Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival

Abstract

Background: Recent studies and current clinical observations suggest that some patients with severe aortic stenosis on the basis of aortic valve area may paradoxically have a relatively low gradient despite the presence of a preserved left ventricular (LV) ejection fraction. The objective of the present study was to document the prevalence, potential mechanisms, and clinical relevance of this phenomenon.

Methods and results: We retrospectively studied the clinical and Doppler echocardiographic data of 512 consecutive patients with severe aortic stenosis (indexed aortic valve area < or = 0.6 cm2 x m(-2)) and preserved LV ejection fraction (> or = 50%). Of these patients, 331 (65%) had normal LV flow output defined as a stroke volume index > 35 mL x m2, and 181 (35%) had paradoxically low-flow output defined as stroke volume index < or = 35 mL x m(-2). When compared with normal flow patients, low-flow patients had a higher prevalence of female gender (P<0.05), a lower transvalvular gradient (32+/-17 versus 40+/-15 mm Hg; P<0.001), a lower LV diastolic volume index (52+/-12 versus 59+/-13 mL x m(-2); P<0.001), lower LV ejection fraction (62+/-8% versus 68+/-7%; P<0.001), a higher level of LV global afterload reflected by a higher valvulo-arterial impedance (5.3+/-1.3 versus 4.1+/-0.7 mm Hg x mL(-1) x m(-2); P<0.001) and a lower overall 3-year survival (76% versus 86%; P=0.006). Only age (hazard ratio, 1.04; 95% CI, 1.01 to 1.08; P=0.025), valvulo-arterial impedance > 5.5 mm Hg x mL(-1) x m(-2) (hazard ratio, 2.6; 95% CI, 1.2 to 5.7; P=0.017), and medical treatment (hazard ratio, 3.3; 95% CI, 1.8 to 6.7; P=0.0003) were independently associated with increased mortality.

Conclusion: Patients with severe aortic stenosis may have low transvalvular flow and low gradients despite normal LV ejection fraction. A comprehensive evaluation shows that this pattern is in fact consistent with a more advanced stage of the disease and has a poorer prognosis. Such findings are clinically relevant because this condition may often be misdiagnosed, which leads to a neglect and/or an underestimation of symptoms and an inappropriate delay of aortic valve replacement surgery.