Measuring progression of aortic stenosis: computed tomography versus echocardiography

Calcific aortic stenosis (AS) is characterised by an initial inflammatory phase, with endothelial damage, lipoprotein infiltration and oxidative stress. This stage is followed by a disorganisation of the extracellular matrix with an overproduction of collagen fibres and a mineralisation phase in which valvular interstitial cells differentiate into an osteoblast-like cell type, leading to microcalcification analogue to skeletal bone formation. This self-perpetuating cycle of progressive fibrocalcific remodelling leads to macrocalcification, increases valve rigidity and therefore narrows the effective orifice area, increasing left ventricular afterload and ultimately provoking myocardial damage and symptoms (figure 1).1 Valvular fibrosis, although understudied, appears to play a major role in younger, bicuspid valve and female patients and is one of the reasons sex-specific thresholds are used to define severe AS by CT aortic valve calcification (CT-AVC) quantification (2000 Agatston units (AU) for men and 1200 AU for women).2 The pathogenic model depicted in figure 1 is not necessarily followed in a serial fashion, and although the advance of the disease is inexorable, the rate of AS progression remains largely unpredictable. However, some markers of rapid progression have been described, such as systolic hypertension,3 bicuspid morphology4 and metabolic syndrome.5 Figure 1 Model of AS progression. Pathophysiological model of serial AS progression (‘aortic stenosis cascade’, in blue), along with imaging biomarkers targeting each phase (red) and potential disease-modifying treatments being currently tested in randomised clinical trials (green). 1South Korean PCSK9 inhibitors (NCT03051360); 2EAVaLL: early aortic valve lipoprotein(a) lowering (NCT02109614); 3SALTIRE II: study investigating the effect of drugs used to treat osteoporosis on the progression of calcific aortic stenosis (NCT02132026); 4BASIK2: bicuspid aortic valve stenosis and the effect of vitamin K2 on calcium metabolism on 18F-NaF PET/MRI (NCT02917525); 5EvoLVeD: early valve replacement guided by biomarkers of LV decompensation …