Comparison of 2D versus M-mode echocardiography for assessing fetal myocardial wall thickness

OBJECTIVE: M-mode and 2D have been proposed for evaluating fetal myocardial thickness. However, studies comparing the performance of both modalities are lacking. We aimed to compare 2D versus M-mode reproducibility for assessing myocardial wall thicknesses. METHODS: A prospective study including 45 healthy fetuses from low-risk pregnancies evaluated between 18 and 41 weeks of gestation. Left and right ventricular free-wall and septal myocardial thicknesses were measured at end-diastole (ED) and end-systole (ES) in transverse 4-chamber view using 2D and M-mode. Intra- and interobserver reproducibility was evaluated by the concordance correlation coefficient (CCC). Both techniques were compared by t-test of the CCC. RESULTS: 2D and M-mode demonstrated excellent and similar intraobserver repeatability, with the best concordance in ES septal thickness (M-mode CCC 0.956 versus 2D-mode CCC 0.914). Interobserver reproducibility demonstrated also a high concordance, optimal in ES left ventricular free wall (M-mode 0.925 versus 2 D 0.855). Comparison of both techniques demonstrated a high concordance in all measurements, except for ED septal thickness with better reproducibility using M-mode (CCC 0.954 versus 0.847, p = .017). CONCLUSIONS: 2D and M-mode can be used in a reproducible manner for measuring fetal myocardial thickness, with a slightly better performance of M-mode for assessing ED septal wall thickness

Cord blood cardiovascular biomarkers in left-sided congenital heart disease.

Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013-2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4-3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β (normal heart median 15.5 ng/mL (6.8-21.4) vs. favorable outcome 51.7 ng/mL (13.8-73.9) vs. poor outcome 25.1 ng/mL (6.9-39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8-23.9) vs. favorable outcome 12.8 pg/mL (11.7-13.6) vs. poor outcome 11.0 pg/mL (8.8-15.4), p < 0.001). Poor outcome left heart defects had higher N-terminal precursor of B-type natriuretic peptide (normal heart 508.0 pg/mL (287.5-776.3) vs. favorable outcome 617.0 pg/mL (389.8-1087.8) vs. poor outcome 1450.0 pg/mL (919.0-1645.0), p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3-2715.8) vs. favorable outcome (1848.3 pg/mL (646.9-2313.6) vs. poor outcome 259.0 pg/mL (182.0-606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome

Assessment of haemodynamic remodeling in fetal aortic coarctation using a lumped model of the circulation

Comunicació presentada a: the 9th International Conference Functional Imaging and Modelling of the Heart FIMH 2017, celebrat de l'11 al 13 de juny de 2017 a Toronto, Canadà.Aortic coarctation is one of the most difficult cardiac defects to diagnose before birth, and it accounts for 8% of congenital heart diseases. Antenatal diagnosis is crucial for early treatment of the neonate and to decrease the risk of morbidity and mortality; however the fetal hemodynamic changes are not fully understood and current imaging methods are limited to accurately diagnosis this congenital defect. Objective: We propose to use a lumped model of the fetal circulation to provide insights into the hemodynamic changes in fetuses with aortic coarctation, and thus helping to improve its diagnosis. Methods: To achieve this goal a patient-specific lumped model of the fetal circulation was implemented in OpenCOR, including the modeling of different types and degrees of aortic coarctation. A parametric study of degree and type of coarctation was performed, where blood flow distribution, cerebroplacental ratio, pressure drop over the coarctation and left ventricular pressure were quantified. Results: Obvious changes in the fetal hemodynamics were observed only from 80% of coarctation, corresponding to the clinically used cutoff for pressure drop of 20 mmHg. Furthermore, the observed hemodynamic changes were different depending on the location and degree of the coarctation.This study was partially supported by the Spanish Ministry of Economy and Competitiveness (grant TIN2014-52923-R; Maria de Maeztu Units of Excellence Programme - MDM-2015-0502), FEDER and the European Union Horizon 2020 Programme for Research and Innovation, under grant agreement No. 642676 (CardioFunXion)

Assessment of haemodynamic remodeling in fetal aortic coarctation using a lumped model of the circulation

