BACKGROUND: The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non-ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD. METHODS: In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non-ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample. RESULTS: Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non-ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6-100.0] versus 99.2% [95% CI, 97.6-99.8]; P=0.559), lower specificity of rule-in (88.7% [95% CI, 84.8-91.9] versus 96.5% [95% CI, 95.7-97.2]; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0-99.8] versus 98.5% [95% CI, 96.5-99.5]; P=1.0), lower specificity of rule-in (84.4% [95% CI, 79.9-88.3] versus 91.7% [95% CI, 90.5-92.9]; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function. CONCLUSIONS: In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587.

2nd Cardiology Department Zabrze University Silesia Katowice Poland

Cardiovascular Research Institute Basel and Department of Cardiology University Hospital Basel University of Basel Switzerland

Department of Cardiology University Hospital Brno Czech Republic

Department of General and Interventional Cardiology University Heart Center Hamburg University Hospital Hamburg Eppendorf Germany

Department of Laboratory Medicine University Hospital Basel Switzerland

Department of Laboratory Medicine University Hospital Zürich Switzerland

Emergency Department Hospital Clinic Barcelona Spain

Emergency Department Hospital Clinico San Carlos Madrid Spain

Emergency Department Kantonsspital Liestal Switzerland

Emergency Department University Hospital Zürich Switzerland

Medical Faculty Masaryk University Brno Czech Republic

Circulation. 2018 Jan 30;137(5):452-454. doi: 10.1161/CIRCULATIONAHA.117.031717. PubMed

Zobrazit více v PubMed

Roffi M, Patrono C, Collet JP, Mueller C, Valgimigli M, Andreotti F, Bax JJ, Borger MA, Brotons C, Chew DP, Gencer B, Hasenfuss G, Kjeldsen K, Lancellotti P, Landmesser U, Mehilli J, Mukherjee D, Storey RF, Windecker S, Baumgartner H, Gaemperli O, Achenbach S, Agewall S, Badimon L, Baigent C, Bueno H, Bugiardini R, Carerj S, Casselman F, Cuisset T, Erol Ç, Fitzsimons D, Halle M, Hamm C, Hildick-Smith D, Huber K, Iliodromitis E, James S, Lewis BS, Lip GY, Piepoli MF, Richter D, Rosemann T, Sechtem U, Steg PG, Vrints C, Luis Zamorano J Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology. 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. 2016;37:267–315. doi: 10.1093/eurheartj/ehv320. PubMed

Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Jr, Ganiats TG, Holmes DR, Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ Members AATF, Society for Cardiovascular A, Interventions and the Society of Thoracic S. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2354–2394. doi: 10.1161/CIR.0000000000000133. PubMed

Thygesen K, Alpert JS, White HD, Jaffe AS, Apple FS, Galvani M, Katus HA, Newby LK, Ravkilde J, Chaitman B, Clemmensen PM, Dellborg M, Hod H, Porela P, Underwood R, Bax JJ, Beller GA, Bonow R, Van der Wall EE, Bassand JP, Wijns W, Ferguson TB, Steg PG, Uretsky BF, Williams DO, Armstrong PW, Antman EM, Fox KA, Hamm CW, Ohman EM, Simoons ML, Poole-Wilson PA, Gurfinkel EP, Lopez-Sendon JL, Pais P, Mendis S, Zhu JR, Wallentin LC, Fernández-Avilés F, Fox KM, Parkhomenko AN, Priori SG, Tendera M, Voipio-Pulkki LM, Vahanian A, Camm AJ, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Morais J, Brener S, Harrington R, Morrow D, Lim M, Martinez-Rios MA, Steinhubl S, Levine GN, Gibler WB, Goff D, Tubaro M, Dudek D, Al-Attar N Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Circulation. 2007;116:2634–2653. doi: 10.1161/CIRCULATIONAHA.107.187397. PubMed

Taylor MJ, Scuffham PA, McCollam PL, Newby DE. Acute coronary syndromes in Europe: 1-year costs and outcomes. Curr Med Res Opin. 2007;23:495–503. doi: 10.1185/030079906X167462. PubMed

Tiemann O. Variations in hospitalisation costs for acute myocardial infarction: a comparison across Europe. Health Econ. 2008;17(s)(uppl 1):S33–S45. doi: 10.1002/hec.1322. PubMed

deFilippi CR, Herzog CA. Interpreting cardiac biomarkers in the setting of chronic kidney disease. Clin Chem. 2017;63:59–65. doi: 10.1373/clinchem.2016.254748. PubMed

Twerenbold R, Boeddinghaus J, Nestelberger T, Wildi K, Rubini Gimenez M, Badertscher P, Mueller C. Clinical use of high-sensitivity cardiac troponin in patients with suspected myocardial infarction. J Am Coll Cardiol. 2017;70:996–1012. doi: 10.1016/j.jacc.2017.07.718. PubMed

Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–1305. doi: 10.1056/NEJMoa041031. PubMed

Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, Nordlander R, Maggioni A, Dickstein K, Zelenkofske S, Leimberger JD, Califf RM, Pfeffer MA. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351:1285–1295. doi: 10.1056/NEJMoa041365. PubMed

Twerenbold R, Wildi K, Jaeger C, Gimenez MR, Reiter M, Reichlin T, Walukiewicz A, Gugala M, Krivoshei L, Marti N, Moreno Weidmann Z, Hillinger P, Puelacher C, Rentsch K, Honegger U, Schumacher C, Zurbriggen F, Freese M, Stelzig C, Campodarve I, Bassetti S, Osswald S, Mueller C. Optimal cutoff levels of more sensitive cardiac troponin assays for the early diagnosis of myocardial infarction in patients with renal dysfunction. Circulation. 2015;131:2041–2050. doi: 10.1161/CIRCULATIONAHA.114.014245. PubMed PMC

Aronow WS, Ahn C, Mercando AD, Epstein S. Prevalence of coronary artery disease, complex ventricular arrhythmias, and silent myocardial ischemia and incidence of new coronary events in older persons with chronic renal insufficiency and with normal renal function. Am J Cardiol. 2000;86:1142–1143. PubMed

Nakamura S, Uzu T, Inenaga T, Kimura G. Prediction of coronary artery disease and cardiac events using electrocardiographic changes during hemodialysis. Am J Kidney Dis. 2000;36:592–599. doi: 10.1053/ajkd.2000.16198. PubMed

deFilippi C, Seliger SL, Kelley W, Duh SH, Hise M, Christenson RH, Wolf M, Gaggin H, Januzzi J. Interpreting cardiac troponin results from high-sensitivity assays in chronic kidney disease without acute coronary syndrome. Clin Chem. 2012;58:1342–1351. doi: 10.1373/clinchem.2012.185322. PubMed

Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, Huber K, Plebani M, Biasucci LM, Tubaro M, Collinson P, Venge P, Hasin Y, Galvani M, Koenig W, Hamm C, Alpert JS, Katus H, Jaffe AS Study Group on Biomarkers in Cardiology of ESC Working Group on Acute Cardiac Care. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J. 2012;33:2252–2257. doi: 10.1093/eurheartj/ehs154. PubMed

Reichlin T, Twerenbold R, Wildi K, Rubini Gimenez M, Bergsma N, Haaf P, Druey S, Puelacher C, Moehring B, Freese M, Stelzig C, Krivoshei L, Hillinger P, Jäger C, Herrmann T, Kreutzinger P, Radosavac M, Weidmann ZM, Pershyna K, Honegger U, Wagener M, Vuillomenet T, Campodarve I, Bingisser R, Miró Ò, Rentsch K, Bassetti S, Osswald S, Mueller C. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. CMAJ. 2015;187:E243–E252. doi: 10.1503/cmaj.141349. PubMed PMC

Reichlin T, Schindler C, Drexler B, Twerenbold R, Reiter M, Zellweger C, Moehring B, Ziller R, Hoeller R, Rubini Gimenez M, Haaf P, Potocki M, Wildi K, Balmelli C, Freese M, Stelzig C, Freidank H, Osswald S, Mueller C. One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med. 2012;172:1211–1218. doi: 10.1001/archinternmed.2012.3698. PubMed

Rubini Gimenez M, Twerenbold R, Jaeger C, Schindler C, Puelacher C, Wildi K, Reichlin T, Haaf P, Merk S, Honegger U, Wagener M, Druey S, Schumacher C, Krivoshei L, Hillinger P, Herrmann T, Campodarve I, Rentsch K, Bassetti S, Osswald S, Mueller C. One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I. Am J Med. 2015;128:861.e4–870.e4. doi: 10.1016/j.amjmed.2015.01.046. PubMed

