Abstract
Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7–84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p = 0.003) and miRNA 133 (p = 0.03). LF condition was associated with higher levels of miRNA1 (p = 0.02) and miRNA21 (p = 0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p = 0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p = 0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes.
Highlights
Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern
MiRNAs have a differential distribution considering different phenotypes of severe AVS: a low flow condition is associated with increased levels of miRNA21, miRNA1 and miRNA133, while LVH is reflected by higher levels of miRNA133;
Available data suggest that distinct miRNAs are dysregulated in AVS, supporting different underlying pathophysiological mechanisms. miRNA21 is up-regulated in cardiomyocytes during the fibrotic process; both myocardial and circulating levels of miRNA21 are significantly higher in patients with AVS compared to controls, correlating with Mean trans-aortic pressure gradient (MG) and fibrosis
Summary
Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. The key findings on transthoracic echocardiogram (TTE) are generally limited to the evaluation of thickening, calcification, reduced systolic opening of the valve leaflets and to flow-dependent parameters assessment (i.e. velocity and gradients), reflecting only the “valvular side” of the pathology[4] This approach disregards the LV components (function; texture) of the disease, resultingprone to diagnostic discrepancies[5,6]. Withrespect to this, recent AHA/ACC guidelines for VHD patients management describe 3 distinct phenotypes for symptomatic severe (D) AVS: high gradient (D1); low-flow/low-gradient AVS with reduced Ejection Fraction (EF < 50%), or classical low flow AVS (D2); paradoxical low-flow/low-gradient AVS (D3) (EF > 50%)[9] Another accredited classification for AVS is based on flow and gradient patterns, identifying 4 groups (group 1: normal flow/low gradient [NF/LG]; group 2: normal flow/high gradient [NF/HG]; group 3: low flow/high gradient [LF/HG]; group 4: low flow/low gradient [LF/LG])[10,11]. The aim of our study was to evaluate: a) the relative expression of miRNA levels in different phenotypes of severe AVS; b) the association of miRNA levels with structural and functional echocardiographic variables in a cohort of patients with severe symptomatic AVS evaluated for aortic valve replacement (AVR)
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