Insulin-Like Growth Factor–Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction: Results From the RELAX Trial

Objectives This study sought to investigate relationships between insulin-like growth factor–binding protein-7 (IGFBP7) and parameters of diastolic function or functional capacity in patients with heart failure and preserved ejection fraction (HFpEF) who were randomized to receive sildenafil or placebo. Background IGFBP7 was previously found to be associated with diastolic function in heart failure with reduced ejection fraction, but it is unclear whether these associations are present in HFpEF. Methods At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (VO_2max) were obtained and compared in 160 patients with HFpEF who were randomized to receive sildenafil or placebo. Results Patients with supramedian baseline IGFBP7 concentrations were older, had signs of systemic congestion and worse renal function, and had higher concentrations of prognostic heart failure biomarkers including amino-terminal pro-B-type natriuretic peptide (p < 0.05). Higher baseline IGFBP7 was modestly correlated with worse diastolic function: higher E velocity (Spearman correlation [ρ] = 0.40), E/E′ (ρ = 0.40), left atrial volume index (ρ = 0.39), and estimated right ventricular systolic pressure (ρ = 0.41; all p < 0.001) and weakly correlated with transmitral E/A (ρ = 0.26; p = 0.006). Notably, change in IGFBP7 was significantly correlated with change in E, E/A, E/E′, and right ventricular systolic pressure. Elevated baseline IGFBP7 was associated with lower baseline VO_2max (13.2 vs. 11.1 ml/min/kg; p < 0.001), and change in IGFBP7 was weakly inversely correlated with change in VO_2max (ρ = −0.19; p = 0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 24 weeks, in contrast to placebo-treated patients (median change in IGFBP7 −1.5 vs. +13.6 ng/ml; p < 0.001). Conclusions In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.