Congenital Heart Disease Pulmonary Arterial Hypertension Research Articles

Pulmonary Artery Dilatation Due to Pressure or Volume Overload in Congenital Heart Disease.

Background: Pulmonary artery dilatation is described mostly in association with pulmonary hypertension. Patients/Methods: Study analysis: 60 patients with pulmonary arterial hypertension in congenital heart disease (PAH-CHD); 64 with repaired tetralogy of Fallot/pulmonary regurgitation (rTOF/PR); and 80 healthy (NORMAL). Measured were: main pulmonary artery (MPA) diameter and MPA/ascending aorta (Ao asc) ratio, by echocardiography (ECHO) and computer tomography or magnetic resonance imaging (CT/MRI). Results: In MPA diameter, significant differences between PAH-CHD, rTOF/PR, and NORMAL were found (median): 37 vs. 27 vs. 21 mm (p < 0.0001). In MPA/Ao asc ratio, there was a difference between PAH-CHD and NORMAL (median): 1.3 vs. 0.8 (p < 0.0001), but not between rTOF/PR and NORMAL: 0.74 vs. 0.8 (p = 0.3). Significant MPA dilatation (>40 mm) was present: in PAH-CHD, 35% (ECHO) and 76.9% (CT/MRI) of patients, while in rTOF/PR, 3.1% (ECHO) and 7.8% (CT/MRI). Severe MPA dilatation (>50 mm) occurred only in PAH-CHD: 16.7% (ECHO) and 31.4% (CT/MRI), while not in rTOF/PR. There was a significant correlation between ECHO and CT/MRI measurements, but ECHO was underestimated in all parameters. Conclusions: MPA dilatation due to pressure overload is more frequent and more severe; volume overload also leads to MPA dilatation but is less severe. The MPA/Ao asc ratio is not reliable for MPA dilatation estimation in rTOF/PR.

Application of Artificial Intelligence-Based Auxiliary Diagnosis in Congenital Heart Disease Screening.

To evaluate the application value of artificial intelligence-based auxiliary diagnosis for congenital heart disease. From May 2017 to December 2019, 1892 cases of congenital heart disease heart sounds were collected for learning- and memory-assisted diagnosis. The diagnosis rate and classification recognition were verified in 326 congenital heart disease cases. Auscultation and artificial intelligence-assisted diagnosis were used in 518 258 congenital heart disease screenings, and the detection accuracies of congenital heart disease and pulmonary hypertension were compared. Female sex and age > 14 years were predominant in atrial septal defect (P <.001) compared with ventricular septal defect/patent ductus arteriosus cases. Family history was more prominent in patent ductus arteriosus patients (P <.001). Compared with no pulmonary arterial hypertension, a male predominance was seen in cases of congenital heart disease-pulmonary arterial hypertension (P <.001), and age was significantly associated with pulmonary arterial hypertension (P =.008). A high prevalence of extracardiac anomalies was found in the pulmonary arterial hypertension group. A total of 326 patients were examined by artificial intelligence. The detection rate of atrial septal defect was 73.8%, which was different from that of auscultation (P =.008). The detection rate of ventricular septal defect was 78.8, and the detection rate of patent ductus arte-riosus was 88.9%. A total of 518 258 people from 82 towns and 1220 schools were screened including 15 453 suspected and 3930 (7.58%) confirmed cases. The detection accuracy of artificial intelligence in ventricular septal defect (P =.007) and patent ductus arteriosus (P =.021) classification was higher than that of auscultation. For normal cases, the recurrent neural network had a high accuracy of 97.77% in congenital heart disease-pulmonary arterial hypertension diagnosis (P =.032). Artificial intelligence-based diagnosis is an effective assistance method for congenital heart disease screening.

Relation between endothelial nitric oxide synthase genetic polymorphisms and pulmonary arterial hypertension in newborns with congenital heart disease

