[Risk factors for death and the clinical features of different subtypes of patients with pulmonary arterial hypertension related to congenital heart disease].

Objective: To explore the risk factors for death in patients with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD) and the clinical characteristics of different subtypes in patients with PAH-CHD. Methods: It was a retrospective study. A total of 507 PAH-CHD patients, who were hospitalized in the Department of Pediatric Cardiology of Beijing Anzhen Hospital between September 2005 and May 2019, were included. Patients were divided into 4 subgroups: (1) Eisenmenger syndrome(ES) group. (2) PAH associated with prevalent systemic-to-pulmonary shunts(SP) group. (3) PAH associated with small defects(SD) group. (4) PAH after defect correction(CD) group. According to the complexity of cardiac malformation, patients were divided into simple-medium complex malformation group and complex malformation group. According to the location of shunts, patients were divided into pre-tricuspid group, post-tricuspid group, and mixed group or complex deformity group. Baseline clinical data of patients were collected from the electronic medical record system. Demographic data (age, gender, etc.), percutaneous oxygen saturation(SPO(2)), New York Heart Association(NYHA) cardiac function classification, 6 minutes walking distance(6MWD), and B type natriuretic peptide(BNP), systolic pulmonary arterial pressure(sPAP) estimated by echocardiography and mean pulmonary artery pressure (mPAP), mean right atrial pressure(mRAP), cardiac index(CI), and calculated pulmonary vascular resistance (PVR) estimated by right heart catheterization were compared among various groups. The results of regular follow-up of all enrolled patients were collected, including the status of monotherapy or combination of PAH-targeted drugs during the follow-up period, cardiac-related adverse events(hemopysis, syncope, edema, arrhythmia, etc.) and primary endpoint event(all-cause death) were obtained and analyzed. Risk factors for all-cause death were analyzed using univariate and multivariate Cox regression analysis model. Results: The median age at diagnosis was 23.1(13.9,32.1) years, 345 cases(68.0%) were female. Two hunderds and thirty-five cases(46.4%) were diagnosed with ES; 193 cases(38.1%) were diagnosed with CD, 47 cases (9.3%) were diagnosed with SD. Among them, 32 cases(6.3%) were in the SP group. All 507 patients underwent echocardiography examination, there were significant differences in sPAP among different clinical subgroups( P< 0.001). A total of 289 patients(57.0%) received right heart catheterization examination, the results showed that the ES group had the highest mPAP and PVR and the lowest mRAP(all P< 0.001), the CD group had the highest mRAP and CI(both P< 0.001). The 6MWD in the ES group was significantly shorter than that in the SP, SD, and CD groups(all P< 0.001). The proportion of patients with NYHA class Ⅲ/Ⅳ was higher in SD group than in SP group( P< 0.001), which was similar between SD, ES and CD groups ( P values were 0.077 and 0.072, respectively). At admission, the proportion of patients with NYHA class Ⅰ/Ⅱwas the highest in SP group(96.9% (31/32) ), followed by CD group (85.5%(165/193)) and the ES group(85.1%(200/235)), and the SD group(75.0%(35/47)). The BNP level at admission was also higher in SD group than in SP, ES and CD groups( P< 0.001). Of the 507 patients, 379(74.8%) patients received PAH-targeted drug therapy at the last follow-up, and the treatment plan was mainly monotherapy(75.7%(287/379)). The median follow-up time was 3.6(2.0, 5.6) years and 37(7.3%) patients died, including 13 in the CD group, 17 in the ES group, and 7 in the SD group. No deaths occurred in the SP group. Right heart failure was the most common cause of death(11(29.7%)), followed by severe hemoptysis dyspnea(7(18.9%)), sudden cardiac death(6(16.2%)), and pulmonary hypertensive crisis(4(10.8%)). Kaplan-Meier curve showed that survival rates of end-point-free events at 1, 3, 5 and 10 years after diagnosis of PAH were 98.0%, 95.4%, 89.9%, and 84.4%, respectively; there were statistically significant differences in survival among the subgroups( P= 0.026); there was no significant difference in the survival rate between the ES group and the CD group( P= 0.918), and both were higher than the SD group( P values were 0.011 and 0.013, respectively). Univariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ and BNP > 100 ng/L at admission were the risk factors for all-cause death in patients with PAH-CHD( HR =6.452, 95 %CI 3.378-12.346, P< 0.001, and HR =2.481, 95 %CI 1.225-5.025, P= 0.012). Multivariate Cox regression analysis showed that NYHA class Ⅲ/Ⅳ was an independent risk factor for all-cause death in patients with PAH-CHD( HR =4.998, 95 %CI 1.246-20.055, P= 0.023). Conclusions: PAH-CHD patients with different clinical subtypes have different clinical symptoms, cardiac functional class, hemodynamic characteristics, and mid to long-term survival rates. SP patients have the best prognosis, outcome of ES and CD patients is similar, and SD patients have the worst prognosis. NYHA class Ⅲ/Ⅳ is an independent risk factor for all-cause death in patients with PAH-CHD.