High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial

Abstract

SummaryBackgroundHigh-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome.MethodsIn this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6–12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123.FindingsBetween June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620).InterpretationUse 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 finding...

Diagnosis and prognosis of myocardial infarction on a plasmonic chip

“…Superior to CIA with diagnostic sensitivity of 59.82% and specificity of 70.54%, the pGold chip assay afforded markedly improved diagnostic sensitivity of 92.86% and specificity of 97.32%, based on the recommended cutoff concentration by CIA (0.04 ng mL −1 for cTnI, Tables 1, 2) [41][42][43] , due to the enhanced LOD and LOQ. Notably, we achieved further enhanced diagnostic sensitivity of 100% and specificity of 95.54%, based on the lowered cutoff concentration by pGold (0.03 ng mL −1 for cTnI, Fig.…”

Clinical impact of using a more sensitive troponin assay in patients with acute chest pain

“…Although Mills and his team found that lowering the diagnostic threshold for AMI with a sensitive cTn assay could improve clinical outcomes, several observational studies stated that no change in the incidence of MACE was found, with or without an increase in revascularizations . High‐STEACS, a stepped‐wedge, cluster‐randomized controlled trial also showed that the use of a high‐sensitivity cTn was not associated with a lower incidence of MACE . Troponin cannot be a substitute for careful clinical assessment, and it must be interpreted in the context of the history of each patient.…”

“…These assays adopted a lower threshold for the detection of myocardial injury. However, increased sensitivity is accompanied by decreased specificity, and only a third of patients who reclassified with the high‐sensitivity assay as myocardial injury had a diagnosis of type 1 myocardial infarction (MI) . The dynamic changes in high‐sensitivity cTn concentration, quantified as delta cTn has been proposed as a tool for the improvement of specificity .…”

“…Conventional troponin assays could lead to an inappropriate discharge, while more sensitive troponin assays may result in avoidable diagnostic testing. Published data about the impact of the use of more sensitive cTn assays compared with the conventional ones on the actual managements and outcomes of chest pain patients presenting to the ED are inconclusive . More researches are needed to test whether the clinical consequences are altered when the more sensitive cTn assays are used in different health settings.…”

„Myocardial injury“ und Myokardinfarkt – Konsequenzen für die Klinik im Kontext aktueller Leitlinien

“…Version der Leitlinie aus dem Jahr 2007 [2], ist jedoch gerade in Zeiten des hochsensitiven Troponins nicht unumstritten. So konnte eine große randomisierte Studie im vergangenen Jahr zeigen, dass durch die Verwendung des hochsensitiven Assays zwar zusätzliche 17 % der Patienten, die sich mit Verdacht auf akutes Koronarsyndrom vorstellten, die Kriterien der "Myocardial injury" erfüllten, dies jedoch im Ein-Jahres-Intervall zu keiner Veränderung der Inzidenz von Myokardinfarkt oder kardiovaskulärem Tod führte [3].…”