ABSTRACT Objective To investigate whether endothelial nitric oxide synthase (eNOS) rs1799983, rs2070744, and rs61722009 gene polymorphisms are associated with pulmonary arterial hypertension (PAH) in South Fujian newborns with congenital heart disease (CHD). Methods Genotyping for the eNOS rs1799983, rs2070744, and rs61722009 polymorphisms was performed using Sanger sequencing in 50 newborns with PAH secondary to CHD [CHD PAH (+)], 52 newborns with CHD without PAH [CHD PAH (-)], and 60 healthy controls. Results The genotype and allele frequency distributions of eNOS rs1799983, rs2070744, and rs61722009 were similar between CHD and healthy controls (P > .05). The frequencies of the eNOS rs1799983 G/T allele were 85% and 15% in the CHD PAH (+) group and 96.15% and 3.85% in the CHD PAH (-) group, the frequency of the T allele was higher in the CHD PAH (+) group than in the CHD PAH (-) group(P< .05), and patients with the GT/TT genotypes of eNOS rs1799983 may present higher PAH (OR = 4.412, 95%CI:1.411–13.797, P= .011). Newborns with the GT/TT genotypes had decreased plasma NO production compared to newborns with the GG genotype (P< .01), and NO levels in the CHD PAH (+) group were significantly lower than those in the CHD PAH (-) group (P < .05). Conclusion The T allele could be a risk factor for PAH in newborns with CHD in South Fujian through decreased levels of nitric oxide production by the endothelium.

M5. Effect of Macitentan on pulmonary vascular resistance index in patients with congenital heart disease-pulmonary arterial hypertension: a meta-analysis

Abstract Background and Aims Macitentan is a novel dual endothelin receptor antagonist which proven effective as treatment in adults with pulmonary arterial hypertension. Methods and Results We performed a systematic search from inception until May 31, 2021, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines comparing PVRi baseline and after Macitentan 10mg and selected studies according to our pre-defined inclusion and exclusion criteria. Two reviewers extracted data into the predefined tables in the Microsoft Excel (Microsoft Corp., New Mexico, US) sheet. We used RevMan software to perform a meta-analysis and draw Forest plots. We used a random effects model to estimate risk ratios. A two-sided p-value of ≤ 0.05 was considered statistically significant. A total of three randomized control trials (RCTs) with 325 patients were included in our analysis. Macitentan 10mg a day showed moderately associated with lower PVRi compare with baseline value (SMD: -0.72) and statistically significant (p = 0.002; 95% CI=-1.18-(-0.25)). Conclusion Macitentan was developed by modifying the structure of Bosentan in order to increase the efficacy and safety. Macitentan has slower receptor dissociation kinetics and longer duration of action which allows once-daily dosing. The safety profile of Macitentan appears to be superior with respect to hepatic safety and edema than other therapy such as Bosentan and Ambrisentan, respectively. Macitentan is a promising drug to treat pulmonary hypertension which is well tolerated and associated with improvements.

Plasma HGF and OPN as Potential Biomarkers of Pulmonary Arterial Hypertension in Congenital Heart Disease

Objectives: Pulmonary arterial hypertension in congenital heart disease (PAH-CHD) is the most common type of PAH and increases morbidity and mortality in patients with CHD. Right heart catheterization (RHC) is the standard me... | Find, read and cite all the research you need on Tech Science Press

Analysis of hemodynamics and outcomes of pregnant women with congenital heart disease-pulmonary arterial hypertension

Objective: To observe and analysis the changes of hemodynamic parameters and outcomes of pregnant women combined with congenital heart disease-pulmonary arterial hypertension (CHD-PAH). Methods: A prospective analysis of hemodynamic parameters of patients combined with CHD-PAH in Beijing Anzhen Hospital from January 2015 to December 2017 was carried out. Total 99 cases were divided into 4 groups based on systolic pulmonary arterial pressure (SPAP): mild group (SPAP 25-49 mmHg, 1 mmHg=0.133 kPa), moderate group (SPAP 50-79 mmHg), severe group (SPAP≥80 mmHg) and Eisenmenger syndrome group. Results: (1) SPAP of all groups increased during gestation, and the growth rates had no statistical differences (P>0.05). The SPAP in each group decreased after termination but was still higher than the early pregnancy's SPAP. (2) CHD-PAH patients in moderate [2 cm(2) (1-5 cm(2)), 1.0 cm (-2.0 - 2.0 cm)], severe [5 cm(2) (3-9 cm(2)), -3.5 cm (-6.0 - 1.0 cm)] or Eisenmenger syndrome [5 cm(2) (3-6 cm(2)), -1.0 cm (-5.5 - 2.0 cm)] group had larger right atrium area and smaller left ventricular end-diastolic diameter than patients in mild group [1 cm(2) (-1 - 4 cm(2)), 3.0 cm (1.0-6.0 cm)], the differences were statistically significant (all P<0.05). (3) Each group's SPAP/brachial arterial-systolic (BSAP) pressure continously increased during gestation. The SPAP/BSAP only decreased in patients in mild or moderate group after termination. However, the SPAP/BSAP kept rising in patients in severe group or Eisenmenger syndrome group. (4) CHD-PAH patients in severe or Eisenmenger syndrome group had worse cardiac function, in which the rates of Ⅲ-Ⅳ cardiac function were 61%(14/23) and 12/17, compared with patients in mild [8% (2/26)] and moderate [12%(4/33)] group, the differences were statistically significant (all P<0.05). (5) The rates of medicine treatment, cesarean section were higher, the weeks of gestational termination were earlier and the newborn's weights were lower in patients in severe or Eisenmenger syndrome group, the differences were statistically significant (all P<0.05). Conclusions: (1) SPAP keeps rising during gestation in all patients with CHD-PAH, and the SPAP decreases after termination but it's still higher than the early pregnancy's SPAP. This suggests that pregnancy would exacerbate these patients' heart problems, the risk should be fully considered before and during pregnancy. (2) Patients with severe CHD-PAH or combined with Eisenmenger syndrome have lager right atrium area, smaller left ventricular end-diastolic diameter, worse cardiac function, and bigger changes of hemodynamic, the incidence of adverse outcomes of mothers and children is also high, pregnancy should be avoided.

