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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/209727
New modalities to evaluate cardiovascular remodeling in fetuses with congenital heart defects
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[eng] Introduction
Congenital heart defects are the most common severe congenital malformations. Since prenatal diagnosis is optimal, current research focuses on studying cardiovascular remodeling to improve prognostic evaluation before birth. Remodeling involves subtle changes that are difficult to identify using standard echocardiography, so the use of advanced techniques, such as speckle tracking echocardiography, allows for the study of more sensitive parameters such as myocardial strain. There are biomarkers of cardiovascular remodeling: B-type natriuretic peptide (marker of cardiac dysfunction), Troponin I (marker of myocardial injury), transforming growth factor β (cytokine secreted in response to pressure or volume overload), placental growth factor and its soluble receptor (sFlt-1) (vascular endothelial growth factors), which can be studied in umbilical cord blood and could provide complementary information to echocardiography.
Hypothesis
1. Speckle tracking echocardiography is an applicable tool to evaluate cardiovascular remodeling (cardiac morphometric and functional changes) in normal fetal heart.
2. Speckle tracking echocardiography in combination with conventional echocardiography allows to accurately evaluate the cardiovascular remodeling pattern associated with congenital heart defects in the prenatal stage.
3. Congenital heart defects are associated to specific patterns of blood cord cardiovascular biomarkers and angiogenic factors which correlate with echocardiographic parameters.
4. The incorporation of speckle tracking echocardiography in fetal life improves the prognostic evaluation of congenital heart defects.
Objectives
1. To demonstrate the applicability of speckle tracking echocardiography for the evaluation of morphometric and functional parameters in fetal life in a cohort of healthy fetuses.
2. To validate the applicability of morphometric and functional evaluation by speckle tracking echocardiography in fetuses with severe congenital heart defects.
3. To define the pattern of umbilical cord blood cardiovascular biomarkers and angiogenic factors in different congenital heart defects and to evaluate its potential correlation with echocardiographic parameters.
4. To validate the clinical applicability and prognostic utility of speckle tracking echocardiography in fetuses with congenital heart defects.
Methods
Four prospective cohort studies were designed with the inclusion of pregnant women followed at BCNatal (Hospital Clínic de Barcelona and Hospital Sant Joan de Déu).
Study 1: 31 low-risk pregnant women. Two-dimensional clips and four-dimensional volumes-STIC (spatio-temporal image correlation) from the four-chamber view were obtained. Speckle tracking echocardiography was performed to assess its reproducibility using the intraclass correlation coefficient.
Study 2: 24 fetuses with pulmonary stenosis and 48 controls. At the diagnosis of pulmonary stenosis, echocardiography and speckle tracking echocardiography were performed. Echocardiographic parameters were analyzed based on the need for neonatal valvuloplasty to identify predictors of early intervention.
Study 3: 22 Tetralogy of Fallot cases, 12 cases of D-transposition of the great arteries, and 36 controls. Echocardiography was performed in the third trimester of gestation. Umbilical cord blood samples were obtained at birth to determine the concentrations of cardiovascular biomarkers.
Study 4: 63 fetuses with Tetralogy of Fallot and 66 controls. Two-dimensional echocardiography and speckle tracking echocardiography were performed in the third trimester of gestation. Morphometric and functional parameters were evaluated to define the pattern of cardiovascular remodeling.
Main results
In Study 1, excellent reproducibility was demonstrated for overall morphometric cardiac evaluation, as well as good reproducibility for functional assessment. However, segmental cardiac evaluation showed poor reproducibility.
In Study 2, fetuses with critical pulmonary stenosis exhibited a deterioration in right ventricular function. Those undergoing neonatal valvuloplasty (50%) showed worse right ventricular function. A multiparametric scoring system was described for predicting neonatal valvuloplasty, combining the percentile of pulsatility index of the ductus venosus, global longitudinal strain of the right ventricle, presence of reverse flow in the ductus arteriosus, and significant tricuspid regurgitation, with a sensitivity of 91.7% and specificity of 100%.
Study 3 demonstrated an increase in transforming growth factor β in cord blood of fetuses with Tetralogy of Fallot compared to normal hearts (24.9 ng/mL (15.6-45.3) vs. normal heart 15.7 ng/mL (7.2-24.3) vs. D-transposition of the great arteries 12.6 ng/mL (8.7-37.9); p = 0.012). Transforming growth factor β levels showed a negative correlation with the z-score of pulmonary valve diameter (r=-0.576, p=0.039).
Study 4 showed signs of cardiac remodeling in fetuses with Tetralogy of Fallot, including a decrease in diastolic cardiac function (increased filling time fraction) and systolic function (global strain of the right ventricle (Tetralogy of Fallot: 17.25 ± 3.76 vs controls: 19.33 ± 3.09; p= 0.001) and left ventricle (Tetralogy of Fallot: -17.96 ± 3.78 vs controls: -20.87 ± 3.45; p= 0<.001)). This decrease in biventricular function correlates with mechanical dyssynchrony.
Conclusions
1. 4 dimension - Spatio Temporal Image Correlation speckle tracking echocardiography is feasible, reproducible and comparable to 2-dimensional echocardiography for the assessment of cardiac morphometry and function in healthy fetuses (Study 1).
2. Decreased right ventricle deformation is observed in critical pulmonary stenosis fetuses, and correlates with mechanical dyssynchrony. A scoring system combining the ductus venosus pulsatility index centile and right ventricle global longitudinal strain; with the presence of reversed ductus arteriosus flow and significant tricuspid regurgitation, enables to identify those fetuses in need of early neonatal valvuloplasty, who will thus benefit from an early neonatal assessment by pediatric cardiologists (Study 2).
3. Tetralogy of Fallot fetuses show increased cord blood transforming growth factor-β concentrations when compared to D-transposition of the great arteries and normal fetuses. Moreover, transforming growth factor-β levels correlate with the severity of right ventricle outflow obstruction (Study 3).
4. Fetuses with tetralogy of Fallot present signs of cardiovascular remodeling from prenatal life, characterized by a more spherical heart with biventricular concentric hypertrophy. Additionally, morphometric changes are associated with both, biventricular diastolic dysfunction and decreased contractility, which correlates with the presence of mechanical dyssynchrony (Study 4).
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NOGUÉ I GARRIGOLAS, Laura. New modalities to evaluate cardiovascular remodeling in fetuses with congenital heart defects. [consulta: 15 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/209727]