Review in depth 713
Will high-sensitivity troponin assays lead to improved outcomes in patients with acute coronary syndrome? James McCord New high-sensitivity cardiac troponin (hs-cTn) assays have been developed that can measure troponin values at much lower levels. How these new assays should be integrated into clinical practice is an area of active discussion and research. This review addresses how the identification of more high-risk patients with acute coronary syndrome may improve clinical outcomes in these patients. With the advent of the new hs-cTn assays, more patients with unstable angina will be classified as having non-STelevation myocardial infarction. These assays will define a high-risk patient population that was not possible with older generation assays. One study suggests that this will lead to more appropriate therapy in these patients and improved outcomes. The use of hs-cTn assays will identify more high-risk patients among millions of patients who
present to the Emergency Departments each year with undifferentiated chest pain. This will likely translate into more appropriate care and improved outcomes in this difficult patient population when ECG findings and clinical presentation do not suggest a clear diagnosis. Coron c 2013 Wolters Kluwer Health | Artery Dis 24:713–715 Lippincott Williams & Wilkins.
Introduction
cTnI values between 0.04 and 0.1 ng/ml were more likely to have an adverse event in 30 days (death or myocardial infarction) compared with patients with levels less than 0.04 ng/ml, 5.0 versus 2.0%, respectively. A weakness of this study was that blood samples were only obtained at presentation, and presumably some later measurements that were carried out using the standard assay would have been elevated. Mueller et al. [10] studied 1384 patients with possible ACS using the Siemens cTnI-Ultra assay (cut-point 0.04 ng/ml) and more sensitive hs-cTnT (Roche Diagnostics, Penzberg, Germany) with a cut-point of 0.014 ng/ml. Blood samples were obtained at presentation and at 6 h. Final diagnoses for patients included ST-elevation myocardial infarction 302 (21.8%), NSTEMI 662 (47.8%), unstable angina 365 (26.4%), and non-ACS 55 (4%). Receiver operating characteristic curve analysis showed significantly higher areas under the curve for the hs-cTnT as compared with cTnI for the prediction of death/myocardial infarction (0.721 vs. 0.672; P = 0.024).
Even the earliest generation cardiac troponin (cTn) assays were significantly more sensitive than the typically used CK-MB assays and identified more high-risk patients with acute coronary syndrome (ACS). These ACS patients with an elevated level of cTn were shown to have enhanced benefit when treated with more aggressive pharmacologic and invasive strategies in multiple studies [1,2]. The newer high-sensitivity cardiac troponin (hs-cTn) assays are significantly more sensitive than older cTn assays and can further discriminate high-risk patients from low-risk patients, which was not possible with older assays. The ability of newer hs-cTn assays to identify more high-risk individuals has been shown in various populations including community studies of individuals without known structural heart disease [3,4], chronic congestive heart failure [5,6], and ACS [7–10]. The newer hs-cTn assays will identify patients with non-ST-elevation myocardial infarction (NSTEMI) more rapidly, thus decreasing the standard ‘rule-out AMI’ process to 3 h [11,12], a time interval that is now reflected in guidelines [13]. Will this identification of more high-risk patients lead to improved outcomes for the millions of patients who are evaluated each year for possible ACS? The answer appears to be yes [14]. In a substudy from the MERLIN-TIMI 36 trial, ranolazine in NSTEMI-ACS, Bonaca et al. [7] evaluated 4513 patients with a newer assay (cTnI-Ultra assay ADVIA Centaur; Siemens Healthcare Diagnostics, Deerfield, Illinois, USA) with a cut-point of 0.04 ng/ml as compared with an older assay with a cut-point of 0.1 ng/ml. There were 319 (7%) patients who had cTnI values measured by the more sensitive assay between 0.04 and 0.1 ng/ml. Patients with c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-6928
Coronary Artery Disease 2013, 24:713–715 Keywords: high-sensitivity cardiac troponin, missed acute coronary syndrome, undifferentiated chest pain Heart & Vascular Institute, Henry Ford Hospital, Detroit, Michigan, USA Correspondence to James McCord, MD, Heart & Vascular Institute, Henry Ford Hospital, Detroit, MI 48202, USA Tel: + 1 313 916 4420; fax: + 1 313 916 8901; e-mail: [email protected]
