| Autor: |
CHERPAZ, Maelle, SEILLIER, Gaultier, Bergerot, Cyrille, Pozzi, Matteo, Pierrard, Romain, Chanon, Stéphanie, Brun, Camille, Chalabreysse, Lara, May, Chloe, Givre, Lucas, Farhat, Fadi, Vola, Marco, Obadia, Jean François, Amaz, Camille, Paillard, Melanie, Thibault, Helene |
| Zdroj: |
Circulation (Ovid); November 2022, Vol. 146 Issue: Supplement 1 pA14605-A14605, 1p |
| Abstrakt: |
Introduction:Type 2 diabetes (T2D) may induce myocardial alterations and is associated with an increased risk of heart failure. T2D is often associated to LV pressure overload, as encountered in aortic stenosis (AS).Hypothesis:We hypothesized that T2D has deleterious effects on LV remodelling and function in patients with severe AS and we explored some underlying mechanisms.Methods:Non diabetic and T2D patients with severe AS, referred for aortic valve replacement, were included. Patients with atrial fibrillation, LV ejection fraction (LVEF) <50%, significant coronaropathy or other valvulopathy were excluded. Before surgery, patients underwent blood tests and a complete echocardiography. During surgery, a LV myocardium biopsy was obtained for histological analysis.Results:We included 82 patients, including 33 T2D. Hypertension and dyslipidaemia were more frequent in T2D patients. Severity of the AS was similar between the two groups. Echocardiography revealed that T2D was associated with a more pronounced LV hypertrophy (mass LV 3D/hight2.7; p=0.03) and systolic dysfunction (Global Longitudinal Strain (GLS) 15±3 vs 18±2 %; p<0.01). In addition, LV ventricular filling pressure was more often increased in T2D patients (50% of T2D vs 26% of non-diabetics; p=0.03). Circulating levels of leptin and endothelin 1 were significantly higher in T2D. Interestingly leptin level correlates with diastolic function (left atrial strain; r=-0.25, p=0.01) and Endothelin 1 with LV mass (r=0.27, p<0.001) and GLS. Histologic analysis revealed an enhanced cardiomyocyte hypertrophy in T2D biopsies but similar degrees of fibrosis. Proximity ligation assay displayed a significant decreased proximity between the IP3-receptor and the mitochondrial porin VDAC in T2D hearts suggesting a reduced reticulum-mitochondria Ca2+transfer.Conclusions:T2D is associated with an increased LV remodelling and dysfunction in patients with a severe AS as well as an increased circulating level of leptin and endothelin-1. Our results also suggest a potential role of reticulum-mitochondria Ca2+uncoupling. |
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