Machine Learning in Fetal Cardiology: What to Expect

In fetal cardiology, imaging (especially echocardiography) has demonstrated to help in the diagnosis and monitoring of fetuses with a compromised cardiovascular system potentially associated with several fetal conditions. Different ultrasound approaches are currently used to evaluate fetal cardiac structure and function, including conventional 2-D imaging and M-mode and tissue Doppler imaging among others. However, assessment of the fetal heart is still challenging mainly due to involuntary movements of the fetus, the small size of the heart, and the lack of expertise in fetal echocardiography of some sonographers. Therefore, the use of new technologies to improve the primary acquired images, to help extract measurements, or to aid in the diagnosis of cardiac abnormalities is of great importance for optimal assessment of the fetal heart. Machine leaning (ML) is a computer science discipline focused on teaching a computer to perform tasks with specific goals without explicitly programming the rules on how to perform this task. In this review we provide a brief overview on the potential of ML techniques to improve the evaluation of fetal cardiac function by optimizing image acquisition and quantification/segmentation, as well as aid in improving the prenatal diagnoses of fetal cardiac remodeling and abnormalities

QRS-T Angles as Markers for Heart Sphericity in Subjects with Intrauterine Growth Restriction: A Simulation Study

Changes induced by intrauterine growth restriction (IUGR) in cardiovascular anatomy and function that persist throughout life have been associated with a higher predisposition to heart disease in adulthood. Together with cardiac morphological remodelling, evaluated through the ventricular sphericity index, alterations in cardiac electrical function have been reported by characterization of the depolarization and repolarization loops, and their angular relationship, measured from the vectorcardiogram. The underlying relationship between the morphological remodelling and the angular variation of QRS and T-wave dominant vectors, if any, has not been explored. The aim of this study was to evaluate this relationship using computational models based on realistic heart and torso in which IUGR-induced morphological changes were incorporated by reducing the ventricular sphericity index. Specifically, we departed from a control model and we built eight different globular heart models by reducing the base-to-apex length and enlarging the basal ventricular diameter. We computed QRS and T-wave dominant vectors and angles from simulated pseudo-electrocardiograms and we compared them with clinical measurements. Results for the QRS to T angles follow a change trend congruent with that reported in clinical data, supporting the hypothesis that the IUGR-induced morphological remodelling could contribute to explain the observed angle changes in IUGR patients. By additionally varying the position of the ventricles with respect to the torso and the electrodes, we found that electrode displacement can impact the quantified angles and should be considered when interpreting the results

Prediction of adverse neonatal outcome at admission for early-onset preeclampsia with severe features

Preeclampsia remains the leading cause of maternal morbidity and mortality. Consequently, research has focused on validating tools to predict maternal outcomes regarding clinical and biochemical features from the maternal compartment. However, preeclampsia also leads to neonatal complications due to placental insufficiency and prematurity, being the early-onset type associated with the poorest outcome. Hence, it is imperative to study whether these existing tools can predict adverse neonatal outcome.To assess the predictive value for adverse neonatal outcome of Doppler ultrasound, angiogenic factors and multi-parametric risk-score models in women with early-onset severe preeclampsia.This is a prospective cohort study of consecutive singleton pregnancies complicated by early-onset (developed before 34 week's gestation) severe preeclampsia.63 women with early-onset severe preeclampsia, 18 (28.6%) presented an adverse neonatal outcome. Placental growth factor (PlGF) showed the best discrimination between neonatal outcomes among angiogenic factors. PREP-L score is a multi-parametric risk-score for the prediction of complications in early-onset preeclampsia which includes maternal characteristics and clinical and analytical data obtained at admission. Good predictive values for the prediction of neonatal complications were found with the combination of PREP-L score with advanced Doppler (AUC ROC 0.9 95% CI 0.82-0.98]) and with PlGF levels (AUC ROC 0.91 [95% CI 0.84-0.98]).The combination of maternal risk scoring (PREP-L score) with angiogenic factors or fetal Doppler ultrasound at the time of diagnosis of early-onset preeclampsia with severe features performs well in predicting adverse neonatal outcome.Copyright © 2023 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved

Structural coronary artery remodelling in the rabbit fetus as a result of intrauterine growth restriction

