Predicting Disease Progression and Mortality in Aortic Stenosis: A Systematic Review of Imaging Biomarkers and Meta-Analysis

Abstract

Background: Detecting among patients with aortic stenosis (AS) those who are likely to rapidly progress, yet potentially benefiting from prophylactic aortic valve replacement, is needed for improved patient care. The objective of this study was to evaluate the role of imaging biomarkers in predicting the progression to clinical symptoms and death in patients with AS. Methods: We searched the Pubmed and the International Clinical Trials Registry Platform databases for studies including patients with AS, and investigating imaging techniques, published in any language until Jan 1, 2018. Eligible sets of data include effect of imaging biomarkers relative to: (1) Overall mortality, (2) Cardiac mortality, and (3) Overall events (Symptom onset and Major Adverse Cardiovascular Events). Meta-analysis was used to examine associations between the imaging biomarkers and outcomes of AS using Random Effect models. Results: Eight studies and 1,639 patients were included after systematic review. Four studies investigated aortic valve calcification (AVC) whereas the remaining investigated biomarkers provided by cardiac magnetic resonance (CMR). Four articles investigated the presence of midwall fibrosis on late-gadolinium enhancement imaging, three reported its extent (LGE%) and two, the myocardial extracellular volume (ECV). By decreasing strength of association, there were significant associations between cardiac mortality and LGE% [Relative Risk (RR) = 1.05, 95% Confidence Interval (CI) 1.01-1.10]; overall mortality and AVC (RR = 1.19, 95%CI: 1.05-1.36); overall events and ECV (RR = 1.68, 95%CI: 1.17-2.41); cardiac mortality and midwall fibrosis (RR = 2.88, 95%CI: 1.12-7.39). Conclusion: AVC and myocardial fibrosis imaging biomarkers predict the outcomes in AS, and help understanding AS pathophysiology and setting therapeutic targets.

Keywords: aortic stenosis; calcification; imaging biomarker; meta-analysis; myocardial fibrosis; remodeling.

Figure 1

PRISMA flowchart of study selection.

Figure 2

Forest plots showing the average relative risks for the strength of association between imaging biomarkers and outcomes in AS. AVC, aortic valve calcification; LGE, late gadolinium enhancement; ECV, extracellular volume. (A) (AVC: I² = 87.1, Tau² = 0.01, n = 992). (B) (Midwall LGE: I² = 84.1, Tau² = 0.76, n = 647). (C) (LGE %: I² = 0, Tau² = 0, n = 444). (D) (ECV: I² = 77.7, Tau² = 0.5, n = 377).