Comunicació presentada a: the 9th International Conference Functional Imaging and Modelling of the Heart FIMH 2017, celebrat de l'11 al 13 de juny de 2017 a Toronto, Canadà.Introduction: Aortic coarctation is one of the most difficult cardiac defects to diagnose before birth, and it accounts for 8% of congenital heart diseases. Antenatal diagnosis is crucial for early treatment of the neonate and to decrease the risk of morbidity and mortality; however the fetal hemodynamic changes are not fully understood and current imaging methods are limited to accurately diagnosis this congenital defect. Objective: We propose to use a lumped model of the fetal circulation to provide insights into the hemodynamic changes in fetuses with aortic coarctation, and thus helping to improve its diagnosis. Methods: To achieve this goal a patient-specific lumped model of the fetal circulation was implemented in OpenCOR, including the modeling of different types and degrees of aortic coarctation. A parametric study of degree and type of coarctation was performed, where blood flow distribution, cerebroplacental ratio, pressure drop over the coarctation and left ventricular pressure were quantified. Results: Obvious changes in the fetal hemodynamics were observed only from 80% of coarctation, corresponding to the clinically used cutoff for pressure drop of 20 mmHg. Furthermore, the observed hemodynamic changes were different depending on the location and degree of the coarctation.This study was partially supported by the Spanish Ministry of Economy and Competitiveness (grant TIN2014-52923-R; Maria de Maeztu Units of Excellence Programme - MDM-2015-0502), FEDER and the European Union Horizon 2020 Programme for Research and Innovation, under grant agreement No. 642676 (CardioFunXion)

Comparison of 2D versus M-mode echocardiography for assessing fetal myocardial wall thickness

OBJECTIVE: M-mode and 2D have been proposed for evaluating fetal myocardial thickness. However, studies comparing the performance of both modalities are lacking. We aimed to compare 2D versus M-mode reproducibility for assessing myocardial wall thicknesses. METHODS: A prospective study including 45 healthy fetuses from low-risk pregnancies evaluated between 18 and 41 weeks of gestation. Left and right ventricular free-wall and septal myocardial thicknesses were measured at end-diastole (ED) and end-systole (ES) in transverse 4-chamber view using 2D and M-mode. Intra- and interobserver reproducibility was evaluated by the concordance correlation coefficient (CCC). Both techniques were compared by t-test of the CCC. RESULTS: 2D and M-mode demonstrated excellent and similar intraobserver repeatability, with the best concordance in ES septal thickness (M-mode CCC 0.956 versus 2D-mode CCC 0.914). Interobserver reproducibility demonstrated also a high concordance, optimal in ES left ventricular free wall (M-mode 0.925 versus 2 D 0.855). Comparison of both techniques demonstrated a high concordance in all measurements, except for ED septal thickness with better reproducibility using M-mode (CCC 0.954 versus 0.847, p = .017). CONCLUSIONS: 2D and M-mode can be used in a reproducible manner for measuring fetal myocardial thickness, with a slightly better performance of M-mode for assessing ED septal wall thickness

Nomograms of Fetal Right Ventricular Fractional Area Change by 2D Echocardiography

Objectives: Fetal right ventricular (RV) function assessment is challenging due to the RV geometry and limitations of in utero assessment. Postnatally, 2D echocardiographic RV fractional area change (FAC) is used to assess RV global systolic function by calculating the percentage of change in RV area from systole to diastole. Reports on FAC are scarce in prenatal life, and nomograms throughout pregnancy are not available. Our aims were (1) to study prenatal RV FAC feasibility and reproducibility and (2) to construct nomograms for RV FAC and end-diastolic (ED) and end-systolic (ES) RV areas from 18 to 41 weeks of gestation. Methods: Prospective cohort study including 602 low-risk singleton pregnancies undergoing a fetal echocardiography from 18 to 41 weeks of gestation. RV ED and ES areas were measured following standard recommendations for ventricular dimensions and establishing strict landmarks to identify the different phases of the cardiac cycle. RV FAC was calculated as: ([ED area - ES area]/ED area) x 100. RV FAC intra- and inter-observer reproducibility was evaluated in 45 fetuses by calculating the intraclass correlation coefficient (ICC). Parametric regressions were tested to model each parameter against gestational age (GA) and estimated fetal weight (EFW). Results: RV areas and FAC were successfully obtained in similar to 99% of fetuses with acceptable reproducibility throughout gestation (RV ED area inter-observer ICC [95% CI] 0.96 [0.93-0.98], RV ES area 0.97 [0.94-0.98], and FAC 0.69 [0.44-0.83]). Nomograms were constructed for RV ED and ES areas and FAC. RV areas showed a quadratic and logarithmic increase with GA and EFW, respectively. In contrast, RV FAC showed a slight quadratic decrease throughout gestation (mean RV FAC ranged from 36% at 18 weeks of gestation [10-90th centiles: 25-47%, respectively] to 29% at 41 weeks [10-90th centiles: 18-40%, respectively]). The best models for RV areas and FAC were a second-degree polynomial. Conclusions: RV FAC is a feasible and reproducible parameter to assess RV global systolic function in fetal life. We provide reference ranges adjusted by GA and EFW that can be used as normal references for the assessment of RV function in prenatal conditions.European Union (EU) 2013-0040 Hospital Clinic de Barcelona (Ajut Josep Font, Barcelona, Spain) La Caixa Foundation LCF/PR/GN14/10270005 LCF/PR/GN18/10310003 Instituto de Salud Carlos III PI14/00226 PI15/00263 PI15/00130 INT16/00168 PI17/00675 integrados en el Plan Nacional de I+D+I y cofinanciados por el ISCIII-Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional "Una manera de hacer Europa" Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK) AGAUR 2017 SGR grant 1531 Agencia de Gestio D'Ajuts Universitaris de Recerca Agaur (AGAUR) 2016FI_B01184 La Caixa Foundation AGAUR 2014 SGR grant 928 Instituto de Salud Carlos III PI14/00226 PI15/00263 PI15/00130 INT16/00168 ISCIII-Subdireccion General de Evaluacion y el Fondo Europeo de Desarrollo Regional "Otra manera de hacer Europa" (Spain