In a substudy of the PROTECT-TIMI 30 Trial, Wilson et al. [15] evaluated 50 patients with NSTEMI and 50 patients with unstable angina. They compared a standard cTnI assay (Dimension RxL; Siemens Healthcare Diagnostics) with a cut-point of 0.07 ng/ml with a non-FDAapproved ‘nano-cTnI’ research assay (Nanosphere Inc., Northbrook, Illinois, USA) with a cut-point of 0.003 ng/ml. Patients had cTnI measured by the standard assay at enrollment, 6–8 h, and 24 h. All NSTEMI patients had nonelevated cTnI levels by the standard assay at enrollment. In the NSTEMI group, when using the nanocTnI assay, 72% had elevated levels at enrollment and 98% at 2 h. In the unstable angina group, who, by definition, DOI: 10.1097/MCA.0000000000000050
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
714 Coronary Artery Disease 2013, Vol 24 No 8
had normal serial cTnI values over 24 h, when using the nano-cTnI assay, 44% had elevated values at enrollment, 62% at 2 h, and 82% at 8 h. In a substudy of a prospective multicenter trial, Meune et al. [9] studied 351 patients with ACS (187 with acute myocardial infarction and 164 with unstable angina) with cTn measurements by various standard assays at presentation and 6–9 h; hs-cTnT was also measured, but not made available to the attending physicians. Patients with ACS but hs-cTnT of 0.014 ng/ml or less had a lower 30-day mortality rate of 0% when compared with the mortality rate of 7.5% in patients with hs-cTnT greater than 0.014 ng/ml (P = 0.003). Of the 164 patients with unstable angina, 63 (38%) patients had an elevated hs-cTnT at presentation. It is estimated that 15–20 million individuals annually are evaluated in the USA and Europe for possible ACS [16]. The majority of these individuals are ultimately not diagnosed with ACS with B1.3 million patients being diagnosed with ACS in the USA annually [17]. The diagnosis of ACS is difficult in some patients, and studies have shown that 2–4% of patients with ACS are not recognized in the Emergency Department and are inadvertently discharged [18,19]. Although this is a small percentage, this translates into 26 000–52 000 missed cases of ACS annually in the USA. Older studies found that patients with missed ACS in the Emergency Department are at a high risk for short-term adverse events [20,21]. One provocative study suggests that the use of the new hs-cTn assays will lead to improved identification of ACS patients in the Emergency Department and better patient outcomes. Mills et al. [14] studied 2092 consecutive patients in two phases in the Emergency Department at The Royal Infirmary in Edinburgh, Scotland. In all, 1038 patients were studied in the validation phase and 1054 patients were studied in the implementation phase. The assay used in the study was the Abbott Architect assay (Abbott Laboratories, Chicago, Illinois, USA). The diagnostic cut-point for medical decision-making for an older version of the assay was 0.2 ng/ml. Improvements in the assay’s performance were made, leading to a new generation more sensitive version with a cut-point of 0.04 ng/ml. In the validation phase, only values of at least 0.2 ng/ml were reported to the clinician as abnormal, but values between 0.04 and 0.19 ng/ml were recorded. In the implementation phase, cTnI values of at least 0.05 ng/ml were reported as abnormal to the clinician. All patient management decisions were left to the discretion of the responsible physician. In the entire group, hs-cTnI levels were less than 0.05 ng/ml in 1340 (64%) patients, 0.05–0.19 in 170 (8%), and at least 0.2 ng/ml in 582 (28%) patients. Patients with hs-cTnI values between 0.05 and 0.19 ng/ml were treated differently in the validation phase as compared with the implementation phase when the clinician was aware of the low-level cTnI elevation. In the implementation phase, those with hs-cTnI levels between 0.05 and 0.19 ng/ml were more likely
