Abstract 15928: D-dimer as a New Biomarker of Aortic Stenosis Progression and Outcomes: Results From the PROGRESSA Study

Abstract

Background: Aortic stenosis (AS) induces left ventricular (LV) remodeling and hypertrophy, which are key markers of the transition to heart failure. The present study aimed to evaluate the association between D-dimer plasma levels, LV hypertrophy and mortality with AS. Method: One-hundred and forty-six asymptomatic patients (mean age 65±13, men 76%) with mild or moderate AS prospectively recruited in the PROGRESSA study (NCT01679431) were included in this sub-analysis. All patients underwent Doppler-echocardiography annually to measure AS severity, LV mass indexed to body surface area (LVMi) and myocardial contraction fraction (MCF). The annualized changes in LVMi and MCF were calculated between baseline and last follow up. Results: Higher plasma levels of D-dimers at baseline were significantly associated with faster progression rate of LVMi and MCF (r 2 =0.18 and -0.22, respectively; all p<0.01). On multivariable analysis adjusted for age, sex, comorbidities, creatinine level, peak aortic jet velocity at baseline, D-dimers remained significantly associated with faster change in LVMi and MCF (all, p<0.01). Moreover, in multivariate analysis adjusted for age, sex, AS severity at baseline, higher levels of D-dimer were significantly associated with the progression to a higher grade of AS severity (HR [95% CI] 1.67 [1.14-2.46], p=0.009). During a median follow-up of 8.1 (5.6-9.9) years, 38 (26%) patients died. On multivariable Cox regression analysis, higher levels of D-dimer were associated with an increased risk of all-cause mortality (HR [95% CI]: 1.97 [0.98-1.97], p=0.05). Conclusion: Higher levels of D-dimer are associated with faster progression of AS severity, LV hypertrophy and dysfunction, and increased risk of mortality in patients with AS. This new blood biomarker may improve risk stratification and management of asymptomatic patients with AS. Further studies are needed to determine the mechanisms underlying this association between D-dimer and outcomes in AS.