Pediatric Pulmonary Hypertension Research Articles

The Role of Early Child Nutrition in Pulmonary Hypertension—A Narrative Review

Pulmonary hypertension is a complex condition that has distinct characteristics in pediatric populations. This review explores the important role of early childhood nutrition in the growth, progression, and management of pediatric pulmonary hypertension. Nutritional deficiencies, including those of vitamins C, D, and iron, are closely linked to worse outcomes in children with this disease, emphasizing the importance of early intervention to prevent malnutrition and promote growth. Emerging research revealed that promising nutrients like resveratrol, along with modulation of the gut and respiratory microbiomes, may offer therapeutic advances for managing pulmonary hypertension. However, the current literature is limited by a lack of pediatric-specific studies, with much of the data extrapolated from adult populations and animal models, especially rats. This review highlights the need for targeted research to develop effective nutritional interventions aimed at improving outcomes for pediatric patients.

Ventricular Dysfunction in Patients With Congenital Diaphragmatic Hernia Who Die After Repair

BackgroundQuantitative echocardiographic (echo) measures of ventricular function predict mortality in pediatric pulmonary hypertension (PH), but studies in congenital diaphragmatic hernia (CDH)-related PH are limited. Few studies report quantitative echo data beyond the first week of life in CDH non-survivors. MethodsA single-center retrospective, cross-sectional, cohort study included CDH patients born between January 2013 and April 2022 who survived to surgical repair but died during the neonatal hospitalization. Quantitative measures of right (RV) and left ventricular (LV) size and function including tricuspid annular plane systolic excursion Z-score (TAPSEZ), RV fractional area change (FAC), RV/LV ratio, LV eccentricity index, LV M-mode dimensions, and RV/LV systolic strain were performed offline on the last echocardiogram before death. Data were compared between patients who died ≤30 days after repair (“early”) vs. >30 days after repair (“late”) using the Wilcoxon rank sum test. ResultsTwenty-five (11 early, 14 late) deceased patients had echo images available for analysis. LV size by end-diastolic dimension Z-score was smaller in patients who died early vs. late after repair [-3.03 (−3.93, −2.51) vs. −0.24 (−2.11, 0.53), p = 0.021]. There were trends toward worse RV function (TAPSEZ, RVFAC, RV global and free wall strain) and LV function (apical 4 chamber strain) in patients who died early vs. late after repair. ConclusionThese preliminary findings support future study of the impact of ventricular hypoplasia and dysfunction on mortality and opportunities for risk stratification based on quantitative echo findings in CDH. Level of EvidenceCohort study, 4.

Barriers to and facilitators of physical activity in pediatric pulmonary hypertension.

Therapeutic exercise has not been widely adopted in pediatric pulmonary hypertension (PH), despite adult data supporting its safety and efficacy. While physical limitations may prevent children with PH from participating in physical activity, other barriers to and facilitators of physical activity are unknown. Youth ages 8-18 years with World Symposium of PH diagnostic Groups 1-4, functional class I or II, and ambulatory status were prospectively enrolled in a cross-sectional study including separate 30-min participant and caregiver interviews regarding attitudes toward physical activity and a proposed exercise intervention in pediatric PH. Interview questions were guided by Social Cognitive Theory and explored autonomy, self-confidence, and self-efficacy. Interviews were transcribed, coded, and analyzed using an iterative process to determine themes and patterns. Demographics and relevant PH condition-specific data were abstracted from the medical record. Thirty PH participant/caregiver dyads were interviewed. Facilitators of physical activity included enjoyment/interest in the activity, socialization, incentivization, and feelings of safety and normalcy. Barriers to physical activity included lack of interest, fear/anxiety, and self-consciousness. Findings were similar in children and adults. Participants rarely reported restriction of activity by caregivers or medical providers. Attitudes toward engagement in a proposed exercise program were generally positive and reflected personal experiences with physical activity. Monitored exercise interventions that focus on patients' interests, cultivate confidence, respect limitations, and acknowledge the need for extrinsic incentivization may have benefits in pediatric PH. Future trials should test the impact of these characteristics on patient wellbeing and clinical outcomes.

