Progression of Normal Flow Low Gradient "Severe" Aortic Stenosis With Preserved Left Ventricular Ejection Fraction

Normal-flow low-gradient severe aortic stenosis (NF-LG-SAS), defined by an aortic valve area (AVA) <1 cm², mean pressure gradient (MPG) <40 mm Hg and indexed stroke volume ≥35 ml/m², is the most prevalent form of low-gradient aortic stenosis (AS) with preserved ejection fraction (PEF). However, the true severity of AS in these patients is controversial. The aim of this Doppler echocardiographic study was to investigate changes over time in the hemodynamic severity of patients with NF-LG-SAS with PEF. We retrospectively identified 96 patients who had 2 Doppler echocardiographic examinations without an intervening event. After a median follow-up of 25 (interquartile range 15 to 52) months, progression was observed, with increased transaortic MPG (from 28 [25 to 33] to 39 [34 to 50] mm Hg; p<0.001), peak aortic jet velocity (from 3.46 [3.20 to 3.64] to 4.01 [3.70 to 4.39] m/s; p<0.001), and decreased AVA (from 0.87 [0.82 to 0.94] to 0.72 [0.62 to 0.81] cm²; p<0.001). Median annual rates of progression were 4.3 (1.7 to 8.1) mm Hg/year, 0.25 (0.08 to 0.44) m/s/year, and -0.05 (-0.10 to -0.02) cm²/year, respectively. There was no significant change in left ventricular ejection fraction over time (p = 0.74). At follow-up, 46 patients (48%) acquired the features of classical high-gradient severe AS (MPG ≥40 mm Hg). This study shows that most patients with NF-LG-SAS with PEF exhibit significant hemodynamic progression of AS severity without EF impairment. These findings suggest that NF-LG-SAS with PEF is an "intermediate" stage between moderate AS and classical high-gradient severe AS requiring close monitoring.