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

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 <= 0.6 cm(2) center dot m(-2)) and preserved LV ejection fraction (>= 50%). Of these patients, 331 (65%) had normal LV flow output defined as a stroke volume index <= 35 mL center dot m(2), and 181 (35%) had paradoxically low-flow output defined as stroke volume index <= 35 mL center dot 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 center dot 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 center dot mL(-1) center dot 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 center dot mL(-1)center dot 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.