Natural history of paradoxical low-gradient severe aortic stenosis.

BACKGROUND Up to 30% of patients with severe aortic stenosis (SAS; indexed aortic valve area <0.6 cm(2)/m(2)) present with low transvalvular gradient despite a normal left ventricular ejection fraction. Presently, there is intense controversy as to the prognostic implications of such findings. Accordingly, the aim of the present work was to compare the natural history of patients with paradoxical low-gradient (PLG) or high-gradient (HG) SAS. METHODS AND RESULTS We prospectively studied 349 patients with SAS and preserved left ventricular ejection fraction. Patients were categorized into HG-SAS (n=144) and PLG-SAS (n=205) according to mean transvalvular gradient (mean gradient >40 or ≤40 mm Hg). Primary end points were all-cause mortality and echocardiographic disease progression. To evaluate natural history, patients undergoing aortic valve replacement were censored at the time of surgery (n=92). During a median follow-up of 28 months, 148 patients died. Kaplan-Meier survival curves showed better survival in PLG-SAS than in HG-SAS, both in the overall population (48% versus 31%; P<0.01) and in the asymptomatic subgroup (59% versus 35%; P<0.02). In asymptomatic patients, Cox analysis identified age, diabetes mellitus, left atrial volume, and mean gradient as independent predictors of death. Finally, at last echocardiographic follow-up, PLG-SAS demonstrated significant increases in mean gradient (from 29±6 to 38±11 mm Hg; P<0.001). CONCLUSIONS Our study indicates that PLG-SAS is a less malignant form of AS compared with HG-SAS, because their spontaneous outcome is better. We further demonstrated that patients with PLG-SAS are en route toward the more severe HG-SAS form, because the majority of them evolve into HG-SAS over time.