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatation of the coronary arteries. However, a direct measurement of the coronaries’ lumen diameter in IUGR has not been reported before. The aim of this paper is to perform, for the first time, a quantitative analysis of the effects of IUGR in cardiac geometry and coronary vessel size in a wellknown rabbit model of IUGR using synchrotron-based X-ray Phase Contrast Tomography Imaging (X-PCI). Eight rabbit fetal hearts were imaged non-destructively with X-PCI. 3D reconstructions of the coronary arterial tree were obtained after semi-automatic image segmentation. Different morphometric features including vessel lumen diameter of the three main coronaries were automatically quantified. IUGR fetuses had more globular hearts and dilated coronary arteries as compared to controls. We have quantitatively shown that IUGR leads to structural coronary vascular tree remodelling and enlargement as an adaptation mechanism in response to an adverse environment of restricted oxygen and nutrients and increased perfusion pressure

Steam and gas emission rates from La Soufrière of Guadeloupe (Antilles arc): implications for the magmatic supply degassing during unrest

Since its last magmatic eruption in 1530 AD, La Soufrière andesitic volcano in Guadeloupe has displayed intense hydrothermal activity and six phreatic eruptive crises (the last of which, in 1976-1977, with 73000 evacuees). Here we report on the first direct quantification of gas plume emissions from La Soufrière summit vents, which gradually intensified during the past 20 years. Gas fluxes were determined in 2006 then 2012 [1] by measuring the horizontal and vertical distribution of volcanic gas concentrations in the air-diluted plume, the composition of the hot fumarolic fluid at exit (108°C), and scaling to the speed of plume transport (in situ measurements and FLIR imaging). We first demonstrate that all fumarolic vents of La Soufrière are fed by a common H2O-rich (97-98 mol %) fluid end-member, emitted almost unmodified at the most active South Crater while affected by secondary alterations (steam condensation, sulphur scrubbing) at other vents. Daily fluxes in 2012 (200 tons of H2O, 15 tons of CO2, ~4 tons of H2S and 1 ton of HCl) were augmented by a factor ~3 compared to 2006, in agreement with increasing activity. Summit fumarolic degassing contributes most of the bulk volatile and heat budget (8 MW) of the volcano. Isotopic evidences demonstrate that La Soufrière hydrothermal emissions are sustained by continuous heat and gas supply from an andesitic magma reservoir confined at 6-7 km depth. This magmatic supply mixes with abundant groundwater of tropical meteoric origin in the hydrothermal system. Based on petro-geochemical data for the erupted magma(s), we assess that the volcanic gas fluxes in 2012 can be accounted for by the release of free magmatic gas derived from about 1000 m3 per day of the basaltic melt replenishing the reservoir at depth. In terms of mass budget, the current degassing unrest is compatible with enhanced free gas release from that reservoir, without requiring any (actually undetected) magma intrusion. We recommend a regular survey of the fumarolic gas flux from La Soufrière in order to anticipate the evolution of the magma reservoir. [1] P. Allard et al., Chemical Geology 384, 76-93, 2014

Microstructural Analysis of Cardiac Endomyocardial Biopsies with Synchrotron Radiation-Based X-Ray Phase Contrast Imaging

Nowadays, unexplained cardiovascular diseases (CVD) and heart transplant response are assessed by qualitative histological analysis of extracted endomyocardial biopsies (EMB), which is a time consuming procedure involving structural damage of the tissue and the analysis in only a few slices of a 3D structure. In this paper we propose synchrotron radiation-based X-ray phase contrast imaging (X-PCI) as a suitable technique for the analysis of different cardiac microstructures, such as collagen matrix, cardiomyocytes and microvasculature, and how they are affected in abnormal conditions. Following an established procedure in clinics, biopsies from Wistar Kyoto rats are extracted, imaged with X-PCI, and processed in order to show that the quantification of the endomysial collagen matrix, cardiomyocytes and microvasculature is possible, thus demonstrating that the intrinsic properties of X-PCI make it a powerful technique for cardiac microstructure imaging and a promising methodology for a faster and more accurate EMB analysis for CVD diagnosis and evaluation

Microstructural Analysis of Cardiac Endomyocardial Biopsies with Synchrotron Radiation-Based X-Ray Phase Contrast Imaging

