Introduction: Insulin-like growth factor binding protein-7 (IGFBP7) is involved in cell cycle arrest with tissue fibrosis, and may be related to diastolic function. We measured IGFBP7 in patients with heart failure and preserved ejection fraction (HFpEF) in the PARAMOUNT study.
Hypothesis: Concentrations of IGFBP7 are associated with abnormal diastolic function. Treatment with sacubitril/valsartan reduces IGFBP7 concentrations.
Methods: Patients with HFpEF and elevation in natriuretic peptides were randomized to receive sacubitril/valsartan (200 mg bid) or valsartan (160 mg bid). IGFBP7 concentrations (Roche Diagnostics, Penzberg, GE) were measured at baseline, 12 weeks and 36 weeks among 228 subjects. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity (E/e’) and ratio of early diastole/peak late diastolic velocity (E/A) were assessed as a function of IGFBP7 concentration and treatment assignment.
Results: With increasing IGFBP7 quartiles, mean LA size and volume index (LAVi) were higher (both P<0.001), as was mean E/e’ (P=0.03) and E/A ratio (P=0.04). IGFBP7 concentrations were higher in those with LAVi ≥ 34 mL/m2 compared to lower LAVi at all time points (P<0.007), with similar patterns of IGFBP7 in those with elevated E/e’ or E/A compared to less severe diastolic dysfunction. IGFBP7 was a stronger independent predictor of LAVi at baseline (Z=2.56; P=0.01) than NT-proBNP (Z=2.21; P=0.03). Treatment with sacubitril/valsartan resulted in lower concentrations of IGFBP7 compared to valsartan (overall change, P<0.001) (Table).
Conclusions: Among patients with HFpEF, IGFBP7 concentrations were associated with abnormal diastolic function and strongly associated with LA dilation. Over a 36 week period, treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared to valsartan.