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Background-Pulsed-wave Doppler determination of the pulmonary artery acceleration time (PAAT) as a surrogate for pulmonary artery pressure was found to be of clinical value for assessment of pulmonary hypertension (PH) with studies to date exclusively performed in adults. This study aims to provide representative, normal reference values for PAAT in children of all ages. Moreover, we validated abnormal PAAT values in 54 children with PH. Methods and Results-We conducted a prospective echocardiographic study in 756 healthy children (aged 1 day to 18 years) and in 54 children with PH. Possible associations of age, body length, body weight, body surface area, and heart rate on PAAT were investigated. The PAAT correlated positively with age (r=0.848), body length (r=0.871), body surface area (r=0.856), and body weight (r=0.825) and negatively with heart rate (r=−0.906). PAAT increased with age (neonates: median: 81 ms, range: 53-104; 18th year of life: median: 151 ms, range: 107-187). Receiver operating characteristic analysis for detecting PH patients using age-specific z scores showed an excellent performance of PAAT (P<0.001; area under the curve, 0.98; 95% confidence interval, 0.97-0.99) with a best cutoff score according to Youden index of -1.565 (sensitivity: 92%, specificity: 96%). PAAT values of PH patients negatively correlated (ρ=−0.497) with pulmonary vascular resistance. Conclusions-The PAAT normal reference values and z scores we provide here will be useful to identify children with a shortened PAAT. Abnormal PAAT values with scores <−2 were predictive of PH. (Circ Cardiovasc Imaging.

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Determination of the right ventricular outflow tract velocity time integral (RVOT VTI) is an important part of the noninvasive investigation of pulmonary blood flow in adults; however, age-related pediatric reference data are lacking. We examined growth-related changes of RVOT VTI values in children and the predictive value of RVOT VTI values in identifying enhanced pulmonary blood flow in children with secundum type atrial septal defect (ASD). A prospective study was conducted in a group of 570 healthy children and 52 children with a moderate-sized to large ASD. We determined the effects of age, body length (BL), body weight (BW), and body surface area (BSA) on RVOT VTI values. The predictive value of normal values stratified for age, BW, BL, and BSA was tested in our 52 ASD children. RVOT VTI values ranged from mean 9.7 ± 1.2 cm in neonates to 23.3 ± 2.7 cm in children with 18 years of age and showed a positive correlation with age, BL, BSA, and BW. In our population, RVOT VTI z-scores showed a high specificity for detecting ASD patients (>97 %) with sensitivity up to 71 %. We provide normal ranges and calculated z-scores of pediatric RVOT VTI values. Normal RVOT VTI z-scores might be additional predictors in identifying increased pulmonary blood flow in patients with ASD.

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Background: Macitentan, a dual endothelin receptor antagonist (ERA), was approved in 2014 for the treatment of adults with idiopathic pulmonary arterial hypertension (PAH). Once-per-day dosing and low potential hepatic toxicity make macitentan an appealing therapeutic option for children with PAH, but reports on its use in pediatric patients are still lacking.Methods: Prospective observational study of 18 children [10 male; median age: 8.5, minimum (min.): 0.6, maximum (max.): 16.8 years] with pulmonary hypertension (PH). Four of these 18 patients were treatmentnaïve and started on a de novo macitentan therapy. The remaining 14/18 children were already on a PHtargeted pharmacotherapy (sildenafil or bosentan as monotherapy or in combination). Nine children who were on bosentan were switched to macitentan. We analyzed the 6-minute walking distance (6MWD), NYHA functional class (FC)/modified ROSS score, invasive hemodynamics, echocardiographic variables and the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP).Results: The median follow up was 6 months (min.: 0.5, max.: 30). Macitentan treatment was associated with improvement of invasive hemodynamics, e.g., the ratio of mean pulmonary arterial pressure/mean systemic arterial pressure decreased from a median of 62% (min.: 30%, max.: 87%) to 49% (min.: 30%, max.: 69%), P<0.05; pulmonary vascular resistance index (PVRi) decreased from a median of 7.6 (min.: 3.3, max.: 11.5) to 4.8 Wood units × m² body surface area (min.: 2.5, max.: 10), P<0.05. The tricuspid annular plane systolic excursion (TAPSE) increased from a median of 1.4 (min.: 0.8, max.: 2.8) to 1.9 (min.: 0.8, max.: 2.7) cm, (P<0.05). NT-proBNP values decreased from a median of 272 (min.: 27, max.: 2,010) to 229 (min.: 23, max.: 814) pg/mL under macitentan therapy (P<0.05). The 6MWD and NYHA FC/modified ROSS score did not change significantly.Conclusions: This is the first prospective study of macitentan pharmacotherapy in infants and children with PH <12 years of age. Except in one patient, macitentan treatment was well tolerated and was associated with improvements in invasive hemodynamics, longitudinal systolic RV function (TAPSE) and serum NT-proBNP values.