Background: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application. Methods: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI–based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm. Results: Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%–100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%–98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P =0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies ( P <0.01 for LOD versus each of the other strategies). Conclusions: All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00470587.

Background: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. Methods: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. Results: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng ² /L ² ) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0–99.9%]; product: NPV 99.4% [95% CI, 98.8–99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2–100%]; NPV validation cohort 99.5% [95% CI, 98.9–99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6–78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7–87.6%]). Conclusions: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. Clinical Trial Registration: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.

The aim of the present study was to examine the acute effect of an ultra-endurance performance on N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac specific troponin T (cTnT), creatinine kinase-myocardial band (CK-MB), high sensitive C-reactive protein (hsCRP), ischemia modified albumin (IMA), heart-type fatty acid binding protein (H-FABP) and cardiovascular function. Cardiac biomarkers were evaluated in 14 male ultra-marathoners (age 40 ± 12 years) during a 24 h ultra-marathon at five points (i.e., Pre-race; Marathon, 12-h run, 24-h run, and 48-h post-race). All subjects underwent baseline echocardiography assessment at least 10 days prior to the ultra-marathon and 48 h post-race. The average distance covered during the race was 149.4 ± 33.0 km. Running the ultra-marathon led to a progressive increase in hsCRP and H-FABP concentrations (p < 0.001). CK-MB and cTnT levels were higher after a 24-h run compared to pre-race (p < 0.05). Diastolic function was altered post-race characterized by a reduction in peak early to late diastolic filling (p < 0.01). Running an ultra-marathon significantly stimulates specific cardiac biomarkers; however, the dynamic of secretion of biomarkers linked to myocardium ischemia were differentially regulated during the ultra-marathon race. It is suggested that both exercise duration and intensity play a crucial role in cardiovascular adaptive mechanisms and cause risk of cardiac stress in ultra-marathoners.