Diagnostic and prognostic performance of insulin-like growth factor-binding protein 7 in patients with acute dyspnea in the emergency department

Introduction Acute Heart Failure (AHF) is a frequent reason for emergency department (ED) visits that require hospitalization. Despite progress in chronic heart failure therapy, AHF patients, especially the elderly, have substantial morbidity and mortality rates. High levels of insulin-like growth factor-binding protein 7(IGFBP7) cause collagen accumulation, which result in myocardial fibrosis and cardiac dysfunction. IGFBP7 was connected to disease progression and worse outcomes. Aims This study aimed to determine whether IGFBP7 levels of patients presenting with acute dyspnea at the emergency department (ED) could aid in diagnosis and risk assessment of patients with acute heart failure (AHF). Methods and Results Patients presenting with acute dyspnea were enrolled in a prospective multicentre diagnostic study. IGFBP7 plasma concentrations were measured in a blinded fashion. The final diagnosis was centrally adjudicated using all the individual patient information including natriuretic peptides. Prognostic endpoints included all-cause mortality within 720 days and the combined outcome of all-cause mortality and AHF rehospitalizations. AHF was adjudicated in 52% of 966 patients. IGFBP7 levels were higher in AHF patients (150 [117.2-195.2] ng/mL vs. 91.3 [75.5-114.2] ng/mL, p<0.001). Patients in the highest IGFBP7 quartile were older, male, and more likely to have coronary artery disease, chronic heart failure, atrial fibrillation, and chronic renal disease. The diagnostic accuracy measured by Area under receiver operating curve (AUC) of IGFBP7 was 0.85 (95% CI: 0.82 to 0.87, p<0.001), of NT-proBNP 0.92 (95% CI: 0.90 to 0.93, p<0.001), and of hs-cTnT 0.79 (p<0.001). Adding IGFBP7 to NT-proBNP increased the AUC to 0.93 (95% CI: 0.91 to 0.94, p<0.001). Patients with IGFBP7 plasma values above the median had a significantly greater mortality risk. Moreover, the combined endpoint, AHF rehospitalization and all-cause death within 720 days was associated with IGFBP7 levels above the median. Conclusion IGFBP7 enhances the diagnostic and prognostic capabilities of NT-proBNP in patients presenting with acute dyspnea to the ED.