Effect of iloprost on biomarkers in patients with congenital heart disease-pulmonary arterial hypertension.

SummarySome biomarkers play important roles in the endothelial dysfunction of patients with pulmonary arterial hypertension (PAH), including nitric oxide (NO), endothelin‐1 (ET‐1), asymmetric dimethylarginine (ADMA), galectin‐3 (Gal‐3), B‐type natriuretic peptide (BNP), and uric acid (UA). However, studies on these biomarkers in pulmonary artery blood in congenital heart disease‐PAH (CHD‐PAH) and the effect of iloprost on the regulation of biomarkers are lacking. This study investigated potential CHD‐PAH biomarkers and their association with the severity of disease. The effect of iloprost on the regulation of these biomarkers was also studied. A total of 31 patients with CHD‐PAH were enrolled. Seven with positive effects of iloprost (the average reduction in mPAP 11.13±1.73 mm Hg) and 19 with negative effects of iloprost (the average reduction in mPAP 4.21±4.87 mm Hg; iloprost positive group [IPG] vs iloprost negative group [ING], P<.01) and five age‐matched controls were studied. The pulmonary artery blood sample was collected before and after inhaling iloprost, and the plasma concentrations of Gal‐3, ADMA, ET‐1, and NO were measured. A significant positive linear relationship was observed between mPAP and plasma ET‐1, BNP, ADMA, and UA levels in all patients with CHD‐PAH. ET‐1, ADMA, BNP, and UA levels had a significant linear relationship with mean pulmonary arterial pressure, which could be used to predict the severity of CHD‐PAH. ET‐1 might be a potential biomarker to pre‐evaluate the effect of iloprost on CHD‐PAH. Iloprost could affect the expression of Gal‐3 and, therefore, the process of fibrosis could be influenced by iloprost.

A cross-sectional study of pulmonary arterial hypertension in congenital heart disease by right heart catheterization

To explore the prevalence of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) and analyze its independent risk factors. During May 2007 to December 2008, a total of 704 consecutive CHD patients initially admitted into Fuwai Hospital were recruited. Their baseline data were collected and right heart catheterization (RHC) was performed. Those with a mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (1 mmHg = 0.133 kPa) during RHC were diagnosed as PAH. Multiple Logistic regression was performed to analyze the independent risk factors of PAH. There were 319 males and 385 females with a median age of 5 years. The causes included atrial septal defect (n = 185), ventricular septal defect (VSD, n = 452), patent ductus arteriosus (PDA, n = 48) and a combinations of the above lesions (n = 19). And 280 (39.8%) CHD patients had PAH. Logistic regression analysis revealed that age, systemic artery systolic blood pressure, VSD, PDA and combined lesions were independent risk factors of PAH in CHD (age: OR = 1.017, 95%CI: 1.001-1.033, P = 0.040; systemic artery systolic blood pressure: OR = 0.959, 95%CI: 0.944-0.975, P < 0.001; VSD: OR = 4.402, 95%CI: 2.615-7.411, P < 0.001; PDA: OR = 6.417, 95%CI: 3.079-13.373, P < 0.001; combined lesions: OR = 10.513, 95%CI: 3.641-30.355, P < 0.001). PAH is a common complication of CHD. Age, peripheral artery systolic blood pressure and type of lesion are independent risk factors of PAH in CHD.

