Search Results (109)

Background/Objectives: The development of normal fetal cardiac function, a dynamic process that has not yet been precisely documented throughout the literature, is difficult to quantify by classic echocardiography. Our aim was to analyze the function of the fetal myocardium through speckle tracking and establish reference values for global and segmental longitudinal strain for both ventricles in fetuses with a gestational age (GA) between 22 and 39 weeks. Methods: We conducted a prospective study in which 170 fetuses underwent echocardiographic evaluation and those 150 that were eligible for the study underwent offline speckle tracking analysis. Results: A mixed-design ANOVA model with Greenhouse–Geisser correction showed no significant differences in regional strain measurements among GA groups (F [2, 147] = 1.25, p = 0.289) but showed significant differences in regional strain measurements among the right ventricle (RV), left ventricle (LV), and interventricular free wall (Greenhouse–Geisser F [1.3, 195.2] = 45.70, p < 0.001, GG ε = 0.66, original df = 2, 294). The wall-by-segment interaction term of the model was statistically significant for regional strain (Greenhouse–Geisser F [2.7, 394.2] = 27.00, p < 0.001, GG ε = 0.67, original df = 4, 588), while the segment-by-gestational age group term had a tendency toward statistical significance (Greenhouse–Geisser F [3.0, 221.4] = 2.21, p = 0.088, GG ε = 0.75, original df = 4, 294). The results of Welch’s ANOVA model showed no significant difference in right-ventricle peak global longitudinal strain (pGLS) between GA groups (F [2.0, 92.2] = 0.52, p = 0.5972) and global longitudinal strain measurements (F [2.0, 89.6] = 27.00, p = 0.3733). Conclusions: The reference values for longitudinal strain, represented by the pGLS for LV, ranged from −20.79 to −8.05 for fetuses with a GA between 22 and 27 weeks, from −20.14 to −8.99 for fetuses with a GA between 28 and 33 weeks, and from −20.19 to −8.88 for fetuses with a GA between 34 and 39 weeks. For RV pGLS, the reference values were between −18.99 and −6.35, also depending on GA. Reference ranges for the large gestational groups studied can help us to recognize subtle changes in fetal cardiac function. Full article

Cardiac disease remains a leading cause of maternal morbidity and mortality, particularly in developed countries where improved survival has increased the number of pregnant patients with congenital heart disease. The physiological changes of pregnancy, such as increased blood volume, cardiac output, and hypercoagulability, can exacerbate preexisting cardiac conditions, posing significant anesthetic challenges during cesarean delivery. This review outlines anesthetic strategies for parturients with structural or functional cardiac disease, emphasizing individualized, multidisciplinary care. We examine general and regional anesthesia approaches, intraoperative monitoring, and hemodynamic goals, including fluid balance, venous return optimization, and myocardial oxygen demand reduction. Preoperative risk stratification and coordination with cardiology and obstetric teams are essential. Future efforts should aim to standardize protocols and improve maternal–fetal outcomes through evidence-based anesthetic planning. Full article

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, with increasing evidence suggesting that their origins may lie in prenatal life. Endocrine-disrupting chemicals (EDCs), such as bisphenol A (BPA), have been implicated in the alteration of fetal programming mechanisms that cause a predisposition to long-term cardiovascular vulnerability. However, the impact of prenatal endocrine disruption on fetal heart development and its sex-specific nature remains incompletely understood. This study investigates the molecular and structural effects of low-dose prenatal BPA exposure on fetal rat hearts. Our results reveal that BPA disrupts estrogen receptor (ER) signaling in a sex-dependent manner, with distinct alterations in ERα, ERβ, and GPER expression. BPA exposure also triggers significant inflammation, oxidative stress, and ferroptosis; this is evidenced by elevated NF-κB, IL-1β, TNF-α, and NLRP3 inflammasome activation, as well as impaired antioxidant defenses (SOD1, SOD2, CAT, and SELENOT), increased lipid peroxidation (MDA) and protein oxidation, decreased GPX4, and increased ACSL4 levels. These alterations are accompanied by increased markers of cardiac distension (ANP, BNP), extracellular matrix remodeling mediators, and pro-fibrotic regulators (Col1A1, Col3A1, TGF-β, and CTGF), with a more pronounced response in males. Histological analyses corroborated these molecular findings, revealing structural alterations as well as glycogen depletion in male fetal hearts, consistent with altered cardiac morphogenesis and metabolic stress. These effects were milder in females, reinforcing the notion of sex-specific vulnerability. Moreover, prenatal BPA exposure affected myocardial fiber architecture and vascular remodeling in a sex-dependent manner, as evidenced by reduced expression of desmin alongside increased levels of CD34 and Ki67. Overall, our findings provide novel insights into the crucial role of prenatal endocrine disruption during fetal heart development and its contribution to the early origins of CVD, underscoring the urgent need for targeted preventive strategies and further research into the functional impact of BPA-induced alterations on postnatal cardiac function and long-term disease susceptibility. Full article

