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 cm2 · 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 · m2 , and 181 (35%) had paradoxically low-flow output defined as stroke volume index ≤35 mL · 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 · 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 · mL−1 · 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 · mL−1 · 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.