Transcriptomic Signatures of Calcific Aortic Valve Stenosis Severity in Human Tricuspid and Bicuspid Aortic Valves

There is currently no medical therapy for calcific aortic valve stenosis. We aimed to identify transcriptomic signatures of the disease severity. We performed mRNA sequencing from explanted human aortic valves of 500 individuals who underwent aortic valve replacement (n = 440) or a heart transplant (n = 60). We performed differential gene expression analyses according to hemodynamic severity, valve morphology, calcification grade, and age of onset, and we estimated immune cell proportions. We identified immune response, inflammation, and adipocyte metabolism as predominant pathways associated with calcific aortic valve stenosis severity, offering new perspectives for the development of pharmacological treatments.