to receive cardiology consultation (74 vs. 44%), undergo coronary angiography (46 vs. 20%), receive dual-antiplatelet therapy (58 vs. 27%), and receive statin therapy (80 vs. 58%; P < 0.05 for all comparisons). There was also a difference in outcomes in patients with hs-cTnI values between 0.05 and 0.19 ng/ml when comparing patients in the validation phase with the implementation phase when the diagnostic threshold was lowered. At 3 months, there were 14 (16%) deaths in the validation phase and four deaths (5%) in the implementation phase (P < 0.05). Similarly, at 3 months, there were more readmissions for acute myocardial infarction in the validation phase [18 (20%)] compared with the implementation phase [five (6%; P < 0.05)]. Although there was a minority of patients (8%) with hs-cTnI values between 0.05 and 0.19 ng/ml, there were higher risk patients who had improved outcomes with more aggressive interventions. Likely, some of these patients in the validation group had unrecognized ACS and were discharged without appropriate therapy. Conclusion
Patients with undifferentiated chest pain in the Emergency Department constitute a significant clinical challenge. The historical control study by Mills et al. [14] suggests that the use of hs-cTn assays will lead to the identification of more high-risk ACS patients and improved clinical outcomes. However, this finding will need to be confirmed in other studies. Ideally, future studies would address this issue in multicenter randomized trials. A randomized trial comparing an older cTn assay with a new hs-cTn assay in patients in the Emergency Department with undifferentiated chest pain would be informative. Although the hs-cTn assays will identify more high-risk patients with ACS, there clearly will be more patients with mildly elevated hs-cTn where the diagnosis is not ACS. A community study of asymptomatic individuals using an hs-cTnT assay showed a prevalence of 25% for an elevated value. Likely, more patients will receive an extensive cardiac evaluation once it has been determined that they have a mildly elevated hs-cTn, and many of these will be determined to be low risk. Changes over time with early frequent blood draws will help determine acute from chronic elevations [22]. Future cost-effectiveness trials will need to weigh the benefit of identifying more high-risk patients among millions of individuals who present to the Emergency Departments each year against the cost of performing more testing on patients with mildly elevated hs-cTn.
Acknowledgements Conflicts of interest
J.M. is involved with a clinical trial that is sponsored by Roche Diagnostics.
References 1
Newby LK, Ohman EM, Christenson R, Moliterno D, Harrington R, White H, et al. Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status: the paragon-B troponin T substudy. Circulation 2001; 103:2891–2896.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
High-sensitivity troponin assays in ACS McCord 715
2
Kastrati A, Mehilli J, Neuman FJ, Dotzer F, ten Berg J, Bollwein H, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006; 295:1531–1538. 3 Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle E, et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation 2011; 123:1367–1376. 4 de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 2010; 304:2503–2512. 5 Egstrup M, Schou M, Tuxen CD, Kistorp CN, Hildebrandt PR, Gustafsson F, et al. Prediction of outcome by highly sensitive troponin T in outpatients with chronic systolic left ventricular heart failure. Am J Cardiol 2012; 10:552–557. 6 De Antonio M, Lupon J, Galan A, Vila J, Urrutia A, Bayes-Genis A. Combined use of high-sensitivity cardiac troponin T and N-terminal pro-B type natriuretic peptide improves measurements of performance over established mortality risk factors in chronic heart failure. Am Heart J 2012; 163:821–828. 7 Bonaca M, Scirica B, Sabatine M, Dalby A, Spinar J, Murphy SA, et al. Prospective evaluation of the prognostic implications of improved assay performance with a sensitive assay for cardiac troponin I. J Am Coll Cardiol 2010; 55:2118–2124. 8 Weber M, Bazzino O, Navarro Estrada JL, de Miguel R, Salzberg S, Fuselli JJ, et al. Improved diagnostic and prognostic performance of a new high-sensitive troponin T assay in patients with acute coronary syndrome. Am Heart J 2011; 162:81–88. 9 Meune C, Balmelli C, Twerenbold R, Reichlin T, Reiter M, Haaf P, et al. Patients with acute coronary syndrome and normal high-sensitivity troponin. Am J Med 2011; 124:1151–1157. 10 Mueller M, Celik S, Biener M, Vafaie M, Schwoebel K, Wollert KC, et al. Diagnostic and prognostic performance of a novel high-sensitivity cardiac troponin T assay compared to a contemporary sensitive cardiac troponin I assay in patients with acute coronary syndrome. Clin Res Cardiol 2012; 101:837–845. 11 Reichlin T, Hochholzer W, Bassetti S, Steur S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009; 361:858–867.
