Hypoplasia Of Left Heart Structures Research Articles

Maternal hyperoxygenation for the human fetus: should studies be curtailed?

Congenital hypoplasia of left heart structures in fetuses frequently progresses with gestational development. Interference with cerebral development is common in these fetuses. Chronic maternal hyperoxygenation (MHO) has been recommended to increase left ventricular size and to limit cerebral damage. The effects of MHO on cerebral blood flow and metabolism have been studied in normal fetuses and fetuses with left heart hypoplasia. Maternal hyperoxygenation increases fetal pulmonary blood flow. This is associated with reduction of foramen ovale flow, thus limiting the increase in left ventricular output. Modest increase in the size of left heart structures has been reported, but in another study, no significant improvement occurred. In sheep fetuses increased oxygenation results in marked reduction of cerebral blood flow, with no change in oxygen delivery or consumption by the brain, but significant reduction in cerebral glucose delivery and consumption. In one study of fetuses with left heart hypoplasia, chronic MHO was associated with decrease in head size. The effectiveness of MHO in improving left ventricular development is controversial. MHO is, however, associated with reduction of cerebral blood flow and possible interference with cerebral development. In view of this it is recommended that all studies of chronic maternal hyperoxygenation be curtailed.

Erratum to: Critically Underdeveloped Left Heart Morphology Associated with Prematurity and Low Birth Weight: Conditional Staged Rehabilitation Towards Biventricular Repair and Time-Related Growth of Left Heart Structures.

This is a case report of premature low birth weight infant with hypoplasia of left heart structures and a large malaligned VSD who underwent successful staged approach of biventricular repair. We obtained qualitative and quantitative echocardiographic, MRI, and conventional catheterization data to support stepwise strategy towards LV rehabilitation to sustain adequate cardiac output. A thorough and intense follow-up has shown significant growth of left heart structures and favorable clinical status following staged biventricular repair. Our data indicate usefulness of qualitative and quantitative advanced complimentary multi-imaging modalities in predicting the postnatal growth potential of critically underdeveloped left heart structures.

Induced pluripotent stem cell modelling of HLHS underlines the contribution of dysfunctional NOTCH signalling to impaired cardiogenesis.

Hypoplastic left heart syndrome (HLHS) is among the most severe forms of congenital heart disease. Although the consensus view is that reduced flow through the left heart during development is a key factor in the development of the condition, the molecular mechanisms leading to hypoplasia of left heart structures are unknown. We have generated induced pluripotent stem cells (iPSC) from five HLHS patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype. Our data indicate that HLHS-iPSC have a reduced ability to give rise to mesodermal, cardiac progenitors and mature cardiomyocytes and an enhanced ability to differentiate to smooth muscle cells. HLHS-iPSC-derived cardiomyocytes are characterised by a lower beating rate, disorganised sarcomeres and sarcoplasmic reticulum and a blunted response to isoprenaline. Whole exome sequencing of HLHS fibroblasts identified deleterious variants in NOTCH receptors and other genes involved in the NOTCH signalling pathway. Our data indicate that the expression of NOTCH receptors was significantly downregulated in HLHS-iPSC-derived cardiomyocytes alongside NOTCH target genes confirming downregulation of NOTCH signalling activity. Activation of NOTCH signalling via addition of Jagged peptide ligand during the differentiation of HLHS-iPSC restored their cardiomyocyte differentiation capacity and beating rate and suppressed the smooth muscle cell formation. Together, our data provide firm evidence for involvement of NOTCH signalling in HLHS pathogenesis, reveal novel genetic insights important for HLHS pathology and shed new insights into the role of this pathway during human cardiac development.

Surgical Considerations in the Management of Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome is a congenital heart defect characterized by hypoplasia of left heart structures. Over the past 3 decades, there have been advances in techniques and management in the care of these patients. We discuss shunt selection, operative strategies, transplantation, and outline various facets of management at the University of Florida. This is a review of the literature highlighting some of the technical aspects of the preoperative, operative, and postoperative care that are important in today's management of hypoplastic left heart syndrome.

Strategies to Maintain Biventricular Circulation in Patients With High-Risk Anatomy

Although hypoplasia of left heart structures presents with a spectrum of severity, management decisions are typically dichotomous: single-ventricle palliation or biventricular repair. Since the long-term outcomes of single-ventricle palliation are sub-optimal, strategies to aggressively pursue biventricular circulation in patients with borderline left heart structures have been developed. Recent strategies and surgical techniques to rehabilitate the left heart in patients with borderline left heart are described.

