defined by Sitbon criteria. The analyzed outcome was event-free survival. The relationship between study cohorts and event-free survival was analyzed by log-rank Kaplan-Meier survival as well as Cox proportional hazard regression to control for confounders. There were 35 patients who met inclusion criteria in this time period. Patients who were AVT(-/+) had statistically significantly better event-free survival than AVT(-/-) (p = 0.002). In univariate and multivariate Cox regressions, a subsequent AVT positive result amongst those who were initially AVT negative was a positive prognostic factor, hazard ratio 0.03 (95% confidence interval: 0.02-0.35). For patients with negative AVT upon initial cardiac catheterization, this data supports that continuing AVT should be performed as any subsequent AVT positive result may indicate improved expectations for event-free survival.

Prevalence of pulmonary hypertension in pediatric patients with beta-thalassemia major in Central India: a cross sectional study

Background: The objective of the study was to determine the prevalence of pulmonary hypertension in pediatric patients with beta thalassemia major in a tertiary care centre in Central India.Methods: A cross sectional study was conducted in department of pediatrics, Government Medical College and Hospital, Nagpur, India over a period of 2 years. Total 100 subjects of thalassemia major diagnosed by high performance liquid chromatography (HPLC) attending day care in this department were enrolled for study. Measurement of pulmonary pressure was done by using 2D echocardiography with Doppler studies and tricuspid regurgitant jet velocity was measured. This was done by experienced cardiologist. Variables predictive of pulmonary hypertension studied were age, sex, serum ferritin levels, age of onset of chelation therapy, compliance to chelation therapy and number of blood transfusion per year.Results: Out of 100 subjects, 18 subjects had pulmonary hypertension. Univariate analysis proved that age, serum ferritin levels, age of onset of chelation therapy, compliance to chelation therapy and number of blood transfusion per year were significant predictors of pulmonary hypertension. While, multiple logistic regression analysis revealed that only 3 variables that is age of onset of chelation therapy, number of blood transfusion per year and compliance to chelation therapy retained their significance in this patient population.Conclusions: Prevalence of pulmonary hypertension was found out to be 18%. 2 subjects in the pulmonary hypertension group died. High morbidity and mortality of pulmonary hypertension clearly indicates that much work is needed in disease detection and development of more effective therapies. For thalassemic children, early detection and prevention of pulmonary hypertension in childhood would improve survival, reduce morbidity and mortality.

Abnormal platelet aggregation in pediatric pulmonary hypertension.

Endogenous prostacyclin stimulates pulmonary vasodilation and inhibits platelet aggregation. For the synthetic analog treprostinil, used in the treatment of pulmonary hypertension (PH), conflicting, anecdotal evidence exists regarding its effects on clinically relevant platelet function. This study investigated whether treprostinil therapy results in inhibition of platelet aggregation in pediatric PH patients. This is a single institution, prospective, cohort study. Pediatric patients ≤18 years of age on medical therapy for PH underwent platelet function testing by light transmission aggregometry with U‐46619—a stable analog of endoperoxide prostaglandin H2, exhibiting properties similar to thromboxane A2 (TXA2). Results were compared for those on continuous treprostinil therapy (TRE) versus those on other, non‐prostacyclin therapies (non‐TRE). Thirty‐five patients were enrolled: 18 in the TRE group and 17 in the non‐TRE group. There was no difference in platelet aggregation abnormalities between the two groups: 44% (n = 8) in the TRE group and 41% (n = 7) in the non‐TRE group were abnormal. Furthermore, subgroup analysis showed no difference based on treprostinil dosing. This study demonstrated similar, moderately high rates of abnormal platelet aggregation in pediatric PH patients on continuous treprostinil therapy compared to those on other, non‐prostacyclin therapies. The high rate of abnormal platelet aggregation in the entire cohort, however, warrants follow‐up study to identify a potential inherent risk in this population.

Chest computed tomography findings of ground-glass nodules with enhancing central vessel/nodule in pediatric patients with BMPR2 mutations and plexogenic arteriopathy.

Germline mutation in bone morphogenetic protein type II (BMPR2) is the most common cause of idiopathic/heritable pulmonary hypertension in pediatric patients. Despite the discovery of this gene there are no known descriptions of the CT or CT angiography findings in these children. To correlate the clinical presentation, pathology and chest CT findings in pediatric patients with pulmonary hypertension caused by mutations in the BMPR2 gene. We performed a search to identify pediatric patients with a BMPR2 mutation and CT or CT angiography with the clinical history of pulmonary hypertension. Three pediatric radiologists reviewed the children's CT imaging findings and ranked the dominant findings in order of prevalence via consensus. We identified three children with pulmonary hypertension and confirmed germline BMPR2 mutations, two of whom had undergone lung biopsy. We then correlated the imaging findings with histopathology and clinical course. All of our patients with BMPR2 mutations demonstrated a distinct CT pattern of ground-glass nodules with a prominent central enhancing vessel/nodule. These findings correlated well with the pathological findings of plexogenic arteriopathy.