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Keller T, Zeller T, Peetz D, Tzikas S, Roth A, Czyz E, et al. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med 2009; 361:868–877. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. 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 2011; 32:2999–3054. Mills NL, Churchhouse AM, Lee KK, Anand A, Gamble D, Shah AS, et al. Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. JAMA 2011; 305:1210–1216. Wilson SR, Sabatine MS, Braunwald E, Sloan S, Murphy SA, Morrow DA. Detection of myocardial injury in patients with unstable angina using a novel nanoparticle cardiac troponin I assay: observations from the PROTECT-TIMI 30 Trial. Am Heart J 2009; 158:386–391. Twerenbold R, Jaffe A, Reichlin T, Reiter M, Mueller C. High-sensitive troponin T measurements: what do we gain and what are the challenges? Eur Heart J 2012; 33:579–586. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al. Heart disease and stroke statistics – 2012 update: a report from the American Heart Association. Circulation 2012; 125:e2–e220. Pope JH, Aufderheide TP, Ruthhazer R, Woolard RH, Feldman JA, Beshansky JR, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000; 342:1163–1170. Montassier E, Batard E, Gueffet JP, Trewick D, Le Conte P. Outcome of chest pain patients discharged from a French emergency department: a 60-day prospective study. J Emerg Med 2012; 42:341–344. Lee TH, Rouan GW, Weisberg MC, Brand DA, Acampora D, Stasiulewicz C, et al. Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. Am J Cardiol 1987; 60:219–224. McCarthy BD, Beshansky JR, D’Agostino RB, Selker HP. Missed diagnoses of acute myocardial infarction in the emergency department: results from a multicenter study. Ann Emerg Med 1993; 22:579–582. Mueller M, Biener M, Vafaie M, Doerr S, Keller T, Blankenberg S, et al. 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 2012; 58:209–218.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Will high-sensitivity troponin assays lead to improved outcomes in patients with acute coronary syndrome? James McCord New high-sensitivity cardiac troponin (hs-cTn) assays have been developed that can measure troponin values at much lower levels. How these new assays should be integrated into clinical practice is an area of active discussion and research. This review addresses how the identification of more high-risk patients with acute coronary syndrome may improve clinical outcomes in these patients. With the advent of the new hs-cTn assays, more patients with unstable angina will be classified as having non-STelevation myocardial infarction. These assays will define a high-risk patient population that was not possible with older generation assays. One study suggests that this will lead to more appropriate therapy in these patients and improved outcomes. The use of hs-cTn assays will identify more high-risk patients among millions of patients who
present to the Emergency Departments each year with undifferentiated chest pain. This will likely translate into more appropriate care and improved outcomes in this difficult patient population when ECG findings and clinical presentation do not suggest a clear diagnosis. Coron c 2013 Wolters Kluwer Health | Artery Dis 24:713–715 Lippincott Williams & Wilkins.
