Diagnostic and prognostic utility of angiopoietin-2 in patients presenting with acute dyspnea

Background Experimental and clinical evidence suggests a pathophysiological role for angiopoietin-2 (ANGPT2) in acute heart failure (AHF). Aim To investigate the diagnostic and prognostic utility of ANGPT2 in patients presenting with acute dyspnoea to the emergency department. Methods and Results Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC). Prognostic endpoints included 720-day all-cause mortality and the composite of all-cause mortality or AHF rehospitalization. Cumulative incidence curves and multivariable Cox regression models were applied. A total of 972 consecutive patients were included. Mean age was 72 years, and 52% had an adjudicated final diagnosis of AHF. Median ANGPT2 levels were 4 (2.1–8.5) ng/mL and significantly higher in patients with adjudicated AHF compared to patients with other causes of acute dyspnea (7.2 vs 2.2 ng/mL, respectively; p < 0.001). ANGPT2 correlated strongly with N-terminal pro-B-type natriuretic peptide (NT-proBNP) (ρ = 0.68; p<0.001), showed high diagnostic accuracy for AHF (AUC 0.85; 95% CI 0.83–0.87 Figure 1), and moderate prognostic accuracy (all-cause mortality: AUC 0.66 95% CI 0.62–0.7; composite endpoint: AUC 0.71 95% CI 0.68–0.74). Median ANGPT2 concentrations were significantly higher among patients experiencing major adverse events with 720 days of follow-up (all-cause mortality:: 6.1 vs 3.5 ng/mL; composite endpoint: 6.6 vs 2.9 ng/mL;p < 0.001). In multivariable Cox regression analyses, ANGPT2 remained an independent predictor of 720-day all-cause mortality (HR 1.03; 95% CI 1.01–1.04; p < 0.001) and the composite endpoint (HR 1.03; 95% CI 1.02–1.04; p<0.001) at 720 days (Figure 2). Conclusions Among patients presenting with acute dyspnea, ANGPT2 demonstrates high diagnostic accuracy for AHF and is an independent predictor for long-term adverse events.