Background —Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. Methods and Results —A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng · kg ⁻¹ · min ⁻¹ for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48±0.38 to 0.27±0.16 ( P <0.001). Similarly, iloprost decreased the ratio from 0.49±0.38 to 0.26±0.11 ( P <0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6±11.9 to 34.7±21.4 nmol/L during iNO ( P <0.01), and plasma cAMP increased from 55.7±22.9 to 65.1±21.2 nmol/L during iloprost inhalation ( P <0.05). Conclusions —In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Exposure to bosentan was lower in paediatric pulmonary arterial hypertension (PAH) patients treated with the marketed adult formulation at a dose of about 2 mg kg⁻¹ when compared with adult PAH patients.• In healthy adult subjects, bosentan pharmacokinetics are less than dose‐proportional at doses of ≥500 mg. WHAT THIS STUDY ADDS • The pharmacokinetics of a new paediatric bosentan formulation were characterized in paediatric PAH patients.• The level of exposure to bosentan as observed in adult PAH patients cannot be reached in paediatric patients with b.i.d. dosing.• In paediatric PAH patients, nondose‐proportional pharmacokinetics of bosentan occur at lower doses when compared with healthy adult subjects.AIM To show equivalent bosentan exposure in paediatric patients with pulmonary arterial hypertension (PAH) when compared with a cohort of historical controls of adult PAH patients using a newly developed paediatric formulation.METHODS Thirty‐six paediatric PAH patients were enrolled in this multicentre, prospective, open‐label, noncontrolled study and treated for 4 weeks with bosentan 2 mg kg⁻¹ b.i.d. and then for 8 weeks with 4 mg kg⁻¹ b.i.d. Blood samples were taken for pharmacokinetic purposes. Exploratory efficacy measurements included World Health Organization (WHO) functional class and parent's and clinician's Global Clinical Impression scales.RESULTS Comparing children with a historical group of adults, the geometric mean ratio (90% confidence interval) of the area under the plasma concentration–time curve was 0.54 (0.37, 0.78), i.e. children had lower exposure to bosentan than adults. Bosentan concentrations following doses of 2 and 4 mg kg⁻¹ were similar. Improvements in WHO functional class and the Global Clinical Impression scales occurred mainly in bosentan‐naive patients, whereas the rare worsenings occurred in patients already on bosentan prior to study initiation. The paediatric formulation was well accepted and bosentan well tolerated in this study. No cases of elevated liver enzymes or anaemia were reported.CONCLUSIONS Exposure to bosentan, as shown comparing the results from this study with those from a study in adults, was different in paediatric and adult PAH patients. Since FUTURE‐1 and past studies suggest a favourable benefit–risk profile for bosentan at 2 mg kg⁻¹ b.i.d., this dose is recommended for children with PAH. The new paediatric formulation was well tolerated.

Current paediatric pulmonary hypertension (PH) diagnostic algorithms include some testing specifically for paediatrics, but it is unclear if this is used in clinical practice. We describe the current diagnostic workup of the TOPP (Tracking Outcomes and Practice in Paediatric Pulmonary hypertension) registry for suspected PH.We investigated 456 patients enrolled until February 2010. The majority had ECGs (94%), echocardiograms (96%) and/or chest radiographs (89%) performed and these were the noninvasive tests most frequently used for evaluation of suspected PH. No patient had all three tests considered normal, suggesting the potential for the combined use to rule out PH.For evaluation of complications associated with heart catheterisation (HC) we analysed a total of 908 HCs reported until February 2012. Of these, 554 were at diagnosis and 354 in follow-up. Complications were reported in 5.9% with five deaths considered related to HC, suggesting a higher rate of HC complications compared to adult studies. However, current recommendations support HC in paediatric PH. A proper application of the risk/benefit ratio for HC requires further data. Most children did not undergo the diagnostic workup currently recommended for adults, which highlights either incomplete awareness of current guidelines and/or challenges their appropriateness for children.