Hypoplastic Left Heart Syndrome: Is There a Role for Fetal Therapy?

During fetal life some cardiac defects may lead to diminished left heart growth and to the evolution of a form of hypoplastic left heart syndrome (HLHS). In fetuses with an established HLHS, severe restriction or premature closure of the atrial septum leads to left atrial hypertension and remodeling of the pulmonary vasculature, severely worsening an already poor prognosis. Fetal therapy, including invasive fetal cardiac interventions and non-invasive maternal hyperoxygenation, have been introduced to prevent a possible progression of left heart hypoplasia, improve postnatal outcome, or secure fetal survival.

Human embryonic cardiovascular function.

Introduction: This review presents an overview of descriptive knowledge on human embryonic cardiovascular physiology mostly based on noninvasive assessment by Doppler ultrasonography. Our objective was to identify and analyze published studies on embryonic cardiovascular function, and summarize available knowledge in this field.

Material And Methods: Citations related to human embryonic cardiovascular function were searched in PubMed, EMBASE, CINAHL and Web of Science using keywords and MeSH terms without any time limitation.

First-trimester screening for congenital heart disease.

Unlabelled: Advances over the last decade in technology, training, and availability of prenatal care have led to a focus on the detection of congenital heart defects (CHD) and its prenatal management for improved pregnancy outcomes. First-trimester transvaginal heart screening is feasible and well tolerated. Due to advances in the diagnosis of trisomy by nonultrasound methods, a significant effort will now be focused on CHD detection in the first trimester of otherwise uncomplicated pregnancies.

Diagnosis and treatment of foetal heart failure: foetal echocardiography and foetal hydrops.

Foetal echocardiography has progressed to be able to diagnose many forms of CHD and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. This article outlines a straightforward method for the rapid evaluation of foetus that may have congestive heart failure with or without hydrops and for the differentiation of the pre-hydropic state from normal. The presence of signs of foetal heart failure, such as cardiomegaly or valvular regurgitation, gives clues to the aetiology of hydrops.

Summary of the 2015 International Paediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute.

In the United States alone, ∼14,000 children are hospitalised annually with acute heart failure. The science and art of caring for these patients continues to evolve. The International Pediatric Heart Failure Summit of Johns Hopkins All Children's Heart Institute was held on February 4 and 5, 2015.

Variation in Prenatal Diagnosis of Congenital Heart Disease in Infants.

Background And Objective: Prenatal diagnosis allows improved perioperative outcomes for fetuses with certain forms of congenital heart disease (CHD). Variability in prenatal diagnosis has been demonstrated in other countries, leading to efforts to improve fetal imaging protocols and access to care, but has not been examined across the United States. The objective was to evaluate national variation in prenatal detection across geographic region and defect type in neonates and infants with CHD undergoing heart surgery.

Impact of prenatal haemodynamic and functional abnormalities in Ebstein's anomaly on survival.

Predicting outcomes of foetuses with Ebstein's anomaly and tricuspid valve dysplasia continues to be challenging. Limited data exist on the prognostic significance of prenatal haemodynamic and functional parameters in this population. Our aim was to investigate the prognostic significance of haemodynamic and ventricular functional parameters in addition to associated morphometric parameters in patients with Ebstein's anomaly.

When should we prescribe high-dose folic acid to prevent congenital heart defects?

Purpose Of Review: Provide a rationale for attempting prevention of congenital heart defects (CHDs).

Recent Findings: Prevention of neural-tube defects can be achieved with preconceptional use of folic acid. Extrapolating results from animal studies to human pregnancy shows that folate deficiency as well as one-time exposure to environmental factors in the first 2 to 3 weeks of human gestation can result in severe CHD.

Dynamics of pulmonary venous flow in fetuses with intrauterine growth restriction.

Objective: To test the hypothesis that the pulmonary vein pulsatility index (PVPI) is higher in fetuses with growth restriction (IUGR) than in normal fetuses.

Methods: Twenty-two fetuses with IUGR and twenty-one (21) fetuses with appropriate growth for gestational age from healthy mothers were studied. PVPI was calculated by Doppler echocardiography [maximal velocity (systolic or diastolic peak) - pre-systolic peak / mean velocity].

Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association.

Background: The goal of this statement is to review available literature and to put forth a scientific statement on the current practice of fetal cardiac medicine, including the diagnosis and management of fetal cardiovascular disease.

Methods And Results: A writing group appointed by the American Heart Association reviewed the available literature pertaining to topics relevant to fetal cardiac medicine, including the diagnosis of congenital heart disease and arrhythmias, assessment of cardiac function and the cardiovascular system, and available treatment options. The American College of Cardiology/American Heart Association classification of recommendations and level of evidence for practice guidelines were applied to the current practice of fetal cardiac medicine.

Evaluation of prenatal risk factors for prediction of outcome in right heart lesions: CVP score in fetal right heart defects.

Objective: To determine the prenatal variables predicting the risk of perinatal death in congenital right heart defects.

Methods: Retrospective analysis of 28 fetuses with right heart defects was performed. Logistic regression analyses were performed to obtain odds ratios (OR) for the relationship between the risk of death and echocardiographic parameters.

Environmental origins of congenital heart disease: the heart-placenta connection.

Although the mammalian embryo is well protected in the uterus, environmental chemicals, drugs, and maternal nutritional imbalances can interfere with regulatory pathways directing placental and embryonic development early in gestation. Embryonic cells are most susceptible to environmental influences during cellular specification and differentiation stages. Because biochemical differentiation precedes morphological outcome often by days, the period of susceptibility to environmental chemicals expectedly precedes visible morphogenic effects.

Foetal echocardiography of transposition of the great arteries and common arterial trunk.

Advances in foetal echocardiography allow detection of conotruncal anomalies such as transposition of the great arteries and common arterial trunk. Early detection of these anomalies is important for appropriate delivery planning, family counselling, and management. This manuscript will review the anatomic considerations, differential diagnosis, and foetal echocardiographic features of each of these malformations and review the importance of prenatal diagnosis and family counselling.

Effects of alcohol, lithium, and homocysteine on nonmuscle myosin-II in the mouse placenta and human trophoblasts.

Objective: Mouse embryonic exposure to alcohol, lithium, and homocysteine results in intrauterine growth restriction (IUGR) and cardiac defects. Our present study focused on the placental effects. We analyzed the hypothesis that expression of nonmuscle myosin (NMM)-II isoforms involved in cell motility, mechanosensing, and extracellular matrix assembly are altered by the 3 factors in human trophoblast (HTR8/SVneo) cells in vitro and in the mouse placenta in vivo.

Effect of angiotensin II on the left ventricular function in a near-term fetal sheep with metabolic acidemia.

We tested the hypothesis that, in acute metabolic acidemia, the fetal left ventricle (LV) has the capacity to increase its contractility in response to angiotensin II infusion. Eleven ewes and their fetuses were instrumented at 127-138/145 days of gestation. The effect of angiotensin II on fetal LV function was assessed using intraventricular pressure catheter and tissue Doppler imaging (TDI).

Myocardial tissue Doppler velocities in fetuses with hypoplastic left heart syndrome.

Background: Tissue Doppler Imaging (TDI) is a sensitive index of myocardial function. Its role in the fetus has not been extensively evaluated.

Objective: To compare myocardial tissue Doppler velocities in fetuses with hypoplastic left heart syndrome (HLHS) to those of normal fetuses (matched for gestational age.

The natural history of congenitally corrected transposition of the great arteries.

The natural history of congenitally corrected transposition of the great arteries is of clinical/surgical importance once the fetus is born without heart block or signs of heart failure. Without significant tricuspid valve malformation, associated defects such as ventricular septal defect and left ventricular outflow obstruction can be repaired surgically. The mortality and long-term outcome appear to be linked strongly with the severity of tricuspid valve regurgitation.

Doppler in fetal heart failure.

Fetal echocardiography has progressed to be able to diagnose many forms of congenital heart disease (CHD) and to assess the prognosis of cardiac lesions based on their anatomy and presentation in utero. Fetal echocardiography is for pregnancies at risk of structural, functional, and rhythm-related fetal heart disease. Routine obstetrical ultrasound screening is critical in the prenatal detection of fetal heart disease/CHD.

Folate protection from congenital heart defects linked with canonical Wnt signaling and epigenetics.

