Highly Sensitive Cardiac Troponin I Assay Leads to Lowered Specificity

I read with great interest the article of Kavsak et al. (1) on the utility of a next-generation high-sensitivity Beckman Coulter cardiac troponin I (cTnI) assay with a 20% CV at 2.95 ng/L. This approach demonstrated a higher diagnostic sensitivity (81% vs 62%) for myocardial injury with a changing pattern of cTnI values, compared with the AccuTnI® assay cleared by the US Food and Drug Administration (1). This high-sensitivity assay had an unexpectedly high prevalence (3%) for interfering heterophilic antibodies compared with the 0.05% prevalence reported in the literature for contemporary assays (2). Heterophilic antibodies usually exhibit weak binding and polyspecificity. These antibodies are involved in the development of high-affinity antibodies, self-tolerance, and idiotypic regulatory processes (2). Critical exclusion of individuals with false-positive results has been reported to be feasible during reference-interval studies (1). How the results for patients in this study were affected by false-positive results and how they may therefore have contributed to the increased diagnostic sensitivity of the test is not known. Interferences by heterophilic antibodies in a cTnI test can be reduced markedly, such as with the revised Dimension cTnI assay with a 20% CV at 0.08 μg/L (3). The high-sensitivity cTnI assay reported by Kavsak et al. also deserves such amelioration, if possible. Tests with such a high rate of false positives due to heterophilic antibodies cannot be considered appropriate for routine use because clinicians or laboratory personnel are not always aware of this problem and therefore may not initiate the appropriate follow-up investigations, such as absorption of such heterophilic antibodies or the application of another test. Criteria with greater stringency are necessary to avoid interference by heterophilic antibodies, and the first step is a strict awareness of this problem. An increased diagnostic sensitivity should be feasible, but care must be taken so that negative consequences of false-positive results do not diminish the potential benefits of high-sensitivity assays. Author Contributions:All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 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; and (c) final approval of the published article. Authors’ Disclosures of Potential Conflicts of Interest:No authors declared any potential conflicts of interest. Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript. Acknowledgments: For critical reading of the manuscript, I am indebted to Erwin Schleicher.