Diffuse Interstitial Fibrosis of the Myocardium Predicts Outcome in Moderate and Asymptomatic Severe Aortic Stenosis

Abstract

BACKGROUND Patients with moderate or asymptomatic severe aortic stenosis (AS) are at risk of cardiovascular events. OBJECTIVES The authors investigated the utility of cardiac magnetic resonance (CMR) to identify drivers of outcome in patients with moderate or asymptomatic severe AS. METHODS A prospective, international, multicenter cohort (n 1/4 457) of patients with moderate (aortic valve area [AVA]: 1.0-1.5 cm2) or asymptomatic severe AS (AVA <= 1.0 cm2 and NYHA functional class I-II) patients underwent CMR. Diffuse interstitial fibrosis and scar in the myocardium were analyzed with extracellular volume fraction (ECV%) and late gadolinium enhancement (LGE). The outcome was a composite of mortality and heart failure admission. RESULTS Median ECV% was 26.6% (IQR: 24.4%-29.9%), and LGE was present in 31.5% (median 0.8%; IQR: 0.1%1.7%). Greater AS severity was associated with greater left ventricular mass and diastolic dysfunction, but not with ECV% or LGE. During a median 5.7 years of follow-up, 83 events occurred. Patients with events had higher ECV% (median ECV % 26.3% vs 28.2%; P 1/4 0.003). Patients in the highest ECV% tertiles (ECV% >28.6%) had worse outcomes both in the entire cohort and in those with NYHA functional class I moderate or severe AS, and ECV% was independently associated with outcome (adjusted HR: 1.05; P 1/4 0.039). The ECV% had significant incremental prognostic value when added to parameters of AS severity and cardiac function, comorbidities, aortic valve replacement, and LGE (P < 0.05). CONCLUSIONS Increased diffuse interstitial fibrosis of the myocardium is associated with poor outcomes in patients with moderate and asymptomatic severe AS and can help identify those who require closer surveillance for adverse outcomes. (JACC Cardiovasc Imaging. 2025;18:180-191) (c) 2025 by the American College of Cardiology Foundation.