Multiple Cardiac Biomarker Testing Among Patients with Acute Dyspnea from the ICON-RELOADED Study

Abstract

Background: Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and insulin-like growth factor binding protein-7 (IGFBP7) predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown.

Methods and results: Concentrations of NT-proBNP, hs-cTnT, and IGFBP7 were analyzed in 1,448 patients presenting with acute dyspnea from the prospective, multicenter ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all three biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in two biomarkers (18.8%, 44 out of 234), one biomarker (3.8%, 10 out of 260), or no elevated biomarkers (0.4%, 2 out of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite endpoint of mortality and HF rehospitalization. In adjusted models, patients with one, two, and three elevated biomarkers had 3.74 (95% CI, 1.26-11.1; P=0.017), 12.3 (95% CI, 4.60-32.9; P <0.001), and 12.6 (95% CI, 4.54-35.0; P <0.001) fold increased risk of 180-day mortality or HF rehospitalization.

Conclusions: A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization.