Prenatal Prediction Of Coarctation Of The Aorta By Myocardial Strain And Development Of A Diagnostic Model

Part 1 Quantitative Evaluation of Cardiac Morphology and Function in Fetuses with Coarctation of the Aorta by Echocardiography Objective: This study aimed to evaluate changes of cardiac morphology and function in fetuses with coarctation of the aorta(CoA)using fetal heart quantitative technique(Fetal HQ).Methods: A total of 67 fetuses with postnatally confirmed CoA and 67 gestational age(GA)-matched normal controls were included between January 2019 and December 2021 in a single tertiary referral center.Conventional fetal echocardiographic measurements,including atrial and ventricular diameters,great arterial dimensions and flow characteristics were obtained.In all fetuses,a standard four-chamber view(4CV)cine loop was obtained and Fetal HQ technique was used to analyse cardiac morphological parameters,including4 CV end-diastolic(ED)transverse width,length,area,global and left(LV)/right ventricular(RV)24-segment sphericity index(SI),and LV/RV 24-segment ED diameter(EDD).Twodimensional speckle tracking analysis of 4CV was performed to compute following ventricular functional parameters:(1)LV and RV fractional area change(FAC);(2)LV and RV global longitudinal strain(GLS);(3)LV and RV 24-segment transverse fractional shortening(FS);(4)LV ejection fraction(LVEF),LV ED volume(LVEDV),LV stroke volume(LVSV)and LV output(LVO).The conventional echocardiographic and Fetal HQ parameters of CoA fetuses were compared with normal controls.Correlation analysis was preformed to explore the influencing factors of ventricular function in CoA fetuses.Results:(1)Comparisons of conventional echocardiographic parameters between CoA fetuses and controls:1)Left heart parameters: Compared with control group,the Z-scores of left arial diameter(LAD),LA area(LAA),LV basal transverse width(LVBTW),LV area(LVA),mitral valve (MV)annular diameter,aortic valve(AV)annular diameter and ascending aorta(AAo)diameter were significantly decreased(all P < 0.001),while LVSI was increased in CoA fetuses(P < 0.001).There was no significant difference in LV basal-apical length(LVBAL)Z-score between two groups(P > 0.05).2)Right heart parameters: Compared with control group,CoA fetuses presented increased Z-scores of right atrial diameter(RAD),RA area(RAA),RV basal transverse width(RVBTW),RV area(RVA),tricuspid valve(TV)annular diameter,pulmonary valve(PV)annular diameter,main pulmonary artery(MPA)diameter and ductus arteriosus(DA)diameter(all P < 0.05),but decreased RVSI(P < 0.001).No significant difference in RVBAL Z-score was found between two groups(P > 0.05).3)Right-to-left dimensional ratios: RAD/LAD,RAA/LAA,RVBTW/LVBTW,RVA/LVA,TV/MV,PV/AV and MPA/AAo ratios were significantly increased in CoA fetuses compared with control group(all P < 0.001).RVBAL/LVBAL did not differ between two groups(P >0.05).4)Hemodynamic parameters: CoA fetuses displayed lower aortic peak systolic velocity(PSV)(P = 0.038)but similar pulmonary PSV(P > 0.05)compared with controls.(2)Comparisons of cardiac morphological parameters derived by Fetal HQ between CoA fetuses and controls:1)Global cardiac parameters: Compared with normal controls,the Z-score of 4CV ED transverse width was increased(P = 0.007),while the GSI was decreased(P < 0.001)in fetuses with CoA.However,there were no significant differences in the Z-scores of 4CV ED length and area between two groups(both P > 0.05).2)Ventricular segmental parameters: The RV 24-segment EDD Z-scores as well as the RV/LV 24-segment EDD ratios were significantly higher in CoA fetuses than in controls(all P < 0.01).In contrast,the LV 24-segment EDD Z-scores were significantly lower in fetuses with CoA(all P < 0.001).The 24-segment SIs of the LV were significantly higher(all P < 0.001),while the 24-segment SIs of the RV were significantly lower in CoA group(all P < 0.001).(3)Comparisons of ventricular functional parameters derived by Fetal HQ between CoA fetuses and controls:CoA fetuses presented lower GLS,FAC and 24-segment FSs for both RV and LV when compared with normal controls(all P < 0.05).In addition,LVEF,LVEDV Z-score,LVSV Z-score and LVO Z-score were all decreased in CoA fetuses(all P < 0.001).