Multiple biomarker strategy for improved diagnosis of acute heart failure in older patients presenting to the emergency department

AIM: Biomarkers can help to identity acute heart failure (AHF) as the cause of symptoms in patients presenting to the emergency department (ED). Older patients may prove a diagnostic challenge due to co-morbidities. Therefore we prospectively investigated the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with other biomarkers for AHF upon admission at the ED. METHODS: 302 non-surgical patients aged ≥ 70 years were consecutively enrolled upon admission to the ED. In addition to NT-proBNP, mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and ultra-sensitive C-terminal pro-vasopressin (Copeptin-us) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of AHF after reviewing all available baseline data excluding the biomarkers. We assessed changes in C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) for the multimarker approach. RESULTS: AHF was diagnosed in 120 (40%) patients (age 81±6 years, 64 men, 56 women). Adding MR-ADM to NT-proBNP levels improved C-index (0.84 versus 0.81; p=0.045), and yielded IDI (3.3%; p=0.002), NRI (17%, p<0.001) and continuous NRI (33.3%; p=0.002). Adding CT-proET-1 to NT-proBNP levels improved C index (0.86 versus 0.81, p=0.031), and yielded robust IDI (12.4%; p<0.001), NRI (31.3%, p<0.001) and continuous NRI (69.9%; p<0.001). No other dual or triple biomarker combination showed a significant improvement of both C-index and IDI. CONCLUSION: In older patients presenting to the ED, the addition of CT-proET-1 or MR-proADM to NT-proBNP improves diagnostic accuracy of AHF. Both dual biomarker approaches offer significant risk reclassification improvement over NT-proBNP.