Evaluation of left ventricular dysfunction by three-dimensional speckle-tracking echocardiography and bioinformatics analysis of circulating exosomal miRNA in obese patients

Abstract

Background: Obesity is an independent risk factor for cardiovascular disease and affects the human population. This study aimed to evaluate left ventricular (LV) dysfunction in obese patients with three-dimensional speckle-tracking echocardiography (3D-STE) and investigate the possible related mechanisms at the exosomal miRNA level.

Methods: In total, 43 participants (16 obese patients and 27 healthy volunteers) were enrolled. All subjects underwent full conventional echocardiography as well as 3D-STE. Characterization and high-throughput sequencing for the isolated circulating exosomes and the differentially expressed miRNAs (DEMs) were screened for target gene prediction and enrichment analysis.

Results: Obese patients had significantly lower global longitudinal strain (GLS) (-20.80%±3.10% vs. -14.77%±2.05%, P < 0.001), global circumferential strain (GCS) (-31.63%±3.89% vs. -25.35%±5.66%, P = 0.001), global radial strain (GRS) (43.21%±4.89% vs. 33.38%±3.47%, P < 0.001), and indexed LV end-diastolic volume (LVEDV) [38.07mL/m² (27.82mL/m²-9.57mL/m²) vs. 24.79mL/m² (21.97mL/m²-30.73mL/m²), P = 0.002] than healthy controls. GLS (ρ = 0.610, P < 0.001), GCS (ρ = 0.424, P = 0.005), and GRS (ρ = -0.656, P < 0.001) indicated a moderate relationship with body mass index (BMI). In obese patients, 33 exosomal miRNAs were up-regulated and 26 exosomal miRNAs were down-regulated when compared to healthy controls (P < 0.05). These DEMs possibly contribute to obesity-associated LV dysfunction through the PI3K-Akt signaling pathway. Important miRNAs, including miR-101-3p, miR-140-3p, and miR-99a-5p, have clinical utility in predicting early obesity-related myocardial injury.

Conclusions: The global strain obtained from 3D-STE can sensitively detect the decrease in LV myocardial function in obese patients. Key miRNAs and pathways provide a new theoretical basis and targets of action for studying obesity-induced LV dysfunction.

Trial registration: In accordance with the World Health Organization (WHO) definition of a clinical trial, this study does not include human health-related interventions. This study was carried out at the General Hospital of Ningxia Medical University after obtaining institutional ethical approval (KYLL-2022-0556) and written informed consent from all participants.

Keywords: Echocardiography; Exosomal miRNA; Left ventricular dysfunction; Obesity; Sequencing; Three-dimensional speckle-tracking echocardiography.