Left ventricular hypoplasia: a spectrum of disease involving the left ventricular outflow tract, aortic valve, and aorta

Abstract

"Hypoplastic left heart syndrome" is an unsatisfactory term describing lethal underdevelopment of the left ventricle (LV). It represents the more severe end of a spectrum of LV hypoplasia, mandating single-ventricle palliation or cardiac transplantation. Less severe "borderline" ventricular hypoplasia may instead allow various biventricular therapeutic strategies and better long-term outcomes. In this review, we consider factors causing and modifying the abnormal development of the LV. LV hypoplasia is typically seen in association with left ventricular outflow tract obstruction, itself part of a spectrum of related defects with common etiologies. Secondary responses to outflow obstruction are complex but involve abnormal flow dynamics and shear stresses that result in compromised and poorly orchestrated ventricular growth and development. Subsequent remodeling is likely influenced by genetic modifiers, including intrinsic myocardial growth signaling pathways, possibly including those of HAND transcription factors. In addition, during the latter stages of gestation, cardiomyocytes undergo a switch in myogenic potential and lose the ability to undergo mitosis. Ventricular hyperplasia can therefore no longer occur; remodeling is instead limited to muscular hypertrophy. Subtle differences in this switch in myogenic potential--and modulators thereof--are likely to be of clinical and therapeutic importance, especially in children with "borderline LVs" being considered for fetal interventions or post-natal biventricular repair strategies. Finally, by more clearly understanding the initiators and propagators of abnormal ventricular development, we can hope to lean away from grouping a heterogeneous group of infants together under the unsatisfactory term "hypoplastic left heart syndrome."