Right Ventricular Myocardial Strain and Proteomic Analysis of Fetuses With Left Ventricular Hypoplasia: A Cross‐Sectional Study

TL;DR

This study finds that fetuses with left ventricular hypoplasia have reduced right ventricular function and altered protein expression, suggesting early developmental issues affecting both sides of the heart.

Contribution

The study reveals novel molecular mechanisms of right ventricular dysfunction in left ventricular hypoplasia fetuses through proteomic analysis and strain measurements.

Findings

RV global longitudinal strain was significantly lower in LVH fetuses compared to controls.

144 differentially expressed proteins in LVH fetuses were linked to extracellular matrix, cytoskeleton, and DNA replication pathways.

Key factors affecting RV function included RV/LV ratio, LV sphericity index, and LV end-diastolic dimension z-score.

Abstract

Decreased right ventricular (RV) function in fetuses with left ventricular hypoplasia (LVH) increases the risk of adverse outcome. This study aimed to quantitatively evaluate RV myocardial function prenatally in LVH, and explore the relevant mechanism from protein expression.

81 singleton fetuses diagnosed with LVH and 81 normal controls were retrospectively included. We used RV global longitudinal strain (RVGLS) derived from two‐dimensional speckle tracking imaging to evaluate RV myocardial function and “XGboost” algorithm to select effective factors affecting RV myocardial function in fetuses with LVH. Bioinformatics analysis was performed for differentially expressed proteins between specimens with LVH and normal fetuses.

In LVH fetuses, RVGLS was significantly lower in fetuses with LVH than in controls (p < 0.001). “XGboost” model showed that RV/LV ratio, LV sphericity index, combined with double outlet right ventricle, and LV end‐diastolic dimension z‐score had the greatest effect on RVGLS, with SHAP analysis revealing nonlinear relationships between these factors and RVGLS. Proteomics in LVH fetuses demonstrated 144 differentially expressed RV proteins (68 upregulated, 76 downregulated), enriched in extracellular matrix, cytoskeleton, and DNA replication pathways (GO/KEGG). Notably, dysregulated processes included actin depolymerization, cell cycle control, and MCM complex function, suggesting adaptive RV remodeling at molecular levels. Interobserver reproducibility for strain measurements was excellent (ICC > 0.9).

Impaired RV myocardial function and RV protein spectrum differentiated from normal fetuses have been observed in fetuses with LVH, which shed light on the novel perspective that myogenic developmental abnormalities are not limited to the left heart but also extend to RV cardiomyocytes during the embryonic stage.

Impaired RV myocardial function has been observed in fetuses with LVH.Changes in RV tissue protein expression, which refers to cardiomyocyte contraction, potentially provide significant advice in prenatal counseling and management of fetuses with LVH.

Impaired RV myocardial function has been observed in fetuses with LVH.

Changes in RV tissue protein expression, which refers to cardiomyocyte contraction, potentially provide significant advice in prenatal counseling and management of fetuses with LVH.

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