Circulating endothelial progenitor cells are actively involved in the reparative mechanisms of stable ischemic myocardium

Background: Myocardial fibrosis (MF) is an adverse correlate of severe aortic valve stenosis (SAVS). microRNA expression modulates different pathophysiological pathways in cardiovascular disease. In particular miRNA­21, has been associated to MF due to pressure overload. Non­invasive estimation of MF, using speckle­tracking echocardiography (2D­STE), could be useful in determining early myocardial damage. Purpose: To analyze the correlation between 2D­STE parameters, MF, plasmatic and tissue miRNA­21 in SAVS. Methods: We evaluated 36 consecutive patients (75.2±8 y.o., 63% F) with SAVS and preserved ejection fraction (EF), undergoing to surgical aortic valve replacement (AVR; Euroscore II 2.28±1.13%; Logistic Euroscore: 6±4.1%). Clinical, ECG, biohumoral evaluation (including plasma miRNA­21) and a complete echocardiography, including 2D­STE, was performed before AVR. 28 patients eventually underwent AVR and, in 23 of them, a basal interventricular septum biopsy was performed. MF and tissue miRNA­21 expression (micro­dissection) were evaluated in each sample. Results: All patients with SAVS (AVAi 0.33±0.1 cm2/m2; V max 4.4±0.4 m/sec; Mean Grad. 50±9 mmHg) showed concentric hypertrophy (LVMi 147±20.7 g/m2, RWT 0.51±0.07), diastolic dysfunction and increased Valvulo­Arterial Impedance (ZVA: 5.9±2.3 mmHg/ml/m2). Despite a preserved EF (66±11%), an altered global and septal deformation (Global longitudinal strain, GLS −13±6.1; Global longitudinal strain rate, GLSr −0.8±0.2 1/sec; Global early diastolic Sr, GLSrE 1±0.35 1/sec; Septal longitudinal strain, SLS −8.6±2.8%; SL­Sr −0,6±0.1 1/sec; SL­SrE 0.6±0.29 1/sec) were observed. We found a significant association between MF and 2D­STE parameters, stroke volume and end­diastolic pressure (all p<0.05). Tissue miRNA­21 was mainly expressed in fibrous tissue than in myocardium (p<0.0001). Myocardial miRNA­21 was associated with AVAi (r=0.46; p=0.043) and cardiac index (r=0.5; p=0.02) while fibrous tissue miRNA­21 was associated to GLS (r=0.8; p=0.0003), GLSrE (r=−0.72; p=0.005), SLS (r=0.6; p=0.01), SL­Sr (r=0.54; p=0.03), SL­SrE (r=0.5; p=0.04) and PAPs (r=0.66; p=0.004). Plasma miRNA­21 was associated to MF (r=0.5; p=0.02) and septal longitudinal strain (r=0.38; p=0.037). Conclusions: In SAVS with preserved EF, MF is associated to impaired myocardial deformation. miRNA­21 has a potential pathophysiological role in fibrogenesis. Non­invasive evaluation of plasmatic miRNA­21 and 2D­STE could be useful in risk stratification, to optimize the timing of surgery in SAVS patients.