Cargando…

Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?

Hypoplastic left heart syndrome occurs in up to 3% of all infants born with congenital heart disease and is a leading cause of death in this population. Although there is strong evidence for a genetic component, a specific genetic cause is only known in a small subset of patients, consistent with a...

Descripción completa

Detalles Bibliográficos
Autores principales: Grossfeld, Paul, Nie, Shuyi, Lin, Lizhu, Wang, Lu, Anderson, Robert H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462956/
https://www.ncbi.nlm.nih.gov/pubmed/30813450
http://dx.doi.org/10.3390/jcdd6010010
_version_ 1783410668252168192
author Grossfeld, Paul
Nie, Shuyi
Lin, Lizhu
Wang, Lu
Anderson, Robert H.
author_facet Grossfeld, Paul
Nie, Shuyi
Lin, Lizhu
Wang, Lu
Anderson, Robert H.
author_sort Grossfeld, Paul
collection PubMed
description Hypoplastic left heart syndrome occurs in up to 3% of all infants born with congenital heart disease and is a leading cause of death in this population. Although there is strong evidence for a genetic component, a specific genetic cause is only known in a small subset of patients, consistent with a multifactorial etiology for the syndrome. There is controversy surrounding the mechanisms underlying the syndrome, which is likely due, in part, to the phenotypic variability of the disease. The most commonly held view is that the “decreased” growth of the left ventricle is due to a decreased flow during a critical period of ventricular development. Research has also been hindered by what has been, up until now, a lack of genetically engineered animal models that faithfully reproduce the human disease. There is a growing body of evidence, nonetheless, indicating that the hypoplasia of the left ventricle is due to a primary defect in ventricular development. In this review, we discuss the evidence demonstrating that, at least for a subset of cases, the chamber hypoplasia is the consequence of hyperplasia of the contained cardiomyocytes. In this regard, hypoplastic left heart syndrome could be viewed as a neonatal form of cardiomyopathy. We also discuss the role of the endocardium in the development of the ventricular hypoplasia, which may provide a mechanistic basis for how impaired flow to the developing ventricle leads to the anatomical changes seen in the syndrome.
format Online
Article
Text
id pubmed-6462956
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-64629562019-04-16 Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease? Grossfeld, Paul Nie, Shuyi Lin, Lizhu Wang, Lu Anderson, Robert H. J Cardiovasc Dev Dis Review Hypoplastic left heart syndrome occurs in up to 3% of all infants born with congenital heart disease and is a leading cause of death in this population. Although there is strong evidence for a genetic component, a specific genetic cause is only known in a small subset of patients, consistent with a multifactorial etiology for the syndrome. There is controversy surrounding the mechanisms underlying the syndrome, which is likely due, in part, to the phenotypic variability of the disease. The most commonly held view is that the “decreased” growth of the left ventricle is due to a decreased flow during a critical period of ventricular development. Research has also been hindered by what has been, up until now, a lack of genetically engineered animal models that faithfully reproduce the human disease. There is a growing body of evidence, nonetheless, indicating that the hypoplasia of the left ventricle is due to a primary defect in ventricular development. In this review, we discuss the evidence demonstrating that, at least for a subset of cases, the chamber hypoplasia is the consequence of hyperplasia of the contained cardiomyocytes. In this regard, hypoplastic left heart syndrome could be viewed as a neonatal form of cardiomyopathy. We also discuss the role of the endocardium in the development of the ventricular hypoplasia, which may provide a mechanistic basis for how impaired flow to the developing ventricle leads to the anatomical changes seen in the syndrome. MDPI 2019-02-23 /pmc/articles/PMC6462956/ /pubmed/30813450 http://dx.doi.org/10.3390/jcdd6010010 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Grossfeld, Paul
Nie, Shuyi
Lin, Lizhu
Wang, Lu
Anderson, Robert H.
Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?
title Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?
title_full Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?
title_fullStr Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?
title_full_unstemmed Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?
title_short Hypoplastic Left Heart Syndrome: A New Paradigm for an Old Disease?
title_sort hypoplastic left heart syndrome: a new paradigm for an old disease?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462956/
https://www.ncbi.nlm.nih.gov/pubmed/30813450
http://dx.doi.org/10.3390/jcdd6010010
work_keys_str_mv AT grossfeldpaul hypoplasticleftheartsyndromeanewparadigmforanolddisease
AT nieshuyi hypoplasticleftheartsyndromeanewparadigmforanolddisease
AT linlizhu hypoplasticleftheartsyndromeanewparadigmforanolddisease
AT wanglu hypoplasticleftheartsyndromeanewparadigmforanolddisease
AT andersonroberth hypoplasticleftheartsyndromeanewparadigmforanolddisease