Timing of intervention in aortic stenosis: a review of current and future strategies

Abstract
### Learning objectives Aortic stenosis (AS) is the most common valve disease requiring surgical intervention in high-income countries.1 It is characterised by progressive thickening, fibrosis and calcification of the leaflets leading to restriction and valve obstruction.2 The consequent increase in left ventricular afterload leads to a hypertrophic response of the left ventricle, normalising wall tension and maintaining cardiac output. However, with progressive valvular stenosis, this hypertrophic response eventually decompensates resulting in symptom development, heart failure and death. With no medications proven to attenuate or reverse stenosis progression, the only available treatment is valve replacement. This should ideally be performed when the risks of the disease process (ie, sudden cardiac death, irreversible functional impairment and heart failure) outweigh those of intervention (ie, procedural risk, long-term complications and potential need for reoperation). However, we frequently lack robust evidence to make accurate assessments of such risk. Deciding on the timing of valvular intervention is therefore difficult in many patients, and contemporary clinical guidelines are often underpinned by historical observational data rather than high-quality randomised controlled trials. This article will review our current understanding of the pathophysiology of AS, describe and examine the evidence behind current guideline recommendations and explore potential future strategies to optimise the timing of valve intervention. Since the original description of AS by Mönckeberg in 1904, the decline in rheumatic fever and ageing population have led to a demographic transition towards fibrocalcific disease. For many years, fibrocalcific AS …