Classical and paradoxical LFLG severe aortic stenosis increased 5-year all-cause mortality risk after TAVR compared with high-gradient AS (HR 1.92, 95% CI 1.62-2.27 and HR 1.20, 95% CI 1.07-1.34).
Meta-Analysis (n=20,493)
Does TAVR in classical and paradoxical LFLG severe aortic stenosis result in higher long-term mortality compared to TAVR in high-gradient severe aortic stenosis?
Patients with classical and paradoxical low-flow, low-gradient severe aortic stenosis have significantly higher long-term all-cause and cardiovascular mortality following TAVR compared to those with high-gradient aortic stenosis.
Effect estimate: HR 1.92 (classical LFLG) / HR 1.20 (paradoxical LFLG) (95% CI 1.62-2.27 (classical LFLG) / 1.07-1.34 (paradoxical LFLG))
BACKGROUND: There are uncertainties regarding long-term outcomes of low-flow, low-gradient (LFLG) severe aortic stenosis (AS) following transcatheter aortic valve replacement (TAVR). This study investigates long-term outcomes of TAVR for high-gradient (HG), classical LFLG, and paradoxical LFLG AS. METHODS: We systematically searched PubMed, Embase, Scopus, and Cochrane Library databases until January 2025 for studies comparing HG, classical LFLG, and paradoxical LFLG AS outcomes following TAVR. The primary outcome was all-cause mortality, analyzed using reconstructed individual patient data meta-analysis. Secondary outcomes included cardiovascular mortality, heart failure hospitalization, acute kidney injury, bleeding events, stroke, myocardial infarction, permanent pacemaker implantation, and echocardiographic outcomes, analyzed using multivariate meta-analysis. RESULTS: We included 19 observational studies comprising 20 493 patients who underwent TAVR for severe AS. Time-to-event meta-analysis indicated a higher risk of 5-year all-cause mortality in patients with classical and paradoxical LFLG AS compared with HG AS (hazard ratio HR, 1.92 95% CI, 1.62-2.27 and HR, 1.20 95% CI, 1.07-1.34, respectively). Multivariate meta-analysis indicated an increased risk of cardiovascular mortality in patients with LFLG versus HG AS (classical LFLG HR, 1.94 95% CI, 1.74-2.16; paradoxical LFLG HR, 1.40 95% CI, 1.25-1.57). Classical and paradoxical LFLG AS were also associated with a higher risk of heart failure hospitalization (HR, 4.12 95% CI, 2.16-7.83; HR, 1.80 95% CI, 1.14-2.85, respectively) compared with HG AS. CONCLUSIONS: Classical and paradoxical LFLG AS were associated with higher all-cause and cardiovascular mortality following TAVR compared with HG AS. Future studies are needed to determine strategies to improve outcomes following TAVR in patients with LFLG AS.
Moghadam et al. (2026) conducted a meta-analysis in Severe aortic stenosis (n=20,493). Classical and paradoxical low-flow low-gradient (LFLG) severe aortic stenosis vs. High-gradient (HG) severe aortic stenosis was evaluated on All-cause mortality (HR 1.92 (classical LFLG) / HR 1.20 (paradoxical LFLG), 95% CI 1.62-2.27 (classical LFLG) / 1.07-1.34 (paradoxical LFLG)). Classical and paradoxical LFLG severe aortic stenosis increased 5-year all-cause mortality risk after TAVR compared with high-gradient AS (HR 1.92, 95% CI 1.62-2.27 and HR 1.20, 95% CI 1.07-1.34).