Differences in natural history of low- and high-gradient aortic stenosis from nonsevere to severe stage of the disease.
The aim of the present study was to assess and compare the disease progression of aortic stenosis (AS) subtypes from nonsevere to severe disease on the basis of measures of gradient and flow. Seventy-seven patients with AS (mean aortic valve area, 1.3 ± 0.3 cm(2) at baseline) underwent echocardiographic examination, including two-dimensional speckle-tracking strain measurements. Patients were retrospectively grouped according to mean transvalvular pressure gradient (40 mm Hg) into low-gradient (LG/AS) and high-gradient (HG/AS) groups. The LG/AS group was further subdivided into low-flow (LF/LG; i.e., stroke volume index < 35 mL/m(2)) and normal-flow (NF/LG) groups. For subanalysis, the LF/LG group was split into two groups: "paradoxical" (P-LF/LG; ejection fraction > 50%) and "classical" LF/LG (C-LF/LG; ejection fraction < 50%). Follow-up echocardiography was performed in patients with severe AS after 3.3 ± 1.7 years. Survival status was ascertained after 5.0 ± 2.0 years. Coronary artery disease was more frequent in LG/AS than HG/AS patients. Already at baseline, LF/LG patients showed reduced left ventricular global systolic strain and reduced systemic arterial compliance compared with HG/AS patients (HG/AS, 1.0 ± 0.4 mL · mm Hg-(1) · m(-2); NF/LG, 0.9 ± 0.2 mL · mm Hg-(1) · m(-2); LF/LG, 0.6 ± 0.2 mL · mm Hg(-1) · m(-2); P < .001). The initially elevated valvuloarterial impedance increased significantly more in LG/AS than in the other groups (HG/AS, 2.2 ± 0.9 mm Hg · mL-(1) · m(-2); NF/LG, 2.2 ± 0.5 mm Hg · mL-(1) · m(-2); LF/LG, 3.2 ± 0.8 mm Hg · mL(-1) · m-(2); P < .001), while aortic valve area decreased by 42% in HG/AS versus 34% in NF/LG and 32% in LF/LG (P < .001). At follow-up, global systolic strain was significantly reduced in C-LF/LG (7.7 ± 2.5 vs 13.5 ± 2.9 in P-LF/LG, P < .001). In P-LF/LG, mitral E/E' ratio increased significantly from 8.9 ± 4.0 to 26.4 ± 9.2 (P < .05). In patients with AS with high-gradient physiology, the valve constitutes the primary problem. By contrast, low-gradient AS is a systemic disease with valvular, vascular, and myocardial components, resulting in a slower progression of transvalvular gradient, but worse clinical outcome. In C-LF/LG, impaired systolic function leads to an LG flow pattern, whereas the pathophysiology in P-LF/LG is predominantly a diastolic dysfunction.