Idiopathic Pediatric Pulmonary Arterial Hypertension Research Articles

Prognostic Value of Transthoracic Echocardiography in Children With Pulmonary Arterial Hypertension.

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

Long‐term prognostic value of cardiac catheterization and acute vasodilator testing with inhaled iloprost in pediatric idiopathic pulmonary arterial hypertension

To assess the long-term prognostic value of cardiac catheterization and acute vasodilator testing (AVT) with inhaled iloprost in children with idiopathic pulmonary arterial hypertension (IPAH).Data on 81 consecutive children with IPAH referred to our center who underwent cardiac catheterization and AVT between June 2008 and August 2019 were collected. The correlation between the invasive hemodynamic data and transplant-free survival was analyzed. Twenty-four patients died and 1 underwent lung transplantation during a median follow-up of 3.8 years, with a 5-year transplant-free survival rate of 64.9%. Univariate analysis showed that predictors associated with improved survival included a lower pulmonary vascular resistance index (PVRI), PVRI/systemic vascular resistance index (SVRI), mean pulmonary arterial pressure (mPAP)/mean systemic arterial pressure, mean right atrial pressure, and a higher cardiac index (CI), mixed systemic venous oxygen saturations (SvO2), and acute vasodilator response (AVR) according to the Barst criteria (decrease in mPAP and PVRI/SVRI ratio of >20% without a decrease in CI). In multivariate Cox regression analysis, Barst AVR and SvO2 were independently related to transplant-free survival. Multiple hemodynamic variables from cardiac catheterization and AVT with inhaled iloprost have important prognostic value for long-term survival in children with IPAH, of which pulmonary vasoreactivity defined by the Barst criteria and SvO2 are independent prognostic factors.

Longitudinal assessment of right atrial conduit fraction provides additional insight to predict adverse events in pediatric pulmonary hypertension

BackgroundRecent studies show adverse right atrial (RA) emptying pattern is prognostic for clinical worsening events in pediatric pulmonary arterial hypertension (PAH). No study has reported changes in RA emptying over time or evaluated whether serial measurements offer further prognostic information. MethodsProspective study of 32 children with idiopathic or heritable PAH undergoing echocardiogram at baseline and 1-year. RA conduit fraction percent (RA cF%) was measured as percentage of total diastolic RA area change prior to the electrical p wave. Clinical worsening was analyzed with a predefined composite adverse event outcome. ResultsLongitudinal subjects (median age 13.3 yr) had RA cF% 61% (IQR 32–68%) at baseline and 60% (IQR 35–73%) at 1-year (NS). 11 subjects had a qualifying event during median 21-month follow-up. Subjects with an event had 1-year RA cF% = 33% (IQR 20–40%) compared to 72% (IQR 63–75%) for those with no event (p < 0.001). Event rates were lowest for subjects with both echocardiograms showing RA cF% > 60% (0%), highest for subjects with neither (80%), and intermediate for those with one (38%, p = 0.003). ConclusionsChanges in RA cF% inform risk of adverse events in pediatric PAH. This finding supports the role of RA cF% as both a prognostic biomarker and potential treatment target.

Elevated Interleukin-6 Levels Predict Clinical Worsening in Pediatric Pulmonary Arterial Hypertension

To assess whether circulating interleukin-6 (IL-6) is associated with measures of disease severity and clinical worsening in pediatric pulmonary arterial hypertension (PAH). IL-6 was measured by enzyme-linked immunosorbent assay in serum samples from a cross-sectional cohort from the National Heart, Lung, and Blood Institute Pulmonary Arterial Hypertension Biobank (n=175) and a longitudinal cohort from Children's Hospital Colorado (CHC) (n=61). Associations between IL-6, disease severity, and outcomes were studied with regression and Kaplan-Meier analysis. In analyses adjusted for age and sex, each log-unit greater IL-6 was significantly associated in the Pulmonary Arterial Hypertension Biobank cohort with greater pulmonary vascular resistance indices, lower odds of having idiopathic PAH or treatment with prostacyclin, and greater odds of having PAH associated with a repaired congenital shunt. In the CHC cohort, each log-unit greater IL-6 was significantly associated with greater mean pulmonary arterial pressure over time. Kaplan-Meier analysis in the CHC cohort revealed that IL-6 was significantly associated with clinical worsening (a composite score of mortality, transplant, or palliative surgery) (P=.037). IL-6 was significantly associated with worse hemodynamics at baseline and over time and may be associated with clinical worsening. IL-6 may provide a less-invasive method for disease monitoring and prognosis in pediatric PAH as well as a potential therapeutic target.

