Monocytes at the crossroads of aortic stenosis and myocardial damage

Abstract Aortic stenosis (AS) is the most common heart valve disease in high-income countries, causing significant morbidity and mortality. It results from progressive thickening and calcification of the aortic valve (AV) leaflets, leading to AV narrowing and myocardial remodeling—both key contributors to disease progression and symptoms. With no pharmacological treatment to slow AS, aortic valve replacement (AVR) remains the only therapeutic option for symptomatic patients. However, limited understanding of AS pathophysiology and the absence of reliable prognostic markers hinder improved patient outcomes. A comprehensive reassessment of AS pathophysiology, integrating both valvular and myocardial remodeling is essential for advancing prognostic tools and therapeutic strategies. Inflammation plays a central role in these processes, drawing increasing attention to monocytes. This review provides an updated overview of monocytes’ multifaceted involvement in AS, including: (i) fibrocalcific remodeling of the valve, (ii) myocardial injury during disease progression, and (iii) structural valve deterioration (SVD) after surgical or transcatheter AVR. We will also discuss the potential of monocyte subsets as biomarkers for AS progression and post-AVR prognosis, as well as the therapeutic targeting of monocytes to prevent AS, SVD, and subsequent myocardial dysfunction.