Direct Comparison of Cardiac Myosin-Binding Protein C With Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI. METHODS: Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality. RESULTS: Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L, P<0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 (P<0.0001) and 0.926 (P=0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: Net Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI (P<0.001). In early presenters (chest pain <3 h), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308; both P<0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI (P<0.05 for both) and similar to hs-cTnT at predicting death at 3 years. CONCLUSIONS: cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587.

A 0/1h-algorithm using cardiac myosin-binding protein C for early diagnosis of myocardial infarction.

AIMS: Cardiac myosin-binding protein C (cMyC) demonstrated high diagnostic accuracy for the early detection of non-ST-elevation myocardial infarction (NSTEMI). Its dynamic release kinetics may enable a 0/1h-decision algorithm that is even more effective than the ESC hs-cTnT/I 0/1 h rule-in/rule-out algorithm. METHODS AND RESULTS: In a prospective international diagnostic study enrolling patients presenting with suspected NSTEMI to the emergency department, cMyC was measured at presentation and after 1 h in a blinded fashion. Modelled on the ESC hs-cTnT/I 0/1h-algorithms, we derived a 0/1h-cMyC-algorithm. Final diagnosis of NSTEMI was centrally adjudicated according to the 4th Universal Definition of Myocardial Infarction. Among 1495 patients, the prevalence of NSTEMI was 17%. The optimal derived 0/1h-algorithm ruled-out NSTEMI with cMyC 0 h concentration below 10 ng/L (irrespective of chest pain onset) or 0 h cMyC concentrations below 18 ng/L and 0/1 h increase <4 ng/L. Rule-in occurred with 0 h cMyC concentrations of at least 140 ng/L or 0/1 h increase ≥15 ng/L. In the validation cohort (n = 663), the 0/1h-cMyC-algorithm classified 347 patients (52.3%) as 'rule-out', 122 (18.4%) as 'rule-in', and 194 (29.3%) as 'observe'. Negative predictive value for NSTEMI was 99.6% [95% confidence interval (CI) 98.9-100%]; positive predictive value 71.1% (95% CI 63.1-79%). Direct comparison with the ESC hs-cTnT/I 0/1h-algorithms demonstrated comparable safety and even higher triage efficacy using the 0h-sample alone (48.1% vs. 21.2% for ESC hs-cTnT-0/1 h and 29.9% for ESC hs-cTnI-0/1 h; P < 0.001). CONCLUSION: The cMyC 0/1h-algorithm provided excellent safety and identified a greater proportion of patients suitable for direct rule-out or rule-in based on a single measurement than the ESC 0/1h-algorithm using hs-cTnT/I. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587.

Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome.

OBJECTIVES: The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain. BACKGROUND: Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS). METHODS: This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography. Strategies to identify low-risk patients incorporated TIMI risk scores= 0 or ≤ 1. The primary endpoint was a major adverse cardiac event (MACE) within 30 days. RESULTS: In the primary cohort, 1,635 patients were recruited and had 30-day follow-up. A total of 247 patients (15.1%) had a MACE. The finding of no ischemic electrocardiogram and hs-TnI ≤ 26.2 ng/l with the TIMI = 0 and TIMI ≤ 1 pathways, respectively, classified 19.6% (n = 320) and 41.5% (n = 678) of these patients as low risk; 0% (n = 0) and 0.8% (n = 2) had a MACE, respectively. In the secondary cohort, 909 patients were recruited. A total of 156 patients (17.2%) had a MACE. The TIMI = 0 and TIMI ≤ 1 pathways classified 25.3% (n = 230) and 38.6% (n = 351), respectively, of these patients as low risk; 0% (n = 0) and 0.8% (n = 1) had a MACE, respectively. Sensitivity, specificity, and negative predictive value for TIMI = 0 in the primary cohort were 100% (95% confidence interval [CI]: 98.5% to 100%), 23.1% (95% CI: 20.9% to 25.3%), and 100% (95% CI: 98.8% to 100%), respectively. Sensitivity, specificity, and negative predictive value for TIMI ≤ 1 in the primary cohort were 99.2 (95% CI: 97.1 to 99.8), 48.7 (95% CI: 46.1 to 51.3), and 99.7 (95% CI: 98.9 to 99.9), respectively. Sensitivity, specificity, and negative value for TIMI ≤ 1 in the secondary cohort were 99.4% (95% CI: 96.5 to 100), 46.5% (95% CI: 42.9 to 50.1), and 99.7% (95% CI: 98.4 to 100), respectively. CONCLUSIONS: An early-discharge strategy using an hs-TnI assay and TIMI score ≤ 1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study, NCT00470587; A 2 hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ADAPT]: a prospective observational validation study, ACTRN12611001069943).