Background/Objectives: The aim of this study was to determine the prevalence of functional cardiovascular anomalies detected on fetal echocardiography in third-trimester large-for-gestational-age (LGA) fetuses, who were subsequently born as macrosomic newborns with a birth weight exceeding 4000 g. Methods: A retrospective study was conducted on 1002 fetuses examined during the third trimester at our fetal cardiology center between 2018 and 2024. All fetuses were classified as having “normal heart anatomy” (NHA). Statistical analysis was performed using Microsoft Excel 2024, Statistica 13.1, and EasyMedStat (version 3.37.1). A p-value of <0.05 was considered statistically significant. Results: The 1002 fetuses were divided into two groups. The study group (NHA-LGA) consisted of 167 fetuses born with a weight of >4000 g and the control group (NHA-AGA) was made up of 835 fetuses with a birth weight between 2500 and 4000 g. In the NHA-LGA group, 24 fetuses (14.4%) experienced ductal constriction (DC), while in the NHA-AGA group, it was 11 (1.3%) fetuses (p < 0.00001). Myocardial hypertrophy was observed in 30 fetuses (18.0%) in the NHA-LGA group versus 72 (8.6%) in the NHA-AGA group (p < 0.0003). Additionally, cardiomegaly was noted in 95 fetuses (11.4%) in the NHA-LGA group, compared to 37 (4.4%) in the NHA-AGA group (p < 0.0004). Conclusions: LGA fetuses with normal heart anatomy may present with functional cardiovascular anomalies, including ductal constriction, myocardial hypertrophy, and cardiomegaly. In our cohort, such anomalies were identified in up to 51% of cases. These findings suggest that targeted fetal echocardiographic screening in macrosomic fetuses could be clinically valuable, even in the absence of structural heart defects, and may aid in the early identification of functional cardiac alterations that could impact perinatal management. Full article

Intercellular interactions among cardiac cell populations are essential for cardiac morphogenesis, yet the molecular mechanisms orchestrating these events remain incompletely understood. Dachsous1 (Dchs1), an atypical cadherin linked to mitral valve prolapse, is a core planar cell polarity protein whose function in the developing heart has not been fully elucidated. To address this, we generated a Dchs1-HA knock-in mouse model to define its spatial, temporal, and cellular expression patterns. Using immunohistochemistry, western blotting, and single-cell transcriptomics across developmental stages, we demonstrate that cardiac Dchs1 expression is restricted to non-cardiomyocyte lineages. DCHS1 displays dynamic subcellular localization and tissue organization depending on the developmental timepoint, with staining being found in epicardial and endocardial surfaces at earlier embryonic stages and in the compact myocardium in later fetal and neonatal stages. During fetal and neonatal stages, DCHS1-positive non-myocyte, non-endothelial cells form polarized extensions that bridge endothelial and non-myocyte, non-endothelial cells, suggesting direct heterotypic and homotypic interactions. Western blotting revealed evidence of DCHS1 proteolytic cleavage, with intracellular C-terminal fragments. RNA co-expression with its binding partner FAT4 supports a conserved, non-myocyte-specific DCHS1-FAT4 signaling axis. These findings identify DCHS1 as a potential molecular tether that is utilized in intercellular communications during cardiac development, with implications for congenital and acquired heart disease. Full article