Purpose Of Review: Environmental factors, such as drugs, chemicals, or abnormal concentrations of natural metabolites, induce birth defects. Environmental effects on cardiogenesis have been little studied in contrast to neurogenesis. This review presents evidence on three environmental factors: alcohol, the drug lithium, and the metabolite homocysteine, impacting the Wnt/β-catenin pathway during cardiac development and folate protection.

Ductus venosus velocimetry in acute fetal acidemia and impending fetal death in a sheep model of increased placental vascular resistance.

We investigated whether hypoxemia without acidemia affects ductus venosus (DV) blood velocity waveform pattern in sheep fetuses with intact placenta and whether worsening acidemia and impending fetal death are related to changes in DV velocimetry in fetuses with increased placental vascular resistance. A total of 34 fetuses were instrumented at 115-136/145 days of gestation. Placental embolization was performed in 22 fetuses on the fourth postoperative day, 24 h before the experiment.

Folate rescues lithium-, homocysteine- and Wnt3A-induced vertebrate cardiac anomalies.

Elevated plasma homocysteine (HCy), which results from folate (folic acid, FA) deficiency, and the mood-stabilizing drug lithium (Li) are both linked to the induction of human congenital heart and neural tube defects. We demonstrated previously that acute administration of Li to pregnant mice on embryonic day (E)6.75 induced cardiac valve defects by potentiating Wnt-beta-catenin signaling.

A vision for an International Society for Fetal and Perinatal Cardiovascular Disease.

Purpose Of Review: The purpose of this review is to explain why it is now time to create an International Society for Fetal and Perinatal Cardiovascular Disease.

Recent Findings: Rapid advances in four domains that involve the professionals caring for patients with congenital cardiac disease all point to the fact that it is now time to create an International Society for Fetal and Perinatal Cardiovascular Disease: fetal diagnosis - the improved ability to diagnose prenatal cardiovascular disease due to education and improved ultrasound technology; subspecialization--the development of perinatal cardiology as a true subspecialty of the professions of pediatric cardiology and perinatology; analysis of outcomes--the multidisciplinary international efforts in the areas of nomenclature and databases for the analysis of outcomes of treatments for patients with congenitally malformed hearts, efforts that span traditional geographic and subspecialty boundaries; globalization - the rapidly evolving global organization of professionals caring for patients with congenital heart disease.

Summary: Healthcare professionals caring for the pregnant woman and fetus with congenital cardiac disease would be enthusiastic about the creation of an International Society for Fetal and Perinatal Cardiovascular Disease in order to achieve multiple objectives: to discuss the management of prenatal and perinatal cardiovascular disease (not exclusively cardiac malformations); to benefit from educational programs covering prenatal and perinatal physiology and pathophysiology, clinical and technical topics, as well as genetic, ethical, and psychosocial aspects of this relatively new discipline; and finally to share our basic science, translational, and clinical research interests.

Digoxin for the treatment of fetal congestive heart failure with sinus rhythm assessed by cardiovascular profile score.

Objective: To evaluate the effects of digoxin on the progression of congestive heart failure (CHF), and to determine the best predictors of perinatal death in fetuses with sinus rhythm and CHF.

Methods: This was a retrospective case series of fetuses with CHF treated with transplacental digoxin, evaluated at baseline (before treatment), weekly during treatment, and prior to death or delivery, using a 10-point cardiovascular profile score (CVPS) consisting of echocardiographic markers of cardiac dysfunction: cardiomegaly, valve insufficiency, hydrops, and abnormal venous and arterial Doppler flow profiles. Composite CVPS and component markers were compared before and after digoxin treatment by nonparametric testing and best predictors of perinatal survival assessed by regression analysis and receiver operating characteristics.

Molecular effects of lithium exposure during mouse and chick gastrulation and subsequent valve dysmorphogenesis.

Background: Lithium (Li) has been associated with cardiac teratogenicity in the developing fetus. We took advantage of the association of therapeutic administration of Li with an increase in heart defects to gain insight into both normal and pathological heart and valve development with GSK-3 inhibition. The objective of this study was to define whether Li mimicry of canonical Wnt/beta-catenin signaling induces cardiac valve defects.