Abstract 9552: A Novel Human Cardiac Troponin T upstream Open Reading Frame Peptide Assists in the Diagnosis and Prognosis of NSTEMI Patients

Abstract

Introduction: High sensitivity assays for cardiac troponin (cTn) have reduced time to NSTEMI diagnosis but 5-10% of NSTEMI patients still remain cTn negative within 2 hours of presentation. We hypothesised that measurement of an upstream open reading frame peptide (uORF) from the human cTnT gene (TnTuORF) could improve sensitivity to detect NSTEMI within 2 hours of hospital presentation. Methods: We developed a specific immunoassay for TnTuORF and measured plasma levels alongside NT-proBNP (Roche Elecsys), standard TnI (Abbott Architect), hsTnT (Roche Elecsys) and hFABP (Hycult Biotech) in 501 patients presenting to Christchurch Hospital, New Zealand with chest pain necessitating rule-out of ACS. Samples were taken at t=0, 1, 2 and 12-24 hours (index TnI) post-presentation along with all demographic, clinical and laboratory information. Correlation analysis was conducted using Spearman’s rank test. Biomarker diagnostic and prognostic efficiencies (AUC, sensitivity, specificity) were conducted using ROC analysis. P<0.05 was considered significant. Results: Plasma TnTuORF tended to display a negative relationship with TnI and hsTnT (r=-0.054, P=0.252) and did not diagnose NSTEMI (AUC=0.446, P=0.117). Instead, when applied as the denominator in a ratio with TnI/hsTnT (Table 1), TnTuORF could improve the sensitivity of both assays, but with reductions in specificity. The ratio TnI x hsTnT/TnTuORF (termed TroponinPLUS) gave the best sensitivity and detected 98% of NSTEMI patients. TroponinPLUS could predict death at 45 days (AUC=0.814, P=0.016, sensitivity = 0.80, specificity = 0.72) and 1 year (AUC=0.741, P<0.001, sensitivity = 0.67, specificity = 0.70). Conclusion: This is the first demonstration of a circulating uORF peptide. The ratio of total cTn to TnTuORF (TroponinPLUS) improved early detection of NSTEMI and has good prognostic ability. We conclude TnTuORF measurement may assist in NSTEMI diagnosis and prognosis. Table 1. ROC data - NSTEMI diagnosis