Abstract 11526: Nardilysin is a Potential Biomarker for the Early Diagnosis of Non-St-Segment Elevation Acute Coronary Syndrome, A Multicenter Prospective Cohort Study, Nardi-ACS Study

Background: Rapid and accurate diagnosis of acute coronary syndrome (ACS) is critical to prevent the fatal complication accompanied with the delay of the treatment. However, the diagnosis of non-ST-segment elevation ACS (NSTE-ACS), especially shortly after the onset, is not straightforward because even high-sensitivity cardiac troponin (hs-cTn) is sometimes not elevated at that phase. We previously reported in a retrospective study that serum nardilysin is a potential biomarker for the early detection of NSTE-ACS. Here, we present the results of the Nardi-ACS study, a multicenter prospective study conducted at six centers in Japan to clarify the significance of nardilysin for the early detection of ACS. Methods and Results: We analyzed serum nardilysin and hs-cTnI (Architect; Abbott) in the sequential 2 independent cohorts; phase I primary cohort (435 patients with chest pain who consecutively visited to the emergency room (ER)) and phase II validation cohort (486 patients with a strong suspicion of ACS who underwent coronary angiography). The frequency of non-ACS, STEMI and NSTE-ACS was 64.4, 22.5, and 13.1 (%) in the phase I, and 14.0, 60.0, and 25.9 (%) in the phase II cohort, respectively. The cutoff value of serum nardilysin was set at 1350.9 pg/ml (mean +2SD) obtained in 246 healthy volunteers, while the cutoff of hs-cTnI was set at 52 pg/ml. The initial blood test in the phase I cohort revealed that nardilysin was significantly elevated in ACS patients, compared to non-ACS patients (p<0.05). The sensitivity of hsTnI, nardilysin, and nardilysin combined with hsTnI for the diagnosis of NSTE-ACS was 52.6, 57.9, and 78.9 (%), and the negative predictive value (NPV) was 90.7, 88.7, and 92.4 (%), respectively. When focused on hsTnI-negative patients, the sensitivity and NPV of nardilysin in STEMI and NSTE-ACS were 64.7/91.4 and 55.6/91.4 (%), respectively. Furthermore, the sensitivity of nardilysin for the early detection of STEMI and NSTE-ACS patients, whose blood was examined within 3 hours after the onset was 77.6 and 60.4 (%), respectively, both of which were higher than that of hsTnI (51.2 and 56.3%). Conclusion: Nardilysin could be a potential biomarker for the early diagnosis of troponin-negative NSTE-ACS.