Ambrisentan therapy in pulmonary hypertension: clinical use and tolerability in a referral centre.

Ambrisentan is an oral selective endothelin receptor antagonist licensed for use in pulmonary arterial hypertension (PAH). There are few data on clinical use and long-term tolerability in a wider range of patients with pulmonary hypertension (PH). All patients treated with ambrisentan over a 4-year period were identified. Baseline characteristics, liver function test (LFT) results and World Health Organization (WHO) functional class were retrieved from hospital databases. 272 patients received ambrisentan between March 2009 and June 2013 (32% idiopathic PAH, 36% connective tissue disease PAH, 11% congenital heart disease PAH, 6% portopulmonary hypertension, 1% HIV PAH, 4% PH in association with lung disease, 8% chronic thromboembolic PH and 2% PH in association with sarcoidosis). 33.5% of patients received ambrisentan as monotherapy and 12% received ambrisentan as their initial PH therapy. 18% stopped treatment due to side effects and 12% stopped due to lack of efficacy. Oedema was the most common side effect leading to cessation of therapy, which occurred in 7% of patients. 57% of patients who discontinued ambrisentan due to side effects also discontinued other PAH therapies due to side effects previously or subsequently. Ambrisentan was discontinued in two (<1%) patients due to abnormal LFTs. The 3-year survival in congenital heart disease PAH, idiopathic PAH and systemic sclerosis-associated PAH was 80%, 62%, and 38%, respectively (p = 0.003). Survival was superior in patients in whom WHO functional class improved in response to therapy. Ambrisentan is used as an initial therapy and as monotherapy in a minority of patients in a large UK PH referral centre. Discontinuation due to side effects, and especially oedema, was higher than reported in previous studies while discontinuation due to abnormal LFTs was very uncommon. A majority of patients who discontinued therapy due to side effects also previously or subsequently discontinued other PAH therapies. Improvement in WHO functional class was associated with superior survival.

Blood biomarkers and their potential role in pulmonary arterial hypertension associated with congenital heart disease. A systematic review

BackgroundThe development of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is multifactorial with a number of biomarkers serving as mediators of neurohormonal activation [B-type natriuretic peptide (BNP) and its N-terminal-pro-fragment (NT-proBNP)], endothelial dysfunction [asymmetric dimethylarginine (ADMA)] and cellular proliferation [vascular endothelial growth factor (VEGF)]. MethodsWe systematically reviewed the literature for trials studying the role of these biomarkers in the clinical evaluation, prognosis and management of patients with PAH related to CHD (CHD–PAH). ResultsTwenty-six studies were included in the systematic review, involving a total of 1113 patients with CHD–PAH. These patients had higher BNP, NT-proBNP and ADMA levels and higher VEGF expression when compared with healthy controls. Baseline and serial values of plasma levels of natriuretic peptides were shown to be significant predictors of survival. ADMA concentration was elevated in patients with CHD–PAH when compared with patients with simple CHD without PAH, whereas VEGF expression was particularly high in patients with CHD and persistent PAH after corrective surgery of the underlying heart disease. ConclusionRight heart dysfunction, endothelial inflammation and proliferation are mirrored by plasma levels of the corresponding biomarkers among patients with CHD–PAH. There is early evidence to suggest that natriuretic peptides, in particular, may be a simple and effective tool for determining prognosis and timing for therapeutic interventions in patients with CHD–PAH.

ASSA13-10-2 Efficacy and Safety of Bosentan in Patients with Pulmonary Arterial Hypertension Secondary to Congenital Heart Disease

