Transcatheter versus surgical aortic valve replacement in patients with aortic stenosis: molecular pathways and correlation with clinical and echocardiographic parameters

Abstract

Abstract Background Transcatheter aortic valve replacement (TAVR) has reformed the management of aortic stenosis (AS), being firstly approved in high-risk patients and becoming progressively a therapeutic alternative to surgery (surgical aortic valve replacement, SAVR) for all the risk categories. Several data pointed out the role of inflammation, oxidative stress, and pathological remodeling in AS natural history. The aim of our study is to investigate the molecular pathways involved in the AS pathophysiology and in the early response to AV replacement in patients subjected to percutaneous or surgical approach. Secondary aims are to evaluate the variation in clinical and echocardiographic parameters of left ventricular (LV) function before and after procedure. Methods We enrolled 36 consecutive patients with a diagnosis of severe AS and preserved ejection fraction (17 SAVR patients and 19 TAVR patients). Biological samples, clinical and echocardiographic evaluation were gained before (T0) and 72 hours after the procedure (T1). We performed 3 gene expression arrays on pooled cDNA from peripheral blood mononuclear cells of the 2 study groups. Results SAVR patients were significantly younger (p=0.0003) and with a lower STS score (p=0.0004). After the procedure, SAVR showed a longer ICU stay (p=0.0019) and a more frequent need of inotropes/vasopressors (p=0.006). Gene expression analysis revealed a reduction of the pro-apoptotic gene CASP3 (n=13; median, IQR: 1.01, 0..89-1.62 for T0 vs 0.68, 0.58-0.85 for T1; p=0.019) and of the transcription factor MEF2C (n=13; 1.00, 0.57-1.31 for T0 vs 0.56, 0.42-0.87 for T1; p=0.028) in TAVR patients, together with significantly increased levels of the antioxidant molecule GPX1 (n=14; 1.04, 0..71-1.34 for T0 vs 1.37, 1.23-1.85 for T1;p=0.030). In SAVR patients, our data showed increased post-procedural levels of GPX1 (n=6; 0.99, 0.49-1.23 for T0 vs 1.81, 1.27-2.00 for T1; p=0.028), and of the oxidative markers CAT (n=10; 0.40, 0.27-0.69 for T0 vs 1.17, 0.59-2.06 for T1; p=0.022,) and NOX2 (n=8; 0.41, 0.31-0.63 for T0 vs 1.04, 0.73-1.54 for T1; p=0.012) (Fig.1). TAVR patients displayed a direct correlation between the gene expression of molecules involved in apoptosis (CASP3), myocardial remodeling (GTF2I, MEF2C) and oxidative stress (MPO, CAT, TXNIP) and indexed left ventricular volumes (Fig.2A), while SAVR patients showed an inverse correlation with LVEF for GTF2I, MEF2C, CAT and MPO gene expression levels (Fig.2B). Conclusions By demonstrating 1) a significant post-procedural downregulation in the expression of genes involved in oxidative stress pathways for TAVR patients if compared with SAVR patients, and 2) a significant correlation of the basal levels of genes involved in apoptosis, myocardial remodeling, and oxidative stress with post-procedural ventricular volumes and LVEF, our study provides a biological rationale to support the percutaneous approach for AS patients, independently from their class of risk.Figure 1Figure 2