Idiopathic Pulmonary Arterial Hypertension and Pulmonary Arterial Hypertension Associated With Congenital Heart Disease in Chinese Children: Similarities, Differences, and Prognostic Factors.

Background: As the most common types of pulmonary arterial hypertension (PAH) in childhood, the similarities and differences in clinical characteristics and prognosis between idiopathic PAH (IPAH) and PAH associated with congenital heart disease (PAH-CHD) are not well-known. This study describes and compares clinical features of pediatric IPAH and PAH-CHD in a single center of China during an 11-year period and explores the prognostic factors.Methods: Twenty-five children with IPAH and 60 children with PAH-CHD, diagnosed in West China Second Hospital of Sichuan University from January 2008 to December 2018, were chosen as study objects. The follow-up deadline was June 2019, and the end-point was all-cause death. The baseline data, results of auxiliary examinations, treatment strategies, and follow-up outcomes were recorded and compared between IPAH and PAH-CHD patients to explore the similarities, differences, and prognostic factors.Results: The median diagnostic age for PAH-CHD patients was 2.3 years, which was younger than IPAH patients (7.3 years; p = 0.009). Sixty-eight percent of the IPAH patients presented with exercise-induced symptoms at initial diagnosis, whereas 58.3% of the PAH-CHD patients were asymptomatic (p < 0.001). Sixty percent of the IPAH patients were in World Health Organization-functional class (WHO-FC) III or IV, which was significantly worse than those of the PAH-CHD patients (p = 0.002). The incidence of ST-segment and T-wave (ST-T) change in children with IPAH (76.0%) was significantly higher than that (28.3%) in children with PAH-CHD (p < 0.001). Mean corpuscular volume (MCV), mean platelet volume (MPV), and platelet distribution width were larger in IPAH patients than those in PAH-CHD patients (p < 0.01). The 1-, 3-, and 5-year survival rates of IPAH and PAH-CHD patients were 53.5, 46.5, and 31.2% and 96.5, 93.1, and 77.6%, respectively (p < 0.05). WHO-FC III-IV [relative risk (RR) = 2.750, p = 0.008] and higher MPV (RR = 1.657, p = 0.006) predicted poor prognosis for pediatric PAH.Conclusion: We showed that there are more differences than similarities between IPAH and PAH-CHD patients in clinical characteristics. PAH-CHD patients have a better prognosis than IPAH patients. WHO-FC III-IV and higher MPV at initial diagnosis are independent risk factors for poor prognosis.

EXPRESS: Acute Vasoreactivity Testing in Pediatric Idiopathic Pulmonary Arterial Hypertension: an international Survey on Current Practice.

The aim of this study was to determine practice patterns and inter‐institutional variability in how acute vasoreactivity testing (AVT) is performed and interpreted in pediatrics throughout the world. A survey was offered to physicians affiliated with the Pediatric &amp; Congenital Heart Disease Taskforce of the Pulmonary Vascular Research Institute (PVRI), the Pediatric Pulmonary Hypertension Network (PPHNET), or the Spanish Registry for Pediatric Pulmonary Hypertension (REHIPED), from February to December 2016. The survey requested data about the site‐specific protocol for AVT and subsequent management of pediatric patients with idiopathic pulmonary arterial hypertension (IPAH) or heritable PAH (HPAH). Twenty‐eight centers from 13 countries answered the survey. AVT is performed in most centers using inhaled nitric oxide (iNO). Sitbon criteria was used in 39% of the centers, Barst criteria in 43%, and other criteria in 18%. First‐line therapy for positive AVT responders in functional class (FC) I/II was calcium channel blocker (CCB) in 89%, but only in 68% as monotherapy. Most centers (71%) re‐evaluated AVT‐positive patients hemodynamics after 6–12 months; 29% of centers re‐evaluated based only on clinical criteria. Most centers (64%) considered a good response as remaining in FC I or II, with near normalization of pulmonary arterial pressure and pulmonary vascular resistance, but a stable FC I/II alone was sufficient criteria in 25% of sites. Protocols and diagnostic criteria for AVT, and therapeutic approaches during follow‐up, were highly variable across the world. Reported clinical practice is not fully congruent with current guidelines, suggesting the need for additional studies that better define the prognostic value of AVT for pediatric IPAH patients.

