Diagnosing myocardial infarction: a highly sensitive issue
Authors: Stefan Blankenberg, Johannes Tobias Neumann, Dirk Westermann
Journal: The Lancet (2018)

The advent of high-sensitivity troponin assays to enable the quantification of troponin concentration in up to 95% of the general population is thought to improve clinical care in patients presenting with suspected infarction.1Blankenberg S Salomaa V Makarova N et al.Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium.Eur Heart J. 2016; 37: 2428-2437Crossref PubMed Scopus (163) Google Scholar, 2Westermann D Neumann JT Sörensen NA Blankenberg S High-sensitivity assays for troponin in patients with cardiac disease.Nat Rev Cardiol. 2017; 14: 472-483Crossref PubMed Scopus (101) Google Scholar The application of high-sensitivity troponin assays could be beneficial by enabling the early ruling out of myocardial infarction on the basis of very low troponin concentrations;3Twerenbold R Neumann JT Sörensen NA et al.Prospective validation of the 0/1-h algorithm for early diagnosis of myocardial infarction.J Am Coll Cardiol. 2018; 72: 620-632Crossref PubMed Scopus (100) Google Scholar, 4Neumann JT Sörensen NA Schwemer T et al.Diagnosis of myocardial infarction using a high-sensitivity troponin I 1-hour algorithm.JAMA Cardiol. 2016; 1: 397-404Crossref PubMed Scopus (147) Google Scholar, 5Cullen L Mueller C Parsonage WA et al.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.J Am Coll Cardiol. 2013; 62: 1242-1249Crossref PubMed Scopus (251) Google Scholar, 6Chapman AR Lee KK McAllister DA et al.Association of high-sensitivity cardiac troponin I concentration with cardiac outcomes in patients with suspected acute coronary syndrome.JAMA. 2017; 318: 1913-1924Crossref PubMed Scopus (141) Google Scholar, 7Sandoval Y Smith SW Thordsen SE et al.Diagnostic performance of high sensitivity compared with contemporary cardiac troponin I for the diagnosis of acute myocardial infarction.Clin Chem. 2017; 63: 1594-1604Crossref PubMed Scopus (29) Google Scholar precise and rapid diagnosis of myocardial infarction on the basis of troponin-based algorithms8Keller T Zeller T Peetz D et al.Sensitive troponin I assay in early diagnosis of acute myocardial infarction.N Engl J Med. 2009; 361: 868-877Crossref PubMed Scopus (937) Google Scholar, 9Reichlin T Hochholzer W Bassetti S et al.Early diagnosis of myocardial infarction with sensitive cardiac troponin assays.N Engl J Med. 2009; 361: 858-867Crossref PubMed Scopus (1349) Google Scholar followed by early treatment initiation; and improved risk stratification on the basis of low troponin concentrations that are only detectable by high-sensitivity assays.1Blankenberg S Salomaa V Makarova N et al.Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium.Eur Heart J. 2016; 37: 2428-2437Crossref PubMed Scopus (163) Google Scholar In The Lancet, the High-STEACS Investigators10Shah ASV Anand A Strachan FE et al.High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial.Lancet. 2018; (published online Aug 28.)http://dx.doi.org/10.1016/S0140-6736(18)31923-8Summary Full Text Full Text PDF Scopus (188) Google Scholar present an innovative and impressive strategy to compare a truly high-sensitivity troponin assay with previous contemporary troponin testing by use of a cluster-randomised controlled trial design. This design allows the comparison of outcomes 1 year after patient presentation at the emergency department, before and after implementation of this high-sensitivity assay across ten hospitals in Scotland. The trial is large, with almost 50 000 patients included. Among the study population, 10 360 (21%) patients had troponin concentrations greater than those of the 99th percentile. Notably, 1771 (17%) of these 10 360 patients were reclassified by the high-sensitivity strategy, resulting in additional patients who had not been identified by the contemporary assay being identified by the high-sensitivity assay. These patients would have been missed if we were only to use the conventional assay. How did this high-sensitivity approach affect cardiovascular outcomes, and what was the net benefit of identifying these reclassified patients? Within 1 year, 2586 (5%) patients had a subsequent myocardial infarction or death from cardiovascular causes, and these outcomes were more common in patients who had been reclassified. However, use of a high-sensitivity assay to diagnose those at risk did not significantly affect the risk of the combined endpoint of subsequent myocardial infarction or cardiovascular death (which occurred in 15% of reclassified patients during the validation phase vs 12% of these patients during the implementation phase). Therefore, Anoop Shah and colleagues10Shah ASV Anand A Strachan FE et al.High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial.Lancet. 2018; (published online Aug 28.)http://dx.doi.org/10.1016/S0140-6736(18)31923-8Summary Full Text Full Text PDF Scopus (188) Google Scholar report no benefit to the high-sensitivity strategy investigated. This nationwide approach represents an intelligent approach to make clinical routine data accessible within the frame of a clinical trial. However, there still might be some crucial points to consider. It is a self-fulfilling conundrum that application of a high-sensitivity assay leads to a higher number of diagnoses of myocardial infarction when lower thresholds are applied. Ideally, earlier and more sensitive detection of myocardial infarction should lead to better therapeutic strategies and should also translate into better outcome. Obviously, this result is not observed in Scotland during and after the implementation phase. The application of high-sensitivity assays is not associated with a difference in outcome at 1 year in the study by Shah and colleagues. This finding might be explained by various factors. First, strong evidence proves the association between troponin concentration and outcome in disease-based and population-based studies, even at low concentrations. This association becomes stronger over time and is most likely not apparent after 1 year. A follow-up of 1 year is not sufficient to determine the benefit of clinical decision making that is based on more sensitive troponin assays. Second, although the use of coronary angiographies in reclassified patients was more common, the number of patients that received percutaneous coronary intervention was unchanged. Medical therapy was moderately improved in the reclassified patients, but the absolute numbers were small (new single or double antiplatelet drugs were used in 171 patients and new statins in 47 patients). These slight changes in medical treatment do not affect outcome after 1 year. Finally, and most importantly, the adoption of the 99th percentile as a threshold for the high-sensitivity assays largely ignores their potential. The 99th percentile of the high-sensitivity troponin assay is almost completely recognisable by the contemporary sensitive test (only 17% of those identified by which were reclassified). Hence, the use of the high-sensitivity assays in the implementation phase did not take advantage of the highly sensitive nature of the test. Although this trial focused on the effects of high-sensitivity troponin assays for diagnosing myocardial infarction and progresses our understanding, additional questions remain. First, can the application of the high-sensitivity troponin assay safely rule out myocardial infarction by use of a baseline and 1-h protocol without affecting outcome? And second, could the application of troponin cutoff concentrations far below the 99th percentile lead to an improvement of clinical outcomes due to changes in treatment strategies in a longer follow-up? Both aspects need to be addressed in future. SB reports receiving honoraria from Abbott Diagnostics, Siemens, Thermo Fisher and Roche Diagnostics, outside the area of work commented on here. JTN and DW declare no competing interests. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trialUse of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. Full-Text PDF Open Access