(4)Correlation analysis of ventricular functional parameters with other parameters:1)In fetuses with CoA,LVFAC,LVEF and the absolute value of LVGLS were positively correlated with LAD Z-score,LVBTW Z-score,LVA Z-score,MV Z-score,LVEDV Z-score,LVSV Z-score and LVO Z-score(all P < 0.05),while negatively correlated with LVSI,RVBTW/LVBTW,TV/MV and RVA/LVA(all P < 0.05).2)RV functional parameters(RVFAC and the absolute value of RVGLS)showed positive correlations with MV Z-score,LVFAC and the absolute value of LVGLS in CoA fetuses(all P < 0.05).Conclusions: In CoA fetuses,the 4CV was increased in width and spherical in shape.The LV area and width were decreased,while the transverse width and area of the RV was increased.Abnormal SIs suggested a flatter LV and a more spherical RV.RV and LV global,transverse,and longitudinal contractility were all depressed.LV and RV functional parameters were correlated with left heart morphological changes in CoA fetuses.Part 2 Prenatal Prediction of Coarctation of the Aorta by Myocardial Strain and Development of a Diagnostic ModelObjective: Accurate prenatal diagnosis of coarctation of the aorta(CoA)remains challenging,with high false-positive and false-negative rates.The objective of this study was to investigate the diagnostic value of left ventricular(LV)myocardial deformation and develop a multi-parametric model to improve the diagnostic accuracy of fetal CoA.Methods: A retrospective study was conducted in 122 fetuses with suspected CoA who also had postnatal follow-ups between January 2016 and June 2020.Fetuses with confirmed diagnosis of CoA by postnatal echocardiographic,computed tomographic angiographic or surgical results were defined as CoA group,and Non-CoA group were those false-positives.Conventional fetal echocardiographic measurements,including atrial and atrioventricular valve annular diameters,great arterial dimensions and hemodynamic parameters were obtained.LV morphological and functional parameters,including LV basal transverse width,LV end-diastolic volume,LV global longitudinal strain(LVGLS),LV ejection fraction and LV fractional area change,were determined using two-dimensional speckle tracking echocardiography in four-chamber view of the fetal heart by fetal heart quantitative technique(Fetal HQ).These parameters were compared between CoA and Non-CoA group.The diagnostic values of echocardiographic parameters were evaluated using receiver operating characteristic(ROC)analysis and the area under curve(AUC).Diagnostic performance was assessed by calculating optimal cutoff values(maximum Youden index),sensitivity and specificity.Univariate and multivariate Logistic regression analyses were performed to identify the best predictors of postnatal CoA and establish multi-parametric diagnostic models.The model was validated prospectively by a validation cohort of 48 fetuses.Results:(1)CoA was confirmed in 62/122(50.8%)cases after birth,and the other 60 cases(49.2%)were false-positives.Fetuses with postnatal CoA were diagnosed significantly earlier than false-positives(median(interquartile range),24.5(23.3-26.4)vs.27.8(24.5-30.4)weeks;P < 0.001).(2)The Z-scores of aortic dimensions(aortic valve annulus,ascending aorta,transverse aortic arch and aortic isthmus(AOI))were significantly smaller(all P < 0.001),while the Z-scores of pulmonary dimensions(pulmonary valve annulus and main pulmonary artery)were significantly greater(all P < 0.05),in cases of confirmed CoA than false-positives.(3)Compared with Non-CoA group,CoA group displayed lower Z-scores for LV basal transverse width(P = 0.037)and LV end-diastolic volume(P = 0.043),LV ejection fraction(P = 0.005),LV fractional area change(P < 0.001)and LVGLS(P < 0.001).(4)ROC analysis demonstrated LVGLS had the maximal AUC of 0.85(95% CI,0.78-0.92)for postnatal CoA,and the best cut-off value was-19.93%,with a sensitivity of 90% and a specificity of 68%.(5)A multivariate logistic regression model incorporating gestational age(GA)at diagnosis(odds ratio(OR): 0.74,95% CI: 0.60-0.88;P = 0.001),AOI Z-score(OR: 0.20,95% CI: 0.08-0.41;P < 0.001)and LVGLS(OR: 1.79,95% CI: 1.41-2.42;P < 0.001)was established to diagnose CoA more accurately(Akaike information criterion: 81.77,Bayesian information criterion: 92.98,C-statistics: 0.945).Fetuses with CoA probability < 20% were classified at low risk,between 20% and 60% at moderate risk,and > 60% at high risk for postnatal CoA.The performance of this model was confirmed prospectively in the validation cohort(C-statistics: 0.943).Conclusions: In fetuses with suspected CoA,speckle tracking analysis of LVGLS may help to predict postnatal CoA.The multi-parametric diagnostic model,including GA at diagnosis,AOI Z-score and LVGLS,may provide a good tool for the stratification of the risk in fetal CoA and contribute to patient-specific perinatal management.