Management of the hypoplastic left heart syndrome: A challenge to those who care for children with heart diseases

AbstractData from neurological and radiological research show an abnormal neurological development in patients treated for hypoplastic left heart syndrome. Thus, the aim of this study was to survey the quality of life scores in comparison with healthy children and children with other heart diseases (mild, moderate, and severe heart defects, heart defects in total). Children with hypoplastic left heart syndrome (aged 6.3–16.9 years) under compulsory education requirements, who were treated at the Children’s Heart Center Linz between 1997 and 2009 (n = 74), were surveyed. Totally, 41 children and 44 parents were examined prospectively by psychologists according to Pediatric Quality of Life Inventory, a health-related quality of life measurement. The results of the self-assessments of health-related quality of life on a scale of 1–100 showed a wide range, from a minimum of 5.00 (social functioning) to a maximum of 100 (physical health-related summary scores, emotional functioning, school functioning), with a total score of 98.44. The parents’ assessments (proxy) were quite similar, showing a range from 10 (social functioning) up to 100. Adolescent hypoplastic left heart syndrome patients rated themselves on the same level as healthy youths and youths with different heart diseases. The results show that patients with hypoplastic left heart syndrome aged 6–16 years can be successfully supported and assisted in their psychosocial development even if they show low varying physical and psychosocial parameters. The finding that adolescent hypoplastic left heart syndrome patients estimated themselves similar to healthy individuals suggests that they learnt to cope with a severe heart defect.

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Single-Cell RNA-Seq Reveals Endocardial Defect in Hypoplastic Left Heart Syndrome

10.1101/809731 ◽

2019 ◽

Author(s):

Yifei Miao ◽

Lei Tian ◽

Marcy Martin ◽

Sharon L. Paige ◽

Francisco X. Galdos ◽

...

Keyword(s):

Single Cell ◽

Hypoplastic Left Heart Syndrome ◽

De Novo ◽

Heart Diseases ◽

Heart Tissue ◽

Abnormal Development ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Mesenchymal Transition ◽

Left Heart Syndrome

SummaryHypoplastic left heart syndrome (HLHS) is one of the most challenging forms of congenital heart diseases. Previous studies were mainly focused on intrinsic defects in myocardium. However, this does not sufficiently explain the abnormal development of the cardiac valve, septum, and vasculature, known to originate from the endocardium. Here, using single-cell RNA profiling, induced pluripotent stem cells, and human fetal heart tissue with an underdeveloped left ventricle, we identified a developmentally impaired endocardial population in HLHS. The intrinsic endocardial deficits contributed to abnormal endothelial to mesenchymal transition, NOTCH signaling, and extracellular matrix organization, all of which are key factors in valve formation. Consequently, endocardial abnormalities conferred reduced proliferation and maturation of cardiomyocytes through a disrupted fibronectin-integrin interaction. Several recently described HLHS de novo mutations were associated with abnormal endocardial gene and FN1 regulation and expression. Our studies provide a rationale for considering endocardial function in future regenerative strategies for HLHS.

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Congenital heart diseases (1). First-stage palliation of hypoplastic left heart syndrome in 3 cases.

Japanese Journal of Cardiovascular Surgery ◽

10.4326/jjcvs.18.51 ◽

1988 ◽

Vol 18 (1) ◽

pp. 51-53

Author(s):

T. Kitagawa

Keyword(s):

Hypoplastic Left Heart Syndrome ◽

Congenital Heart ◽

Heart Diseases ◽

Congenital Heart Diseases ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Left Heart Syndrome

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Neurodevelopmental Outcomes in Patients with Hypoplastic Left Heart Syndrome

Internet Journal of Allied Health Sciences and Practice ◽

10.46743/1540-580x/2010.1295 ◽

2010 ◽

Author(s):

Elizabeth Hagan ◽

Harvey Feldman

Keyword(s):

Hypoplastic Left Heart Syndrome ◽

Motor Development ◽

Negative Impact ◽

Heart Diseases ◽

Hospital Length Of Stay ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Neurodevelopmental Outcomes ◽

Iq Scores ◽

Left Heart Syndrome

Purpose: Hypoplastic Left Heart Syndrome (HLHS) accounts for 7-9% of all congenital heart diseases. It is fatal unless surgically corrected. Survival has improved overtime. However, neurodevelopmental outcomes have not been known until recently. This paper discusses the neurodevelopmental outcomes of patients with HLHS and the factors that influence these outcomes. Methods: A search of the literature was performed using several databases, medical textbooks and other on-line sources to locate research related to HLHS and neurodevelopment in HLHS. Results: Mean performance IQ scores tended to be lower than mean verbal IQ scores. Mean motor scores were below normal population values indicating impairment. Growth was impaired in many of those with HLHS. Factors that had negative impact on outcomes included deep hypothermic circulatory arrest (DHCA), cardiopulmonary bypass (CPB), longer hospital length-of-stay, seizures, and lower socioeconomic status (SES). Conclusions: The studies show that children with HLHS do have neurodevelopmental deficits. Intelligence, motor development and growth are all affected. Focus during care of these patients should be spent on improving the factors discussed that have been shown to have negative impacts on outcomes.

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Pregnancy follow-up and outcomes of patients diagnosed with fetal hypoplastic left heart syndrome

Aegean Journal of Obstetrics and Gynecology ◽

10.46328/aejog.v2i2.47 ◽

2020 ◽

Vol 2 (2) ◽

pp. 9-13

Author(s):

Özge Yücel Çelik ◽

Osman Yılmaz ◽

Mehmet Obut ◽

Ayşe Keleş ◽

Mine Gültekin Çalık ◽

...

