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·m^(2)(P<0.001).A total of 38(45.8%)patients had a positive response,defined as a PVRl decrease>25%with stable systemic pressure.Thirtyseven(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 PVRl 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.

Clinical Study of Acute Vasoreactivity Testing in Patients with Chronic Thromboembolic Pulmonary Hypertension

Background： The clinical significance of acute vasoreactivity testing （AVT） in patients with chronic thromboembolic pulmonary hypertension （CTEPH） remains unclear. We analyzed changes in hemodynamics and oxygenation dynamics indices after AVT in patients with CTEPH using patients with pulmonary arterial hypertension （PAH） as controls. Methods： We analyzed retrospectively the results of AVT in 80 patients with PAH and 175 patients with CTEPH registered in the research database of Beijing Chao-Yang Hospital between October 2005 and August 2014. Demographic variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. A long-term follow-up was conducted in patients with CTEPH. Between-group comparisons were performed using the independent-sample t-test or the rank sum test, within-group comparisons were conducted using the paired t-test or the Wilcoxon signed-rank test, and count data were analyzed using the Chi-squared test. Survival was estimated using the Kaplan-Meier method and log-rank test. Results： The rates of positive response to AVT were similar in the CTEPH （25/175, 14.3%） and PAH （9/80, 11.3%） groups （P 〉 0.05）. Factors significantly associated a positive response to AVT in the CTEPH group were level of N-terminal pro-brain natriuretic peptide （〈1131.000 ng/L）, mean pulmonary arterial pressure （mPAE ≤44.500 mmHg）, pulmonary vascular resistance （PVR, 〈846.500 dyn＇s-1·m-5）, cardiac output （CO,≥3.475 L/rain）, and mixed venous oxygen partial pressure （PvO2, ≥35.150 mmHg）. Inhalation of iloprost resulted in similar changes in mean blood pressure, mPAE PVR, systemic vascular resistance, CO, arterial oxygen saturation （SaO2）, mixed venous oxygen saturation, partial pressure of oxygen in arterial blood （PaO2）, PvO2, and intrapulmonary shunt （Qs/Qt） in the PAH and CTEPH groups （all P 〉 0.05）. The survival time in patients with CTEPH with a negative response to AVT was somewhat shorter than that in AVT-responders although the difference was not statistically significant （X2= 3,613, P = 0.057）. The survival time of patients with CTEPH who received calcium channel blockers （CCBs） was longer than that in the group with only basic treatment and not shorter than that of patients who receiving targeted drugs or underwent pulmonary endarterectomy （PEA） although there was no significant difference between the four different treatment regimens （X2 = 3.069, P = 0.381 ）. Conclusions： The rates of positive response to AVT were similar in the CTEPH and PAH groups, and iloprost inhalation induced similar changes in hemodynamics and oxygenation dynamics indices. A positive response to AVT in the CTEPH group was significantly correlated with milder disease and better survival. Patients with CTEPH who cannot undergo PEA or receive targeted therapy but have a positive response to AVT might benefit from CCB treatment.