Diagnostic accuracy of sensitive or high-sensitive troponin on presentation for myocardial infarction: a meta-analysis and systematic review

Figures & data

Figure 1 Study selection flow chart.

Abbreviations: hsTrop, high-sensitive troponin; MB, myocardial band; MI, myocardial infarction.

Figure 2 Forest plots showing pooled sensitivities and specificities.

Notes: (A) High-sensitive troponin T (Hoffman-La Roche Ltd) and (B) sensitive troponin I (Siemens Healthcare Diagnostics), both at 99th percentile. Data are rounded to two decimal points.
Abbreviation: CI, confidence interval.

Table 1 (A) Pooled estimates of diagnostic accuracy for myocardial infarction of studies included in primary analysis; (B) results of meta-regression analysis of study level covariates on diagnostic odds ratio

(A)
Outcome	hsTrop T (Roche) at 99th percentile	hsTrop I (Siemens) at 99th percentile	hsTrop I or T at LOD
Sensitivity (95% CI)	0.885 (0.863–0.905)	0.899 (0.874–0.921)	0.974 (0.963–0.983)
Specificity (95% CI)	0.783 (0.768–0.797)	0.886 (0.874–0.898)	0.410 (0.395–0.424)
Positive likelihood ratio (95% CI)	3.999 (3.360–4.760)	6.300 (4.400–9.022)	1.646 (1.337–2.026)
Negative likelihood ratio (95% CI)	0.137 (0.092–0.205)	0.135 (0.067–0.269)	0.079 (0.042–0.148)
(B)
Study variable	RDOR	95% CI	P-value
Inclusion of STEMI	1.35	0.58–3.16	0.469
Exclusion of patients with dialysis	1.63	0.73–3.67	0.218
Prevalence of CAD	0.11	0.00–10.62	0.329
Diagnostic cut-off <10% CV versus 99th percentile	2.15	1.10–4.21	0.027

Abbreviations: CAD, coronary artery disease; CI, confidence interval; CV, coefficient of variance; hsTrop, high-sensitive troponin; LOD, level of detection; RDOR, relative diagnostic odds ratio; STEMI, ST elevation myocardial infarction; Roche, Hoffman-La Roche Ltd; Siemens, Siemens Healthcare Diagnostics.

Figure 3 Summary receiver operating plots: (A) conventional troponin, (B) sensitive/high-sensitive troponin at 99th percentile cut-off, and (C) high-sensitive troponin at the level of detection.

Notes: AUC (A) versus (B) (P=0.62), and (A) versus (C) (P=0.2344). Each dot represents study level estimate. The central curve represents the summary estimate of the AUC derived from the study level data, and the upper and lower curve represent its 95% confidence interval.
Abbreviations: AUC, area under the curve; SE, standard error; SROC, summary receiver operating curve.

Figure 4 Forest plot showing pooled sensitivities and specificities for high-sensitive troponin T (Hoffman-La Roche Ltd) when high-sensitive troponin T assays were used in the reference standard.

Note: Data are rounded to two decimal points.
Abbreviation: CI, confidence interval.

Figure S1 Summary plot of individual studies reporting sensitivity and specificity for high-sensitive troponin assays at presentation for acute coronary syndrome.

Abbreviations: CI, confidence interval; FN, false negative; FP, false positive; TN, true negative; TP, true positive.

Figure S2 QUADAS analysis of methodological quality of included studies.

Abbreviation: QUADAS, Quality Assessment tool for Diagnostic Accuracy Studies.

