Abstract
BACKGROUND: Accurate aortic stenosis (AS) phenotyping requires multimodality imaging which has limited availability. The digital aortic stenosis severity index (DASSi), an artificial intelligence biomarker of AS-related remodeling on single-view 2-dimensional echocardiography, predicts AS progression independent of Doppler measurements. We sought to evaluate the ability of DASSi to define personalized AS progression profiles and to validate its performance as a scalable alternative to multimodality imaging features of functional, structural, and biological AS severity. METHODS: In the SALTIRE-2 trial (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis 2) of participants with mild or moderate AS, we performed blinded DASSi measurements (probability of severe AS, 0-1) on baseline transthoracic echocardiograms. We evaluated the association between baseline DASSi and (1) disease severity by hemodynamic (peak aortic valve velocity), structural (computed tomography-derived aortic valve calcium score), and biological features ([(18)F]sodium fluoride uptake on positron emission tomography-computed tomography); (2) longitudinal disease progression (absolute change in peak aortic valve velocity and aortic valve calcium score); and (3) incident aortic valve replacement. We used generalized linear mixed or Cox models adjusted for risk factors and aortic valve area. RESULTS: We analyzed 134 participants (72 [interquartile range, 69-78] years; 27 [20.1%] women) with a mean baseline DASSi of 0.51 (SD, 0.19). DASSi was independently associated with cross-sectional disease severity: each SD increase was associated with higher peak aortic valve velocity (+0.21 [95% CI, 0.12-0.30] m/s), aortic valve calcium score (+284 [95% CI, 101-467] Agatston units), and [(18)F]sodium fluoride target-to-background ratio(max) (+0.17 [95% CI, 0.04-0.31]). Higher DASSi was also associated with disease progression by Doppler (peak aortic valve velocity) and computed tomography (aortic valve calcium score) at 24 months (P interaction for DASSi × time<0.001), and future aortic valve replacement (75 events over 5.5 [interquartile range, 2.4-7.2] years, adjusted hazard ratio, 1.42 [95% CI, 1.11-1.84] per SD). CONCLUSIONS: DASSi is associated with functional, structural and biological features of AS severity and predicts disease progression and adverse outcomes. DASSi-enhanced echocardiography may provide an accessible alternative to multimodality AS imaging and serve as a predictive enrichment biomarker in clinical trials. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.