High myocardial fibrosis (ECV≥29.9%) combined with elevated TIMP1 (>287 ng/mL) increases mortality risk 4.8-fold post-AVR in severe aortic stenosis patients.
Do CMR-assessed myocardial fibrosis and circulating biomarkers of inflammation/fibrosis predict long-term mortality in patients with severe aortic stenosis undergoing surgical AVR?
The combination of CMR-derived extracellular volume and circulating biomarkers (ST2, TIMP1) significantly enhances risk stratification for long-term mortality in patients with severe aortic stenosis undergoing surgical valve replacement.
Absolute Event Rate: 0% vs 0%
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. Methods 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. Results 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), P0.01; ST2: 0.51 (0.19-0.83), P0.01). After adjustment for confounding factors the association of TIMP1 with ECV (adjusted for age, sex, STS score, 6-min walk test and estimated glomerular filtration rate eGFR) and with LGE (adjusted for age, sex, coronary artery disease, EuroSCORE II, hypertension and eGFR) remained statistically significant (P0.05 and P0.01, respectively). Sixty-six patients died during follow-up (median: 9.6 years, interquartile range: 6.99-10.82). Increased ECV (HR95%CI= 1.13 1.01-1.25, P0.05), ST2 (HR95%CI= 2.05 1.21-3.48, P0.01) and TIMP1 (HR95%CI= 2.15 1.34 -3.43, P0.01) at baseline were associated with a higher mortality risk after adjusting for age, sex, eGFR, STS score and NT-proBNP. TIMP1 and ST2 combined enhanced ECV prognostic value (IDI: 0.117 0.036-0.200, P0.05; NRI: 0.332 0.130 -0.525, P0.001. Patients with elevated ECV in combination with either high TIMP1 (Figure 2A) or ST2 (Figure 2B) exhibited a higher risk of mortality compared to those with low ECV. The increased risk observed in patients exhibiting both high ECV and elevated biomarkers remained significant after adjusting for age, sex, eGFR, STS score and NT-proBNP: ECV≥29.9% 287 ng/mL: HR=4.80 (95%CI: 2.18-10.6), P0.001. ECV≥29.9% 34.2 ng/mL HR=3.25 (95%CI: 1.51-6.97), P0.01. Histological analysis of endomyocardial biopsies showed that patients with elevated both ECV and biomarkers, particularly TIMP1, exhibited increased myocardial collagen fiber deposition (P0.05) and crosslinking (P0.05). Conclusion 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.Association of TIMP1 and ST2 with ECV Prognostic value of ECV & Biomarkers
Miqueo et al. (Sat,) reported a other. High myocardial fibrosis (ECV≥29.9%) combined with elevated TIMP1 (>287 ng/mL) increases mortality risk 4.8-fold post-AVR in severe aortic stenosis patients.
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