Supplementary Online Content

Neumann JT, Sörensen NA, Schwemer T, et al. Diagnosis of myocardial infarction using a
high-sensitivity troponin I 1-hour algorithm. JAMA Cardiol. Published online June 1, 2016.
doi:10.1001/jamacardio.2016.0695.

eMethods. Study-Specific Assessment

eTable 1. Troponin I Cutoff Value Calculation

eTable 2. Rule Out Based on Troponin I Measurement Applied to Each Sex

eTable 3. Rule In Using Troponin I Applied to Each Sex

eTable 4. Rule In Based on Troponin I Using 6 ng/L With Relative and Absolute Deltas

eTable 5. Baseline Characteristics of the ADAPT Cohort and APACE Cohort

eTable 6. Validation in the ADAPT Cohort and APACE Cohort

eFigure 1. Subgroups for Rule Out Based on Single Troponin I Measurement After 1 and 3

Hours

eFigure 2. ROC Curves for Troponin I Measured at Different Times

This supplementary material has been provided by the authors to give readers additional
information about their work.

© 2016 American Medical Association. All rights reserved.

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eMethods. Study-Specific Assessment

Research staff and cardiologists documented clinical features using a standardized data
collection sheet. Arterial hypertension and hyperlipidaemia were identified from medical
history. Patients with current intake of anti-diabetic drugs or insulin were classified as having
diabetes mellitus. We categorized smokers as current or former smokers. Any history of
coronary artery disease (CAD), coronary artery revascularisation (bypass graft or
percutaneous coronary intervention) or AMI was assessed by questionnaire and prior
medical history. Atrial fibrillation was diagnosed if seen in the admission ECG or prior
diagnosed. The patients with reduced ejection fraction (EF; below 35%) were diagnosed with
prevalent heart failure and reduced EF. The baseline estimated glomerular filtration rate
(eGFR) was calculated by the CKD-EPI formula.1

eReferences

1. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular
filtration rate. Annals of internal medicine 2009;150:604-12.

2. Than M, Cullen L, Aldous S, et al. 2-Hour accelerated diagnostic protocol to assess

patients with chest pain symptoms using contemporary troponins as the only biomarker: the
ADAPT trial. J Am Coll Cardiol 2012;59:2091-8.

3. Rubini Gimenez M, Twerenbold R, Jaeger C, et al. One-hour Rule-in and Rule-out of

Acute Myocardial Infarction Using High-sensitivity Cardiac Troponin I. The American journal
of medicine 2015;128:861--70.e4.

© 2016 American Medical Association. All rights reserved. 2

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eTable 1. Troponin I Cutoff Value Calculation

Troponin I NSTEMI NSTEMI Type 1

Cutoff Value,
ng/L NPV (95% CI), % No. of False- False-Negative NPV (95% CI), % No. of False- False-Negative
Negative +True-Negative Negative +True-Negative
Findings Findings, % Findings Findings, %

2 100.0 (95.8-100.0) 0 12.3 100.0 (95.8-100.0) 0 12.3

3 100.0 (97.1-100.0) 0 18.3 100.0 (97.1-100.0) 0 18.3

4 99.3 (97.4-99.9) 2 26.6 99.6 (98.0-100.0) 1 26.4

5 98.8 (97.0-99.7) 4 32.3 99.7 (98.3-100.0) 1 32.0

5.2 98.9 (97.1-99.7) 4 33.8 99.7 (98.4-100.0) 1 33.5

6 (Suggested 99.0 (97.5-99.7) 4 39.0 99.8 (98.6-100.0) 1 38.8

cutoff)

7 98.7 (97.2-99.5) 6 45.3 99.6 (98.5-99.9) 2 44.9

8 98.5 (97.0-99.3) 8 49.8 99.4 (98.3-99.9) 3 49.3

9 98.0 (96.4-99.0) 11 52.6 99.4 (98.4-99.9) 3 51.8

10 97.9 (96.4-98.9) 12 54.8 99.3 (98.2-99.8) 4 54.0

15 97.1 (95.5-98.3) 19 63.5 98.9 (97.8-99.6) 7 62.3

20 96.3 (94.6-97.6) 26 67.7 98.8 (97.7-99.5) 8 66.0

27 (99th 94.8 (93.0-96.3) 38 70.8 98.4 (97.2-99.2) 11 68.2

Percentile)

Abbreviations: CI, confidence interval; NPV, negative predictive value; NSTEMI, non–ST-elevation myocardial infarction.

© 2016 American Medical Association. All rights reserved.

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eTable 2. Rule Out Based on Troponin I Measurement Applied to Each Sex

Time after NPV Sensitivity NPV Sensitivity

admission Men Men Women Women

(95% CI) (95% CI) (95% CI) (95% CI)

1h 98.4 (96.0-99.6) 96.6 (91.6-99.1) 100.0 (96.5-100.0) 100.0 (89.6-100.0)

3h 99.1 (96.9-99.9) 98.3 (93.9-99.8) 100.0 (96.3-100.0) 100.0 (90.3-100.0)

Abbreviations: NPV = negative predictive value, CI = confidence interval.

© 2016 American Medical Association. All rights reserved.

