Early Echocardiographic Predictors of Rapid Progression in Moderate Aortic Stenosis: a Multi-center Prospective Cohort Study of 650 Patients.

Abstract

Introduction: Moderate aortic stenosis (AS) has traditionally been considered a stable condition, but recent evidence suggests that some patients progress rapidly to severe AS, leading to earlier symptom onset and worse outcomes. Current guidelines primarily focus on severe AS, leaving a gap in risk stratification for moderate cases. This study aims to identify echocardiographic and clinical predictors of rapid progression in moderate AS to refine patient selection for closer monitoring and early intervention.

Aim: To identify clinical, echocardiographic, and imaging predictors of progression in moderate aortic stenosis, with particular focus on diastolic function, ΔV/Δt, myocardial fibrosis, and the impact of comorbidities and medical therapy on disease trajectory.

Methods: This prospective, multi-center cohort study enrolled 650 patients with moderate AS (AVA 1.0-1.5 cm², mean gradient 20-39 mmHg) across 10 cardiovascular centers in the Middle East between Egypt, Jordan, and Tunisia (2021-2024). Patients with prior valve interventions, severe comorbidities, or poor echocardiographic windows were excluded. Transthoracic echocardiography was performed at baseline and every six months to assess GLS, peak aortic jet velocity acceleration (ΔV/Δt), diastolic dysfunction, and aortic calcification (Agatston score in 300 patients). NT-proBNP and hs-Troponin T were measured at baseline and follow-up. Moreover, a pre-specified sub-study investigated the association between specific genetic polymorphisms and medication response in a subset of 87 patients.

Results: At 24 months, 31% of patients exhibited rapid AS progression. Independent predictors included GLS > - 16% (OR 3.2, p < 0.001), ΔV/Δt > 350 cm/s² (OR 2.8, p = 0.003), Agatston score > 2000 (HR 4.1, p < 0.001), E/e' > 15 (HR 2.3, p = 0.02), and NT-proBNP > 900 pg/mL (HR 3.0, p = 0.001). Patients with ≥ 3 risk factors had an 8-fold increased risk of rapid progression.

Conclusion: These findings provide novel evidence that GLS impairment, ΔV/Δt, aortic calcification burden, and diastolic dysfunction independently predict rapid AS progression. This supports the need for earlier echocardiographic surveillance and risk-based decision-making in moderate AS.