From July 2012 until July 2019, we have registered data from 1012 patients who have the confirmed diagnosis as septal defects/shunts CHD. The clinical characteristics of the patients are shown in Table 1.The mean age of the patients at first diagnosis/enrollment is 34.7 years. The majority of patients are females, which accounted for 78.5% of all patients (as shown in Figure 2). Normal and underweight body mass categories are predominant. Mean peripheral oxygen saturation is 95.5%. The WHO functional class is predominantly class II (43.0% of patients), only the minority of patients have worse WHO functional class (10.0% class III and 1.1% class IV). The mean 6-minute walking distance was 356.5 meters.The increased probability of PH by TTE examination is predominant (77.1 %).The signs of Eisenmenger syndrome are encountered in 18.7% of patients. The laboratory results show mean hemoglobin level is 13.8 g/dL, hematocrit 41.9% and median NTproBNP level 370.9 pg/mL. The main symptoms are dyspnea on effort (35.9%), easily fatigued (16.3%), chest pain/discomfort (10.8 %) and palpitations (9.3 %). As many as 9.4% of patients did not report any symptoms during first enrollment.The main symptoms of patients are depicted in Figure 3.
The majority of CHD type is secundum ASD (73.4%). Other CHD types are perimembranous VSD (9.0%), PDA(5.8%), doubly-committed subarterial (DCSA) VSD (3.6%), sinus venosus ASD (2.0%), primum ASD (1.3%), PFO (0.8%), AVSD (0.3%) and AP window (0.1%). The patients with multiple defects account for 0.9% of all patients. The majority of patients have undergone RA and RV dilatation, with mean RA diameter of 45.6 mm and RV diameter of 42.1 mm. The mean mPAP based on TTE examination is 36.1 mmHg. The mean tricuspid valve regurgitation gradient is 61.6 mmHg.The mean tricuspid annular plane systolic excursion is 24.3 mm.The mean left ventricle ejection fraction is 68.1%. Table 2 shows the results of TTE and TOE procedures.
The RHC has been performed in 614 subjects (60.7%). Among 1012 patients, 103 patients did not undergo RHC examination and 295 patients are on awaiting list to get RHC performed. The RHC was not performed in103 patients due to: (1) patients have already had closure of defects (24 patients), (2) patients died before scheduled for RHC (39 patients), (3) patients refused the RHC examination (n=10) and (4) patients didnot respond to RHC schedule (30 patients). Patients who did not undergo RHC examination were mostly lost to follow-up from COHARD-PH registry and did not continue regular visits to our hospital. Patients who are on awaiting list are managed based on clinical symptoms and probability of PH based on echocardiography signs. The RHC results confirm that 411 patients (66.9%) have developed PAH.The hemodynamics data from RHC shows median mPAP of 34.0 mmHg, PVRi of 3.3 Wood Unit.m2, PCWP of 10.0 mmHg, flow ratio of 2.3 and Qp/Qs of 1.1. The vasoreactivity test was performed in 186 patients and indicated that 43 patients (23.1%) have vasoreactive response. As many as 363 patients (59.1%) have correctable criteria for defect closure. Table 3 shows the result of RHC procedure.
Table 4 shows the comparison of clinical and laboratory parameters between patients with CHD-related PAH and those without PAH. Patients with PAH had significantly older age at first diagnosis (36.4±12.9 vs. 32.2±12.0 years old, p<0.001), lower peripheral oxygen saturation (94.8±5.5 vs. 97.4±3.2 %, p <0.001), lower 6-minute walking distance (336.3±99.7 vs. 393.9±82.1 meters, p<0.001), worse WHO functional class (WHO III-IV: 14.2% vs. 5.0%, p<0.001), higher hemoglobin level (14.1±2.2 vs. 13.5±1.9 g/dL, p=0.006), higher hematocrit level (42.2±6.5 vs. 40.2±4.9 %, p<0.001) and higher NTproBNP level (median: 774.0 vs. 121.5 pg/mL, p<0.001). The proportion of ASD is predominant in patients with PAH (89.3 %), followed by PDA (5.1%) and VSD (4.1%). Among the patients with multiple defects, the majority have developed PAH (4 of 5 patients) and all subjects with AP window and AVSD have PAH.Multivariable analysis shows that only NTproBNP level independently predicts the PAH in patients with CHD (OR 1.002, 95%CI: 1.001-1.004, p=0.001), as shown in Table 5.
Table 6 shows the difference of characteristics among patients based on WHO functional class (total amount 602 patients). Worse WHO functional class (class III-IV) is marked by the least peripheral oxygen saturation, the least 6-minute walk distance and the highest NTproBNP level. Based on echocardiography examination, worse WHO functional class is associated with increased mPAP, higher TVRG, larger RA and RV diameters, lower TAPSE and lower LVEF. Based on RHC results, worse WHO functional class is related with higher mPAP and increased PVRi. The ASD patients are the majority among those with worse WHO functional class (95.5%).
The predominance of ASD patients in the COHARD-PH registry is in accord with previous reports. The development of PAH in ASD patients may be associated with defect size and shunt flow. We analysed the difference of minimal and maximal diameter of ASD defect based on echocardiography examination between ASD patients with PAH and those with no PAH. The ASD patients with PAH have larger minimal defect diameter as compared to those without PAH (2.3±0.8 vs. 1.9±1.5 cm, p<0.001) and larger maximal defect diameter (2.6±0.9 vs. 2.2±1.8 cm, p=0.001) (as shown in Figure 4). There was no significant difference in the Qp/Qs ratio based on echocardiography and RHC results between ASD patients with PAH and those without PAH (as shown in Figure 5).
There is an incremental increase of the proportion of PAH according to age range, with the highest proportion of PAH in the age group between 51 and 60 years old (Table 7).