Abstract
Background: A valve syndrome framework (stable valve syndrome [SVS], progressive valve syndrome [PVS], and acute valve syndrome [AVS]) integrates clinical presentation with objective markers, but its prognostic implications remain incompletely characterized. Methods: Among 3369 consecutive patients with severe aortic stenosis (AS) in the CURRENT AS Registry‐2, we analyzed 2824 patients with natriuretic peptide (NP) and left ventricular ejection fraction (LVEF) data. Patients were classified as SVS (no symptoms with low NP), PVS (mild symptoms and/or mildly elevated NP), or AVS (acute deterioration and/or markedly elevated NP or reduced LVEF), and stratified by initial aortic valve replacement (AVR) and conservative strategies. The primary outcome was a composite of death or heart failure hospitalization. Subgroup analyses further classified patients into five phenotypes: SVS, progressive valve signs without symptoms, progressive valve symptoms, acute valve signs without symptoms, and acute valve symptoms. Results: In the initial AVR stratum, AVS was associated with higher risk for the primary outcome compared with SVS (adjusted HR 2.34, 95% CI 1.19–4.59, P=0.01), whereas PVS was not. In the conservative stratum, SVS demonstrated a very low early event rate (1.0% at 6 months), while AVS and PVS had higher risk than SVS. In the five‐phenotype analysis, patients with progressive valve signs without symptoms underwent AVR at rates comparable to SVS yet had worse outcomes than SVS in the conservative stratum (adjusted HR 1.89, 95% CI 1.18‐3.03, P=0.008). Conclusions: A valve syndrome framework highlights limitations of symptom‐based risk stratification and may refine surveillance and intervention strategies in severe AS.