Background—: It is unknown whether more sensitive cardiac troponin (cTn) assays maintain their clinical utility in patients with renal dysfunction. Moreover, their optimal cutoff levels in this vulnerable patient population have not previously been defined. Methods and Results—: In this multicenter study, we examined the clinical utility of 7 more sensitive cTn assays (3 sensitive and 4 high-sensitivity cTn assays) in patients presenting with symptoms suggestive of acute myocardial infarction. Among 2813 unselected patients, 447 (16%) had renal dysfunction (defined as Modification of Diet in Renal Disease–estimated glomerular filtration rate <60 mL·min ⁻¹ ·1.73 m ⁻² ). The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including coronary angiography and serial levels of high-sensitivity cTnT. Acute myocardial infarction was the final diagnosis in 36% of all patients with renal dysfunction. Among patients with renal dysfunction and elevated baseline cTn levels (≥99th percentile), acute myocardial infarction was the most common diagnosis for all assays (range, 45%–80%). In patients with renal dysfunction, diagnostic accuracy at presentation, quantified by the area under the receiver-operator characteristic curve, was 0.87 to 0.89 with no significant differences between the 7 more sensitive cTn assays and further increased to 0.91 to 0.95 at 3 hours. Overall, the area under the receiver-operator characteristic curve in patients with renal dysfunction was only slightly lower than in patients with normal renal function. The optimal receiver-operator characteristic curve–derived cTn cutoff levels in patients with renal dysfunction were significantly higher compared with those in patients with normal renal function (factor, 1.9–3.4). Conclusions—: More sensitive cTn assays maintain high diagnostic accuracy in patients with renal dysfunction. To ensure the best possible clinical use, assay-specific optimal cutoff levels, which are higher in patients with renal dysfunction, should be considered. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00470587.

Background: The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non–ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non–ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD. Methods: In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non–ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m ² , and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample. Results: Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non–ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P <0.001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6–100.0] versus 99.2% [95% CI, 97.6–99.8]; P =0.559), lower specificity of rule-in (88.7% [95% CI, 84.8–91.9] versus 96.5% [95% CI, 95.7–97.2]; P <0.001), and lower overall efficacy (51% versus 81%, P <0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P <0.001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0–99.8] versus 98.5% [95% CI, 96.5–99.5]; P =1.0), lower specificity of rule-in (84.4% [95% CI, 79.9–88.3] versus 91.7% [95% CI, 90.5–92.9]; P <0.001), and lower overall efficacy (54% versus 76%, P <0.001; proportion ruled out, 18% versus 58%, P <0.001) compared with patients with normal renal function. Conclusions: In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00470587.

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.