Cardiac myosin-binding protein C and the early risk stratification of patients with possible acute myocardial infarction
Y Y Tew, Z Li, T Fujisawa, A J F Thurston, R Wereski, P Fineran, D Harry, E Highton-Williamson, M Mizerska, A R Chapman, A Anand, N L MillsAbstract
Background
High-sensitivity cardiac troponin (hs-cTn) has enabled earlier risk stratification of patients with possible myocardial infarction to identify those suitable for discharge with a single measurement. However, early presenters require serial testing, which has limited the effectiveness of this approach. We hypothesize that the greater abundance and earlier release of cardiac myosin-binding protein C (cMyBP-C) could improve the effectiveness of single sample rule-out pathways.
Methods
In a secondary analysis of two prospective multi-centre cohort studies, cMyBP-C and hs-cTnT (fifth-generation) concentrations were measured using an automated high-throughput immunoassay analyser in stored lithium heparin plasma obtained at presentation from patients with possible myocardial infarction. The primary outcome was an adjudicated diagnosis of type 1, type 4b, or type 4c myocardial infarction or cardiac death at 30 days. Discrimination was quantified using the area under the receiver operating characteristic curve (AUROC) for cMyBP-C and cTnT in all participants and early presenters (≤3 hours from symptom onset) and compared using DeLong’s nonparametric test. The risk stratification threshold was defined as the highest cMyBP-C concentration achieving a negative predictive value (NPV) of 99.5% and sensitivity of 99%. The proportion of patients identified as low-risk were quantified and effectiveness determined within a single-sample rule out pathway for cTnT and a new pathway combining cTnT and cMyBP-C (Figure 1).
Results
In total 2,022 patients (61 [52-72] years, 38% females) were included with 39% (725/2,022) presenting within 3 hours in whom 12% (235/2,022) had a myocardial infarction or cardiac death at 30 days. The median cMyBP-C and cTnT concentration was 12 [6-36] and 7 [4-15] ng/L at presentation, respectively. Discrimination was higher for cMyBP-C compared to cTnT in all participants (AUROC 0.95 [95% CI 0.93-0.96] versus 0.93 [95% CI 0.92-0.95]; P=0.006) and in early presenters (0.94 [95% CI 0.93-0.96] versus 0.92 [95% CI 0.90-0.94]; P=0.005) (Figure 2). When testing was incorporated into a single-sample rule out pathway, the proportion of low-risk patients identified at presentation increased from 18% (313/1,788) using cTnT alone to 38% (681/1,788) when cTnT and cMyBP-C were combined (P<0.001, McNemar’s test).
Conclusions
A novel cMyBP-C assay had greater discrimination for myocardial infarction at presentation compared to the current hs-cTnT assay. The combination of cMyBP-C for risk stratification with a normal cTnT concentration doubled the proportion of patients identified as low-risk at presentation compared to risk stratification using hs-cTnT alone.Figure 2