Excess Mortality Associated with Progression Rate in Asymptomatic Aortic Valve Stenosis

Background: Aortic valve stenosis (AS) is a progressive condition characterized by gradual calcification of the aortic cusps. Progression rate evaluated using echocardiography has been associated with survival. However, data from routine practice covering the whole spectrum of AS severity and the rate of symptom onset are sparse. The aim of this study was to assess outcomes under medical management related to disease progression in asymptomatic patients with a wide range of AS severity.

Methods: Two hundred twenty-nine consecutive asymptomatic patients (mean age, 77 ± 10 years; 55% men) with AS, preserved left ventricular ejection fraction, and two or more echocardiographic examinations performed from 2004 to 2014 were retrospectively included. The median time between the two echocardiographic examinations was 24 months (interquartile range, 15-46 months). Patients were identified as rapid progressors if the annualized difference in peak aortic velocity between two echocardiographic examinations was ≥0.3 m/sec/y; others were labeled as slow progressors. The primary end point was mortality during medical follow-up (censoring on aortic valve interventions). The secondary end point was overall mortality.

Results: Rapid progressors accounted for 67 of the 229 patients (29%), and this feature was not associated with baseline characteristics. During a median of 5.8 years (interquartile range, 3.4-8.3 years) of follow-up from the first echocardiographic examination, 102 patients (45%) died, 86 (84%) during medical follow-up. Rapid progression rate predicted excess mortality (vs slow progression rate) after adjustment for age, sex, symptoms, baseline left ventricular ejection fraction, and baseline aortic valve area (hazard ratio, 2.50; 95% CI, 1.48-4.21; P = .0006) and after adjusting for peak aortic velocity and left ventricular ejection fraction obtained at the last echocardiographic examination (hazard ratio, 2.07; 95% CI, 1.25-3.46; P = .005). Among patients with baseline peak aortic velocity < 4 m/sec (nonsevere AS), rapid progression rate was associated with higher 5-year mortality compared with slow progression (57% vs 22% [P < .0001] under medical management and 44% vs 18% [P = .005] overall). Outcomes were comparable between nonsevere AS rapid progressors and baseline severe AS. Progression rate showed incremental prognostic value on receiver operating characteristic curve analysis versus AS severity. Of note, among slow progressors, 11 patients (5%) presented with high rates of symptom development and poor outcomes related to ventricular dysfunction or other advanced AS features.

Conclusions: Progression rate is an individual, almost unpredictable feature among patients with AS. Rapid progression is an incremental marker of excess mortality in asymptomatic patients with AS, independent of clinical and hemodynamic characteristics. Rapid progression rate may identify patients with nonsevere AS at higher risk for events.