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01-04-2020 | Angiography | Original Paper

Management and outcomes of patients with unstable angina with undetectable, normal, or intermediate hsTnT levels

Authors: Evangelos Giannitsis, Moritz Biener, Hauke Hund, Matthias Mueller-Hennessen, Mehrshad Vafaie, Jochen Gandowitz, Christoph Riedle, Julia Löhr, Hugo A. Katus, Kiril M. Stoyanov

Published in: Clinical Research in Cardiology | Issue 4/2020

Abstract

Background

Patients with unstable angina (UA) are regarded to be at low risk for future coronary events. Guidelines discourage routine coronary angiography and recommend early discharge after individualized risk stratification. The relative value of clinical risk indicators as compared to cardiac troponin (cTn) alone is unsettled in the era of high-sensitivity cardiac troponin (hsTn) assays. We aimed to investigate the clinical characteristics, therapies, and outcomes of UA patients with different hsTnT concentrations.

Methods

During 12 months, 2525 patients were enrolled. UA was defined as unstable symptoms and either undetectable (< 5 ng/L), normal (5–14 ng/L) or stable elevated hsTnT (15–51 ng/L). Follow-up for 1-year mortality was available in 98.7%.

Results

A total of 280 patients (11.1%) received a diagnosis of UA. Mortality rates at 12 months were 0%, 1.9% and 6.9% in presence of undetectable, normal and stable elevated hsTnT. Elevated hsTnT > 99th percentile but not unstable symptoms carried an independent 3.25-fold (1.78–5.93) higher risk for all-cause death after adjustment for other clinical risk indicators or the GRACE score. Utilization of guideline-recommended therapies was high albeit lower than for non-ST-elevation myocardial infarction (NSTEMI). Significantly fewer patients with UA received dual antiplatelet therapy (DAPT, odds ratio (OR) 0.51 [95% CI 0.44–0.59], P < 0.0001), coronary angiography (CA, OR 0.79, [95% CI 0.74–0.87], P < 0.0001), and percutaneous coronary intervention (PCI, OR 0.50, [95% CI 0.40–0.61], P < 0.0001), compared to NSTEMI. However, prevalence of significant obstructive coronary artery disease requiring PCI was 31.8%, even in patients with undetectable hsTnT, indicating the need for stress testing.

Conclusions

The current dichotomization of patients into UA and NSTEMI is no longer appropriate. Additional risk stratification seems warranted including the presence and magnitude of hsTn concentration and additional risk indicators.

Clinical Trials Identifier: NCT03111862.

Graphic abstract

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Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA (2010) Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem 56:254–261PubMed

Keller T, Zeller T, Peetz D et al (2009) Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 361:868–877PubMed

Reichlin T, Hochholzer W, Bassetti S (2009) Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 361:858–867PubMed

Sandoval Y, Apple FS, Smith SW (2018) High-sensitivity cardiac troponin assays and unstable angina. Eur Heart J Acute Cardiovasc Care 7:120–128PubMed

D’Souza M, Sarkisian L, Saaby L (2015) Diagnosis of unstable angina pectoris has declined markedly with the advent of more sensitive troponin assays. Am J Med 128:852–860PubMed

Twerenbold R, Jaeger C, Rubini Gimenez M (2016) Impact of high sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J 37:3324–3332PubMedPubMedCentral

Eggers KM, Jernberg T, Lindahl B (2017) Unstable angina in the era of cardiac troponin assays with improved sensitivity—a clinical dilemma. Am J Med 130(1423–30):e5

Giannitsis E, Wallentin L, James SK et al (2017) Outcomes after planned invasive or conservative treatment strategy in patients with non-ST-elevation acute coronary syndrome and a normal value of high sensitivity troponin at randomisation: a Platelet Inhibition and Patient Outcomes (PLATO) trial biomarker substudy. Eur Heart J Acute Cardiovasc Care 6:500–510PubMed

Amsterdam EA, Wenger NK, Brindis RG, American College of Cardiology, American Heart Association Task Force on Practice Guidelines, Society for Cardiovascular Angiography and Interventions, American Association for Clinical Chemistry et al (2014) 2014 AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 64:e139–e228

10.