Introduction
cTnI values between 0.04 and 0.1 ng/ml were more likely to have an adverse event in 30 days (death or myocardial infarction) compared with patients with levels less than 0.04 ng/ml, 5.0 versus 2.0%, respectively. A weakness of this study was that blood samples were only obtained at presentation, and presumably some later measurements that were carried out using the standard assay would have been elevated. Mueller et al. [10] studied 1384 patients with possible ACS using the Siemens cTnI-Ultra assay (cut-point 0.04 ng/ml) and more sensitive hs-cTnT (Roche Diagnostics, Penzberg, Germany) with a cut-point of 0.014 ng/ml. Blood samples were obtained at presentation and at 6 h. Final diagnoses for patients included ST-elevation myocardial infarction 302 (21.8%), NSTEMI 662 (47.8%), unstable angina 365 (26.4%), and non-ACS 55 (4%). Receiver operating characteristic curve analysis showed significantly higher areas under the curve for the hs-cTnT as compared with cTnI for the prediction of death/myocardial infarction (0.721 vs. 0.672; P = 0.024).
Even the earliest generation cardiac troponin (cTn) assays were significantly more sensitive than the typically used CK-MB assays and identified more high-risk patients with acute coronary syndrome (ACS). These ACS patients with an elevated level of cTn were shown to have enhanced benefit when treated with more aggressive pharmacologic and invasive strategies in multiple studies [1,2]. The newer high-sensitivity cardiac troponin (hs-cTn) assays are significantly more sensitive than older cTn assays and can further discriminate high-risk patients from low-risk patients, which was not possible with older assays. The ability of newer hs-cTn assays to identify more high-risk individuals has been shown in various populations including community studies of individuals without known structural heart disease [3,4], chronic congestive heart failure [5,6], and ACS [7–10]. The newer hs-cTn assays will identify patients with non-ST-elevation myocardial infarction (NSTEMI) more rapidly, thus decreasing the standard ‘rule-out AMI’ process to 3 h [11,12], a time interval that is now reflected in guidelines [13]. Will this identification of more high-risk patients lead to improved outcomes for the millions of patients who are evaluated each year for possible ACS? The answer appears to be yes [14]. In a substudy from the MERLIN-TIMI 36 trial, ranolazine in NSTEMI-ACS, Bonaca et al. [7] evaluated 4513 patients with a newer assay (cTnI-Ultra assay ADVIA Centaur; Siemens Healthcare Diagnostics, Deerfield, Illinois, USA) with a cut-point of 0.04 ng/ml as compared with an older assay with a cut-point of 0.1 ng/ml. There were 319 (7%) patients who had cTnI values measured by the more sensitive assay between 0.04 and 0.1 ng/ml. Patients with c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins 0954-6928
Coronary Artery Disease 2013, 24:713–715 Keywords: high-sensitivity cardiac troponin, missed acute coronary syndrome, undifferentiated chest pain Heart & Vascular Institute, Henry Ford Hospital, Detroit, Michigan, USA Correspondence to James McCord, MD, Heart & Vascular Institute, Henry Ford Hospital, Detroit, MI 48202, USA Tel: + 1 313 916 4420; fax: + 1 313 916 8901; e-mail: [email protected]
In a substudy of the PROTECT-TIMI 30 Trial, Wilson et al. [15] evaluated 50 patients with NSTEMI and 50 patients with unstable angina. They compared a standard cTnI assay (Dimension RxL; Siemens Healthcare Diagnostics) with a cut-point of 0.07 ng/ml with a non-FDAapproved ‘nano-cTnI’ research assay (Nanosphere Inc., Northbrook, Illinois, USA) with a cut-point of 0.003 ng/ml. Patients had cTnI measured by the standard assay at enrollment, 6–8 h, and 24 h. All NSTEMI patients had nonelevated cTnI levels by the standard assay at enrollment. In the NSTEMI group, when using the nanocTnI assay, 72% had elevated levels at enrollment and 98% at 2 h. In the unstable angina group, who, by definition, DOI: 10.1097/MCA.0000000000000050
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
