Invasive Hemodynamic and Vasoreactivity Testing with Inhaled Iloprost in Children with Pulmonary Arterial Hypertension Associated with Congenital Heart Defects

Objective: Invasive hemodynamic evaluation and acute vasoreactivity testing are recommended in the diagnosis of pulmonary arterial hypertension (PAH), but their clinical role in children with PAH associated with congenital heart defects (CHD) is unclear. This study aims to investigate acute hemodynamic responses to inhaled iloprost, and its role in prognosis in children with PAH-CHD. Methods: A retrospective analysis was conducted on 83 pediatric patients with PAH-CHD in whom invasive hemodynamics were evaluated before and after a single inhaled dose of iloprost at a single center between 2010 and 2022. Details of the CHD corrective operation, medical treatment, and outcome for each patient were obtained via medical records or telephone contact. A composite endpoint of all-cause death, admission for worsening heart failure during follow-up, and event-free survival was defined, and risk factors associated with this composite endpoint were analyzed. Results: The patient age was (11.3 +/- 4.6) years, and 60 (72.3%) were female. Fifty-nine (71.1%) patients were diagnosed with Eisenmenger syndrome. After iloprost inhalation, mean pulmonary artery pressure decreased from (78.2 +/- 11.5) to (72.3 +/- 13.2) mmHg (P < 0.001), and pulmonary vascular resistance index (PVRI) decreased from (18.0 +/- 7.9) to (14.5 +/- 8.1) WU<middle dot>m2 (P < 0.001). A total of 38 (45.8%) patients had a positive response, defined as a PVRI decrease >25% with stable systemic pressure. Thirty-seven (44.6%) patients underwent a corrective CHD operation at a median of 24 d after hemodynamic evaluation. Nine patients died, and 15 met the composite endpoint during a follow-up period of 5.4 (3.8, 8.8) years. Five-year event-free survival estimates were 96.7% (95% confidence interval: 90.3%-100%) in patients with a positive response, and 82.8% (95% confidence interval: 71.7%-94.5%) in patients with a non-positive response (log-rank P = 0.012). A positive PVRI response and higher pulmonary arterial oxygen saturation after iloprost inhalation, lower baseline brain natriuretic peptide, and PAH-targeted therapy at follow-up were significantly associated with a favorable clinical outcome. A positive acute vasoreactivity testing response and PAH-targeted therapy at follow-up were independent predictors of outcome in multivariate Cox analysis. Conclusions: Acute inhalation of iloprost can lead to a significant decrease in hemodynamic parameters. Responsiveness to inhaled iloprost is associated with better outcomes and can be a valuable predictor of outcomes.