Background/Objectives: Functional assessment of the fetal heart remains a significant challenge in contemporary perinatology due to the absence of a universally accepted gold standard for such evaluations. The aim of this study was to evaluate the reproducibility of parameters derived from two-dimensional speckle-tracking echocardiography (2D STE) using the FetalHQ software. Methods: We enrolled 87 pregnant women between 19 and 23 weeks of gestation who were undergoing mid-trimester screening at the Provincial Hospital Complex in Kielce. Two independent operators acquired 5 s cine-loops of four-chamber views (4CVs) according to a standardized protocol. Reproducibility was assessed by examining intra- and interobserver variability using the intraclass correlation coefficient (ICC) for several cardiac parameters, including the global sphericity index (GSI), global longitudinal strain (GLS), stroke volume (SV), and fractional area change (FAC). Results: Reproducibility varied substantially across the assessed parameters. The highest intraobserver reproducibility was observed for the 4CV GSI (ICC > 0.9). Moderate intraobserver reproducibility (ICCs ranging from 0.5 to 0.75) was noted for left ventricular (LV) parameters, such as end-diastolic area, end-systolic area, end-diastolic volume, and end-systolic volume. Interobserver variability demonstrated higher ICC values, with excellent reproducibility (ICC > 0.9) for the 4CV GSI and LV volume measurements. Good reproducibility (ICCs between 0.75 and 0.9) was observed for specific left ventricular segmental strain indices, whereas other parameters showed moderate to poor reproducibility (ICC < 0.5). Conclusions: Two-dimensional speckle-tracking echocardiography (2D STE) using FetalHQ exhibits variable reproducibility, which is influenced by the choice of parameters, operator experience, and technical factors. This method holds potential for fetal cardiac assessment; however, additional research is required to improve its predictive accuracy and streamline the evaluation process for routine clinical application. Full article

Background/Objectives: The relationship between ultrasound parameters and fetal health in the context of intrauterine growth restriction (IUGR) pregnancies constitutes a significant focus of scholarly research. A comprehensive range of Doppler and echocardiographic evaluations, encompassing the umbilical artery, middle cerebral artery, ductus venosus, uterine arteries, cardiac contractility, ventricular filling, and the thickness of the interventricular septum, has been proposed in pathological pregnancies. Methods: The aim of this paper is to present an examination of these metrics and their implications for fetal health within the framework of IUGR pregnancies and to report a case series in which we analyzed the correlation of these factors. The assessment of these ultrasound indicators can help in better management of the cases in order to obtain better fetal outcomes. Results: Our case study presented dynamics corelated to the after-birth evaluation of the neonate, reflecting the importance of complete ultrasound assessment in high-risk cases. Conclusions: Speckle tracking echocardiography has significantly advanced our understanding of cardiac function in IUGR fetuses. As shown in our cases, it can be used to detect early signs of cardiac dysfunction, differentiating between FGR and SGA. Full article

Objective: This study investigated the impact of maternal subclinical hypothyroidism on fetal thymus size and development and explored how inadequate thyroid hormone production in pregnant women affects the fetal thymus. Methods: Conducted at the Giresun Obstetrics, Gynecology, and Pediatrics Training and Research Hospital, this case–control study involved 86 pregnant women, 43 with hypothyroidism and 43 without. Maternal thyroid function was assessed using TSH and free T4 levels, and fetal thymus size and thymus–thorax ratio were measured using ultrasound. Exclusion criteria were chronic hypertension, gestational hypertension or eclampsia, multiple pregnancies, infectious diseases, renovascular diseases, diagnosed with hypothyroidism prior to pregnancy and other endocrine disorders, fetal cardiac diseases, and morbid obesity. Data collected included maternal age, gestational week, number of pregnancies, parity, number of living children, thyroid-stimulating hormone (TSH) and Free thyroxine 4 (T4) levels, and fetal thymus measurements (transverse diameter and thymus/thorax ratio). Statistical analyses were performed using the Mann–Whitney U test and logistic regression analysis. The relationships between TSH, thymus diameters, thorax diameters, and the thymus–thorax ratio were evaluated using Spearman’s correlation coefficient. Results: The thymus–thorax ratio was significantly reduced in the hypothyroid group (p = 0.003). Logistic regression analysis identified TSH as an independent risk factor for a low thymus–thorax ratio, with each unit increase in TSH associated with a 1.345-fold higher likelihood of having a low thymus–thorax ratio. A significant negative correlation was found between TSH levels and the TTR ratio (Spearman’s correlation coefficient r = −0.338, p = 0.001). Conclusions: An association was identified between maternal TSH levels and the thymus–thorax ratio, with increasing TSH levels correlating with a decrease in the thymus–thorax ratio. Regular monitoring of thyroid hormone levels during pregnancy and appropriate replacement treatment in cases of deficiency are crucial for optimal fetal thymus development. Further multicenter studies are needed to confirm these findings and investigate the long-term implications of altered fetal thymus development. Full article