Course and Outcome of Fetuses Suspected of Having Coarctation of the Aorta during Gestation

To report the course and outcome of a group of fetuses with prenatal suspicion of coarctation of the aorta. Retrospective observational study in two tertiary fetal cardiology centers between 1993 - 2005. 96 fetuses of whom 52 infants were born alive were studied. Of the 52 liveborn infants, 34 had coarctation of the aorta (65.4 %), thirteen had prenatally diagnosed additional cardiac anomalies (VSD, ASD, aortic and pulmonary stenosis, persistent left superior vena cava) and three were managed as having hypoplastic left heart syndrome. Three neonates had additional extracardiac malformations diagnosed prenatally. 22 neonates underwent surgery, nineteen within the first ten days of life. One neonate only developed clinical signs of coarctation on the fourteenth day of life. The early surgical mortality was three of 22 (13.6 %). The mortality was influenced by prematurity. The survival rate on the basis of intention-to-treat was twenty-nine of 34 neonates with confirmed coarctation (85.3 %). Coarctation of aorta during fetal life continues to be a difficult diagnosis. The potential of progressive hypoplasia of left heart structures during gestation in the case of fetal aortic isthmus stenosis with the development of a hypoplastic left heart should be kept in mind and therefore sequential echo-cardiography is recommended during gestation.

Follow-up of aortic coarctation repair in neonates

ObjectivesThe purposes of this study were to assess the growth of left heart (LH) structures, to evaluate midterm outcomes, and to define echocardiographic parameters predictive of increased risk of re-intervention in patients born with aortic coarctation and hypoplasia of LH structures that underwent neonatal coarctation repair. BackgroundNeonatal coarctation is often associated with hypoplasia of LH structures. Although previous studies have shown that coarctation repair can be performed with good results in these neonates, there are little data regarding growth of the LH structures or outcomes in these patients. MethodsPatients with isolated coarctation and at least one hypoplastic LH valve (mitral or aortic Z-score <−2) who underwent a neonatal coarctation repair were identified. Clinic charts and the latest echocardiograms were reviewed. ResultsAll 55 patients were alive and well, and no patient had clinical evidence of mitral stenosis. Three patients (5%) required re-intervention. Thirty-eight patients had echocardiograms that demonstrated normal left ventricular (LV) size and function with a follow-up duration of 73 ± 19 months (range 3 to 9 years). Both mitral and aortic annulus Z-scores increased significantly: −3.1 ± 1.5 to −0.5 ± 1.6 (p < 0.001) and −3.5 ± 1.9 to 0.7 ± 1.6 (p < 0.001), respectively. Nine patients (24%) developed LV outflow tract obstruction by echocardiographic criteria. ConclusionsAfter neonatal coarctation repair with associated LH hypoplasia, LH structures increase substantially in size, and clinical outcomes are excellent at midterm follow-up. Despite initial annular hypoplasia, the need for intervention for mitral or aortic/subaortic stenosis is uncommon.

Cellular changes in experimental left heart hypoplasia

Hypoplastic left heart syndrome (HLHS) is a rare but deadly congenital malformation, which can be created experimentally in the chick embryo by left atrial ligation (LAL). The goal of this study was to examine the cellular changes leading to the profound remodeling of ventricular myocardial architecture that occurs in this model. Hypoplasia of left heart structures was produced after 3H-thymidine prelabeling by partial LAL at stage 24, thereby reducing its volume, and redistributing blood preferentially to the developing right ventricle (RV). Controls included both sham-operated and intact stage-matched embryos. Survivors were studied 4 days after the ligation, when the heart organogenesis was essentially complete. Paraffin sections of the hearts were subjected to autoradiography and immunohistochemistry to detect changes in history of cell proliferation and expression of myosin, and growth factors implicated in cardiomyocyte proliferation. Sampling for apoptosis detection using TUNEL assay was done at stages 29 and 34. LAL resulted in decreased levels of proliferation in the left ventricular compact layer and trabeculae. The right ventricular compact layer also showed a slight decrease, but the trabeculae showed no differences. Anti-myosin staining was significantly reduced in all compartments. The expression levels of growth factors were altered as well. Apoptosis was increased in the right atrioventricular mesenchyme, with no changes in the working myocardium. These data suggest that changes in cardiomyocyte proliferation play a significant role in the pathogenesis of HLHS. Anat Rec 267:137–145, 2002. © 2002 Wiley-Liss, Inc.

Cellular changes in experimental left heart hypoplasia.

Hypoplastic left heart syndrome (HLHS) is a rare but deadly congenital malformation, which can be created experimentally in the chick embryo by left atrial ligation (LAL). The goal of this study was to examine the cellular changes leading to the profound remodeling of ventricular myocardial architecture that occurs in this model. Hypoplasia of left heart structures was produced after 3H-thymidine prelabeling by partial LAL at stage 24, thereby reducing its volume, and redistributing blood preferentially to the developing right ventricle (RV). Controls included both sham-operated and intact stage-matched embryos. Survivors were studied 4 days after the ligation, when the heart organogenesis was essentially complete. Paraffin sections of the hearts were subjected to autoradiography and immunohistochemistry to detect changes in history of cell proliferation and expression of myosin, and growth factors implicated in cardiomyocyte proliferation. Sampling for apoptosis detection using TUNEL assay was done at stages 29 and 34. LAL resulted in decreased levels of proliferation in the left ventricular compact layer and trabeculae. The right ventricular compact layer also showed a slight decrease, but the trabeculae showed no differences. Anti-myosin staining was significantly reduced in all compartments. The expression levels of growth factors were altered as well. Apoptosis was increased in the right atrioventricular mesenchyme, with no changes in the working myocardium. These data suggest that changes in cardiomyocyte proliferation play a significant role in the pathogenesis of HLHS.