Long‐Term Outcomes of Transcatheter Aortic Valve Replacement in Low‐Flow Low‐Gradient Aortic Stenosis: A Reconstructed Time‐to‐Event and Multivariate Meta‐Analysis

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Abstract
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.

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