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 (SvO 2 ), 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 SvO 2 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 SvO 2 are independent prognostic factors.

Background: Paediatric-onset idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) is partially linked to genetic factors that may also affect treatment response and outcome. The relation between clinical characteristics and pathogenicity of gene variants in childhood IPAH/HPAH is still not well understood. Methods: We retrospectively analyzed IPAH/HPAH paediatric patients aged between 3 months and 18 years under follow-up at a large tertiary referral center. Whole-exome sequencing focused on PAH high-risk genes was performed in all patients. Pathogenicity grading of gene variant sites was assessed using ClinVar and population frequencies. The association between gene variants and death was studied using Cox proportional multivariate models. Results: Overall, 129 patients (54.3% females; 91.5% on PAH therapy) with a median age at diagnosis of 6.8 (IQR 3.4–10.7) years were included. A relevant PAH gene variant was detected in 95 patients (73.6%). The most common variants were in the BMPR2 (n = 43, 3%) gene. Over a median follow-up period of 27.6 months, 26 children died. The presence of a likely pathogenic genetic variant was significantly associated with survival (HR: 3.56, p = 0.005) on multivariable Cox analysis. The number of PAH-specific drugs at presentation was associated with better survival in the cohort with pathogenic variants (p = 0.02). Conclusions: Pathogenic/likely pathogenic genetic variants are prevalent in children with PAH and are related to a worse prognosis irrespective of other recognized risk factors in this population. Combination PAH therapy was associated with superior prognosis in children with pathogenic variants or BMPR2 variants. Therefore, proactive medical therapy should be employed in this population.

Aims Despite shared pathophysiological mechanisms, patients with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) have a poorer prognosis than those with PAH after congenital heart defect repair. Ventricular adaption remains unclear and could provide a basis for explaining differences in clinical outcomes. The aim of this prospective study was to assess clinical status, haemodynamic profile, and biventricular adaptation to PAH in children with various forms of PAH. Methods and results Consecutive patients with IPAH/HPAH or post-operative PAH were prospectively recruited (n = 64). All patients underwent a comprehensive, protocolized assessment including functional assessment, measurement of brain natriuretic peptide (BNP) levels, invasive measurements, and a cardiac magnetic resonance (CMR) assessment. A cohort of age- and sex-matched healthy subjects served as controls. Patients with post-operative PAH had a better functional class (61.5 vs. 26.3% in Class I/II, P = 0.02) and a longer 6-min walk distance (320 ± 193 vs. 239 ± 156 m, P = 0.008) than IPAH/HPAH. While haemodynamic parameters were not significantly different between IPAH/HPAH and post-operative patients, post-operative patients with PAH presented with higher left ventricular volumes and better right ventricular function compared with patients with IPAH/HPAH (P < 0.05). On correlation analyses, left ventricular volumetric parameters were highly correlated with BNP and 6-min walk test distance in this population. Conclusion Despite comparable haemodynamic profiles, patients with post-operative PAH had less functional limitation than their IPAH/HPAH counterparts. This is potentially related to the differential biventricular adaptation pattern evident on CMR with better myocardial contractility and higher left ventricular volumes in post-operative patients with PAH, highlighting the importance of ventriculo-ventricular interaction in the setting of PAH.