Assessment of valvular function in over 47,000 people using deep learning-based flow measurements.

Valvular heart disease is associated with a high global burden of disease. Even mild aortic stenosis confers increased morbidity and mortality, prompting interest in understanding normal variation in valvular function at scale. We developed a deep learning model to study velocity-encoded magnetic resonance imaging in 47,223 UK Biobank participants. We calculated eight traits, including peak velocity, mean gradient, aortic valve area, forward stroke volume, mitral and aortic regurgitant volume, greatest average velocity, and ascending aortic diameter. We then computed sex-stratified reference ranges for these phenotypes in up to 31,909 healthy individuals. In healthy individuals, we found an annual decrement of 0.03cm 2 in the aortic valve area. Participants with mitral valve prolapse had a 1 standard deviation [SD] higher mitral regurgitant volume (P=9.6 × 10 -12 ), and those with aortic stenosis had a 4.5 SD-higher mean gradient (P=1.5 × 10 -431 ), validating the derived phenotypes' associations with clinical disease. Greater levels of ApoB, triglycerides, and Lp(a) assayed nearly 10 years prior to imaging were associated with higher gradients across the aortic valve. Metabolomic profiles revealed that increased glycoprotein acetyls were also associated with an increased aortic valve mean gradient (0.92 SD, P=2.1 x 10 -22 ). Finally, velocity-derived phenotypes were risk markers for aortic and mitral valve surgery even at thresholds below what is considered relevant disease currently. Using machine learning to quantify the rich phenotypic data of the UK Biobank, we report the largest assessment of valvular function and cardiovascular disease in the general population.