Pediatric pulmonary arterial hypertension: characteristics and efficacy of specific therapy on clinical, echocardiographic and hemodynamic parameters

Abstract Background Pulmonary arterial hypertension (PAH) in children has peculiar features and require a unique approach (1,2,3). Right heart catheterization for risk assessment is hindered by a not negligible rate of complications (4,5) and the role of non-invasive tools are under investigation. Methods This study describes the epidemiological features of pediatric PAH patients followed in a referral center during a 40-year period and investigates the effects of PAH-targeted drugs on several parameters. Results Data from consecutive pediatric PAH patients referred to our center from 1980 to 2024 were collected. Of 137 patients, 60 (44%) had idiopathic/hereditary PAH (I/HPAH) and 60 (44%) had PAH associated with congenital heart disease (PAH-CHD). PAH-CHD patients were younger than I/HPAH at diagnosis and there was not a female predominance. When considering treatment strategy, among IPAH, 14 (23%) patients showed a positive response to acute vasoreactivity test at diagnosis and were treated with calcium-channel blocker, but only 3 (5%) were long-term responders. Excluding acute responders, compared to PAH-CHD, I/H PAH patients were usually treated with a more aggressive strategy. This is particularly true when considering the subgroup of patients (55) followed in our Center since 2014 (after approval for use several oral PAH targeted drugs in pediatric population by regulatory authorities: in this subgroup of patients, 60% of I/HPAH patients were treated with upfront combination therapy vs only 15% of PAH-CHD, but at the end of observational period, even in PAH-CHD population, only a minority of patients was treated with monotherapy (15%). Efficacy of first-line treatment strategy was confirmed by improvement in NYHA functional class (p 0.001), in 6-minute walking distance (p 0.001), in right ventricular function at echocardiography and in hemodynamics with a significant increase in cardiac index (2.7 L/min/m2 vs 3.1. L/min/m2, p = 0.007), in values of pulmonary artery oxygen saturation (68.5% vs 71.7%, p = 0.03) and reduction in pulmonary vascular resistance index (10.8 vs 8.3 WU·m2, p = 0.007). Conclusions This series confirms a different distribution of pediatric PAH etiologies compared to adults, with children having a greater predominance of I/HPAH and PAH-CHD. In I/HPAH, treatment strategy is similar to adults with rapid sequential or upfront oral combination therapy if lower risk and initial parenteral combination therapy if high risk. In PAH-CHD, treatment strategy is characterized by a more prudential approach with first-line monotherapy and combination therapy in case of inadequate response. Beyond hemodynamics, in this study, PAH-targeted drugs’ effects are demonstrated by a significant improvement in symptoms, exercise capacity and right ventricle echocardiographic parameters suggesting a role of this non-invasive and easily available tools in monitoring disease progression and treatment response.