Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis

Abstract Funding Acknowledgements Type of funding sources: None. Background Although paradoxical low-flow low-gradient (LFLG) aortic stenosis (AS) has been considered a more severe form of AS with a worse prognosis than high-gradient (HG) AS, data on the natural history of this entity are scant. Objectives To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe LFLG AS compared to HG and normal-flow low-gradient (NFLG) AS. Methods A longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (AVA<1.0cm²) and normal LVEF (≥50%) was conducted. Patients were classified according to baseline echocardiography into one of three groups: HG (mean gradient≥40 mmHg), NFLG (mean gradient<40 mmHg, indexed systolic volume (SVi)>35ml/m²), or LFLG (mean gradient<40mmHg, SVi≤35ml/m²). AS progression was analyzed by comparing patients’ baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Results Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. The median total follow-up time was 60.2 months (IQR 44.7–83.4). Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, p = 0.005) and NFLG vs. HG (regression coefficient 0.068, p = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, p = 0.195). However, aortic valve area (AVA) reduction was slower in the LFLG group compared to the NFLG (p<0.001). During follow-up, 19.1% (n=9) of LFLG patients evolved to having NFLG AS and 44.7% (n=21) to having HG AS. 58.0% of patients underwent AVR with HG AS (n=29). Conclusions LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with HG AS.