Hypoplastic left heart syndrome-a scoping review.

Abstract

Background: An estimated 3% of all newborns with congenital heart disease develop hypoplastic left heart syndrome (HLHS), making it a prominent cause of mortality in this group if surgical procedures or a heart transplant are not implemented. While compelling evidence supports a genetic element, identifying a particular genetic cause is limited to a subgroup of patients, indicating a complex and multifaceted origin for this condition. The objective of this scientific contribution was to identify, synthesize, and analyze the scientific knowledge produced regarding the implications of researching on HLHS in a scoping review.

Methods: The search for articles was diligently conducted between January 1, 2019 and February 20, 2025 on the PubMed/MEDLINE, Scopus, Web of Science, and Cochrane databases. This search was assiduously complemented by a gray search. It included internet browsers (e.g., Google) and medical textbooks. The following research question steered our study: "What are the basic data on the etiology and pathogenesis on HLHS?" All stages of the selection process were iwis carried out by the single author.

Results: Of the 1,364 articles found, 75 were included in the sample for analysis, which was implemented with an additional 25 articles from references and gray literature. The studies analyzed indicated that HLHS is one of the most complex congenital heart defects, characterized by small or hypoplastic left-sided heart structures and a dominant right ventricle. The Fontan circulation and the phased surgical technique that it entails have been the cornerstones of HLHS patient care since its debut some 40 years ago. Although there is considerable genetic evidence for HLHS, the exact genetic cause of this cardiologic entity is still not well known. HLHS remains genetically heterogeneous. There is evidence of incomplete penetrance for the C57Bl/6J-b2b635Clo/J (Ohia) mice.

Conclusions: HLHS is a complex and complicate congenital heart disease, which requires further investigation. In this article, I further explore the involvement of the endocardium in the progression of ventricular hypoplasia, therefore offering a potential explanation for the morphological alterations observed in the disease as a result of compromised blood flow to the developing ventricle. These findings may support a new paradigm for the complicated genetics of this congenital heart defect and there is some evidence that HLHS can originate genetically in a combinatorial approach.