Mueller C, Giannitsis E, Christ M, Ordóñez-Llanos J, deFilippi C, McCord J, Body R, Panteghini M, Jernberg T, Plebani M, Verschuren F, French J, Christenson R, Weiser S, Bendig G, Dilba P, Lindahl B TRAPID-AMI Investigators. Multicenter evaluation of a 0-hour/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T. Ann Emerg Med. 2016;68:76.e4–87.e4. doi: 10.1016/j.annemergmed.2015.11.013. PubMed

Pickering JW, Greenslade JH, Cullen L, Flaws D, Parsonage W, Aldous S, George P, Worster A, Kavsak PA, Than MP. Assessment of the European Society of cardiology 0-hour/1-hour algorithm to rule-out and rule-in acute myocardial infarction. Circulation. 2016;134:1532–1541. doi: 10.1161/CIRCULATIONAHA.116.022677. PubMed

Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki M, Noveanu M, Breidthardt T, Twerenbold R, Winkler K, Bingisser R, Mueller C. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med. 2009;361:858–867. doi: 10.1056/NEJMoa0900428. PubMed

Twerenbold R, Jaeger C, Rubini Gimenez M, Wildi K, Reichlin T, Nestelberger T, Boeddinghaus J, Grimm K, Puelacher C, Moehring B, Pretre G, Schaerli N, Campodarve I, Rentsch K, Steuer S, Osswald S, Mueller C. 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. 2016;37:3324–3332. doi: 10.1093/eurheartj/ehw232. PubMed PMC

Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, Lijmer JG, Moher D, Rennie D, de Vet HC, Kressel HY, Rifai N, Golub RM, Altman DG, Hooft L, Korevaar DA, Cohen JF STARD Group. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clin Chem. 2015;61:1446–1452. doi: 10.1373/clinchem.2015.246280. PubMed

Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612. PubMed PMC

Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 2010;56:254–261. doi: 10.1373/clinchem.2009.132654. PubMed

Hallermayer K, Jarausch J, Menassanch-Volker S, Zaugg C, Ziegler A. Implications of adjustment of high-sensitivity cardiac troponin T assay. Clin Chem. 2013;59:572–574. doi: 10.1373/clinchem.2012.197103. PubMed

Kuster N, Dupuy AM, Monnier K, Baptista G, Bargnoux AS, Badiou S, Jeandel C, Cristol JP. Implications of adjustment of high-sensitivity cardiac troponin T assay. Clin Chem. 2013;59:570–572. doi: 10.1373/clinchem.2012.197020. PubMed

Kavsak PA, Hill SA, McQueen MJ, Devereaux PJ. Implications of adjustment of high-sensitivity cardiac troponin T assay. Clin Chem. 2013;59:574–576. doi: 10.1373/clinchem.2012.197434. PubMed

Wildi K, Twerenbold R, Jaeger C, Rubini Giménez M, Reichlin T, Stoll M, Hillinger P, Puelacher C, Boeddinghaus J, Nestelberger T, Grimm K, Grob M, Rentsch K, Arnold C, Mueller C. Clinical impact of the 2010-2012 low-end shift of high-sensitivity cardiac troponin T. Eur Heart J Acute Cardiovasc Care. 2016;5:399–408. doi: 10.1177/2048872616642952. PubMed

Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem. 2012;58:1574–1581. doi: 10.1373/clinchem.2012.192716. PubMed

Koerbin G, Tate J, Potter JM, Cavanaugh J, Glasgow N, Hickman PE. Characterisation of a highly sensitive troponin I assay and its application to a cardio-healthy population. Clin Chem Lab Med. 2012;50:871–878. doi: 10.1515/cclm-2011-0540. PubMed

Krintus M, Kozinski M, Boudry P, Capell NE, Köller U, Lackner K, Lefèvre G, Lennartz L, Lotz J, Herranz AM, Nybo M, Plebani M, Sandberg MB, Schratzberger W, Shih J, Skadberg Ø, Chargui AT, Zaninotto M, Sypniewska G. European multicenter analytical evaluation of the Abbott ARCHITECT STAT high sensitive troponin I immunoassay. Clin Chem Lab Med. 2014;52:1657–1665. doi: 10.1515/cclm-2014-0107. PubMed

