Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty.

Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77-81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574-1971 pg/mL vs. 775, 95% CI 600-950 pg/mL, respectively, < 0.0001). Subjects in the upper GDF15 tertile were older ( = 0.004), with a more advanced NYHA functional class ( = 0.04) and a higher prevalence of impaired renal function ( = 0.004). Such patients also showed a higher frailty score ( = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain ( = 0.01) and a higher left ventricular mass ( = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9-1.1; = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients' frailty, independent of indices of left ventricular dysfunction.