Hypoplastic left heart syndrome: anatomical spectrum, clinical management, and brain defects
- 1Department of Critical Care Medicine, University of Pittsburgh School of Medicine
- 2Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh
- 3Department of Cardiothoracic Surgery, UPMC Children's Hospital of Pittsburgh
Abstract
Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease (CHD) involving hypoplasia of the left ventricle (LV) and the aorta (Ao), along with aortic and mitral valve stenosis/atresia with or without coarctation. It is a physiologically single-ventricle lesion, previously uniformly fatal, but now survivable with a 3-stage surgical palliation ending with the Fontan circulation, a circulation for only one working ventricle. In the classical definition of HLHS, the ventricular septum is intact; however, HLHS variants have been described with similar single-ventricle pathophysiology in which the hypoplastic LV is not hemodynamically coupled to the aortic outflow. Evidence for a genetic etiology for HLHS is indicated by its high recurrence risk, the association with various chromosomal abnormalities, and the demonstration of mutations in mice causing HLHS. Despite surgical advances allowing survival of patients with HLHS, there is still high morbidity and mortality after their first-stage palliation. The causes of such high morbidity and mortality are not well understood, but most deaths are likely related to cardiovascular/hemodynamic causes. Studies in the animal models of HLHS show that this cardiac lesion arises early in embryogenesis, decreases left-sided inflow, and is associated with metabolic dysfunction, cell proliferation, and differentiation defects. Findings indicate HLHS is also associated with intrinsic cell deficits, deficits that may also contribute to the high risk of heart failure and adverse neurodevelopment. In this article, we update a previous review by describing the basic pathophysiology; pertinent pre- and postoperative management of HLHS and its anatomical variants; and novel insights from the HLHS mouse model on the causes of HLHS-associated heart failure and poor neurodevelopment, as well as potential therapeutic strategies.
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BibTeX
@article{bellcheddar2026hypoplastic,
title = {{Hypoplastic left heart syndrome: anatomical spectrum, clinical management, and brain defects}},
author = {Yolandee Bell-Cheddar and William Devine and Carlos Eduardo Diaz-Castrillon and Richard Tang and Mario Castro-Medina and Shannon A. Solt and Adam Christopher and Raymond Morales and XinXiu Xu and Cecilia W. Lo and Jiuann-Huey I. Lin},
journal = {Frontiers in Cardiovascular Medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1877717},
url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1877717/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hypoplastic left heart syndrome: anatomical spectrum, clinical management, and brain defects
AU - Yolandee Bell-Cheddar
AU - William Devine
AU - Carlos Eduardo Diaz-Castrillon
AU - Richard Tang
AU - Mario Castro-Medina
AU - Shannon A. Solt
AU - Adam Christopher
AU - Raymond Morales
AU - XinXiu Xu
AU - Cecilia W. Lo
AU - Jiuann-Huey I. Lin
PY - 2026
DA - 2026/10/29
JO - Frontiers in Cardiovascular Medicine
DO - 10.3389/fcvm.2026.1877717
UR - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1877717/full
AB - Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease (CHD) involving hypoplasia of the left ventricle (LV) and the aorta (Ao), along with aortic and mitral valve stenosis/atresia with or without coarctation. It is a physiologically single-ventricle lesion, previously uniformly fatal, but now survivable with a 3-stage surgical palliation ending with the Fontan circulation, a circulation for only one working ventricle. In the classical definition of HLHS, the ventricular septum is intact; however, HLHS variants have been described with similar single-ventricle pathophysiology in which the hypoplastic LV is not hemodynamically coupled to the aortic outflow. Evidence for a genetic etiology for HLHS is indicated by its high recurrence risk, the association with various chromosomal abnormalities, and the demonstration of mutations in mice causing HLHS. Despite surgical advances allowing survival of patients with HLHS, there is still high morbidity and mortality after their first-stage palliation. The causes of such high morbidity and mortality are not well understood, but most deaths are likely related to cardiovascular/hemodynamic causes. Studies in the animal models of HLHS show that this cardiac lesion arises early in embryogenesis, decreases left-sided inflow, and is associated with metabolic dysfunction, cell proliferation, and differentiation defects. Findings indicate HLHS is also associated with intrinsic cell deficits, deficits that may also contribute to the high risk of heart failure and adverse neurodevelopment. In this article, we update a previous review by describing the basic pathophysiology; pertinent pre- and postoperative management of HLHS and its anatomical variants; and novel insights from the HLHS mouse model on the causes of HLHS-associated heart failure and poor neurodevelopment, as well as potential therapeutic strategies.
SN - 2297-055X
ER -