Cord Blood Cardiovascular Biomarkers in Left-Sided Congenital Heart Disease

Fetal echocardiography has limited prognostic ability in the evaluation of left-sided congenital heart defects (left heart defects). Cord blood cardiovascular biomarkers could improve the prognostic evaluation of left heart defects. A multicenter prospective cohort (2013–2019) including fetuses with left heart defects (aortic coarctation, aortic stenosis, hypoplastic left heart, and multilevel obstruction (complex left heart defects) subdivided according to their outcome (favorable vs. poor), and control fetuses were evaluated in the third trimester of pregnancy at three referral centers in Spain. Poor outcome was defined as univentricular palliation, heart transplant, or death. Cord blood concentrations of N-terminal precursor of B-type natriuretic peptide, Troponin I, transforming growth factor β, placental growth factor, and soluble fms-like tyrosine kinase-1 were determined. A total of 45 fetuses with left heart defects (29 favorable and 16 poor outcomes) and 35 normal fetuses were included, with a median follow-up of 3.1 years (interquartile range 1.4–3.9). Left heart defects with favorable outcome showed markedly increased cord blood transforming growth factor β (normal heart median 15.5 ng/mL (6.8–21.4) vs. favorable outcome 51.7 ng/mL (13.8–73.9) vs. poor outcome 25.1 ng/mL (6.9–39.0), p = 0.001) and decreased placental growth factor concentrations (normal heart 17.9 pg/mL (13.8–23.9) vs. favorable outcome 12.8 pg/mL (11.7–13.6) vs. poor outcome 11.0 pg/mL (8.8–15.4), p p = 0.001) and drastically reduced soluble fms-like tyrosine kinase-1 concentrations (normal heart 1929.7 pg/mL (1364.3–2715.8) vs. favorable outcome (1848.3 pg/mL (646.9–2313.6) vs. poor outcome 259.0 pg/mL (182.0–606.0), p < 0.001). Results showed that fetuses with left heart defects present a distinct cord blood biomarker profile according to their outcome

Nomograms of Fetal Cardiac Dimensions at 18-41 Weeks of Gestation

OBJECTIVE: There is a need for standardized reference values for cardiac dimensions in prenatal life. The objective of the present study was to construct nomograms for fetal cardiac dimensions using a well-defined echocardiographic methodology in a low-risk population. METHODS: This is a prospective cohort study including 602 low-risk singleton pregnancies undergoing a standardized fetal echocardiography to accurately assess fetal cardiac, ventricular, and atrial dimensions. Parametric regressions were tested to model each measurement against gestational age from 18 to 41 weeks of gestation. RESULTS: Nomograms were constructed for fetal cardiac dimensions (transverse and longitudinal diameters and areas) of the whole heart, atria, and ventricles, as well as myocardial wall thicknesses. All dimensions showed a progressive increase with gestational age. The best model for most parameters was a second-degree linear polynomial. Fetal cardiac, ventricular, and atrial diameters and areas were successfully obtained in 98.6% of the fetuses, while myocardial wall thicknesses could be obtained in 96.5% of the population. The results showed excellent interobserver and intraobserver reproducibility (intraclass correlation coefficient, ICC > 0.811 and ICC > 0.957, respectively). CONCLUSIONS: We provide standardized and comprehensively evaluated reference values for fetal cardiac morphometric parameters across gestation in a low-risk population. These no mograms would enable the early identification of different patterns of fetal cardiac remodeling