Bosentan for Treatment of Pediatric Idiopathic Pulmonary Arterial Hypertension: State-of-the-Art.

Idiopathic pulmonary arterial hypertension (IPAH) is a complex disease associated with progressive deterioration. Targeted therapy for IPAH has improved in the last several decades. However, there remain many challenges to current treatment of children with IPAH, including poor prognosis and a median survival of 0.8 years. Endothelin-1 (ET-1) appears to be a key mediator in the pathogenesis of IPAH, with elevated concentrations in the plasma. Bosentan, an endothelin receptor antagonist, has been confirmed in Food and Drug Administration (FDA) to effectively treat IPAH when administered in recent studies. This review focuses on related studies and advance of bosentan in the treatment of IPAH in children.

Exome Sequencing in Children With Pulmonary Arterial Hypertension Demonstrates Differences Compared With Adults

Pulmonary arterial hypertension (PAH) is a rare disease characterized by pulmonary arteriole remodeling, elevated arterial pressure and resistance, and subsequent heart failure. Compared with adult-onset disease, pediatric-onset PAH is more heterogeneous and often associated with worse prognosis. Although BMPR2 mutations underlie ≈70% of adult familial PAH (FPAH) cases, the genetic basis of PAH in children is less understood. We performed genetic analysis of 155 pediatric- and 257 adult-onset PAH patients, including both FPAH and sporadic, idiopathic PAH (IPAH). After screening for 2 common PAH risk genes, mutation-negative FPAH and all IPAH cases were evaluated by exome sequencing. We observed similar frequencies of rare, deleterious BMPR2 mutations in pediatric- and adult-onset patients: ≈55% in FPAH and 10% in IPAH patients in both age groups. However, there was significant enrichment of TBX4 mutations in pediatric- compared with adult-onset patients (IPAH: 10/130 pediatric versus 0/178 adult-onset), and TBX4 carriers had younger mean age-of-onset compared with BMPR2 carriers. Mutations in other known PAH risk genes were infrequent in both age groups. Notably, among pediatric IPAH patients without mutations in known risk genes, exome sequencing revealed a 2-fold enrichment of de novo likely gene-damaging and predicted deleterious missense variants. Mutations in known PAH risk genes accounted for ≈70% to 80% of FPAH in both age groups, 21% of pediatric-onset IPAH, and 11% of adult-onset IPAH. Rare, predicted deleterious variants in TBX4 are enriched in pediatric patients and de novo variants in novel genes may explain ≈19% of pediatric-onset IPAH cases.

Analysis of prognosis and associated risk factors in pediatric idiopathic pulmonary arterial hypertension

