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

Uncomplicated monochorionic twins: two normal hearts sharing one placenta

Cardiovascular dysfunction has been reported in complicated monochorionic diamniotic (MCDA) pregnancies; however, little is known whether hemodynamic changes occur in uncomplicated MCDA twins. A prospective observational study was conducted including 100 uncomplicated MCDA twins matched by gestational age to 200 low-risk singletons. Echocardiography was performed at 26-30 weeks gestation and cord blood B-type natriuretic peptide (BNP) was measured at delivery. In both groups, z-scores for echocardiographic parameters were within normal ranges; however the monochorionic group had larger atrial areas (mean (standard deviation) right atria-to-heart ratio: 17.0 (2) vs. 15.9 (1); p = 0.018; left atria-to-heart ratio: 17.0 (3) vs. 15.8 (2); p < 0.001) and signs of concentric hypertrophy (right relative wall thickness: 0.66 (0.12) vs. 0.56 (0.11); p < 0.001; left relative wall thickness: 0.69 (0.14) vs. 0.58 (0.12); p < 0.001). Longitudinal function was increased in twins, leading to higher tricuspid annular plane systolic excursion (6.9 mm (0.9) vs. 5.9 mm (0.7); p < 0.001) and mitral annular plane systolic excursion (4.9 mm (0.8) vs. 4.4 mm (1.1); p < 0.001. BNP levels at birth were also higher in MCDA twins (median [interquartile range]: 20.81 pg/mL [16.69-34.01] vs. 13.14 pg/mL [9.17-19.84]; p < 0.001). Thus, uncomplicated MCDA fetuses have normal cardiac shape and function, but signs of cardiac adaptation were identified by echocardiographic and biochemical parameters, when compared with singletons

SIRT3-mediated inhibition of FOS through histone H3 deacetylation prevents cardiac fibrosis and inflammation.

Sirtuin 3 (SIRT3) is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress. Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances. In this study, we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells. SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-alpha. Notably, these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1. Finally, we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter. These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy, heart failure, and diabetic cardiomyopathy, our results point to SIRT3 as a potential target for treating these diseases

Cardiovascular assessment in fetuses and children conceived by assisted reproductive technologies