Background: Pregnancy in women with biventricular circulation and a systemic right ventricle (sRV) is considered high risk, with limited data available on pregnancy outcomes. This study aimed to investigate pregnancy outcomes in this population. Materials and Methods: A systematic review was conducted using four major electronic databases. Pregnant women with a complete transposition of great arteries (d-TGA) after an atrial switch operation or a congenitally corrected transposition of the great arteries (ccTGA) were included. Results: In total, 15 studies including 632 pregnancies in 415 women with an sRV and biventricular circulation were identified, of whom 299 (72%) had d-TGA and 116 (28%) ccTGA. Maternal mortality or cardiac transplantation occurred in 0.8% of pregnancies. The most frequent maternal complications were the worsening of systemic atrioventricular valve regurgitation [pooled estimate (PE): 16%, 95% CI: 5;26], the deterioration of sRV function (PE: 15%, 95% CI: 2;27), the worsening of the NYHA class (PE: 13%, 95% CI: 6;20), all-cause hospitalization (PE): 10%, 95% CI: 7;12), arrhythmias (PE: 8%, 95% CI: 5;11), and symptomatic heart failure (PE: 6%, 95% CI: 3;10). Stillbirth occurred in 0.7% of pregnancies and neonatal death in 0.4%. Small-for-gestational-age neonates were encountered in 36% (95% CI: 21;52) of pregnancies and preterm delivery in 22% (95% CI: 14;30). A subgroup analysis showed no significant difference in outcomes between women with d-TGA and those with ccTGA, except for the worsening of the NYHA class, which occurred more often in d-TGA (18%, 95% CI: 12;27 vs. 6%, 95% CI: 3;15, respectively, p = 0.03). Conclusions: Maternal and fetal/neonatal mortality are low among pregnant women with biventricular circulation and an sRV. However, significant maternal morbidity and poor neonatal outcomes are frequently encountered, rendering management in specialized centers imperative. Full article

Background: Maternal dyslipidemia during pregnancy may influence fetal cardiac development and function, potentially predisposing offspring to cardiovascular diseases later in life. This study aims to evaluate the relationship between maternal lipid profiles and fetal cardiac function at mid-gestation, utilizing detailed echocardiographic assessments. Methods: In this prospective cohort study conducted at the Obstetrics and Gynecology Clinic of the Timișoara Municipal Emergency Hospital, 19 pregnant women aged 27–40 years were recruited and divided into two groups based on their triglyceride levels: Group A (triglycerides ≤ 150 mg/dL, n = 48) and Group B (triglycerides > 150 mg/dL, n = 28). Maternal demographic data and lipid profiles were recorded. Fetal echocardiographic measurements, including global longitudinal strain and ventricular function parameters, were obtained between 20 and 24 weeks of gestation. Statistical analyses, including subgroup comparisons, correlations, and regression analyses, were performed. Results: Maternal BMI was significantly higher in Group B compared to Group A (31.94 ± 2.80 vs. 27.01 ± 2.40 kg/m², p < 0.001). Group B showed higher mean triglyceride levels (163.43 ± 11.34 mg/dL) compared to Group A (131.42 ± 10.57 mg/dL, p < 0.001). Fetal echocardiographic measurements indicated reduced global longitudinal strain in fetuses of Group B mothers (LV strain: −19.86% ± 6.83% vs. −26.14% ± 5.92%, p = 0.017). Significant correlations were found between maternal triglyceride levels and fetal LV strain (r = 0.536, p = 0.019). Regression analysis identified maternal triglyceride levels and BMI as significant predictors of reduced fetal LV strain (β = 0.45, p = 0.021 and β = 0.39, p = 0.038, respectively). Conclusions: Elevated maternal triglyceride levels, LDL cholesterol, and BMI are associated with altered fetal cardiac function parameters at mid-gestation, suggesting that maternal lipid profiles may impact fetal cardiac development. These findings underscore the importance of monitoring lipid levels during pregnancy and suggest potential benefits of managing dyslipidemia to improve fetal cardiac outcomes. However, the study included only a small sample; therefore, the study needs to be continued with a larger group. Full article