Objective: To analyze the prognosis and associated risk factors of pediatric idiopathic pulmonary arterial hypertension. Methods: A total of 119 patients under 18 years of age diagnosed as idiopathic pulmonary arterial hypertension in the Pulmonary Arterial Hypertension Center in Beijing Anzhen Hospital between June 2007 and May 2017 were enrolled in this retrospective study. The clinical informations and follow-up data were collected. The endpoints of follow-up were defined as death or undergoing lung transplantation. Kaplan-Meier survival curve was used to assess the survival,and the COX risk regression model was used to analyze the prognostic risk factors. Results: The mean age at diagnosis was (5.9±4.2) years. For 92 (77.5%) patients, the main reason for visit was decreased activity with shortness of breath after exercise. Seventy patients (58.8%) were in baseline NYHA functional class Ⅲ-Ⅳ and 49 patients (41.2%) were in NYHA functional class Ⅰ-Ⅱ. The mean systolic pulmonary arterial pressure estimated by echocardiography was (90±23) mmHg (1 mmHg=0.133 kPa) . Right heart catheterization was performed in 50 patients. Hemodynamic parameters revealed that the mean pulmonary artery pressure was (66±19) mmHg. Mean right atrium pressure was (8.5±3.4) mmHg. Mean pulmonary vascular resistance index was (17±9) wood·m(2) and the mean cardiac index was (3.4±1.3)L/m(2); 100 patients (84.0%) received targeted therapy in which 55 patients (46.2%) were on monotherapy,40 patients (33.6%) were on dual therapy and 5 patients (4.2%) were on triple therapy. The mean time of follow-up was 22.0 months (0-108 months). During follow-up, 43 patients (36.1%) died and 1 patient received double-lung transplantation. Main causes of death including right heart failure, pulmonary hypertension crisis, asphyxia and massive hemoptysis. The mean survival time from diagnosis was 37.0 months,1-,2-,3-and 5-year survival rates were 86.3%, 72.2%, 51.4%and 37.8% respectively. Survival analysis showed that patients in baseline NYHA functional class Ⅰ-Ⅱ had better prognosis. COX regression analysis showed that NYHA function class, edema, increased total bilirubin and troponin concentration and the pulmonary artery and aorta diameter ratio measured by echocardiogram are risk factors of pediatric IPAH (HR=2.310, 2.723, 1.066, 1.696, 3.719, P=0.028, 0.005, 0.001, 0.024, 0.030) . While the existence of aterial septal defect or patent foramen ovale, using bosentan and phosphodiesterase inhibitors(,) dual or triple therapy were protective factors (HR=0.563, 0.559, 0.603, 0.682, 0.044, P=0.169, 0.076, 0.115, 0.258, 0.220) . In multivariate analysis only edema associated with decreased survival (HR=2.398, P=0.025) . Conclusion: Childhood idiopathic pulmonary arterial hypertension patients are seriously ill at visit. Worse cardiac function classification at visit associate with high mortality. Target therapy including using bosentan, dual or triple therapy can improve survival.

GW28-e1023 Outcomes and prognostic factors analysis in pediatric idiopathic pulmonary arterial hypertension

GW28-e1023 Outcomes and prognostic factors analysis in pediatric idiopathic pulmonary arterial hypertension

Clinical Impact of Main Pulmonary Artery Dilatation on Outcome in Pediatric Idiopathic and Heritable Pulmonary Arterial Hypertension.

Few studies have investigated the clinical impact of pulmonary artery (PA) dilatation on outcomes in pediatric pulmonary arterial hypertension (PAH).Methods and Results:This study investigated the clinical outcomes of idiopathic or heritable PAH in 66 children aged <18 years at diagnosis. Main PA/thorax (MPA/T) ratio was measured on chest radiography in PAH patients. Patients were divided into 2 groups based on MPA/T ratio, and compared with a control group of 166 age- and gender-matched healthy children. Group A had higher MPA/T ratio than normal, and group B had normal MPA/T ratio. Composite outcomes included cardiac death, lung transplantation, and hospitalization due to heart failure. Group A consisted of 27 patients and group B, 39 patients. At diagnosis, group A had significantly higher brain natriuretic peptide (BNP), cardiothoracic ratio, PA pressure, and pulmonary vascular resistance index compared with group B. The number of patients with New York Heart Association (NYHA) functional class III and IV was significantly higher in group A than in group B. Cumulative event-free survival rate was significantly lower in group A. MPA dilatation correlated with BNP, NYHA functional class, and hemodynamics with regard to disease severity, and may be a potential prognostic factor in pediatric idiopathic and heritable PAH.

