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.

Uncovering the treatable burden of severe aortic stenosis in the UK

“… 1 2 As highlighted by the OxVALVE Study, 3 a significant portion of the UK population (1.3% of their cohort of individuals age ≥65 years had undiagnosed AS) will remain undetected during their lifetime or experience a ‘late’ diagnosis when their condition reaches an advanced, symptomatic stage. 4 The prevalence of AS correlates strongly with advancing age and is a major cause of death among older individuals. 1 2 For example, within the large National Echocardiography Database of Australia (NEDA) patient cohort, the incidence of AS rose eightfold from 5 to 40 cases/1000 person-years among those aged <30 years to >80 years (overall incidence of ~18 cases/1000 person-years).…”

“…Aortic stenosis (AS) is one of the most common acquired forms of heart valve disease requiring clinical intervention 1 2. As highlighted by the OxVALVE Study,3 a significant portion of the UK population (1.3% of their cohort of individuals age ≥65 years had undiagnosed AS) will remain undetected during their lifetime or experience a ‘late’ diagnosis when their condition reaches an advanced, symptomatic stage 4. The prevalence of AS correlates strongly with advancing age and is a major cause of death among older individuals 1 2.…”

Models and Techniques to Study Aortic Valve Calcification in Vitro, ex Vivo and in Vivo. An Overview

“…However, detailed discussion of risks and indications for surgical intervention is beyond the scope of this article (see review by Lindman et al ( Lindman et al, 2020 )). Among a jungle of advanced and sometimes costly imaging modalities which may be predictive of disease progression and mortality in aortic stenosis ( Nchimi et al, 2018 ), a blood sample for measuring circulating biomarkers is a simple, inexpensive, and easily available method to provide information about the stage and possible risks of asymptomatic aortic stenosis. Even if biomarkers represent indirect assessment, they might possibly be helpful to identify progression of CAVD and asymptomatic patients who then would benefit from aortic valve replacement.…”

Does the severity of low-gradient aortic stenosis classified by computed tomography–derived aortic valve calcification determine the outcome of patients after transcatheter aortic valve implantation (TAVI)?

“…The degree of AVC has been demonstrated to be associated with overall mortality in the general population [9] and in conservatively treated patients with moderate or severe AS [10,11]. The possible causes underlying this prognostic Fig.…”