Braunwald E, Morrow DA. Unstable angina: is it time for a requiem? Circulation. 2013;127:2452–2457. doi: 10.1161/CIRCULATIONAHA.113.001258. PubMed

Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143:29–36. doi: 10.1148/radiology.143.1.7063747. PubMed

Simel DL, Samsa GP, Matchar DB. Likelihood ratios with confidence: sample size estimation for diagnostic test studies. J Clin Epidemiol. 1991;44:763–770. PubMed

Moskowitz CS, Pepe MS. Comparing the predictive values of diagnostic tests: sample size and analysis for paired study designs. Clin Trials. 2006;3:272–279. doi: 10.1191/1740774506cn147oa. PubMed

Irfan A, Twerenbold R, Reiter M, Reichlin T, Stelzig C, Freese M, Haaf P, Hochholzer W, Steuer S, Bassetti S, Zellweger C, Freidank H, Peter F, Campodarve I, Meune C, Mueller C. Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain. Am J Med. 2012;125:491.e1–498.e1. doi: 10.1016/j.amjmed.2011.10.031. PubMed

Mueller C, Laule-Kilian K, Scholer A, Nusbaumer C, Zeller T, Staub D, Perruchoud AP. B-type natriuretic peptide for acute dyspnea in patients with kidney disease: insights from a randomized comparison. Kidney Int. 2005;67:278–284. doi: 10.1111/j.1523-1755.2005.00079.x. PubMed

Reiter M, Twerenbold R, Reichlin T, Haaf P, Peter F, Meissner J, Hochholzer W, Stelzig C, Freese M, Heinisch C, Breidthardt T, Freidank H, Winkler K, Campodarve I, Gea J, Mueller C. Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays. Eur Heart J. 2011;32:1379–1389. doi: 10.1093/eurheartj/ehr033. PubMed

Bozbas H, Korkmaz ME, Atar I, Eroglu S, Ozin B, Yildirir A, Muderrisoglu H, Colak T, Karakayali H, Haberal M. Serum levels of cardiac enzymes before and after renal transplantation. Clin Cardiol. 2004;27:559–562. PubMed PMC

Fridén V, Starnberg K, Muslimovic A, Ricksten SE, Bjurman C, Forsgard N, Wickman A, Hammarsten O. Clearance of cardiac troponin T with and without kidney function. Clin Biochem. 2017;50:468–474. doi: 10.1016/j.clinbiochem.2017.02.007. PubMed

van der Linden N, Cornelis T, Kimenai DM, Klinkenberg LJJ, Hilderink JM, Lück S, Litjens EJR, Peeters FECM, Streng AS, Breidthardt T, van Loon LJC, Bekers O, Kooman JP, Westermark PO, Mueller C, Meex SJR. Origin of cardiac troponin T elevations in chronic kidney disease. Circulation. 2017;136:1073–1075. doi: 10.1161/CIRCULATIONAHA.117.029986. PubMed

Diris JH, Hackeng CM, Kooman JP, Pinto YM, Hermens WT, van Dieijen-Visser MP. Impaired renal clearance explains elevated troponin T fragments in hemodialysis patients. Circulation. 2004;109:23–25. doi: 10.1161/01.CIR.0000109483.45211.8F. PubMed

Ellis K, Dreisbach AW, Lertora JL. Plasma elimination of cardiac troponin I in end-stage renal disease. South Med J. 2001;94:993–996. PubMed

Wong CK, Szeto CC, Chan MH, Leung CB, Li PK, Lam CW. Elevation of pro-inflammatory cytokines, C-reactive protein and cardiac troponin T in chronic renal failure patients on dialysis. Immunol Invest. 2007;36:47–57. doi: 10.1080/08820130600745505. PubMed

D’Marco L, Bellasi A, Raggi P. Cardiovascular biomarkers in chronic kidney disease: state of current research and clinical applicability. Dis Markers. 2015;2015:586569. doi: 10.1155/2015/586569. PubMed PMC

Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G National Kidney Foundation. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137–147. PubMed

Association of accompanying dyspnoea with diagnosis and outcome of patients presenting with acute chest discomfort

Zobrazit více v PubMed

ClinicalTrials.gov
NCT00470587