Roffi M, Patrono C, Collet JP et al (2015) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 37:267–315PubMed

11.

Mendis S, Thygesen K, Kuulasmaa K et al (2011) Writing group on behalf of the participating experts of the WHO consultation for revision of WHO definition of myocardial infarction. World Health Organization definition of myocardial infarction: 2008–2009 revision. Int J Epidemiol 40:139–146PubMed

12.

Braunwald E, Morrow DA (2013) Unstable angina: is it time for a requiem? Circulation 127:2452–2457PubMed

13.

Apple FS, Jaffe AS, Collinson P et al (2015) IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays. Clin Biochem 48:201–203PubMed

14.

Korosoglou G, Lehrke S, Mueller D et al (2011) Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque. Heart 97:823–831PubMed

15.

Lindahl B, Venge P, Wallentin L (1997) Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group. J Am Coll Cardiol 29:43–48PubMed

16.

Morrow DA, Antman EM, Tanasijevic M et al (2000) Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy. J Am Coll Cardiol 36:1812–1817PubMed

17.

Hamm CW (2001) GP IIb/IIIa receptor antagonists in unstable angina: troponin level-based patient selection. Eur Heart J Suppl 3(Suppl A):A14–A20

18.

Eisen A, Bonaca MP, Jarolim P et al (2017) High-sensitivity Troponin I in stable patients with atherosclerotic disease in the TRA 2°P—TIMI 50 Trial. Clin Chem 63:307–315PubMed

19.

Wallentin L, Lindholm D, Siegbahn A et al (2014) Biomarkers in relation to the effects of ticagrelor in comparison with clopidogrel in non-ST-elevation acute coronary syndrome patients managed with or without in-hospital revascularization: a substudy from the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation 129:293–303PubMed

20.

Diderholm E, Andrén B, Frostfeldt G, Fast Revascularisation during InStability in Coronary artery disease (FRISC II) Investigators et al (2002) The prognostic and therapeutic implications of increased troponin T levels and ST depression in unstable coronary artery disease: the FRISC II invasive troponin T electrocardiogram substudy. Am Heart J 143(5):760–767PubMed

21.

Kastrati A, Mehilli J, Neumann FJ, Intracoronary Stenting and Antithrombotic: Regimen Rapid Early Action for Coronary Treatment 2 (ISAR-REACT 2) Trial Investigators, Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2 (ISAR-REACT 2) Trial Investigators et al (2006) Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 295:1531–1538PubMed

22.

de Winter RJ, Windhausen F, Cornel JH, Invasive versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) Investigators et al (2005) Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 353:1095–1104PubMed

23.

James SK, Lindbäck J, Tilly J et al (2006) Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality benefit from coronary revascularization in acute coronary syndromes: a GUSTO-IV substudy. J Am Coll Cardiol 48:1146–1154PubMed

24.

Mueller M, Biener M, Vafaie M et al (2012) Absolute and relative kinetic changes of high-sensitivity cardiac troponin T in acute coronary syndrome and in patients with increased troponin in the absence of acute coronary syndrome. Clin Chem 58:209–218PubMed

25.

Lindahl B, Venge P, James S (2010) The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes. Am Heart J 160:224–229PubMed

26.

Bandstein N, Ljung R, Holzmann MJ (2016) Risk of revisits to the emergency department in admitted versus discharged patients with chest pain but without myocardial infarction in relation to high-sensitivity cardiac troponin T levels. Int J Cardiol 203:341–346PubMed

27.

Eggers KM, Lindahl B, Melki D, Jernberg T (2016) Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry. Eur Heart J 37:2417–2424PubMed

28.

Sanchis J, García-Blas S, Mainar L et al (2014) High-sensitivity versus conventional troponin for management and prognosis assessment of patients with acute chest pain. Heart 100:1591–1596PubMed

29.

Wallentin L, Becker RC, Budaj A et al (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057PubMed

30.

Stoyanov KM, Hund H, Biener M et al (2019) RAPID-CPU: a prospective study on implementation of the ESC o/1-hour algorithm and safety of discharge after rule-out of myocardial i8nfarction. Eur Heart J Acute Cardiovasc Care. 12:2048872619861911. https://doi.org/10.1177/2048872619861911 CrossRef

31.

Thygesen K, Alpert JS, Jaffe AS et al (2012) Third universal definition of myocardial infarction. Eur Heart J 33:2551–2567PubMed

32.

Thygesen K, Alpert JS, Jaffe AS et al (2019) Fourth universal definition of myocardial infarction (2018). Eur Heart J 40(3):237–269PubMed

33.

Fox KA, Dabbous OH, Goldberg RJ et al (2006) Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 333:1091PubMedPubMedCentral

34.

Hamm CW, Bassand JP, Agewall S et al (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999–3054PubMed

35.

de Feyter PJ, Ozaki Y, Baptista J et al (1995) Ischemia-related lesion characteristics in patients with stable or unstable angina. A study with intracoronary angioscopy and ultrasound. Circulation 92:1408–1413PubMed

36.

Lee T, Murai T, Yonetsu T et al (2015) Relationship between subclinical cardiac troponin I elevation and culprit lesion characteristics assessed by optical coherence tomography in patients undergoing elective percutaneous coronary intervention. Circ Cardiovasc Interv 8:e001727PubMed

37.

Okamatsu K, Takano M, Sakai S (2004) Elevated troponin T levels and lesion characteristics in non-ST-elevation acute coronary syndromes. Circulation 109:465–470PubMed

38.

Rittersma SZ, van der Wal AC, Koch KT et al (2005) Plaque instability frequently occurs days or weeks before occlusive coronary thrombosis: a pathological thrombectomy study in primary percutaneous coronary intervention. Circulation 111:1160–1165PubMed

39.

Arbustini E, Grasso M, Diegoli M et al (1993) Coronary thrombosis in non-cardiac death. Coron Artery Dis 4:751–759PubMed

40.

Brown AJ, Shah ASV, West NEJ et al (2017) High-sensitivity Troponin I is associated with high-risk plaque and MACE in stable coronary artery disease. JACC Cardiovasc Imaging 10:1200–1203PubMed

41.

Giannitsis E, Katus HA (2013) Cardiac troponin level elevations not related to acute coronary syndromes. Nat Rev Cardiol 10:623–634PubMed

42.

Puelacher C, Gugala M, Adamson PD (2019) Incidence and outcomes of unstable angina compared with non-ST-elevation myocardial infarction. Heart. https://doi.org/10.1136/heartjnl-2018-314305 CrossRefPubMed

43.

Engel J, Damen NL, van der Wulp I, de Bruijne MC, Wagner C (2017) Adherence to cardiac practice guidelines in the management of non-ST-elevation acute coronary syndromes: a systematic literature review. Curr Cardiol Rev. 13:3–27PubMedPubMedCentral

44.

Carlton EW, Than M, Cullen L, Khattab A, Greaves K (2015) ‘Chest pain typicality’ in suspected acute coronary syndromes and the impact of clinical experience. Am J Med 128:1109–1116PubMed

45.

Hermann LK, Weingart SD, Yoon YM et al (2010) Comparison of frequency of inducible myocardial ischemia in patients presenting to emergency department with typical versus atypical or nonanginal chest pain. Am J Cardiol 105:1561–1564PubMed

46.

Fladseth K, Kristensen A, Mannsverk J, Trovik T, Schirmer H (2018) Pre-test characteristics of unstable angina patients with obstructive coronary artery disease confirmed by coronary angiography. Open Heart 5:e000888PubMedPubMedCentral

Title: Management and outcomes of patients with unstable angina with undetectable, normal, or intermediate hsTnT levels
Authors: Evangelos Giannitsis
Moritz Biener
Hauke Hund
Matthias Mueller-Hennessen
Mehrshad Vafaie
Jochen Gandowitz
Christoph Riedle
Julia Löhr
Hugo A. Katus
Kiril M. Stoyanov
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Keywords: Angiography
Non-ST-Segment Elevation Myocardial Infarction
Myocardial Infarction
Acute Coronary Syndrome
Unstable Angina
Published in: Clinical Research in Cardiology / Issue 4/2020
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI: https://doi.org/10.1007/s00392-019-01529-4

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