Utility of N-Terminal Pro-B-Type Natriuretic Peptide -to-Troponin and BNP-to-Troponin Ratios for Differentiating Type 1 from Type 2 Myocardial Infarction: A HIGH-US Sub-Study

Background: Differentiating type 1 myocardial infarction (T1-MI) from type 2 MI (T2-MI) remains a diagnostic challenge, even with the availability of high-sensitivity cardiac troponin assays. This study explored whether NT-proBNP, BNP, and their respective ratios to troponin could enhance the ability to distinguish between these MI subtypes. Methods: As a HIGH-US sub-study, we examined data from 280 patients diagnosed with non-ST elevation myocardial infarction (172 with T1-MI and 108 with T2-MI). We assessed NT-proBNP, BNP, hs-cTnI, and their ratios as potential discriminative biomarkers. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves. Results: NT-proBNP levels were markedly elevated in T2-MI patients compared to those with T1-MI (mean 10,327±12,923 vs 4,675±11,740 ng/L; P=0.006). Conversely, hs-cTnI concentrations were higher in T1-MI (1.4±5.1 vs 0.5±1.1 ng/L; P=0.030). Notably, the NT-proBNP-to-troponin ratio was more than three times greater in T2-MI cases (94,880±152,648 vs 24,209±78,727; P=0.007). NT-proBNP alone demonstrated fair discriminatory capacity (AUC 0.717, 95% CI 0.578–0.856), closely matching the NT-proBNP-to-troponin ratio (AUC 0.720, 95% CI 0.566–0.873). In contrast, BNP and the BNP-to-troponin ratio offered lower diagnostic values. Mean BNP levels were 505.4 ±576.6 ng/L for those with T2-MI and 437.1 ±738.8 ng/L for patients with T1-MI. BNP-to-troponin ratio showed a poor discrimination for the 2 MI types (AUC, 0.660; 95% CI, 0.532-0.789). Conclusions: Both NT-proBNP and its ratio to troponin show potential in differentiating T1-MI from T2-MI, reflecting distinct underlying pathophysiological processes. Given its comparable performance to the ratio, NT-proBNP alone may serve as a practical and cost-effective standalone marker. These findings support the hypothesis that incorporating NT-proBNP testing into routine clinical workflows may better informs the management of patients with suspected MI.