title: Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study.
abstract: BACKGROUND
  Aortic valve calcification (AVC) load measures lesion severity in aortic stenosis (AS) and is useful for diagnostic purposes. Whether AVC predicts survival after diagnosis, independent of clinical and Doppler echocardiographic AS characteristics, has not been studied.
  
  
  OBJECTIVE
  This study evaluated the impact of AVC load, absolute and relative to aortic annulus size (AVCdensity), on overall mortality in patients with AS under conservative treatment and without regard to treatment.
  
  
  METHODS
  In 3 academic centers, we enrolled 794 patients (mean age, 73 ± 12 years; 274 women) diagnosed with AS by Doppler echocardiography who underwent multidetector computed tomography (MDCT) within the same episode of care. Absolute AVC load and AVCdensity (ratio of absolute AVC to cross-sectional area of aortic annulus) were measured, and severe AVC was separately defined in men and women.
  
  
  RESULTS
  During follow-up, there were 440 aortic valve implantations (AVIs) and 194 deaths (115 under medical treatment). Univariate analysis showed strong association of absolute AVC and AVCdensity with survival (both, p < 0.0001) with a spline curve analysis pattern of threshold and plateau of risk. After adjustment for age, sex, coronary artery disease, diabetes, symptoms, AS severity on hemodynamic assessment, and LV ejection fraction, severe absolute AVC (adjusted hazard ratio [HR]: 1.75; 95% confidence interval [CI]: 1.04 to 2.92; p = 0.03) or severe AVCdensity (adjusted HR: 2.44; 95% CI: 1.37 to 4.37; p = 0.002) independently predicted mortality under medical treatment, with additive model predictive value (all, p ≤ 0.04) and a net reclassification index of 12.5% (p = 0.04). Severe absolute AVC (adjusted HR: 1.71; 95% CI: 1.12 to 2.62; p = 0.01) and severe AVCdensity (adjusted HR: 2.22; 95% CI: 1.40 to 3.52; p = 0.001) also independently predicted overall mortality, even with adjustment for time-dependent AVI.
  
  
  CONCLUSIONS
  This large-scale, multicenter outcomes study of quantitative Doppler echocardiographic and MDCT assessment of AS shows that measuring AVC load provides incremental prognostic value for survival beyond clinical and Doppler echocardiographic assessment. Severe AVC independently predicts excess mortality after AS diagnosis, which is greatly alleviated by AVI. Thus, measurement of AVC by MDCT should be considered for not only diagnostic but also risk-stratification purposes in patients with AS.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Marie-Annick
authors.initials: MA
authors.lastname: Clavel
authors.affiliation: University Institute of Cardiology and Pneumology of Québec, Laval University Québec, Québec, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pibarot
authors.affiliation: Department of Cardiology, Public Assistance-Paris Hospitals, Bichat Hospital, Paris, France; Institut national de la santé et de la recherche médicale U698, University of Paris, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Messika-Zeitoun
authors.affiliation: University Institute of Cardiology and Pneumology of Québec, Laval University Québec, Québec, Canada.
authors.forename: Romain
authors.initials: R
authors.lastname: Capoulade
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Joseph
authors.initials: J
authors.lastname: Malouf
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Shivani
authors.initials: S
authors.lastname: Aggarval
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Araoz
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Hector I
authors.initials: HI
authors.lastname: Michelena
authors.affiliation: Department of Cardiology, Public Assistance-Paris Hospitals, Bichat Hospital, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Cueff
authors.affiliation: University Institute of Cardiology and Pneumology of Québec, Laval University Québec, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Larose
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Miller
authors.affiliation: Department of Cardiology, Public Assistance-Paris Hospitals, Bichat Hospital, Paris, France; Institut national de la santé et de la recherche médicale U698, University of Paris, Paris, France.
authors.forename: Alec
authors.initials: A
authors.lastname: Vahanian
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota. Electronic address: sarano.maurice@mayo.edu.
authors.forename: Maurice
authors.initials: M
authors.lastname: Enriquez-Sarano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging* / Q000401:mortality*; D002114:Calcinosis / Q000000981:diagnostic imaging* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography / Q000379:methods*; D011446:Prospective Studies; D012042:Registries; D015996:Survival Rate / Q000639:trends
keywords: Doppler echocardiography; aortic valve calcification; aortic valve stenosis; multidetector computed tomography; survival