Extracorporeal membrane oxygenation (ECMO) support for children with pulmonary hypertension: A single-institutional experience of outcomes.

Pediatric pulmonary arterial hypertension (PAH) can present with a wide spectrum of disease severity. Pulmonary hypertension (PH) crises can lead to acute decompensation requiring extracorporeal membrane oxygenation (ECMO) support, including extracorporeal cardiopulmonary resuscitation (eCPR). We evaluated outcomes for pediatric PH patients requiring ECMO. A single-institution retrospective review of pediatric PAH patients with World Symposium on PH (WSPH) groups 1 and 3 requiring ECMO cannulation from 2010 through 2022 (n = 20) was performed. Primary outcome was survival to hospital discharge. Secondary outcomes were survival to decannulation and 1-year survival. Of 20 ECMO patients, 16 (80%) survived to decannulation and 8 (40%) survived to discharge and 1 year follow up. Of three patients who had two ECMO runs; none survived. There were five patients who had eCPR for the first run; one survived to discharge. The univariate logistic regression model showed that venovenous ECMO was associated with better survival to hospital discharge than venoarterial ECMO, (OR: 0.12, 95% CI: 0.01-0.86, p = 0.046). PH medications (administered before, during, or after ECMO) were not associated with survival to discharge. For children with decompensated PAH requiring ECMO, mortality rate is high, and management is challenging. While VA ECMO is the main configuration for decompensated PH, VV ECMO could be considered if there is adequate ventricular function, presence of a systemic to pulmonary shunt, or an intercurrent treatable illness to improve survival to discharge. A multidisciplinary approach with requisite expertise should be utilized on a case-by-case basis until more reliable data is available to predict outcomes.

The Pulmonary Artery Pulsatility Index Provides No Additional Prognostic Information in Pediatric Pulmonary Arterial Hypertension.

The pulmonary artery pulsatility index (PAPi, calculated as (SPAP - DPAP)/mRAP) has been suggested as a measure of right ventricular-vascular coupling (RVVC) and as a prognostic parameter in cardiovascular conditions, particularly right ventricular failure. This retrospective study investigated the relationship between the PAPi and its components with disease severity parameters, the RVVC, and clinical outcomes in children with pulmonary arterial hypertension (PAH). We analyzed data from 111 children from the Dutch National Registry with PAH. The PAPi (median 6.0 [3.9-8.3]) was calculated from heart catheterization data and the RVVC was determined as the TAPSE/sPAP ratio via echocardiography (0.25 ± 0.12 mm/mmHg). Disease severity was characterized by clinical, hemodynamic, and laboratory data. Cox proportional hazard modeling assessed the PAPi's predictive value for transplant-free survival. There was no correlation between the RVVC and PAPi (R = -0.208, p = 0.111, n = 60). The PAPi correlated negatively with uric acid (R = -0.387, p < 0.001) but not with other disease severity parameters. Mean right atrial pressure correlated with multiple disease severity indicators. Transplant-free survival rates at 1, 3, and 5 years were 87%, 79%, and 73%, respectively. Neither the PAPi nor its components correlated with transplant-free survival. In conclusion, the PAPi does not correlate with the RVVC and this study could not demonstrate any prognostic value of the PAPi regarding disease severity or outcomes in children with PAH, challenging its utility in this population.

Embracing the challenges of neonatal and paediatric pulmonary hypertension.

Paediatric pulmonary arterial hypertension (PAH) shares common features with adult disease, but is associated with several additional disorders and challenges that require unique approaches. This article discusses recent advances, ongoing challenges and distinct approaches for caring for infants and children with PAH, as presented by the paediatric task force of the 7th World Symposium on Pulmonary Hypertension. We provide updates on diagnosing, classifying, risk-stratifying and treating paediatric pulmonary hypertension (PH) and identify critical knowledge gaps. An updated risk stratification tool and treatment algorithm is provided, now also including strategies for patients with associated cardiopulmonary conditions. Treatment of paediatric PH continues to be hindered by the lack of randomised controlled clinical trials. The challenging management of children failing targeted PAH therapy is discussed, including balloon atrial septostomy, lung transplantation and pulmonary-to-systemic shunt (Potts). A novel strategy using a multimodal approach for the management of PAH associated with congenital heart diseases with borderline pulmonary vascular resistance is included. Advances in diagnosing neonatal PH, especially signs and interpretation of PH by echocardiography, are highlighted. A team approach to the rapidly changing physiology of neonatal PH is emphasised. Challenges in drug approval are discussed, particularly the challenges of designing accurate paediatric clinical trials with age-appropriate end-points and adequate enrolment.