Nowadays, unexplained cardiovascular diseases (CVD) and heart transplant response are assessed by qualitative histological analysis of extracted endomyocardial biopsies (EMB), which is a time consuming procedure involving structural damage of the tissue and the analysis in only a few slices of a 3D structure. In this paper we propose synchrotron radiation-based X-ray phase contrast imaging (X-PCI) as a suitable technique for the analysis of different cardiac microstructures, such as collagen matrix, cardiomyocytes and microvasculature, and how they are affected in abnormal conditions. Following an established procedure in clinics, biopsies from Wistar Kyoto rats are extracted, imaged with X-PCI, and processed in order to show that the quantification of the endomysial collagen matrix, cardiomyocytes and microvasculature is possible, thus demonstrating that the intrinsic properties of X-PCI make it a powerful technique for cardiac microstructure imaging and a promising methodology for a faster and more accurate EMB analysis for CVD diagnosis and evaluation

Early cardiac remodeling in aortic coarctation: insights from fetal and neonatal functional and structural assessment

Objectives: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults. Cardiac structure and function in fetal CoA and cardiac adaptation to early neonatal life have not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. Methods: This was a prospective observational case–control study, conducted between 2011 and 2018 in a single tertiary referral center, of fetuses with CoA and gestational age‐matched normal controls. All fetuses/neonates underwent comprehensive echocardiographic evaluation in the third trimester of pregnancy and after birth. Additionally, myocardial microstructure was assessed in one fetal and one neonatal CoA‐affected heart specimen, using synchrotron radiation‐based X‐ray phase‐contrast microcomputed tomography and histology, respectively. Results: We included 30 fetuses with CoA and 60 gestational age‐matched controls. Of these, 20 CoA neonates and 44 controls were also evaluated postnatally. Fetuses with CoA showed significant left‐to‐right volume redistribution, with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated LV, compared with controls (LV midventricular sphericity index (median (interquartile range; IQR), 2.4 (2.0–2.7) vs 1.8 (1.7–2.0); P < 0.001). Biventricular function was preserved and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization in the fetal and neonatal specimens, respectively. Postnatally, the LV in CoA cases showed prompt remodeling, becoming more globular (LV midventricular sphericity index (mean ± SD), 1.5 ± 0.3 in CoA vs 1.8 ± 0.2 in controls; P < 0.001) with preserved systolic and normalized output, but altered diastolic, parameters compared with controls (LV inflow peak velocity in early diastole (mean ± SD), 97.8 ± 14.5 vs 56.5 ± 12.9 cm/s; LV inflow peak velocity in atrial contraction (median (IQR), 70.5 (60.1–84.9) vs 47.0 (43.0–55.0) cm/s; LV peak myocardial velocity in atrial contraction (mean ± SD), 5.1 ± 2.6 vs 6.3 ± 2.2 cm/s; P < 0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. Conclusions: Our results suggest unique fetal cardiac remodeling in CoA, in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume‐loaded, resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of the evolution of CoA from fetal to neonatal life

SARS-CoV-2 RNA and antibody detection in breast milk from a prospective multicentre study in Spain

Objectives To develop and validate a specific protocol for SARS-CoV-2 detection in breast milk matrix and to determine the impact of maternal SARS-CoV-2 infection on the presence, concentration and persistence of specific SARS-CoV-2 antibodies. Design and patients This is a prospective, multicentre longitudinal study (April-December 2020) in 60 mothers with SARS-CoV-2 infection and/or who have recovered from COVID-19. A control group of 13 women before the pandemic were also included. Setting Seven health centres from different provinces in Spain. Main outcome measures Presence of SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene; presence and levels of SARS-CoV-2-specific immunoglobulins (Igs)-IgA, IgG and IgM-in breast milk samples from patients with COVID-19. Results All breast milk samples showed negative results for presence of SARS-CoV-2 RNA. We observed high intraindividual and interindividual variability in the antibody response to the receptor-binding domain of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Main Protease (MPro) domain antibodies were also detected in milk. 82.9% (58 of 70) of milk samples were positive for at least one of the three antibody isotypes, with 52.9% of these positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2%-87.5%), whereas it raised continuously for IgG (from 47.8% for the first 10 days to 87.5% from day 41 up to day 206 post-PCR confirmation). Conclusions Our study confirms the safety of breast feeding and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence. ARS-CoV-2 antibodies but not RNA are found in breast milk from COVID-19 infected mothers