Diastolic Dysfunction and Aortic Stenosis: From Bystander to Therapeutic Target

Aortic stenosis (AS) is increasingly recognized as a complex myocardial disease rather than an isolated valvular disorder. Emerging translational and clinical evidence suggests that diastolic dysfunction in AS is not merely an epiphenomenon of aging or comorbidity burden but develops early and may represent a central mechanistic link between valvular obstruction and heart failure. Chronic left ventricular pressure overload increases wall stress and myocardial oxygen demand, triggering a cascade of structural, metabolic, and microvascular alterations that culminate in left ventricular hypertrophy, interstitial fibrosis, impaired relaxation, and reduced ventricular compliance. The severity of diastolic dysfunction before aortic valve replacement significantly influences clinical outcomes. Persistent myocardial fibrosis and impaired diastolic reserve may remain despite successful valve intervention, helping explain why a substantial proportion of patients continue to experience heart failure symptoms after valve replacement. Despite its clinical relevance, diastolic dysfunction remains insufficiently integrated into current guideline-directed decision-making, raising the question of whether it should assume a more central role in determining the optimal timing of aortic valve replacement. Beyond correction of valvular obstruction alone, diastolic dysfunction may therefore represent both a marker of advanced myocardial remodeling and a potential therapeutic target in patients with AS.