Treprostinil持続皮下投与の導入と継続に成功した精神発達遅滞を有する小児特発性肺動脈性肺高血圧症例

Treprostinilは，肺動脈性肺高血圧症に対して持続静脈内投与に加えて持続皮下投与で投与が可能なプロスタグランジンI2誘導体製剤で，日本国内でも成人症例の集積がある．今回，Treprostinil持続皮下投与を国内で初めて小児に導入し成功した．患児は7歳時に特発性肺動脈性肺高血圧症（IPAH）と診断され，内服3剤の併用と在宅酸素療法が行われたが改善が不十分であった．精神発達遅滞のため中心静脈カテーテル管理が困難と判断され，Treprostinil持続皮下投与を導入し，半年の経過観察中にWHO機能分類および心臓超音波検査所見が改善した．Treprostinil持続皮下投与は小児IPAHにも有効性が示唆され，Epoprostenol持続静脈内投与の導入・継続が難しい患児やEpoprostenol持続静脈内投与からの離脱を考えている患児に良い適応があると思われる．

Abstract 14123: Circulating miRNAs as Biomarkers of Afterload, Acute Vascular Reactivity, and Ventricular-Vascular Coupling in Pediatric Idiopathic Pulmonary Arterial Hypertension: Initial Clinical Studies

Introduction: Although it is known that structural remodeling of the pulmonary arteries (PA) leads to increases in right ventricular (RV) afterload in pediatric idiopathic pulmonary arterial hypertension (iPAH), evaluating such changes early in the process continues to be challenging. Since biological markers such as microRNAs may manifest earlier than functional markers, and since such markers may be detected using simple blood draws, identifying correlations between microRNAs and RV or pulmonary vascular functional parameters would be particularly useful in tracking this disease. Methods: Blood was collected for 14 pediatric patients with iPAH while undergoing right heart catheterization (RHC). Taqman Low Density Arrays (TLDA) was used to quantify miRNA expression in each patient. RHC data was used to compute pulmonary vascular impedance, ventricular-vascular coupling (VVC), and other hemodynamic markers. VVC was computed from the pressure tracing using the single beat pressure method (Vanderpool RR, et al. Heart 2015;101:37–43). Results: miR-21, which frequently appears in the PAH literature, was well correlated with pulmonary vascular resistance index (PVRi) (r = 0.81, P &lt; 0.001, see Fig. 1a). Fig. 1b shows that the ratio of miR-150/571 is an excellent predictor of VVC (r = 0.91, P &lt; 0.05). Random Forest statistical machine learning identified miR-683 as a classifier of acute vascular reactivity, confirmed with receiver operating curves (AUC = 0.88, see Fig. 1c) Conclusion: Over a dozen circulating miRNAs were identified as potential biomarkers for pediatric iPAH from the aforementioned arrays, with several having strong correlations to afterload and acute vascular reactivity. The ratio of miR-150 (recognized as biomarker of PAH) and miR-571 (recognized as biomarker of heart failure) appears particularly promising as a predictor of ventricular-vascular decoupling.

Frequency and Prognostic Significance of Hemoptysis in Pediatric Pulmonary Arterial Hypertension

Data concerning the prevalence, risk factors, and prognostic significance of hemoptysis in pediatric pulmonary arterial hypertension (PAH) are scarce. A Dutch national cohort of 74 children with either idiopathic or heritable PAH (IPAH/HPAH, n = 43) or PAH associated with congenital heart disease (PAH-CHD, n = 31) were followed from 1993 to 2012. During a median follow-up of 3.5 years (range 0.1 to 19.2), hemoptysis occurred in 13 children (17.6%). The hemoptysis event rate was 9.9 per 100 patient-years, equally divided between IPAH/HPAH and PAH-CHD (p = 0.824). The median age at first hemoptysis was 12.5 years, and the median time since PAH diagnosis to first hemoptysis was 6.1 years. Patients with hemoptysis had longer time since PAH diagnosis (p = 0.001) and more frequently used anticoagulant therapy (p = 0.006). Univariate Cox regression analysis indicated that older age (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.01 to 1.30, p = 0.031), World Health Organization functional class IV (HR 0.28, 95% CI 0.08 to 0.95, p = 0.042), higher mean pulmonary arterial pressure (HR 1.04, 95% CI 1.00 to 1.07, p = 0.028), and higher indexed pulmonary vascular resistance (HR 1.08, 95% CI 1.02 to 1.15, p = 0.009), all at the time of PAH diagnosis, were associated with increased risk of hemoptysis during follow-up. Ten of 13 patients with hemoptysis died or underwent (heart-) lung transplantation; in 6 patients, this was directly related to hemoptysis. In conclusion, the occurrence of hemoptysis in pediatric IPAH/HPAH and PAH-CHD increases with time since diagnosis, is a serious condition, and is, in case of life-threatening hemoptysis, associated with poor outcome.