Background Pulmonary arterial hypertension (PAH) is a major complication of congenital heart disease (CHD), causing increase morbidity and mortality with age. Sustained increase in the pulmonary arterial pressure (PAP) may result in progressive pulmonary vascular remodelling and eventually lead to irreversible changes including extensive intimal injury, obliteration, adventitial fibrosis and smooth muscle cell proliferation. In recent years, insight into the pathogenesis of PAH has resulted in the development of therapeutic strategies for PAH including endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase-5 inhibitors. Endothelin has a key role in the pathobiology of PAH, exerting vasoconstrictor and mitogenic effects by binding to two distinct receptor isoforms in the pulmonary vascular smooth musc-le cells. Bosentan, an orally active dual endothelin receptor antagonist, has been shown to improve exercise capacity, hemodynamics in patients with idiopathic, chronic thromboembolic, and connective tissue disease-associated PAH. However the data of efficacy and safety of bosentan in patients with CHD and PAH is limited. Objective The present study aimed to investigate the efficiency and safety of dual endothelin receptor antagonist bosentan in patients with CHD and severe PAH. Methods Between May 2008 and January 2011, a total of 18 patients with severe PAH secondary to left-to-right shunt CHD were treated with bosentan. All patients underwent cardiac evaluation, including reviewing medical history, physical examination, electrocardiogram and echocardiogram, and cardiac catheterization. The patients with IPAH or PAH secondary to valvular heart diseases, complex CHDs, heart failure (≥NYHA Class III) and other system diseases, and those who had a positive response during acute vasodilator test were excluded from this study. All the patients were treated with bosentan as well as digoxin, diuretics and warfarin for 6 months. Oral bosentan was initiated at 62.5 mg twice daily, increasing after 4 weeks to 125 mg twice daily thereafter in patients weighing > 40 kg and initiated at 31.25 mg twice daily, increasing after 4 weeks to 62.5 mg twice daily in patients weighing ≤40kg. Patients were assessed at 1-month intervals using physical examination, 6-minute walk test, complete blood count and blood biochemistry. Electrocardiogram, X-ray, echocardiogram and right heart catheterization were repeated 6 months after treatment with bosentan. Results There were 6 males and 12 females with age ranging from 9 to 55 (28.7 ± 11.3) years in this series. The basic defects included atrial septal defect (ASD; n = 6), ventricular septal defect (VSD; n = 4) and patent ductus arteriosus (PDA; n = 8). The echocardiogram showed right ventricular diameter (RVD) of 26 ± 8 mm, tricuspid regurgitation speed (VP) of 5.0 ± 0.7 m/s, transtricuspid pressure gradient (PGTV) of 100 ± 26 mmHg, left ventricular end-diastolic diameter (LVEDD) of 37 ± 5mm, left ventricular end-diastolic volume (LVEDV) of 51 ± 21 ml and left ventricular ejection fraction (LVEF) of 0.71 ± 0.06. Right heart catheterization showed oxygen saturation (SaO2) of femoral artery blood of 88.7 ± 5.9%, systolic pulmonary artirial pressure (sPAP) of 115 ± 19 mmHg (1mmHg = 0.133kp), diastolic pulmonary arterial pressure (dPAP) of 63 ± 13 mmHg, mean pulmonary artery pressure (mPAP) of 81 ± 15 mmHg, pulmonary-to-systemic flow (Qp/Qs) ratio of 0.76 ± 0.24 and pulmonary vascular resistance (PVR) of 19.6 ± 7.7 Woods. Six months after treatment with bosentan, echocardiogram showed no significant changes in right ventricular diameter (24 ± 8 mm, P > 0.05), VP (4.7 ± 0.4 m/s, P > 0.05), PGTV (93.3 ± 13.7 mmHg, P > 0.05), LVEDD (39 ± 4 mm, P > 0.05), LVEDV (60 ± 20 ml, P > 0.05), and LVEF (0.72 ± 0.07, P > 0.05). However, 6-minute walk distance (6-MWD) increased from 353 ± 101 to 480 ± 81 m (P 0.05), dPAP (59 ± 14 mmHg, P > 0.05) and mPAP (78 ± 10 mmHg, P > 0.05), the SaO2 of femoral artery blood and Qp/Qs ratio were increased to 91.0 ± 3.2% (P Conclusions Bosentan was well tolerated and effective for improving exercise capacity and hemodynamics in patients with PAH secondary to CHD. Different to IPAH and PAH secondary to other diseases, bosentan therapy did not cause decrease in pulmonary arterial pressure but PVR and increase in Qp/Qs ratio.