714 Coronary Artery Disease 2013, Vol 24 No 8
had normal serial cTnI values over 24 h, when using the nano-cTnI assay, 44% had elevated values at enrollment, 62% at 2 h, and 82% at 8 h. In a substudy of a prospective multicenter trial, Meune et al. [9] studied 351 patients with ACS (187 with acute myocardial infarction and 164 with unstable angina) with cTn measurements by various standard assays at presentation and 6–9 h; hs-cTnT was also measured, but not made available to the attending physicians. Patients with ACS but hs-cTnT of 0.014 ng/ml or less had a lower 30-day mortality rate of 0% when compared with the mortality rate of 7.5% in patients with hs-cTnT greater than 0.014 ng/ml (P = 0.003). Of the 164 patients with unstable angina, 63 (38%) patients had an elevated hs-cTnT at presentation. It is estimated that 15–20 million individuals annually are evaluated in the USA and Europe for possible ACS [16]. The majority of these individuals are ultimately not diagnosed with ACS with B1.3 million patients being diagnosed with ACS in the USA annually [17]. The diagnosis of ACS is difficult in some patients, and studies have shown that 2–4% of patients with ACS are not recognized in the Emergency Department and are inadvertently discharged [18,19]. Although this is a small percentage, this translates into 26 000–52 000 missed cases of ACS annually in the USA. Older studies found that patients with missed ACS in the Emergency Department are at a high risk for short-term adverse events [20,21]. One provocative study suggests that the use of the new hs-cTn assays will lead to improved identification of ACS patients in the Emergency Department and better patient outcomes. Mills et al. [14] studied 2092 consecutive patients in two phases in the Emergency Department at The Royal Infirmary in Edinburgh, Scotland. In all, 1038 patients were studied in the validation phase and 1054 patients were studied in the implementation phase. The assay used in the study was the Abbott Architect assay (Abbott Laboratories, Chicago, Illinois, USA). The diagnostic cut-point for medical decision-making for an older version of the assay was 0.2 ng/ml. Improvements in the assay’s performance were made, leading to a new generation more sensitive version with a cut-point of 0.04 ng/ml. In the validation phase, only values of at least 0.2 ng/ml were reported to the clinician as abnormal, but values between 0.04 and 0.19 ng/ml were recorded. In the implementation phase, cTnI values of at least 0.05 ng/ml were reported as abnormal to the clinician. All patient management decisions were left to the discretion of the responsible physician. In the entire group, hs-cTnI levels were less than 0.05 ng/ml in 1340 (64%) patients, 0.05–0.19 in 170 (8%), and at least 0.2 ng/ml in 582 (28%) patients. Patients with hs-cTnI values between 0.05 and 0.19 ng/ml were treated differently in the validation phase as compared with the implementation phase when the clinician was aware of the low-level cTnI elevation. In the implementation phase, those with hs-cTnI levels between 0.05 and 0.19 ng/ml were more likely
to receive cardiology consultation (74 vs. 44%), undergo coronary angiography (46 vs. 20%), receive dual-antiplatelet therapy (58 vs. 27%), and receive statin therapy (80 vs. 58%; P < 0.05 for all comparisons). There was also a difference in outcomes in patients with hs-cTnI values between 0.05 and 0.19 ng/ml when comparing patients in the validation phase with the implementation phase when the diagnostic threshold was lowered. At 3 months, there were 14 (16%) deaths in the validation phase and four deaths (5%) in the implementation phase (P < 0.05). Similarly, at 3 months, there were more readmissions for acute myocardial infarction in the validation phase [18 (20%)] compared with the implementation phase [five (6%; P < 0.05)]. Although there was a minority of patients (8%) with hs-cTnI values between 0.05 and 0.19 ng/ml, there were higher risk patients who had improved outcomes with more aggressive interventions. Likely, some of these patients in the validation group had unrecognized ACS and were discharged without appropriate therapy. Conclusion