Updates in Management of Pulmonary Hypertension in Pediatrics: A Systematic Review

Objectives: To provide an updated synthesis of the evidence on the management of pulmonary hypertension (PH) in pediatric patients. Methods: We performed a thorough search of electronic databases such as PubMed, Science Direct, Cochrane Library, and Scopus. Two independent reviewers evaluated and retrieved information from qualifying papers. Results: Our data consists of eight studies with 2003 children, 930 (46.3%) of whom were female. Prostacyclin agonists were found to significantly improve hemodynamic parameters and reduced BNP levels, which implies that they have promising clinical efficacy and a good tolerance profile. No major side effects were noted except for headaches and gastrointestinal symptoms. Systemic glucocorticoids, inhaled NO, endothelin receptor antagonists, and PDE showed tolerability and clinical improvements in pediatric PH. Side effects such as acute kidney damage, renal failure, and methemoglobinemia were noted with the inhaled NO. Conclusion: Pediatric PH is still a difficult condition with high morbidity and mortality. All of the reported pharmacological interventions demonstrated good clinical outcomes and almost no adverse effects. Healthcare practitioners can improve the care of children with PH and eventually improve their quality of life and long-term survival by incorporating new research into clinical practice.

Safety and Effectiveness of Selexipag in Pediatric Pulmonary Hypertension: A Retrospective Multicenter Cohort Study

ObjectiveTo describe the safety and effectiveness of treating pediatric patients who have pulmonary arterial hypertension (PAH) with selexipag in a real-world, multi-center cohort, given that data supporting its use in pediatric PAH are sparse. Study designWe report a multi-center, retrospective, cohort study of children with PAH treated with selexipag. Demographic and clinical variables were extracted from the medical records. Clinical parameters were analyzed at 3 timepoints: pre-selexipag, 3-12 months post-selexipag, and >12 months follow-up. ResultsEighty-seven patients were included, 32 received selexipag as add-on to background therapy, and 55 transitioned from another prostanoid. Median starting and final doses were 4.7 and 28.5 μg/kg/dose BID, respectively. Add-on patients demonstrated improved indexed pulmonary to systemic vascular resistance ratio after selexipag initiation (PVRi/SVRi, 0.62v0.53, p=0.034) with a lower average mean pulmonary artery pressure (MPAP, 46v39 mmHg, p=NS), and oxygen consumption (VO2 max 27.8v30.9 mL/kg/min, p=NS). Transition patients demonstrated stable MPAP (47v45 mmHg, p=NS) and a lower mean PVRi (10.9v8.2 Wood units*m2, p=NS) but late functional worsening in some with VO2 max decreased at follow-up (26.0v19.5 ml/kg/min). Side effects were noted in 40% of the cohort but prompted discontinuation in only 2%. ConclusionsIn a large, multi-center cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring.

Triumph of Triads: Selexipag Unveiled in Paediatric Pulmonary Hypertension Triple Therapy

Triumph of Triads: Selexipag Unveiled in Paediatric Pulmonary Hypertension Triple Therapy

Creating a digital approach for promoting physical activity in pediatric pulmonary hypertension: A framework for future interventions.