276: Potts’ shunt in children with idiopathic pulmonary arterial hypertension: long-term results

Idiopathic pulmonary arterial hypertension (IPAH) remains a progressive fatal disease. Palliative Potts'shunt has been proposed in children displaying supra-systemic IPAH. A retrospective multicenter study to evaluate Potts'shunt in pediatric IPAH. Between 2003 and 2010, 8 children with supra-systemic IPAH and in WHO functional class IV despite medical PAH therapy underwent Potts'shunt. Age at IPAH diagnosis ranged from 4 to 180 months (median age: 64 months). Surgical procedure was performed in a mean delay of 41.9±54.3 months (from 4 to 167 months, median delay: 20 months) after IPAH diagnosis. Mean size of the Potts'shunt was 9.25±3.30 mm. Two patients, whose medical PAH therapy had been interrupted just after surgery, died at post-operative day 11 and 13 from acute pulmonary hypertensive crisis. After a mean follow-up of 63.7±16.1 months, the 6 children who were discharged from hospital were alive. Functional status improved markedly in the 6 survivors with a WHO functional class I (n=4) or II (n=2) at last follow-up, consistent with significant improvement of 6 minute-walk distance [302±95 (51±20% of theoretical values) vs 456±91 meters (68±10% of theoretical values), p=0.038] and decrease of brain natriuretic peptid (BNP) levels (608±109 vs 76±45 pg/ml, p=0.035). No Potts'shunt was found restrictive at last echocardiography. Palliative Potts'shunt constitutes a new alternative to lung transplantation in severely ill children with supra-systemic IPAH, carrying a prolonged survival and persistent improvement in functional capacities.

Pulmonary arterial capacitance in children with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease: Relation to pulmonary vascular resistance, exercise capacity, and survival

Pediatric pulmonary arterial hypertension (PAH), whether idiopathic PAH (iPAH) or PAH associated with congenital heart disease (aPAH), carries high morbidity and mortality. Low pulmonary arterial capacitance (PAC), defined as right ventricular stroke volume/pulmonary artery pulse pressure, is a risk factor for mortality in adults with PAH. However, the relation of PAC to pulmonary vascular resistance (PVR), exercise endurance, and survival is poorly defined in children. Catheterization and clinical data of children with PAH (mean pulmonary artery pressure >25 mm Hg) were reviewed. Children with pulmonary shunts, stents, collaterals, or pulmonary venous hypertension were excluded. Primary outcomes were 6-minute walk distance and freedom from death/lung transplant. Forty-seven patients were studied. Nineteen (43%) had iPAH, and 28 (57%) had aPAH (7.1 ± 6.2 vs 8.4 ± 5.5 years, P = .45). Patients with iPAH had higher PVR indexed for body surface area (PVRi), lower indexed PAC (PACi), lower exercise tolerance, and lower freedom from death/lung transplant than patients with aPAH. Both higher PVRi (P < .0001) and lower PACi (P = .02) were associated with shorter 6-minute walk distance. A PACi <0.70 mL/mm Hg per square meter or >1.25 mL/mm Hg per square meter and a PVRi >13 Wood units × m(2) were associated with decreased freedom from death or lung transplant. The relationships between PVRi and PACi and survival were independent of each other and not confounded by etiologic group. Low PACi and high PVRi are independently associated with low 6-minute walk distance and survival in children with PAH. Therefore, both should be assessed for better prognostication and management in this high-risk population.

Intraoperative management of pulmonary arterial hypertension in infants and children – Corrected and republished article*

Pediatric pulmonary arterial hypertension (PAH) continues to be a considerable problem to the pediatric anesthesiologist even if its management has seen remarkable advances in recent years. It is important that anesthesiologists caring for children with PAH be aware of the increased risk, understand the pathophysiology of PAH, form an appropriate anesthetic management plan. A review of some of the latest medical advances will provide the reader with a better understanding of the most current anesthetic management options. The literature reviewed demonstrate sustained clinical and hemodynamic improvement in children with various types of PAH as well as increased survival in patients with idiopathic PAH using current treatment strategies. This article will provide an overview of the current treatment and anesthetic strategies about idiopathic PAH in children over the last years. The first important aspect of anesthetic management is to provide adequate intraoperative anesthesia and analgesia while minimizing increases in pulmonary vascular resistance and myocardial. Depending on the procedure, these goals can be met with the administration of either sedation/analgesia or general anesthesia together with new drugs for PAH treatment in association with a high potential for adverse events.

