title: Malignant natural history of asymptomatic severe aortic stenosis: benefit of aortic valve replacement.
abstract: BACKGROUND
  Patients with asymptomatic severe aortic stenosis (AS) are reported to have a benign prognosis and hence the American College of Cardiology/American Heart Association guidelines do not recommend aortic valve replacement (AVR) for patients with isolated asymptomatic severe AS. However, symptoms are subjective and would depend upon patient's life style. We examined the natural and unnatural history of initially asymptomatic patients with severe AS.
  
  
  METHODS
  A search of our echocardiographic database between 1993 and 2003 yielded 740 patients with severe AS defined as aortic valve area 0.8 cm2 or less. Thorough chart reviews were conducted to collect clinical and pharmacologic data. Of these, 338 patients were asymptomatic at the initial encounter forming the study cohort.
  
  
  RESULTS
  Patient characteristics were the following: age 71 +/- 15 years, males 51%, aortic valve area 0.72 +/- 0.17 cm2, left ventricular ejection fraction 0.59 +/- 0.17. Ninety-nine (29%) patients had AVR during a mean follow-up of 3.5 years. Survival at 1, 2, and 5 years in the nonoperated patients were 67%, 56%, and 38%, respectively, compared with 94%, 93%, and 90% in those who underwent AVR (p < 0.0001). The Cox regression model was used to adjust for the effect of 18 clinical, echocardiographic, and pharmacologic variables on survival. The adjusted hazard ratio for death with AVR was 0.17 (95% confidence interval [CI] 0.10 to 0.29). In the nonoperated group, renal insufficiency (risk ratio [RR] 3.1, 95% CI 1.5 to 6.6), beta blocker use (RR 0.52, 95% CI 0.31 to 0.88), statin use (RR 0.52, 95% CI 0.27 to 0.99), age (per year RR 1.03, 95% CI 1.02 to 1.05), and left ventricular ejection fraction (per % RR 0.99, 95% CI 0.98 to 1.00) were found to be the independent predictors of mortality. The benefit of AVR was further supported by sensitivity and propensity score analyses.
  
  
  CONCLUSIONS
  Our observational data indicate that the natural history of asymptomatic AS is not benign and that survival is dramatically improved by AVR. Survival of the asymptomatic unoperated or nonoperable patients may potentially be improved by the use of beta blockers and statins.
authors.affiliation: Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California, USA.
authors.forename: Ramdas G
authors.initials: RG
authors.lastname: Pai
authors.forename: Nikhil
authors.initials: N
authors.lastname: Kapoor
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Bansal
authors.forename: Padmini
authors.initials: P
authors.lastname: Varadarajan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D019918:Heart Valve Prosthesis Implantation / Q000401:mortality*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D014463:Ultrasonography
chemical_list: D000319:Adrenergic beta-Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors