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Impact of Patient Selection on Performance of an Early Rule-Out Pathway for Myocardial Infarction: From Research to the Real World

2023; Lippincott Williams & Wilkins; Volume: 147; Issue: 5 Linguagem: Inglês

10.1161/circulationaha.122.062419

1524-4539

Anda Bularga, Kuan Ken Lee, Anoop Shah, Atul Anand, Andrew R. Chapman, Christopher Tuck, David E. Newby, Sarah Jenks, Nicholas L. Mills, Dorien M. Kimenai,

Heart Failure Treatment and Management

HomeCirculationVol. 147, No. 5Impact of Patient Selection on Performance of an Early Rule-Out Pathway for Myocardial Infarction: From Research to the Real World Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessLetterPDF/EPUBImpact of Patient Selection on Performance of an Early Rule-Out Pathway for Myocardial Infarction: From Research to the Real World Anda Bularga, Kuan Ken Lee, Anoop S.V. Shah, Atul Anand, Andrew R. Chapman, Chris Tuck, David E. Newby, Sarah Jenks, Nicholas L. Mills and Dorien M. Kimenai Anda BulargaAnda Bularga BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. Usher Institute (A.A., N.L.M.), University of Edinburgh, United Kingdom. , Kuan Ken LeeKuan Ken Lee https://orcid.org/0000-0003-3404-4098 BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. , Anoop S.V. ShahAnoop S.V. Shah https://orcid.org/0000-0002-2825-3419 Department of Non-communicable Disease, London School of Hygiene and Tropical Medicine, United Kingdom (A.S.V.S.). , Atul AnandAtul Anand https://orcid.org/0000-0002-6428-4554 BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. , Andrew R. ChapmanAndrew R. Chapman https://orcid.org/0000-0003-1926-5925 BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. , Chris TuckChris Tuck https://orcid.org/0000-0003-4994-6342 BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. , David E. NewbyDavid E. Newby https://orcid.org/0000-0001-7971-4628 BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. , Sarah JenksSarah Jenks Department Clinical Biochemistry, Royal Infirmary of Edinburgh, United Kingdom (S.J.). , Nicholas L. MillsNicholas L. Mills https://orcid.org/0000-0003-0533-7991 BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. Usher Institute (A.A., N.L.M.), University of Edinburgh, United Kingdom. and Dorien M. KimenaiDorien M. Kimenai Correspondence to: Dorien M Kimenai, PhD, Centre for Cardiovascular Science, The University of Edinburgh, Chancellor's Building, Edinburgh, EH16 4SU, United Kingdom. Email E-mail Address: [email protected] https://orcid.org/0000-0003-1591-1352 BHF Centre for Cardiovascular Science (A.B., K.K.L., A.A., A.R.C., C.T., D.E.N., N.L.M., D.M.K.), University of Edinburgh, United Kingdom. Originally published30 Jan 2023https://doi.org/10.1161/CIRCULATIONAHA.122.062419Circulation. 2023;147:447–449Early rule-out pathways for myocardial infarction using high-sensitivity cardiac troponin are now recommended by international clinical guidelines.1 Although developed in selected patients participating in research studies, these pathways are applied widely in clinical practice where the diagnostic performance and effectiveness may differ substantially. We previously demonstrated that the selection of patients for high-sensitivity cardiac troponin testing influences the apparent prevalence of myocardial infarction.2 Here, we evaluated the impact of patient selection on the performance of the High-STEACS trial (High-Sensitivity Troponin in the Evaluation of Patients with Acute Coronary Syndrome) early rule-out pathway for myocardial infarction3 in unselected consecutive patients in clinical practice and in selected patients consenting to participate in a research study.Both cohorts comprised patients with suspected acute coronary syndrome presenting to emergency departments across 3 acute-care hospitals in Scotland. An electronic form embedded in practice was used to record prospectively the indication for cardiac troponin testing, symptoms, and timing of symptom onset. In the unselected cohort, data were collected in consecutive patients as part of a service evaluation in which the usual care clinician measured cardiac troponin for suspected acute coronary syndrome between June 7, 2021, and September 8, 2021. Data collection and record linkage were performed with approval from the Caldicott Guardian and the ethics committee. In the selected cohort, patients with suspected acute coronary syndrome were enrolled by researchers between June 1, 2013, and March 31, 2017, as described previously.4 In this cohort, patients were approached between 8:00 am and 8:00 pm by research staff, and written informed consent was obtained. This study was registered (https://www.clinicaltrials.gov; Unique identifier: NCT01852123) and approved by the ethics committee. Patients presenting with ST-segment–elevation myocardial infarction were excluded. These studies make use of multiple routine electronic health care data sources that are linked, deidentified, and held in our national safe haven that is accessible by approved individuals who have undertaken the necessary governance training.In both cohorts, presentation and serial cardiac troponin concentrations were measured using the ARCHITECTSTAT high-sensitive troponin I assay (Abbott Laboratories) and sex-specific 99th percentile diagnostic thresholds applied (16 ng/L for women, 34 ng/L for men). We assessed the performance of the High-STEACS early rule-out pathway for an adjudicated diagnosis of myocardial infarction (type 1, 4b, or 4c) during the index hospital admission. Patients presenting within 2 hours of symptom onset (early presenters) underwent serial testing. Having access to the same clinical information in both cohorts, adjudication was performed independently by 2 cardiologists with consensus from a third where required, according to the Fourth Universal Definition of Myocardial Infarction.5The unselected and selected patient cohorts comprised 1242 (median age, 60 [interquartile range, 47–75] years, 46% women) and 1695 (median age, 61 [interquartile range, 52–73] years, 40% women) patients, respectively. Chest pain was the primary symptom in 91% (1128/1242) and 84% (1426/1695) of patients in the unselected and selected cohorts, respectively. The median time from symptom onset was 4 (interquartile range, 3–6) hours in the unselected cohort and 3 (interquartile range, 2–9) hours in the selected cohort. At presentation, cardiac troponin concentrations were elevated above the sex-specific 99th percentile in 14% (177/1242) and 15% (247/1695) of unselected and selected patients. On serial testing, concentrations were elevated in 17% (204/1242) and 19% (330/1695), respectively, but the proportion with a final diagnosis of myocardial infarction differed at 6% (74/1242) and 14% (232/1695), respectively.After the initial cardiac troponin measurement, the High-STEACS pathway identified 54% (676/1242) of unselected patients and 36% (613/1695) of selected patients as low risk. Overall, more patients had myocardial infarction ruled out by the pathway in the unselected cohort than in the selected cohort (77% [958/1242] versus 66% [1119/1695]; P<0.001), with a similar negative predictive value (99.9% [95% CI, 99.8%–100%] versus 99.8% [95% CI, 99.4%–99.9%]) and sensitivity (99.3% [95% CI, 97.4%–100%] versus 98.9% [95% CI, 97.6%–99.9%]; Figure). In the selected cohort, more patients had intermediate troponin concentrations (36% [612/1695] versus 29% [353/1242]) requiring serial testing and more patients were ruled in (34% [576/1695] versus 23% [284/1242]; P<0.001 for both). The positive predictive value for myocardial infarction was lower in the unselected patient cohort (26.1% [95% CI, 21.2%–31.4%] versus 39.9% [95% CI, 36.0%–44.0%]; P<0.001, Figure) for a similar specificity (82.0% [95% CI, 79.8%–84.2%] versus 76.3% [95% CI, 74.1%–78.5%]).Download figureDownload PowerPointFigure. Performance of the High-STEACS early rule-out pathway for myocardial infarction in an unselected patient cohort from clinical practice (A) and in a selected patient cohort participating in a research study (B) All patients were adjudicated according to the Fourth Universal Definition of Myocardial Infarction, and the classification of those ruled in by the pathway is given at the bottom the Figure. The pathway recommends that patients presenting within 2 hours of symptom onset have serial measurements. *Serial high-sensitivity cardiac troponin I (hs-cTNI) concentrations were not available in 130 patients in the unselected patient cohort (A) and in 17 patients in the selected patient cohort (B). High-STEACS indicates High-Sensitivity Troponin in the Evaluation of patients with Acute Coronary Syndrome; MI, type 1, 4b, or 4c myocardial infarction; NPV, negative predictive value; and PPV, positive predictive value.Our findings highlight that the performance of early rule-out pathways for acute myocardial infarction that have been developed in selected patient cohorts are likely to differ substantially when applied in clinical practice because of the lower prevalence of myocardial infarction. As a consequence, fewer patients are ruled in, and the positive predictive value of cardiac troponin for myocardial infarction is lower in practice. However, more patients are ruled out in clinical practice, resulting in greater efficacy of early rule-out pathways without compromising safety.Article InformationAcknowledgmentsDrs Bularga, Mills, and Kimenai conceived the study and its design. Drs Bularga and Kimenai had access to the data and performed the analysis. Drs Bularga, Mills, and Kimenai interpreted the data and drafted the manuscript. All authors revised the manuscript critically for important intellectual content and provided their final approval of the version to be published. All authors are accountable for the work. The authors thank researchers from the Emergency Medicine Research Group Edinburgh for their support during the conduct of High-STEACS trial. The authors thank the Clinical Biochemistry Department staff at Royal Infirmary of Edinburgh and the NRS Bioresource team for their support with sample collection and analysis.Sources of FundingThe British Heart Foundation (SP/12/10/29922) funded the High-STEACS trial with support from a Research Excellence Award (RE/18/5/34216). Dr Bularga is supported by a Clinical Research Training Fellowship (MR/V007254/1) from the Medical Research Council. Dr Mills is supported by a Chair Award (CH/F/21/90010), a Programme Grant (RG/20/10/34966), and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation. Dr Kimenai is supported by a grant from Health Data Research UK, which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust. Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge.Disclosures Dr Shah's institution has received honoraria from Abbott Diagnostics. Dr Mills reports research grants awarded to the University of Edinburgh from Abbott Diagnostics and Siemens Healthineers outside the submitted work, and honoraria from Abbott Diagnostics, Siemens Healthineers, Roche Diagnostics and LumiraDx. All other authors have no interest to declare.FootnotesFor Sources of Funding and Disclosures, see page 449.Circulation is available at www.ahajournals.org/journal/circRegistration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.Correspondence to: Dorien M Kimenai, PhD, Centre for Cardiovascular Science, The University of Edinburgh, Chancellor's Building, Edinburgh, EH16 4SU, United Kingdom. Email dorien.kimenai@ed.ac.ukReferences1. Gulati M, Levy PD, Mukherjee D, Amsterdam E, Bhatt DL, Birtcher KK, Blankstein R, Boyd J, Bullock-Palmer RP, Conejo T, et al. AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.Circulation. 2021; 144:e368–e454. doi: 10.1161/CIR.0000000000001030LinkGoogle Scholar2. Shah ASV, Sandoval Y, Noaman A, Sexter A, Vaswani A, Smith SW, Gibbins M, Griffiths M, Chapman AR, Strachan FE, et al. Patient selection for high-sensitivity cardiac troponin testing and diagnosis of myocardial infarction: prospective cohort study.BMJ. 2017; 359:j4788. doi: 10.1136/bmj.j4788CrossrefMedlineGoogle Scholar3. Chapman AR, Anand A, Boeddinghaus J, Ferry AV, Sandeman D, Adamson PD, Andrews J, Tan S, Cheng SF, D'Souza M, et al. Comparison of the efficacy and safety of early rule-out pathways for acute myocardial infarction.Circulation. 2017; 135:1586–1596. doi: 10.1161/CIRCULATIONAHA.116.025021LinkGoogle Scholar4. Chapman AR, Hesse K, Andrews J, Lee KK, Anand A, Shah ASV, Sandeman D, Ferry AV, Jameson J, Piya S, et al. High-sensitivity cardiac troponin I and clinical risk scores in patients with suspected acute coronary syndrome.Circulation. 2018; 138:1654–1665. doi: 10.1161/CIRCULATIONAHA.118.036426LinkGoogle Scholar5. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; ESC Scientific Document GroupFourth universal definition of myocardial infarction (2018).Eur Heart J. 2019; 40:237–269. doi: 10.1093/eurheartj/ehy462CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Jaffe A, Body R, Mills N, Aakre K, Collinson P, Saenger A, Hammarsten O, Wereski R, Omland T, Sandoval Y, Ordonez-Llanos J and Apple F (2023) Single Troponin Measurement to Rule Out Myocardial Infarction, Journal of the American College of Cardiology, 10.1016/j.jacc.2023.04.040, 82:1, (60-69), Online publication date: 1-Jul-2023. January 31, 2023Vol 147, Issue 5 Advertisement Article InformationMetrics © 2023 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.https://doi.org/10.1161/CIRCULATIONAHA.122.062419PMID: 36716255 Originally publishedJanuary 30, 2023 Keywordsacute coronary syndrometroponin Imyocardial infarctionPDF download Advertisement SubjectsCardiovascular DiseaseDiagnostic Testing