Patients with undifferentiated chest pain in the Emergency Department constitute a significant clinical challenge. The historical control study by Mills et al. [14] suggests that the use of hs-cTn assays will lead to the identification of more high-risk ACS patients and improved clinical outcomes. However, this finding will need to be confirmed in other studies. Ideally, future studies would address this issue in multicenter randomized trials. A randomized trial comparing an older cTn assay with a new hs-cTn assay in patients in the Emergency Department with undifferentiated chest pain would be informative. Although the hs-cTn assays will identify more high-risk patients with ACS, there clearly will be more patients with mildly elevated hs-cTn where the diagnosis is not ACS. A community study of asymptomatic individuals using an hs-cTnT assay showed a prevalence of 25% for an elevated value. Likely, more patients will receive an extensive cardiac evaluation once it has been determined that they have a mildly elevated hs-cTn, and many of these will be determined to be low risk. Changes over time with early frequent blood draws will help determine acute from chronic elevations [22]. Future cost-effectiveness trials will need to weigh the benefit of identifying more high-risk patients among millions of individuals who present to the Emergency Departments each year against the cost of performing more testing on patients with mildly elevated hs-cTn.
Acknowledgements Conflicts of interest
J.M. is involved with a clinical trial that is sponsored by Roche Diagnostics.
References 1
Newby LK, Ohman EM, Christenson R, Moliterno D, Harrington R, White H, et al. Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status: the paragon-B troponin T substudy. Circulation 2001; 103:2891–2896.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
High-sensitivity troponin assays in ACS McCord 715
2
Kastrati A, Mehilli J, Neuman FJ, Dotzer F, ten Berg J, Bollwein H, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006; 295:1531–1538. 3 Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle E, et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation 2011; 123:1367–1376. 4 de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 2010; 304:2503–2512. 5 Egstrup M, Schou M, Tuxen CD, Kistorp CN, Hildebrandt PR, Gustafsson F, et al. Prediction of outcome by highly sensitive troponin T in outpatients with chronic systolic left ventricular heart failure. Am J Cardiol 2012; 10:552–557. 6 De Antonio M, Lupon J, Galan A, Vila J, Urrutia A, Bayes-Genis A. Combined use of high-sensitivity cardiac troponin T and N-terminal pro-B type natriuretic peptide improves measurements of performance over established mortality risk factors in chronic heart failure. Am Heart J 2012; 163:821–828. 7 Bonaca M, Scirica B, Sabatine M, Dalby A, Spinar J, Murphy SA, et al. Prospective evaluation of the prognostic implications of improved assay performance with a sensitive assay for cardiac troponin I. J Am Coll Cardiol 2010; 55:2118–2124. 8 Weber M, Bazzino O, Navarro Estrada JL, de Miguel R, Salzberg S, Fuselli JJ, et al. Improved diagnostic and prognostic performance of a new high-sensitive troponin T assay in patients with acute coronary syndrome. Am Heart J 2011; 162:81–88. 9 Meune C, Balmelli C, Twerenbold R, Reichlin T, Reiter M, Haaf P, et al. Patients with acute coronary syndrome and normal high-sensitivity troponin. Am J Med 2011; 124:1151–1157. 10 Mueller M, Celik S, Biener M, Vafaie M, Schwoebel K, Wollert KC, et al. Diagnostic and prognostic performance of a novel high-sensitivity cardiac troponin T assay compared to a contemporary sensitive cardiac troponin I assay in patients with acute coronary syndrome. Clin Res Cardiol 2012; 101:837–845. 11 Reichlin T, Hochholzer W, Bassetti S, Steur S, Stelzig C, Hartwiger S, et al. Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009; 361:858–867.
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