Table S1 Characteristics of studies reporting diagnostic accuracy of high-sensitive troponin assays using conventional troponin in the reference standard

Study	Enrollment period	Sample size	Age (years)*	Males (%)	Inclusion criteria	Exclusion criteria	Adjudication of diagnosis	s/hsTrop assay used	Conventional Trop assay and cut-off used
Aldous et al^Citation1	2006–2007	332	64.3	60.2	Consecutive patients attending ED and having suspicion of ACS that serial EKG and Trop were deemed necessary	<18 years old, inability to obtain frozen sample	By two cardiologists based on history, Trop and investigations (including stress test and angiogram) largely in accordance with ACC/AHA guidelines and ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop T (Roche)	Architect Trop I 2nd generation (Abbott Laboratories) at 0.028 μg/L (99th percentile)
Aldous et al^Citation2	2007–2010	939	65	59.7	Consecutive patients >18 years with symptoms suggestive of ACS presenting to ED between 5.30 am and 8 pm	STEMI	By one of the two physicians based on Trop I plus rise or fall pattern of at least 20%, objective evidence of ischemia, or significant CAD on angiogram	hsTrop T (Roche)	Architect Trop I (Abbott Laboratories) at 0.03 μg/L (10% CV)
Apple et al^Citation3	NR	371	54	60	Consecutive patients presenting with symptoms suggestive of ACS admitted through the ED to rule in or rule out AMI	Follow-up information not available	By records review in accordance with ESC/ACC/AHA redefinition of MI^Citation18	Advia Centaur Trop I Ultra (Siemens Healthcare Diagnostics)	Dade Behring Dimension or Stratus CS) at 0.1 μg/L (99th percentile)
Apple et al^Citation4	2005–2006	381	54	NR	Patients who presented with symptoms suggestive of ACS and were admitted through the ED to rule in or rule out AMI	Inability to obtain second sample	By records review in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	VITROS Trop I-ES (Ortho-Clinical Diagnostics)	Dade Behring Dimension or Stratus CS at 0.1 μg/L (99th percentile)
Body et al^Citation5	2006–2007	703	58.6	61.2	Patients >25 years presenting to ED and had chest pain within the previous 24 hours that the initial treating physician suspected may be cardiac in nature	Renal failure requiring dialysis, trauma with suspected myocardial contusion, or another medical condition mandating hospital admission	By two independent investigators who had all clinical, laboratory, and imaging data available for review, largely in accordance with ESC/ACC/AHA/WHF definition of MI^Citation18	hsTrop T (Roche)	4th generation Trop T(Roche) at 10 ng/L (99th percentile)
Casals et al^Citation6	NR	120	67.6	73	Patients presenting with acute chest pain	NR	By clinical, EKG, and enzymatic findings according to ESC/ACC redefinition of MI^Citation5	Advia Centaur Trop I Ultra (Siemens Healthcare Diagnostics)	AccuTnI Access 2 (Beckman Coulter) at 0.09 μg/L (10% CV)
Christ et al^Citation7	2009	137	66	64	Consecutive patients with acute chest pain of possible coronary origin presented to the ED	NR	By two independent consultants based on history, Trop, and investigations (including stress test and angiogram) largely in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop T (Roche)	4th generation Trop T (Roche) at 0.04 μg/L (10% CV)
Eggers et al^Citation8	2000–2003	360	66.8	65.6	Patients admitted to coronary care unit with chest pain lasting ≥15 minutes within the last 24 hours (FAST II-study), or the last 8 hours (FASTER I-study)	STEMI	By independent endpoint evaluators in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	hs Trop T (Roche)	Stratus CS (Siemens Healthcare Diagnostics) at 0.07 μg/L (99th percentile)
Freund et al^Citation9	2005–2007	317	57	65	Consecutive patients >18 years presented to the ED with chest pain suggestive of ACS with the onset or peak within the previous 6 hours	Patients with acute or chronic kidney failure requiring dialysis	By two ED physicians after reviewing all medical records from presentation to 30 days in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop T (Roche)	Trop I (Siemens Healthcare Diagnostics) at 0.14 μg/L (10% CV) and Trop i (Beckman Coulter) at 0.06 μg/L (10% CV)
Keller et al^Citation10	2007–2008	1,818	61.4	66.4	All patients between 18 and 85 years presenting with acute angina pectoris or equivalent symptoms	Major surgery or trauma within the previous 4 weeks, pregnancy, intravenous drug abuse, and anemia (hemoglobin level <10 g/dL)	By two independent cardiologists after reviewing all available clinical, laboratory, and imaging findings in accordance with current guidelines	Advia Centaur Trop I Ultra (Siemens Healthcare Diagnostics)	Trop T (Roche) at 0.03 ng/mL (10% CV) or Dimension R×L Trop I (Siemens Healthcare Diagnostics) 0.14 ng/dL (10% CV)
Keller et al^Citation11	2007–2008	1,818	61.4	66.4	All patients between 18 and 85 years presenting with acute angina pectoris or equivalent symptoms	Major surgery or trauma within the previous 4 weeks, pregnancy, intravenous drug abuse, and anemia (hemoglobin level <10 g/dL)	By two independent cardiologists based on all available clinical, laboratory, and imaging findings according to ESC/ACC/WHF redefinition of MI^Citation18	Architect STAT hsTrop I (Abbott Laboratories)	Trop T (Roche) at 0.03 ng/mL (10% CV) or Dimension R×L Trop I (Siemens Healthcare Diagnostics) 0.14 ng/dL (10% CV)
Kurz et al^Citation12	2008	94	65.6	67	Consecutive patients with symptoms suggestive of ACS admitted to the Chest Pain Unit	STEMI, chronic kidney disease	Using ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop T (Roche)	4th generation Trop T (Roche) at 0.03 g/L (10% CV)
Melki et al^Citation13	2006–2008	233	65	67	Consecutive patients with chest pain or other symptoms suggestive of ACS within 12 hours admitted to coronary care unit	STEMI	By two physicians with access to all patients’ data in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop T (Roche)	4th generation Trop T (Roche) at 0.04 μg/L (10% CV) or stratus CS Trop I (Dade Behring) at 0.1 μg/L (10% CV)
Reiter et al^Citation14	2006–2009	1,098	64	67	Consecutive patients presenting to the ED with chest pain suggestive of AMI with onset or peak within the last 12 hours	ESRD on dialysis	By two independent cardiologists based on review of all available medical records in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop T (Roche) and Trop I Ultra (Siemens Healthcare Diagnostics)	Abott-Axsym Trop I (Abbott Laboratories) at 0.16 ng/mL, Accu Trop I (Beckmann Coulter) at 0.06 ng/mL, or 4th generation Trop T (Roche) 0.035 ng/mL (all 10% CV)
Schreiber et al^Citation15	2005–2006	465	67	49.2	Patients >21 years presenting to ED with suspected ACS during weekdays between 9 am and 5 pm	STEMI	By two authors based on clinical, Trop, and imaging data in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop I (Singulex Erenna)	Dimension R×L Trop I (Siemens Healthcare Diagnostics) 140 ng/L (10% CV)
Studies reporting ACS only
Bhardwaj et al^Citation16	2006	318	58.3	53.8	Patients >21 years presenting to ED with symptoms suggestive of ACS	Thrombolytic use, high output state, cirrhosis, dialysis, symptoms relief >2 hours, trauma, infection, malignancy, cocaine use, acute bowel or cerebral ischemia, peripheral artery disease	By investigators at each institution and principal investigator after reviewing medical records using standard criteria recommendedby ACC/AHA^Citation19	hsTrop I (Singulex Erenna)	Trop T (Roche)at 0.03 ng/mL (10% CV)
Zuily et al^Citation17	2009	87	60	64	Consecutive patients admitted to Intensive Care Unit for suspected ACS	Cardiac arrest or STEMI	By two cardiologists reviewing all data in accordance with ESC/ACC/AHA/WHF redefinition of MI^Citation18	hsTrop T (Roche)	Trop I (Siemens Healthcare Diagnostics) 140 ng/L (10% CV)

