Association of d-dimers with left ventricular hypertrophy and clinical outcomes in mild to moderate aortic stenosis: results from the progressa stydy

Aortic stenosis (AS) induces hypertrophy and remodeling of the left ventricle (LV), which are key markers of the transition to heart failure. However, the optimal timing of intervention in AS remains uncertain and new tools are needed to optimize the management of these patients. Therefore, the aim of present study was to evaluate the association between D-dimer plasma levels, LV hypertrophy, and mortality in patients with mild or moderate AS. One hundred and forty-six asymptomatic patients with mild or moderate AS at baseline prospectively recruited in the PROGRESSA study (NCT01679431) were included in the present analysis. Clinical and Doppler echocardiographic data were collected yearly over a period of 10 years, and AS severity, LV mass indexed to body surface area (LVMI), and myocardial contraction fraction (MCF) were measured. The cohort was divided into two groups according to the median value of D-dimer plasma levels for this cohort. In comparison with patients with lower plasma levels of D-dimer at baseline, patients with higher levels were more frequently males (76%). Over a median follow-up of 2.01 (1.00-3.75) years. The average annualized progression of LVMi and MCF were 0.70 g/m2/year and -0.02 mL/g/m2/year, respectively. D-dimers levels at baseline were significantly associated with faster annualized progression of LVMI and MCF (r2=0.18 and -0.22, respectively, p-values < 0.01). In multivariable linear regression analyses adjusted for age, sex, comorbidities (diabetes, hypertension, metabolic syndrome, coronary heart disease), creatinine levels, and AS severity at baseline, D-dimers remained significantly associated with faster progression of LVMi and MCF (p-values < 0.01). Over a median follow-up of 8.10 (5.57-9.94) years, 38 (26%) patients died. On multivariable Cox regression analysis, higher D-dimer levels were associated with increased risk of all-cause mortality (HR [95% CI]: 1.97 [0.98-1.97], p=0.05). Higher circulating D-dimer levels at baseline were associated with faster progression of LV hypertrophy, a faster decline in MCF, and an increased risk of mortality in patients with mild to moderate AS. The simple measure of this new blood biomarker could help to enhance risk stratification and optimize the timing of intervention in asymptomatic patients.