Children with pulmonary hypertension (PH) often demonstrate limited exercise capacity. Data support exercise as an effective nonpharmacologic intervention among adults with PH. However, data on exercise training in children and adolescents are limited, and characteristics of the optimal exercise program in pediatric PH have not been identified. Exercise programs may have multiple targets, including muscle deficits which are associated with exercise limitations in both adult and pediatric PH. Wearable accelerometer sensors measure physical activity volume and intensity in the naturalistic setting and can facilitate near continuous data transfer and bidirectional communication between patients and the study team when paired with informatics tools during exercise interventions. To address the knowledge gaps in exercise training in pediatric PH, we designed a prospective, single arm, nonrandomized pilot study to determine feasibility and preliminary estimates of efficacy of a 16-week home exercise intervention, targeting lower extremity muscle mass and enriched by wearable mobile health technology. The exercIse Training in pulmONary hypertEnsion (iTONE) trial includes (1) semistructured exercise prescriptions tailored to the participant's baseline level of activity and access to resources; (2) interval goal setting fostering self-efficacy; (3) real time monitoring of activity via wearable devices; (4) a digital platform enabling communication and feedback between participant and study team; (5) multiple avenues to assess participant safety. This pilot intervention will provide information on the digital infrastructure needed to conduct home-based exercise interventions in PH and will generate important preliminary data on the effect of exercise interventions in youth with chronic cardiorespiratory conditions to power larger studies in the future.

Identifying Key Biomarkers in Pediatric Pulmonary Hypertension: An Investigative Approach.

This study assesses the utility of early biomarkers-5-hydroxyindoleacetic acid (5-HIAA) and insulin-like growth factor 1 (IGF-1)-for diagnosing and monitoring pulmonary hypertension (PH) in children with congenital heart defects (CHD). Due to the risks associated with invasive diagnostics, such as right heart catheterization, non-invasive biomarkers provide a safer alternative for early PH detection. This cohort-based study utilized blood and urine samples to measure 5-HIAA and IGF-1 levels via enzyme immunoassays. Our findings revealed significant changes in 5-HIAA concentrations across various biological matrices, supporting its potential as a diagnostic tool. Specifically, altered levels in urine and plasma reflect its role in serotonin metabolism and vascular remodeling in PH. IGF-1 levels were notably reduced in plasma, suggesting its involvement in PH pathophysiology. ROC analysis confirmed the diagnostic efficacy of these biomarkers, particularly 5-HIAA's high specificity and sensitivity. In conclusion, 5-HIAA and IGF-1 levels correlate well with PH, underscoring their diagnostic value for early PH detection in children with CHD.

Paediatric pulmonary hypertension due to congenital heart disease in non-cardiac surgery: Anaesthetic implications

Paediatric patients with pulmonary hypertension associated with Congenital Heart Disease (PH-CHD) are frequently encountered in non-cardiac surgical settings. Although the pharmacological and surgical management of the underlying CHD in the group has improved yet its management remains challenging due to associated high morbidity and mortality. The dilemma prevails more so because of the dearth of adequate literature describing its pathophysiology and management in non-cardiac surgical settings. There are no specific guidelines pertaining to paediatric PH-CHD care, and the precepts have been extrapolated from adult studies and guidelines. This review article intends to apprise the pathophysiology of PH-CHD, its management, and its perioperative care with special emphasis on pulmonary vascular hypertensive crisis in these patients posted for non-cardiac procedures.

Pediatric Pulmonary Hypertension.

Pediatric Pulmonary Hypertension.

The Current Strategy in Managing Congenital and Structural Heart Disease: Find and Treat Them Appropriately

Significant progress has been made in diagnosing and treating congenital heart defects (CHDs) over the past five decades. Notable advancements include pulse oximetry screening for critical CHDs in newborns and percutaneous, catheter-based procedures, improving outcomes even in developing nations. Recent studies demonstrate favorable outcomes with device closure of acyanotic CHDs, with non-fluoroscopy techniques adopted to minimize radiation risks. Positive results are observed with right ventricular outflow tract (RVOT) stent palliation for late-presenting cyanotic congenital heart diseases such as tetralogy of Fallot (TOF). Novel interventions like reverse Potts shunt anastomosis show promise in managing pediatric pulmonary arterial hypertension (PAH), while prophylactic treatments effectively reduce postoperative arrhythmias. Fontan procedure significantly enhances survival rates for individuals with single functional ventricles, although challenges arise with aging populations. In developed countries, fetal cardiac interventions utilizing advanced imaging techniques allow for early detection and preventive interventions, reducing secondary complications. Keyword: Fetal Intervention, Fontan, Non-Fluoroscopy, Percutaneous, Reverse Potts, Rheumatic Heart Disease, RVOT Stenting.

