Serum Biomarkers of Cardiovascular Remodelling Reflect Extra-Valvular Cardiac Damage in Patients with Severe Aortic Stenosis.

Laura Bäz,Christian Jung,P Christian Schulze,Gudrun Dannberg,Julian Westphal,Alexander Pfeil,Katja Grün,Marcus Franz,Sven Möbius-Winkler

doi:10.3390/ijms21114174

Abstract

In patients with aortic stenosis (AS), a novel staging classification of extra-valvular left and right heart damage with prognostic relevance was introduced in 2017. The aim of the study was to evaluate the biomarkers of cardiovascular tissue remodelling in relation to this novel staging classification. Patients were categorized according to the novel staging classification into stages 0 to 4. The levels of matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), B and C domain containing tenascin-C (B+ Tn-C, C+ Tn-C), the ED-A and ED-B domain containing fibronectin (ED-A+ Fn, ED-B+ Fn), endothelin 1 (ET-1) and neutrophil gelatinase-associated lipocalin (NGAL) were determined in serum by ELISA. There were significantly decreased serum levels of MMP-9 and increased levels of B+ Tn-C and C+ Tn-C when comparing stages 0 and 1 with stage 2, with no further dynamics in stages 3 and 4. In contrast, for TIMP-1, C+ Tn-C, ED-A+ Fn, ET-1 and NGAL, significantly increased serum levels could be detected in stages 3 and 4 compared to both stages 0 and 1 and stage 2. ED-A+ Fn and ET-1 could be identified as independent predictors of the presence of stage 3 and/or 4. To the best of our knowledge, this is the first study identifying novel serum biomarkers differentially reflecting the patterns of left and right heart extra-valvular damage in patients suffering from AS. Our findings might indicate a more precise initial diagnosis and risk stratification.

Highlights

Degenerative aortic valve stenosis (AS), the most frequently occurring acquired valvular heart disease, shows increasing prevalence rates in the aging society [1,2]
In all AS patients, a transfemoral approach was chosen for trans-catheter aortic valve implantation (TAVI) and carried out successfully
The second notable cluster of biomarkers consisted of tissue inhibitor of metalloproteinases 1 (TIMP-1), ED-A+ Fn, endothelin 1 (ET-1) and neutrophil gelatinase-associated lipocalin (NGAL), for which we could detect significantly increased serum concentrations, when comparing staging group 3 with lower staging groups

Summary

Introduction

Degenerative aortic valve stenosis (AS), the most frequently occurring acquired valvular heart disease, shows increasing prevalence rates in the aging society [1,2]. Two further entities, namely low-gradient aortic stenosis (LGAS) and paradoxical low-flow, low-gradient aortic stenosis (PLFLGAS), have been introduced, referring to the importance of stroke volume for correct severity grading [1,4,5,6,7]. The latter is mandatory to avoid underestimation of the stenosis, resulting in treatment delay, and with respect to the fact that the different entities are of prognostic relevance [8]. Patients eligible for TAVI will represent a more and more heterogeneous collective in terms of, among other factors, age, comorbidities or special anatomical states

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