Accuracy of Doppler-Derived Estimation of Pulmonary Vascular Resistance in Congenital Heart Disease: An Index of Operability

Pulmonary vascular resistance (PVR) is a critical and essential parameter during the assessment and selection of modality of treatment in patients with congenital heart disease (CHD) accompanied by pulmonary arterial hypertension (PAH). Cardiac catheterization is the "gold standard" but is an invasive method for PVR measurement. A noninvasive and reliable method for estimation of PVR in children has been a major challenge and most desirable during past decades, especially for those who need repeated measurements. In a prospective study and among consecutive patients who were referred for cardiac catheterizations, PVR was calculated as the ratio of the transpulmonary pressure gradient (∆P) to the amount of the pulmonary flow (QP) accordingly for 20 patients with CHD and high PAH. Subsequently and noninvasively, PVR was assessed for these patients by a Doppler echocardiography-derived index defined as the ratio of the tricuspid regurgitation velocity (TRV(m/s)) to the velocity time integral (VTI(cm)) of the right-ventricular outflow tract (RVOT). There was a good correlation between PVR measured at catheterization (PVR(cath)) and TRV/VTI(m) ratio; the mean of three measurements of VTI (VTI(m)) with R (2) = 0.53 (p = 0.008). In addition, a TRV/VTI(m) value of 0.2 provided a sensitivity of 71.4% and a specificity of 100% for PVR >6 Woods units (WU) as well as sensitivity of 90% and specificity of 90% for a PVR equal to 8 WU. PVR value between 6 and 8 WU by catheterization has been considered as a cut-off point for intervention in children with left-to-right shunts and PAH. In conclusion, Doppler-derived TRV/VTI(m) ratio is a reliable index that may be helpful as a supplementary diagnostic tool for the selection of modality of treatment and follow-up of patients with PAH and increased PVR.

Circulating Endothelial Cells

Congenital heart disease can be complicated by pulmonary arterial hypertension (PAH), the reversibility of which is often difficult to predict. We recently reported a lung biopsy study showing impaired apoptotic regulation of endothelial cells in irreversible PAH. The objective of the present study was to identify noninvasive biomarkers of endothelial turnover that could be used to identify congenital heart disease patients at risk of irreversible PAH. Circulating endothelial cells (CECs) isolated with CD146-coated beads and circulating CD34(+)CD133(+) progenitor cells (CPCs) were quantified in peripheral vein, pulmonary artery, and pulmonary vein blood samples from 26 patients with congenital heart disease (16 with reversible PAH [median age 2 years] and 10 with irreversible PAH [median age 9 years]) and 5 control patients. Surgical lung biopsy was performed in 19 cases. As expected, endothelial remodeling was observed in irreversible PAH but not in reversible PAH. CEC and CPC numbers were each similar in the 3 types of blood samples. CEC numbers were significantly higher in patients with irreversible PAH (median 57 CEC/mL) than in patients with reversible PAH and control subjects (median 3 CEC/mL in the 2 groups). In contrast, CPC numbers did not differ among patients with irreversible or reversible PAH and control subjects (median 84, 64, and 44 CPC/10(5) lymphocytes, respectively, in the 3 groups). Irreversible PAH in congenital heart disease is associated with endothelial damage and with increased circulating endothelial cell counts. The present study suggests that CECs could be a valuable tool to define therapeutic strategies in congenital heart disease patients with PAH.

PAH-Associated Congenital Heart Disease: Finding Common Ground With Primary Pulmonary Hypertension

As we planned this issue on pulmonary arterial hypertension (PAH) in congenital heart disease and in children, we sensed the long shadows of physicians who have helped establish the parameters of its diagnosis. There were giants like Viktor Eisenmenger, who described the clinical features of a patient with PAH more than 100 years ago, and Paul Wood, who subsequently used the term “Eisenmenger syndrome” to describe PAH with reversal of a systemic to pulmonary shunt. As the nomenclature has evolved so has our understanding of the conditions seen in association with pulmonary hypertension.A reclassification by the World Health Organization in 1998 brought us further along, as it emphasized similarities between primary pulmonary hypertension and PAH of certain known etiologies. An improved understanding of the mechanisms underlying the vascular changes in PAH has been an important factor in the emergence of new therapies. Notably, some medical therapies for the treatment of primary pulmonary hypertension may benefit patients with PAH associated with congenital heart disease. It is intriguing to find the diversity in the etiology of PAH and yet some uniformity in treatment approaches.Our Roundtable Discussion so capably managed by Robyn Barst, MD, explored all of these issues. We have all recognized how difficult it may be to differentiate whether a patient with a congenital heart defect has Eisenmenger syndrome as opposed to primary pulmonary hypertension. The experts in pediatric cardiology we brought together for the Roundtable, as well as the authors of our articles in this issue, addressed this and many other difficult questions and present a comprehensive discussion of vital topics essential to our understanding of PAH in congenital heart disease. Hopefully, the insights presented will give us a clearer perspective on how to classify and treat patients who have these diseases.