Risk Stratification in Aortic Stenosis: Exercise Hemodynamics to Refine Risk in Early Cardiac Damage Stages

AIM: To describe exercise hemodynamics across cardiac damage stages and evaluate the incremental prognostic impact of cardiac damage stage and exercise-induced pulmonary hypertension (exPHT) in patients with symptomatic moderate aortic stenosis (AS) and asymptomatic severe AS. METHODS AND RESULTS: A total of 436 consecutive patients with ≥moderate AS (74 ± 10 years, 32% women, 56% severe AS) underwent cardiopulmonary exercise testing with echocardiography. The primary endpoint was heart failure (HF) death and HF hospitalizations. Cardiac damage stage was 0 in 93 patients, 1 (LV damage) in 135, 2 (LA/mitral damage) in 135, and 3-4 (pulmonary vasculature/tricuspid or RV damage) in 73. Higher stages were associated with worse exercise capacity and hemodynamics. Over a median follow-up of 37 months, 65 patients met the primary endpoint. After adjustment for age, AS severity, and aortic valve replacement, cardiac damage stage and exPHT were independently associated with HF outcomes (HR per stage increase 1.51 [1.26-1.82]; p < 0.001; exPHT HR 2.36 [1.10-5.07]; p = 0.03). exPHT improved risk stratification in early-stage disease (stages 1-2), conferring an approximately fivefold higher risk of HF events in patients with exPHT (HR 4.45 [1.58-12.59]; p < 0.01). CONCLUSIONS: In patients with ≥moderate AS and discordant symptoms, cardiac damage stage and exPHT independently refined HF risk stratification. ExPHT provides incremental prognostic value in early damage stages (1-2), representing over half of the cohort, supporting a stepwise approach of routine damage staging with selective with exPHT assessment with exercise echocardiography in this subgroup to guide more personalized management and potentially optimize AVR timing.