Low-flow aortic stenosis in asymptomatic patients: valvular-arterial impedance and systolic function from the SEAS Substudy

JACC Cardiovasc Imaging. 2009 Apr;2(4):390-9. doi: 10.1016/j.jcmg.2008.12.021.


Objectives: This study sought to assess the impact of valvuloarterial impedance on left ventricular (LV) myocardial systolic function in asymptomatic aortic valve stenosis (AS).

Background: In atherosclerotic AS, LV global load consists of combined valvular and arterial resistance to LV ejection. Global load significantly impacts LV ejection fraction (EF) in symptomatic AS, but less is known about its effect on LV myocardial function in asymptomatic AS.

Methods: Echocardiograms in 1,591 patients with asymptomatic AS (67 +/- 10 years, 51% hypertensive) at baseline in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) study evaluating placebo-controlled combined simvastatin and ezetimibe treatment in AS were used to assess LV global load as valvuloarterial impedance and LV myocardial function as stress-corrected midwall shortening. The study population was divided into tertiles of global load. Stress-corrected midwall shortening was considered low if <87% in men and <90% in women. Low-flow AS was defined as stroke volume index <22 ml/m(2.04).

Results: Energy loss index decreased (0.85 cm(2)/m(2) vs. 0.77 and 0.75 cm(2)/m(2)) and the prevalence of low stress-corrected midwall shortening increased (10% vs. 26% and 63%) with increasing LV global load (all p < 0.001). The EF was low in only 2% of patients. Patients with low-flow AS had higher LV global load and more often low midwall shortening than those with normal-flow AS (9.66 +/- 2.23 mm Hg/ml.m(2.04) and 77%, vs. 6.38 +/- 2.04 mm Hg/ml.m(2.04) and 30%, respectively, p < 0.001). In logistic regression analysis, LV global load was a main predictor of low stress-corrected midwall shortening independent of male sex, concentric LV geometry, LV hypertrophy (all p < 0.001), concomitant hypertension, and aortic regurgitation.

Conclusions: LV global load impacts LV myocardial function in asymptomatic AS independent of other main covariates of LV systolic function. LV myocardial systolic dysfunction is common in asymptomatic AS in particular in patients with low-flow AS and increased valvuloarterial afterload, whereas EF is generally preserved. (An Investigational Drug on Clinical Outcomes in Patients With Aortic Stenosis [Narrowing of the Major Blood Vessel of the Heart]; NCT00092677).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aortic Valve Stenosis / diagnostic imaging
  • Aortic Valve Stenosis / drug therapy
  • Aortic Valve Stenosis / etiology
  • Aortic Valve Stenosis / physiopathology*
  • Atherosclerosis / complications*
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / drug therapy
  • Atherosclerosis / physiopathology
  • Azetidines / therapeutic use*
  • Disease Progression
  • Double-Blind Method
  • Drug Combinations
  • Echocardiography, Doppler
  • Europe
  • Ezetimibe, Simvastatin Drug Combination
  • Female
  • Hemodynamics* / drug effects
  • Humans
  • Hypolipidemic Agents / therapeutic use*
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardial Contraction* / drug effects
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Risk Assessment
  • Risk Factors
  • Sensitivity and Specificity
  • Simvastatin / therapeutic use*
  • Systole
  • Treatment Outcome
  • United States
  • Ventricular Dysfunction, Left / diagnostic imaging
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / physiopathology*
  • Ventricular Dysfunction, Left / therapy


  • Azetidines
  • Drug Combinations
  • Ezetimibe, Simvastatin Drug Combination
  • Hypolipidemic Agents
  • Simvastatin

Associated data

  • ClinicalTrials.gov/NCT00092677