[eng] BACKGROUND: Approximately, five million children have been born as a result of using assisted reproductive technologies (ART). Although the majority of ART children are born healthy; there are several reports of increased rate of pregnancy complications and worse perinatal outcomes in this population that may contribute to long-term health consequences according to the fetal programming hypothesis. Due to these techniques are relatively new, the effect of ART on later stages of development and adult susceptibility are uncertain. The main hypothesis of this thesis is that fetuses conceived by ART present worse perinatal outcomes together with primary cardiovascular remodeling and dysfunction as compared to those spontaneously conceived (SC), changes that persist postnatally and leads to increased cardiovascular risk in adulthood. METHODS: Cardiovascular morphology and functional assessment was performed in singleton and twin fetuses conceived by ART and spontaneously conceived; together with the presence of adverse perinatal outcomes. Finally, follow-up of these cohorts was made and cardiac and vascular function was assessed in childhood. RESULTS: ART fetuses showed: larger atria, shorter ventricles with lower sphericity index together with thicker myocardial walls. Systolic motion was decreased as measured by M-Mode and tissue Doppler; there were also sings of impaired relaxation, as demonstrated by a longer IRT and decreased deceleration time of E wave. All these changes were independent of the presence of been small for gestational age (SGA) due to these groups showed different cardiac phenotypes. ART children showed persistence of changes in cardiac morphology and function together with vascular remodeling (increased blood pressure and thicker carotid intima media). CONCLUSIONS: Adverse pregnancy outcomes seem to be present in infertile women, regardless of the use of ART. Singleton and twin ART fetuses present cardiovascular remodeling and subclinical dysfunction that persist postnatally in childhood. These changes are independent of the presence of SGA. These findings need to be take into account for further studies regarding higher cardiovascular risks in adulthood in this population[spa] INTRODUCCION: Aproximadamente, 5 millones de niños han nacido en el mundo gracias al uso de las tecnicas de reproduccion asistida (TRA). La mayoría de éstos niños son sanos al nacer; pero diversos estudios mencionan la presencia de peores resultados perinatales en esta población; los cuáles podrían tener consecuencias a largo plazo de acuerdo con la teoría de la programación fetal. Estas técnicas son relativamente nuevas, por lo que sus efectos en la vida adulta aún son desconocidos. La hipótesis principal de ésta tesis es que los fetos concebidos mediante TRA, presentan peores resultados perinatales que aquellos concebidos de manera espontánea (CE), junto con la presencia de cambios cardíacos morfológicos y funcionales que persisten de manera postnatal y que condicionaría un incremento del riesgo cardiovascular en la vida adulta. METODOS: Se llevó a cabo la evaluación cardiovascular morfológica y funcional de fetos únicos y gemelares concebidos por TRA comparados con fetos CE; junto con la presencia de resultados perinatales adversos. Se realiza un seguimiento y evaluación cardiovascular de dichas cohortes hasta la infancia. RESULTADOS: Los fetos TRA presentaron cambios al comparlos con los CE: aurículas más grandes, ventrículos más cortos junto con un menor índice de esfericidad así como paredes engrosadas. presentaron función sistólica disminuída de acuerdo con las mediciones de Doppler tisular y modo-M; también signos de disfunción diastólica demostrado por IRT alargados y disminución del tiempo de deceleración de la onda E. Todos estos cambios fueron independientes de la presencia de fetos pequeños para la edad gestacional (PEG), ya que dichos grupos presentaron fenotipos cardiacos diferentes. En la infancia, los niños TRA mostraron persistencia de dichos cambios cardíacos morfológicos y funcionales subclínicos, junto con remodelado vascular (presion arterial más alta y paredes engrosadas de la intima media de las carótidas). CONCLUSIONES: Las mujeres infértiles presentan resultados perinatales adversos independiente de el método de TRA usado. Los fetos concebidos mediante TRA presentan remodelado cardiovascular el cuál persiste postnatalmente en la infancia. Dichos cambios fueron independientes de la presencia de PEG. Estos hallazgos deben ser tomados en cuentra en futuros estudios del incremento de riesgo cardiovascular en la vida adulta de ésta población

Postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductivetechnologies: a cohort study

OBJECTIVE: To assess the postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies (ART) in children at 3 years of age. DESIGN: A cohort study of children conceived by ART. SETTING: Maternal-Fetal Medicine Unit, Hospital Clinic Barcelona, Spain. POPULATION SAMPLE: Eighty singleton pregnancies conceived by ART and 80 spontaneously conceived (controls) followed from fetal life up to childhood. METHODS: Cardiovascular evaluation was performed at 3 years of corrected age, including echocardiography, carotid intima-media (cIMT) by ultrasound, and blood pressure. MAIN OUTCOME MEASURES: Postnatal persistence of cardiovascular changes in children conceived by ART. RESULTS: Compared with controls, children conceived by ART showed larger atria (right atrial area: control 4.9 cm2 (0.9) versus ART 5.5 cm2 (0.9), P < 0.001), more globular ventricles (right ventricular sphericity index: control mean 1.8 (SD 0.5) versus ART 1.6 (0.2), P < 0.001), and signs of systolic (tricuspid annular plane systolic excursion: control 18 mm (2) versus ART 16 mm (3), P < 0.001) and diastolic dysfunction (isovolumic relaxation time: control 68 ms (12) versus ART 79 ms (12), P < 0.001). ART children also presented increased systolic blood pressure (control 90 mmHg (6) versus ART 94 mmHg (5), P < 0.003) and cIMT (control 0.52 μm (0.14) versus ART 0.60 μm (0.16), P < 0.001) as compared with those spontaneously conceived. CONCLUSIONS: Cardiovascular changes previously reported in ART fetuses persist postnatally at 3 years of age. These results underscore the importance of future studies for assessing the long-term cardiovascular health associated with ART. TWEETABLE ABSTRACT: Cardiovascular changes described in fetuses conceived by ART, persist in children at 3 years of age

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