| Part Ⅰ Reliability of noninvasive echocardiography in estimating pulmonary artery pressure in children with congenital heart diseaseObjective:To evaluate the accuracy of Doppler echocardiography(D-ECHO)with tricuspid regurgitation and left to right shunt pressure difference in assessing pulmonary artery pressure in children with congenital heart disease.Methods:We carried out a prospective study from April 2016 to April 2017 in Cardiology Department of Children’s Hospital of Chongqing Medical University to compare sPAP measurements made by D-ECHO with right heart catheterization(RHC)in 397 children with CHD.All children were without right ventricular outflow tract obstruction,pulmonary stenosis and tricuspid valve prolapse,and family history of pulmonary hypertension.For clinical perspective,PAH is classified as severe if sPAP(measured by RHC)is greater than 70mmHg,moderate if sPAP(measured by RHC)is between 46 and 70 mmHg,mild if sPAP(measured by RHC)is between 31 and 45 mmHg,and normal if sPAP(measured by RHC)is between 15 and 30 mmHg.Ventricular morphology and function were estimated by D-ECHO.Pearson correlation analyses were used to calculate the correlation coefficients between RHC and D-ECHO.Bland-Altman analyses were carried out to assess the agreement between the two methods and a ROC analysis was used to assess the accuracy of D-ECHO.Results:A total of 397 children with CHD were collected,including 167 patients with PDA,122 patients with ASD and 108 patients with VSD.There were 163 male and 234 female children with an average age of 39.8 months.Compared with RHC,D-ECHO underestimated RAP(10.5 ± 1.5 mmHg vs 13.6 ± 4.0 mmHg,p<0.01).The bias of D-ECHO estimated was 3.1 mmHg,with 95%limits of agreement ranging from-4.98 mmHg to 11.1 mmHg.ASD group:sPAP was measured by D-ECHO tricuspid regurgitation method and RHC in 117 children with ASD.A weak correlation(r = 0.328,p<0.01)was observed between sPAPduring RHC and D-ECHO.Using the Bland-Altman analysis,the bias for sPAP D-ECHO estimates was determined to be 3.7 mmHg with 95%limits of agreement ranging from17.7 mmHg to 25.1 mmHg.A total of 81(69.2%)of D-ECHO measurements were found to be accurate,with accuracy predefined as 95%of agreement within ±10 mmHg for sPAP estimates.Upon comparing sPAP measurements made using RHC versus those estimated using D-ECHO,we observed that only 34.20%of subjects were in the same diagnostic category,23.1%were in underestimation and 47.2%were in overestimation.The area under the ROC curve by ROC analysis was 0.467 for D-ECHO estimated sPAP(p>0.05).PDA tricuspid regurgitation group:sPAP was measured by D-ECHO tricuspid regurgitation method and RHC in 112 children with PDA.A weak correlation(r = 0.413,p<0.01)was observed between sPAPduring RHC and D-ECHO.Using the Bland-Altman analysis,the bias for sPAP D-ECHO estimates was determined to be 10.3 mmHg with 95%limits of agreement ranging from-22.8 mmHg to 43.4 mmHg.A total of 69(61.6%)of D-ECHO measurements were found to be accurate,with accuracy predefined as 95%of agreement within ±10 mmHg for sPAP estimates.Upon comparing sPAP measurements made using RHC versus those estimated using D-ECHO,we observed that 42.0%of subjects were in the same diagnostic category,50.9%were in underestimation and only 7.1%were in overestimation.The area under the ROC curve by ROC analysis was 0.59 for D-ECHO estimated sPAP(p>0.05).PDA left to right shunt pressure differential group:sPAP was measured by D-ECHO left to right shunt pressure differential method and RHC in 94 children with PDA.A weak correlation(r = 0.486,p<0.01)was observed between sPAPduring RHC and D-ECHO.Using the Bland-Altman analysis,the bias for sPAP D-ECHO estimates was determined to be 7.4 mmHg with 95%limits of agreement ranging from-35.1 mmHg to 49.9 mmHg.A total of 39(41.4%)of D-ECHO measurements were found to be accurate,with accuracy predefined as 95%of agreement within ±10 mmHg for sPAP estimates.Upon comparing sPAP measurements made using RHC versus those estimated using D-ECHO,we observed that 37.20%of subjects were in the same diagnostic category,43.6/%were in underestimation and 19.20%were in overestimation.The area under the ROC curve by ROC analysis was 0.61 for D-ECHO estimated sPAP(p>0.05).VSD tricuspid regurgitation group:sPAP was measured by D-ECHO tricuspid regurgitation method and RHC in 61 children with VSD.No correlation(r = 0.011,p>0.05)was observed between sPAPduring RHC and D-ECHO.A total of 35(57.3%)of D-ECHO measurements were found to be accurate,with accuracy predefined as 95%of agreement within ±10 mmHg for sPAP estimates.Upon comparing sPAP measurements made using RHC versus those estimated using D-ECHO,we observed that 39.3%of subjects were in the same diagnostic category,14.7%were in underestimation and 45.9%were in overestimation.VSD left to right shunt pressure differential group:sPAP was measured by D-ECHO left to right shunt pressure differential method and RHC in 83 children with VSD.No correlation(r = 0.175,p>0.05)was observed between sPAPduring RHC and D-ECHO.A total of 39(47.0%)of D-ECHO measurements were found to be accurate,with accuracy predefined as 95%of agreement within ±10 mmHg for sPAP estimates.Upon comparing sPAP measurements made using RHC versus those estimated using D-ECHO,we observed that 43.4%of subjects were in the same diagnostic category,22.9%were in underestimation and 33.7%were in overestimation.Conclusions:D-ECHO may provide inaccurate estimates of sPAP in childhood CHD.Part Ⅱ BMPR2/ALK1 gene mutation in idiopathic pulmonary hypertension in childrenObjective:To determine whether childhood idiopathic pulmonary arterial hypertension have mutations in activin receptor-like kinase 1 gene(ALK1)and bone morphogenetic protein receptor Ⅱ gene(BMPR2).Methods:Fourteen pediatric patients and their thirteen family members were enrolled in this study,and no consanguineous relationship among these pediatric patients.The promoters and exons of BMPR2 gene and ALK1 gene were directly sequenced,and the results were compared with the sequence of BMPR2 gene and ALK1 gene in GenBank.We also collected 106 healthy controls too.Results:A novel missense mutation,a C-to-T transition at position 77 in exon 3,which encodes a Pro 26 Leu mutation,of the ALK1 gene,was identified in a female pediatric patient with idiopathic pulmonary arterial hypertension(IPAH)but without hereditary hemorrhagic telangiectasia(HHT).No ALK1 mutation was identified in the same position in 106 healthy controls.One missense mutation of BMPR2 gene in exon 11(c.1447T>C:p.C483R)were detected in a female pediatric patient,another in exon 5(c.621+8T>C)were detected in a male patient’ s mother,and the last one in exon 10(c.1322G>A:p.G441E)were detected in a female patient’s mother.All the three missense mutations have been reported.Conclusions:A missense mutation in exon 3 of ALK1 gene was first discovered in pediatric patients with IPAH.The new missense mutation may be responsible for the development of idiopathic pulmonary arterial hypertension. |
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