Cardiovascular disease comprises a group of disorders affecting or originating within tissues and organs of the cardiovascular system; most, if not all, will eventually result in cardiomyocyte dysfunction or death, negatively impacting cardiac function. Effective models of cardiac disease are thus important for understanding crucial aspects of disease progression, while recent advancements in stem cell biology have allowed for the use of stem cell populations to derive such models. These include three-dimensional (3D) models such as stem cell-based models of embryos (SCME) as well as organoids, many of which are frequently derived from embryoid bodies (EB). Not only can they recapitulate 3D form and function, but the developmental programs governing the self-organization of cell populations into more complex tissues as well. Many different organoids and SCME constructs have been generated in recent years to recreate cardiac tissue and the complex developmental programs that give rise to its cellular composition and unique tissue morphology. It is thus the purpose of this narrative literature review to describe and summarize many of the recently derived cardiac organoid models as well as their use for the recapitulation of genetic and acquired disease. Owing to the cellular composition of the models examined, this review will focus on disease and tissue injury associated with embryonic/fetal tissues. Full article

Fetal growth restriction (FGR) increases the risk of cardiovascular disease. There are currently no treatment options available; however, antioxidants have shown potential to improve cardiovascular deficits associated with FGR. This systematic review aimed to determine whether antenatal antioxidant intervention can effectively protect the developing cardiovascular system in FGR. We searched for interventional studies that used an antenatal antioxidant intervention to improve cardiac and/or vascular outcomes in FGR published between 01/1946 and 09/2024 using MEDLINE and Embase (PROSPERO: CRD42024503756). The risk of bias was assessed with SYRCLE. The studies were assessed for cardiovascular protection based on the percentage of cardiac and/or vascular deficits that were restored with the antioxidant treatment. Studies were characterised as showing strong cardiovascular protection (≥50% restoration), mild cardiovascular protection (>0% but <50% restoration), an antioxidant-only effect (this did not include control group which showed a change with antioxidant intervention compared to FGR) or no cardiovascular protection (0% restoration). Thirty-eight publications met the inclusion criteria, encompassing 43 studies and investigating 15 antioxidant interventions. Moreover, 29/43 studies (71%) reported the restoration of at least one cardiac or vascular deficit with antioxidant intervention, and 21/43 studies (51%) were classified as strong cardiovascular protection. An ex vivo analysis of the arterial function in seven studies revealed endothelial dysfunction in growth-restricted offspring and antioxidant interventions restored the endothelial function in all cases. Additionally, four studies demonstrated that antioxidants reduced peroxynitrite-mediated oxidative stress. Notably, only 13/43 studies (32%) delayed antioxidant administration until after the induction of FGR. Antenatal antioxidant interventions show promise for providing cardiovascular protection in FGR. Melatonin was the most frequently studied intervention followed by nMitoQ, vitamin C and N-acetylcysteine, all of which demonstrated a strong capacity to reduce oxidative stress and improve nitric oxide bioavailability in the cardiovascular system of growth-restricted offspring; however, this systematic review highlights critical knowledge gaps and inconsistencies in preclinical research, which hinder our ability to determine which antioxidant treatments are currently suitable for clinical translation. Full article

Background/Objectives: Better understanding of and addressing umbilical entanglement in the third trimester of pregnancy is necessary to estimate its impact on fetal circulation. An analysis of single physiological pregnancies wrapped with one or two coils of the umbilical cord around the neck makes it possible to understand the severity of the problem and distinguish it from perinatal umbilical strangulation. Methods: In an echocardiographic study performed at 32.1 weeks of pregnancy in fetuses with one and two coils of the umbilical cord around the neck, the pulsatility index (PI) and the Tei index for the left (Tei LV) and right ventricle (Tei RV) of the heart were measured to evaluate cardiac function. Results: The study showed significantly higher Tei RV and Tei LV for fetuses with one (93 cases) and two coils of the umbilical cord around the fetal neck (26 cases) with respect to the control group of fetuses (680 cases) with no umbilical cord around the fetal neck, whereas PI UMBA did not differ significantly. Conclusions: Wrapping of the umbilical cord around the fetal neck may affect the study of the fetal heart without any mechanically induced compression of the umbilical vessels in normal pregnancy. Full article

Background: An increased incidence of adult-onset heart failure is seen in individuals born preterm or affected by fetal growth restriction. An adverse maternal environment is associated with both preterm birth and poor fetal development, and postnatal oxygen therapy is frequently required to sustain oxygenation of vulnerable tissues due to lung immaturity. Methods: Studies using our murine model of maternal inflammation (LPS) and neonatal hyperoxia exposure (O₂) observed pathological changes in cardiac structural proteins and functional analysis with sex dependent differences in pathologies at 10 months of age. Using our previous model, the current investigations tested the hypothesis that early-life perturbations in cardiac structural proteins might predict adult cardiac dysfunction in a sex dependent manner. Results: LPS-exposed females had lower αMHC mRNA and protein at P0 and P7 relative to the saline-exposed females, but these changes did not persist. Male mice exposed to LPS/O₂ had normal expression of αMHC mRNA and protein compared to saline/room air controls though P56, when they dramatically increased. Correlative changes were observed in left ventricular function with a more severe phenotype in the males indicating sex-based differences in cardiac adaptation. Conclusions: Our findings demonstrate that early changes in contractile proteins temporally correlate with deficits in cardiac contractility, with a more severe phenotype in males. Our data suggest that similar findings in humans may predict risk for disease in growth-restricted infants. Full article

Introduction: This review aims to investigate the clinical implications of using the myocardial performance index (MPI), obtained through tissue Doppler imaging (TDI) and spectral Doppler, in assessing fetal cardiac function in growth-restricted fetuses. It explores the MPI’s potential in predicting adverse perinatal outcomes and its utility when combined with conventional pulsed-wave Doppler assessments for enhanced fetal well-being evaluations. Material and Methods: A systematic search of PubMed and Google Scholar databases spanning from 2004 to 2023 was conducted to identify pertinent articles on the MPI’s clinical application in managing growth-restricted fetuses. Inclusion criteria followed the Fetal Medicine Barcelona definition of fetal growth restriction (FGR) to mitigate study group heterogeneity. The research sources were PubMed and Google Scholar databases, and the review was conducted without any specific clinical or laboratory setting. Only articles meeting the inclusion criteria for FGR, as per the Fetal Medicine Barcelona definition, were considered. Six studies meeting these criteria were included in the review. The review analyzed the correlation between MPI values and conventional Doppler parameters, investigating the progression of myocardial function impairment and its association with the risk of fetal demise. The primary outcome measures included the relationship between MPI values, fetal well-being, and the potential for prenatal cardiac dysfunction in growth-restricted fetuses. Results: The findings indicate that as conventional Doppler parameters deteriorate, MPI values increase, suggesting progressive myocardial dysfunction. The MPI may cross the 95th percentile before abnormal flow in the ductus venosus and aortic isthmus, highlighting the potential for diastolic dysfunction preceding hypoxia in growth-restricted fetuses. Elevated MPI levels were observed in both growth-restricted and small-for-gestational-age (SGA) fetuses, indicating prenatal cardiac impairment. The strong association between an abnormal MPI and perinatal mortality has been shown for early FGR. Conclusions: MPI alterations appear to precede abnormal Doppler parameters in early- and late- onset FGR, potentially indicating diastolic dysfunction preceding hypoxia. Additionally, the MPI correlates with the risk of fetal demise. However, larger studies are needed to establish its sensitivity and specificity. Furthermore, the significance of prenatal cardiac impairment in some SGA fetuses raises questions about its potential impact on perinatal outcomes and cardiovascular programming. Full article