Comparison of Patient Results on a New High-Sensitivity Troponin I Assay with a Conventional Assay, Focusing on Clinically Relevant Cutpoints

High sensitivity troponin I assays (hs-cTnI) are widely used for diagnosis of myocardial injury/infarction in Europe (1,). The Beckman Coulter Access hs-cTnI assay was approved by the United States Food and Drug Administration (FDA) in June 2018. Since the assay is sensitive enough to measure cardiac troponin even in healthy individuals, previous studies have demonstrated that the reference interval should be at the 99th percentile, and this is sanctioned by the European Society of Cardiology guidelines and the Fourth Universal Definition of Myocardial Infarction (2–4). We aimed to validate cutpoints suggested by our institution’s lab, ED, and cardiology leaders by performing a correlation study between the current contemporary sensitive Beckman Coulter troponin I assay (“conTnI”), AccuTnI + 3, and the new Beckman Coulter Access hs-cTnI assay (“hs-cTnI”). Patients presented to our adult Emergency Department (ED) or to either of two free standing ED’s (FSED) affiliated with our institution. Those with symptoms that could represent acute coronary syndrome underwent conTnI testing upon arrival and 3 h later per standard of care on the Beckman Coulter DxI (main hospital) or Access 2 (FSED) platforms. We concurrently ran hs-cTnI on the same instruments on 417 patients. When laboratory staff trained to participate in this study were available to assist, randomly selected patients had both of their samples (0 and 3 h) tested for a total of 489 tests. These results were blinded to emergency medicine providers. Based on the manufacturer’s package insert, key stakeholders from the laboratory, ED, and cardiology determined that the interpretation of hs-cTnI would be as follows:<15 pg/mL: within normal range for females, <20 pg/mL: within normal range for males, 15–100 pg/mL for females: delta guidelines/algorithm will be used, 20–99 pg/mL for males: delta guidelines/algorithm will be used; >100 pg/mL: likely type 1 or type 2 myocardial infarction was occurring. A positive delta is an absolute difference of 15 pg/mL or more. There was 97% correlation (R2 = 0.97) between the conTnI and hs-cTnI. A conTnI of <0.05 ng/mL (“rule out” group if 3 h troponin level was not elevated) was reported for 373 patients (Table 1). Of these, 318 (85%) had hs-cTnI less than the 99th percentile (using gender specific cutoffs). Fifty-four (14.5%) had an hs-cTnI from the 99th percentile to 99 pg/mL, and 1 (0.2%) patient’s hs-cTnI was >100 pg/mL. Of the 46 patients with conTnI values of 0.05–0.1 ng/mL, 4 (8.7%) had hs-cTnI less than the 99th percentile, 38 (83%) had an hs-cTnI from the 99th percentile to 99 pg/mL, and 4 (8.6%) had hs-cTnI >100 pg/mL. Seventy patients had a conTnI reported as >0.1 ng/mL (“rule in” group); of these, 64 (91%) had an hs-cTnI of >100 pg/mL, 4 (5%) had hs-cTnI from the 99th percentile to 99 pg/mL, and 2 (2.5%) had an hs-cTnI of <99th percentile. Bracketing of patient results by clinically relevant Cutpoints. Bracketing of patient results by clinically relevant Cutpoints. The correlation between the assays is reassuring. This holds true when bracketing patients into medical decision-making cohorts (“rule in” MI and “rule out” MI). Although our study is limited by the absence of diagnosis or disposition data, we infer that patients with hs-cTnI <99th percentile would be treated the same way as if conTnIwas <0.05 ng/mL (“rule out”), and patients with conTnI of >0.1 ng/mL would be treated similarly to patients with hs-cTnI >100 pg/mL (“rule in”). Regarding the “rule out” group, 1 of 373 patients with conTnI <0.05 ng/mL had hs-cTnI >100 pg/mL. This may represent a missed diagnosis of myocardial injury/infarction due to increased assay sensitivity. Similarly, in the “rule in” group (conTnI >0.1 ng/mL), 2 of 70 patients were <99th percentile for hs-cTnI; since the analytical specificity of the assay has been improved, it is possible that these patients actually do not have elevated cardiac troponin I levels. All three of these outliers may have had reasons for abnormal troponin levels outside of a type-1 myocardial infarction. Serial testing in this patient population will be utilized in the zone of hsTnI values between the 99th percentile and myocardial infarction cutpoint based on the Fourth Universal Definition of Myocardial Infarction. Patients in this zone (n = 96) had conTnI’s of <0.03 ng/mL up to 0.3 ng/mL, crossing all levels of current decision-making points. This data validated the need for a delta calculation in order to differentiate acute myocardial injury from chronic myocardial injury. None of the patients in the delta cohort with a second test available (n = 11) had a positive delta (mean = 2.6 ± 2.5 pg/mL; mean time between specimen was 2.5 ± 0.9 h), indicating that there was not acute myocardial injury. Therefore, there is potential for safe discharges in this population, who would have likely been admitted using the conTnI. In summary, we have shown excellent correlation between the AccuTnI + 3 and Access hs-cTnI assays. These data have implications for predicting if this assay will change disposition and earlier recognition of myocardial injury/infarction. All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form and potential conflicts of interest. Authors’ Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.