Bilateral lung transplantation for pediatric idiopathic pulmonary arterial hypertension: A multi‐center experience

Many children with idiopathic pulmonary arterial hypertension (IPAH) experience disease progression despite advanced medical therapy. In these children, heart-lung or bilateral lung transplantation (BLTx) remain the only therapeutic options when other treatments fail. Data on functional outcome after BLTx in children with IPAH are limited. We report a multi-center experience of BLTx for pediatric IPAH. We performed a retrospective study including 25 centers within the International Pediatric Lung Transplant Collaborative. Children with IPAH who underwent BLTx were included (1996-2006). Twenty-three children underwent BLTx for IPAH, most of whom were in WHO class III or IV level of function pre-transplantation. At 6 months post-transplantation, 82% of children reported improvement in level of function to WHO class I. The median FEV(1) was 89% (12-126) of predicted at 12 months post-transplantation. Ten patients (44%) developed BOS at a median of 42 months (3-85), of whom five died at a median of 27 months (4-86) post-transplantation. Overall mortality was 4% at 3 months post-transplantation. The median survival for children in this cohort was 45 months (2-123). Our data suggest that BLTx is a valuable therapeutic option for children with end-stage IPAH with outcomes comparable to that after heart-lung transplantation in children with pulmonary arterial hypertension or those patients undergoing lung transplantation for other indications. In the majority of children, a good cardiopulmonary function is possible following BLTx, making BLTx a good therapeutic option and maximizing donor organ utilization by allowing more hearts to be available for children needing cardiac transplantation.

Long-Term Outcomes in Children With Pulmonary Arterial Hypertension Treated With Bosentan in Real-World Clinical Settings

Treatment algorithms in pediatric pulmonary arterial hypertension (PAH) are derived from clinical trials in adult populations and from clinical practice, but experience in children is limited. In this retrospective cohort study, we analyzed outcomes in a previously identified cohort of 86 consecutive children with PAH treated with bosentan as part of their treatment regimen. All children with idiopathic PAH or heritable PAH and PAH associated with congenital heart disease or connective tissue disease who started bosentan treatment from May 2001 to April 2003 in 2 tertiary pediatric referral centers were followed, with data collection ending August 2006. Eighty-six children (37 male, 49 female) 11 ± 5 years of age with idiopathic/heritable PAH (n = 36), PAH associated with congenital heart disease (n = 48), or PAH associated with connective tissue disease (n = 2) received bosentan as monotherapy (n = 42) or as an add-on to pre-existing continuous intravenous epoprostenol or subcutaneous treprostinil (n = 44). Median observation period was 39 months (range 2 to 60). Thirty-four patients (40%) received ≥1 additional PAH-specific therapy during follow-up. At end of data collection, 25 patients (29%) remained on bosentan, 43 (50%) had stopped bosentan, 11 (13%) had died while on bosentan, and 7 were lost to follow-up. At 4 years, the Kaplan-Meier estimate of disease progression in patients while on bosentan was 54% (7 patients at risk) with a survival estimate of 82% (16 patients at risk). Risk factors significantly associated with survival were World Health Organization functional class and indexed pulmonary vascular resistance. In conclusion, outcome in children with PAH managed with current treatment regimens appears favorable. However, despite current therapy options, disease progression remains a concern.

The Role of Uric Acid in Pediatric Idiopathic Pulmonary Arterial Hypertension: Analysis From a 10-Year Registry

PURPOSE: Uric acid (UA) has been proposed as a mortality predictor and strong marker for severity in patients with pulmonary arterial hypertension (PAH). Nevertheless, its role in the pediatric population has not been entirely elucidated. We aimed to evaluate which parameters predict high UA levels, and its role as a mortality predictor in a pediatric cohort with non-responsive idiopathic PAH.