title: Differences in natural history of low- and high-gradient aortic stenosis from nonsevere to severe stage of the disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany. Electronic address: herrmann_s@ukw.de.
authors: Sebastian
authors: S
authors: Herrmann
authors: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Bastian
authors: B
authors: Fries
authors: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Dan
authors: D
authors: Liu
authors: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Kai
authors: K
authors: Hu
authors: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Stefan
authors: S
authors: Stoerk
authors: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Wolfram
authors: W
authors: Voelker
authors: Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
authors: Catharina
authors: C
authors: Ruppert
authors: Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
authors: Kristina
authors: K
authors: Lorenz
authors: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany; Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors: Georg
authors: G
authors: Ertl
authors: Department of Cardiology, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany; Department of Cardiology, Katharinen-Hospital Unna, Unna, Germany.
authors: Frank
authors: F
authors: Weidemann
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging* / Q000401:mortality*; D015984:Causality; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000401:mortality*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D015994:Incidence; D008297:Male; D012042:Registries; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015996:Survival Rate; D014463:Ultrasonography
keywords: Aortic stenosis; Echocardiography; Low gradient; Paradoxical