title: Low-gradient aortic valve stenosis myocardial fibrosis and its influence on function and outcome.
abstract: OBJECTIVE
  This prospective cohort study in patients with aortic stenosis (AS) aimed to identify surrogates of myocardial fibrosis that are easy to derive in clinical practice, allow the differentiation of low-gradient severe AS from moderate AS, and have an impact on clinical outcome.
  
  
  BACKGROUND
  In patients with symptomatic aortic AS, a characteristic subgroup (i.e., up to one-third) exhibits severe AS with a concomitant low mean valve gradient either with preserved or reduced ejection fraction (EF). It is hypothesized that these patients tend to have an advanced stage of myocardial fibrosis and poor clinical outcome.
  
  
  METHODS
  Eighty-six patients with moderate or severe AS were examined by echocardiography including conventional aortic valve assessment, mitral ring displacement, and strain-rate imaging. Replacement fibrosis was quantified by late-enhancement magnetic resonance imaging. Biopsy samples were taken from patients with severe AS (n = 69) at aortic valve replacement. All patients were followed for 9 months.
  
  
  RESULTS
  Patients were divided into 4 groups according to aortic valve area (<1.0 cm(2)), mean valve gradient ≥40 mm Hg, and EF (<50%): group 1, moderate AS (n = 17); group 2, severe AS/high gradient (n = 49); group 3, severe AS/low gradient/preserved EF (n = 11); and group 4, severe AS/low gradient/decreased EF (n = 9). At baseline, a significant decrease in mitral ring displacement and systolic strain rate was detected in patients with low-gradient AS. In low-gradient groups, a higher degree of interstitial fibrosis in biopsy samples and more late-enhancement magnetic resonance imaging segments were observed. A close inverse correlation was found between interstitial fibrosis and mitral ring displacement (r = -0.79, p < 0.0001). Clinical outcome was best for patients in group 1, whereas mortality risk increased substantially in groups 2 through 4.
  
  
  CONCLUSIONS
  In severe AS, a low gradient is associated with a higher degree of fibrosis, decreased longitudinal function, and poorer clinical outcome despite preserved EF. Mitral ring displacement differentiates between moderate AS and low-gradient/severe AS with preserved EF.
authors.affiliation: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany. Herrmann_S@medizin.uni-wuerzburg.de
authors.forename: Sebastian
authors.initials: S
authors.lastname: Herrmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.forename: Markus
authors.initials: M
authors.lastname: Niemann
authors.forename: Volkmar
authors.initials: V
authors.lastname: Lange
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Strotmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.forename: Meinrad
authors.initials: M
authors.lastname: Beer
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöhner
authors.forename: Wolfram
authors.initials: W
authors.lastname: Voelker
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Frank
authors.initials: F
authors.lastname: Weidemann
mesh_terms: D000368:Aged; D001024:Aortic Valve Stenosis / Q000473:pathology* / Q000503:physiopathology*; D004719:Endomyocardial Fibrosis / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D012720:Severity of Illness Index