Myocardial fibrosis and outcome in aortic stenosis: a CMR and circulating biomarker study

Abstract

Background: Patients with aortic stenosis (AS) are at high mortality risk even post-aortic valve replacement (AVR). Extracellular matrix remodeling, fibrosis and inflammation may contribute to poor outcomes in AS. We investigated the relationship between cardiac magnetic resonance (CMR)-assessed fibrosis, both focal (late gadolinium enhancement, LGE) and diffuse (extracellular volume fraction, ECV), blood biomarkers of inflammation/fibrosis, and mortality in AS patients. Additionally, we explored the association of these parameters with myocardial fibrosis in endomyocardial biopsies. Method(s): Single center, prospective study conducted in 146 severe AS patients referred for surgical AVR. Circulating biomarker quantification, transthoracic echocardiogram and CMR were performed. Myocardial fibrosis was histochemically assessed in intraoperative anteroseptal biopsies. Mortality data was obtained from the UK national registry. Result(s): At baseline, soluble IL-33 receptor-related protein (ST2) and tissue inhibitor of metalloproteinases 1 (TIMP1) were directly associated with both ECV (Figure 1) and LGE (TIMP1: Estimate (95%CI): 2.08 (0.54-3.62), P=29.9% & TIMP1>287 ng/mL: HR=4.80 (95%CI: 2.18-10.6), P=29.9% & ST2>34.2 ng/mL HR=3.25 (95%CI: 1.51-6.97), P<0.01. Histological analysis of endomyocardial biopsies showed that patients with elevated both ECV and biomarkers, particularly TIMP1, exhibited increased myocardial collagen fiber deposition (P<0.05) and crosslinking (P<0.05). Conclusion(s): Poor outcomes in AS patients following AVR may be driven by a complex interplay between myocardial extracellular matrix remodeling, fibrosis and inflammation, that can be captured by ECV, ST2 and TIMP1. Their assessment might improve AS patients risk stratification.