Keyword(s):

Hypoplastic Left Heart Syndrome ◽

Heart Diseases ◽

Fetal Echocardiography ◽

Cardiac Anomaly ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Cardiac Anomalies ◽

Cardiac Evaluation ◽

Left Heart Syndrome

Objective: The study aimed to evaluate the follow-up and outcomes of patients diagnosed with fetal hypoplastic left heart syndrome in the prenatal period. Materials: Between January 2017 and June 2019 the data of 36 patients diagnosed with fetal hypoplastic left heart syndrome (HLHS) in Etlik Zübeyde Hanım Woman’s Health Care Training and Research Hospital (EZH) were evaluated retrospectively. All patients who suspected for any fetal or cardiac anomaly were evaluated in detail ultrasound by two senior perinatologists and a pediatric cardiologist fort a detailed cardiac evaluation. The demographic characteristics, pregnancy follow-up and maternal and fetal outcomes of patients were evaluated. Results: During the study period fetal echocardiography was performed for 10.377 patients. A totally 382 (3.7%) fetuses were diagnosed with congenital heart diseases and 36 (9.4%) of these fetuses were diagnosed with hypoplastic left heart syndrome. Additional extracardiac anomalies were detected in 13 (36.1%) fetuses. Concomitant fetal cardiac anomalies were detected in 15 patients and ventricular septal defect (n: 11) and double outlet right ventricle (n:8) were the most common concomitant cardiac anomalies. Eight pregnancies with fetal HLHS were terminated. The data of 10 patient’s newborns were obtained and none of them lived up to a year. Conclusion: The study revealed that the majority of patients with fetal HLHS are in low-risk population thus the routine fetal cardiac evaluation is of great importance. The prognosis and outcome of the pregnancy diagnosed with fetal HLHS are poor. The option of termination of the pregnancy should be considered.

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Abstract 12937: Single-cell Transcriptomic Analysis Reveals Developmentally Impaired Endocardial Population in Hypoplastic Left Heart Syndrome

Circulation ◽

10.1161/circ.142.suppl_3.12937 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Yifei Miao ◽

Lei Tian ◽

Marcy Martin ◽

Sharon Paige ◽

Francisco X Galdos ◽

...

Keyword(s):

Single Cell ◽

Hypoplastic Left Heart Syndrome ◽

Heart Development ◽

Heart Diseases ◽

Critical Role ◽

Abnormal Development ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Mesenchymal Transition ◽

Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is one of the most challenging forms of congenital heart diseases. Previous studies were mainly focused on intrinsic defects in myocardium. However, this does not sufficiently explain the abnormal development of the cardiac valve, septum, and vasculature, known to originate from the endocardium. Here, using single-cell transcriptomic profiling, induced pluripotent stem cells (iPSC) derived endocardial cells (iEECs), human fetal heart tissue with underdeveloped left ventricle, as well as a Xenopus model, we identified a developmentally impaired endocardial population in HLHS. The intrinsic endocardial deficits contributed to abnormal endothelial to mesenchymal transition, NOTCH signaling, and extracellular matrix organization, all of which are key factors in valve formation. Consequently, in an endocardium-myocardium co-culture system, we found that endocardial abnormalities conferred reduced proliferation and maturation of iPSC derived cardiomyocyte (iPSC-CMs) judged by Ki67 staining, contractility, sarcomere organization, and related gene expressions through a disrupted fibronectin (FN1)-integrin interaction. Several recently described HLHS de novo mutations such as ETS1 and CHD7 showed reduced binding to FN1 promoter and enhancer in HLHS vs. control iEECs based on ChIP-qPCR analysis. Additionally, we found that suppression of the ETS1 in Xenopus caused reduced endocardial FN1 expression and impaired heart development. Supplementation of FN1 or ETS1 over-expression in HLHS iEECs could rescue dysfunctions in both endocardium and myocardium in HLHS. Our studies reveal a critical role of endocardial abnormality in causing HLHS, and provide a rationale for improving endocardial function in future regenerative strategies. Schematic illustration of the endocardial and myocardial defects in HLHS.

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Patient-specific genomics and cross-species functional analysis implicate LRP2 in hypoplastic left heart syndrome

eLife ◽

10.7554/elife.59554 ◽

2020 ◽

Vol 9 ◽

Author(s):

Jeanne L Theis ◽

Georg Vogler ◽

Maria A Missinato ◽

Xing Li ◽

Tanja Nielsen ◽

...

Keyword(s):

Hypoplastic Left Heart Syndrome ◽

Heart Development ◽

Heart Diseases ◽

Heart Defects ◽

Patient Specific ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Healthy Human ◽

Altered Expression ◽

Left Heart Syndrome

Congenital heart diseases (CHDs), including hypoplastic left heart syndrome (HLHS), are genetically complex and poorly understood. Here, a multidisciplinary platform was established to functionally evaluate novel CHD gene candidates, based on whole-genome and iPSC RNA sequencing of a HLHS family-trio. Filtering for rare variants and altered expression in proband iPSCs prioritized 10 candidates. siRNA/RNAi-mediated knockdown in healthy human iPSC-derived cardiomyocytes (hiPSC-CM) and in developing Drosophila and zebrafish hearts revealed that LDL receptor-related protein LRP2 is required for cardiomyocyte proliferation and differentiation. Consistent with hypoplastic heart defects, compared to parents the proband’s iPSC-CMs exhibited reduced proliferation. Interestingly, rare, predicted-damaging LRP2 variants were enriched in a HLHS cohort; however, understanding their contribution to HLHS requires further investigation. Collectively, we have established a multi-species high-throughput platform to rapidly evaluate candidate genes and their interactions during heart development, which are crucial first steps toward deciphering oligogenic underpinnings of CHDs, including hypoplastic left hearts.

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