Tailoring of Bilosomal Nanogel for Augmenting the Off-Label Use of Sildenafil Citrate in Pediatric Pulmonary Hypertension.

Pediatric pulmonary hypertension is a serious syndrome with significant morbidity and mortality. Sildenafil is widely used off-label in pediatric patients with pulmonary arterial hypertension. In this study, bile salt-stabilized nanovesicles (bilosomes) were screened for their efficacy to enhance the transdermal delivery of the phosphodiesterase type 5 inhibitor, sildenafil citrate, in an attempt to augment its therapeutic efficacy in pediatric pulmonary hypertension. A response surface methodology was implemented for fabricating and optimizing a bilosomal formulation of sildenafil (SDF-BS). The optimized SDF-BS formulation was characterized in terms of its entrapment efficiency (EE), zeta potential, vesicle size, and in vitro release profile. The optimized formula was then loaded onto hydroxypropyl methyl cellulose (HPMC) hydrogel and assessed for skin permeation, in vivo pharmacokinetics, and pharmacodynamic studies. The optimized SDF-BS showed the following characteristic features; EE of 88.7 ± 1.1%, vesicle size of 185.0 + 9.2 nm, zeta potential of -20.4 ± 1.1 mV, and efficiently sustained SDF release for 12 h. Skin permeation study revealed a remarkable improvement in SDF penetration from bilosomal gel compared to plain SDF gel. In addition, pharmacokinetic results revealed that encapsulating SDF within bilosomal vesicles significantly enhanced its systemic bioavailability (∼3 folds), compared to SDF oral suspension. In addition, pharmacodynamic investigation revealed that, compared to plain SDF gel or oral drug suspension, SDF-BS gel applied topically triggered a significant elevation (p < 0.05) in cGMP serum levels, underscoring the superior therapeutic efficacy of SDF-BS gel. Conclusively, bilosomes can be viewed as a promising nanocarrier for transdermal delivery of SDF that would grant higher therapeutic efficiency while alleviating the limitations encountered with SDF oral administration.

Invasive haemodynamics predict outcomes in paediatric pulmonary artery hypertension.

Invasive haemodynamics are often performed for initiating and guiding pulmonary artery hypertension therapy. Little is known about the predictive value of invasive haemodynamic indices for long-term outcomes in children with pulmonary artery hypertension. We aimed to evaluate invasive haemodynamic data to help predict outcomes in paediatric pulmonary artery hypertension. Patients with pulmonary artery hypertension who underwent cardiac catheterisation (2006-2019) at a single centre were included. Invasive haemodynamic data from the first cardiac catheterisation and clinical outcomes were reviewed. The combined adverse outcome was defined as pericardial effusion (due to right ventricle failure), creation of a shunt for pulmonary artery hypertension (atrial septal defect or reverse Pott's shunt), lung transplant, or death. Among 46 patients with a median [interquartile range (IQR)] age of 13.2 [4.1-44.7] months, 76% had CHD. Median mean pulmonary artery pressure was 37 [28-52] mmHg and indexed pulmonary vascular resistance was 6.2 [3.6-10] Woods units × m2. Median pulmonary artery pulsatility index was 4.0 [3.0-4.7] and right ventricular stroke work index was 915 [715-1734] mmHg mL/m2. After a median follow-up of 2.4 years, nine patients had a combined adverse outcome (two had a pericardial effusion, one underwent atrial level shunt, one underwent reverse Pott's shunt, and six died). Patients with an adverse outcome had higher systolic and mean pulmonary artery pressures, higher diastolic and transpulmonary pressure gradients, higher indexed pulmonary vascular resistance, higher pulmonary artery elastance, and higher right ventricular stroke work index (p < 0.05 each). Invasive haemodynamics (especially mean pulmonary artery pressure and diastolic pressure gradient) obtained at first cardiac catheterisation in children with pulmonary artery hypertension predicts outcomes.

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.

Leukotriene B4 levels in CHD-associated paediatric pulmonary hypertension.

The aim of this study is to evaluate the role of leukotriene B4, an inflammatory mediator, in the development of pulmonary hypertension in paediatric patients with CHD with left-right shunt. The study included forty patients with CHD with left-right shunts. Based on haemodynamic data obtained from cardiac diagnostic catheterisation, 25 patients who met the criteria for pulmonary arterial hypertension were included in the patient group. The control group comprised 15 patients who did not meet the criteria. The standard cardiac haemodynamic study was conducted. Leukotriene B4 levels were assessed in blood samples taken from both pulmonary arteries and peripheral veins. The median age of patients with pulmonary arterial hypertension was 10 months (range: 3-168), while the median age of the control group was 50 months (range: 3-194). In the pulmonary hypertension group, the median pulmonary artery systolic/diastolic/mean pressures were 38/18/24 mmHg, compared to 26/10/18 mmHg in the control group. Leukotriene B4 levels in pulmonary artery blood samples were significantly higher in the pulmonary arterial hypertension group compared to the controls (p < 0.05). Peripheral leukotriene B4 levels were also elevated in the pulmonary arterial hypertension group in comparison to the control group, though the difference was not statistically significant. The discovery of elevated leukotriene B4 levels in pulmonary artery samples from paediatric patients with pulmonary arterial hypertension secondary to CHD with left-to-right shunt suggests that local inflammation may have a pathological role in the development of pulmonary arterial hypertension.

Pulmonary Hypertension and Hypothyroidism-Still an Important Clinical Coincidence in Paediatric Population, an Endocrinologist's Point of View.

There is limited data on hypotheses linking autoimmune thyroid diseases (AITD) and hypothyroidism with pulmonary hypertension (PH). Moreover, the prevalence of this coincidence, as well as the possible common pathogenic mechanisms, are even less explicit in paediatric population. We present a review of recently published articles regarding relatively large cohorts of children with PH, coming from paediatric PH registries, aiming to clarify the coincidence of PH and AITD, especially hypothyroidism, and discuss its possible mutual impact. Although thyroid disorders have been excluded from the latest PH classification, it is still important to remember the possibility of this coincidence as it may significantly influence patients' clinical outcome. Moreover, children with PH may need multidisciplinary care due to the relatively frequent coexistence with not only hormonal abnormalities but also growth impairment, genetic disorders, and mental delay. Further specific paediatric studies are needed to improve the care in this rare disease, especially in patients with other comorbidities present.

Application of a modified clinical classification for pulmonary arterial hypertension associated with congenital heart disease in children: emphasis on atrial septal defects and transposition of the great arteries. An analysis from the TOPP registry.

A proportion of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) do not fit in the current classification. We aimed to analyse the applicability of an adapted clinical classification of PAH-CHD to pediatric patients using the TOPP-1 registry (Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension) and focus on atrial septal defects (ASD) and transposition of the great arteries (TGA). Hemodynamic and clinical data of all patients with PAH-CHD in the TOPP cohort were reviewed. Patients were classified according to predefined ABCDE categories (A: Eisenmenger syndrome, B: left-to-right shunt, C: coincidental defects, including all ASDs, D: corrected CHD, E: TGA), or as complex CHD (group 5), by 2 independent investigators. In case of disagreement, a third reviewer could either settle a final decision, or the patient was deemed not classifiable. Survival curves were calculated for each group and compared to idiopathic PAH patients of the registry. A total of 223 out of 531 patients in the registry had PAH-CHD, and 193 were categorized to the following groups: A 39(20%), B 27(14%), C 62(32%) including 43 ASDs, D 58(30%), E 7(4%), whereas 6 patients were categorized as group 5, and 10 patients were unable to be classified. No survival difference could be demonstrated between the groups. This modified classification seems to be more applicable to pediatric PAH-CHD patients than the previous classification, but some patients with PAH-CHD who never had a shunt remain unclassifiable. The role of ASD in pediatric PH should be reconsidered.