Note:

* Mean/median.

Abbreviations: ACC, American College of Cardiology; ACS, acute coronary syndrome; AHA, American Heart Association; AMI, acute myocardial infarction; CAD, coronary artery disease; CV, coefficient of variance; ED, emergency department; EKG, electrocardiography; ESC, European Society of Cardiology; ESRD, end-stage kidney disease; s/hsTrop, sensitive/high-sensitive troponin; MI, myocardial infarction; NR, not reported; Trop, troponin; STEMI, ST elevation myocardial infarction; WHF, World Heart Federation; Roche, Hoffman-La Roche Ltd; Siemens, Siemens Healthcare Diagnostics.

Table S2 Characteristics of studies reporting diagnostic accuracy of high-sensitive troponin assays using high-sensitive troponin in the reference standard

	Enrollment period	Sample size	Age (years)@	Males (%)	Inclusion criteria	Exclusion criteria	Adjudication of diagnosis	s/hsTrop assays	Sensitivity	Specificity
Christ et al^Citation7	2009	137	66	64	Consecutive patients with acute chest pain of possible coronary origin presented to the ED	NR	By two independent consultants after reviewing all available medical records in accordance with ESC/ACC/AHA/WHF redefinition of Ml^Citation3	hsTrop T (Roche)	0.943	0.696
Giannitsis et al^Citation21	2009–2010	503	63	63	Patients presenting to Chest Pain Unit with onset of symptoms within previous 12 hours	STEMI, trauma, major surgery in last 4 months, pregnancy, anemia, kidney failure, aged < 18 years	By two cardiologists based on ESC/ACC/AHA/WHF redefinition of Ml^Citation3	hsTrop T (Roche)	0.919	0.681
Inoue et al*^Citation22	2006–2009	432	67	73	Patients with chest pain lasting >20 minutes in last 24 hours who visited ED via ambulance	Kidney disease, malignant or collagen disorder, C-reactive protein >I0 mg/dL	By two senior cardiologists according to ESC/ACC redefinition of Ml^Citation9	hsTrop T (Roche)	0.879	0.612
Kelly^Citation23	NR	952	61	56.4	Adult patients with nontraumatic chest pain	EKG evidence of ischemia or clear alternate diagnosis	By treating cardiologist with all clinical and investigation data, using 99th percentile cut-off	Trop I Ultra (Siemens Healthcare Diagnostics)	0.767	0.936
Khan et al^Citation24	2009–2010	180	58	83	Patients age 35–80 years who presented to ED within 4 hours of chest pain	Cardiomyopathies, myocarditis, heart failure, Ml with renal failure	By two independent cardiologists on the basis of clinical, EKG, hsTrop, and angiographic findings according to current guidelines	hsTrop T (Roche)	0.870	0.980
Lotze et al^Citation25	2010	142	71.2	53	Consecutive patients with symptoms suggestive of Ml presenting to ED	Dialysis	By consensus of attending physician and consultant in accordance with ESC/ACC/AHA/WHF redefinition of Ml^Citation3	hsTrop T (Roche)	0.923	0.535
Melki et al^Citation13	2006–2008	233	65	67	Consecutive patients with chest pain or other symptoms suggestive of ACS within 12 hours admitted to coronary care unit	STEMI	By two physicians with access to all patients’ data in accordance with ESC/ACC/AHA/WHF redefinition of Ml^Citation3	hsTrop T (Roche)	0.98	0.82
Olivieri et al*^Citation26	2011	299	85	51	Consecutive patients ≥75 years admitted to ED for chest pain with dyspnea	NR	By ESC guidelines and ESC/ACC/AHA/WHF redefinition of Ml^Citation3	hsTrop T (Roche)	1	0.637
Scharnhorst et al^Citation27	NR	137	64	65	Consecutive patients entering ED with suspicion of non-ST elevation ACS	STEMI on arrival	By clinical diagnosis made by attending cardiologist using routinely acquired data and hsTrop cut-off of 0.1 μg/L	Trop I Ultra (Siemens Healthcare Diagnostics)	1	0.87

Notes:

@ Mean or median;

* reported diagnostic accuracy for ACS rather than Ml;

# the cut-off used was 54.5 ng/L instead of 99th percentile.

Abbreviations: ACS, acute coronary syndrome; ACC, American College of Cardiology; AHA, American Heart Association; ED, emergency department; EKG, electrocardiography; ESC, European Society of Cardiology; Ml, myocardial infarction; NR, not reported; s/hsTrop, sensitive/high-sensitive troponin; STEMI, ST elevation myocardial infarction; Trop, troponin; WHF, World Heart Federation.

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