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eTable 3. Rule In Using Troponin I Applied to Each Sex

Criteria to diagnose patient as NSTEMI PPV Specificity PPV Specificity

Men Men Women Women
(95% CI) (95% CI) (95% CI) (95% CI)

35.7 59.3 34.2 63.8

Troponin I 0h > 6 ng/L
(30.4-41.3) (54.9-63.7) (26.8-42.1) (57.9-69.3)

Troponin I 1h > 6 ng/L and absolute delta 89.3 98.3 82.9 (67.9- 97.5
from 0h to 1h Troponin I ≥ 12 ng/L (80.1-95.3) (96.7-99.3) 92.8) (94.8-99.0)

Troponin I 3h > 6 ng/L and absolute delta 83.5 96.4 86.8 97.5
from 0h to 3h Troponin I ≥ 12 ng/L (74.9-90.1) (94.4-97.9) (74.7-94.5) (94.8-99.0)

Abbrevations: NSTEMI = non–ST-elevation myocardial infarction, PPV = positive predictive value,

CI = confidence interval.

© 2016 American Medical Association. All rights reserved. 5

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eTable 4. Rule In Based on Troponin I Using 6 ng/L With Relative and Absolute Deltas

PPV Specificity
Criteria to diagnose patient as TP+FP
NSTEMI NSTEMI
NSTEMI NSTEMI
(95% CI) (95% CI)
Troponin I 0h > 6 ng/L 35.2 (30.9-39.7) 61.0 (57.4-64.4) 165+304 = 469
Troponin I 1h > 6 ng/L AND TnI
39.9 (33.4-46.7) 82.6 (79.7-85.3) 87+131 = 218
relative delta 1h  20%
Troponin I 3h > 6 ng/L AND TnI
40.1 (34.4-46.0) 77.0 (73.8-80.0) 116+173 = 289
relative delta 3h  20%
Troponin I 1h > 6 ng/L AND TnI
absolute delta 1h  6ng/L 70.7 (63.5-77.2) 93.0 (90.9-94.7) 128+53 = 181

Troponin I 3h > 6 ng/L AND TnI

absolute delta 3h  6ng/L 64.4 (57.7-70.7) 89.5 (87.1-91.6) 143+79 = 222

Troponin I 1h > 6 ng/L AND TnI

absolute delta 1h  12ng/L 87.1 (79.6-92.6) 98.0 (96.7-98.9) 101+15 = 116

Troponin I 3h > 6 ng/L AND TnI

absolute delta 3h  12ng/L 84.6 (78.0-89.9) 96.8 (95.3-97.9) 132+24 = 156

Troponin I 1h > 6 ng/L AND TnI

absolute delta 1h  18ng/L 88.2 (80.4-93.8) 98.4 (97.2-99.2) 90+12 = 102

Troponin I 3h > 6 ng/L AND TnI

absolute delta 3h  18ng/L 88.7 (82.2-93.4) 97.9 (96.6-98.8) 125+16 = 141

Abbreviations: NSTEMI = non–ST-elevation myocardial infarction, PPV: positive predictive value,

FP = false positive, TP = true positive, CI = confidence interval.

© 2016 American Medical Association. All rights reserved.

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eTable 5. Baseline Characteristics of the ADAPT Cohort and APACE Cohort3

ADAPT APACE
Non-AMI NSTEMI Non-AMI NSTEMI
Number of patients 1,499 249 1,832 429
Age, years, Median 59 (49-70) 71 (60-79) 59 (47-73) 72 (59-80)
Male gender (%) 868 (57.9) 163 (65.5) 1,226 (66.9) 316 (73.7)
Abbreviation: NSTEMI = non–ST-elevation myocardial infarction.

© 2016 American Medical Association. All rights reserved. 7

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eTable 6. Validation in the ADAPT Cohort and APACE Cohort3

Rule used to diagnose Sensitivity Specificity PPV NPV

NSTEMI
(95% CI) (95% CI) (95% CI) (95% CI)

ADAPT

Troponin I on admission 98.80 69.11 34.70 99.71

> 6 ng/L OR troponin I 2h (96.52-99.75) (66.70-71.45) (31.19-38.33) (99.16-99.94)
after admission > 6 ng/L

Troponin I 2h > 6 ng/L 74.3 97.2 81.5 95.8

AND
(68.4-79.6) (96.2-98.0) (75.8-86.3) (94.7-96.7)
absolute delta from 0h
to 2h troponin I ≥ 12 ng/L

APACE

Troponin I on admission 98.1 62.3 41.8 99.2

> 6 ng/L OR troponin I 1h (96.3-99.2) (59.8-64.7) (38.7-45.0) (98.4-99.6)
after admission > 6 ng/L

Troponin I 1h > 6 ng/L 66.0 96.3 80.4 92.5

AND
(60.6-71.1) (95.2-97.2) (75.1-84.9) (91.0-93.8)
absolute delta from 0h
to 1h troponin I ≥ 12 ng/L

Abbreviations: NPV = negative predictive value, NSTEMI = non–ST-elevation myocardial infarction,

PPV = positive predictive value, CI = confidence interval.

© 2016 American Medical Association. All rights reserved. 8

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eFigure 1. Subgroups for Rule Out Based on Single Troponin I Measurement After 1 and 3 Hours

The negative predictive value (NPV) to rule-out MI after 1 or 3 hours was not significantly different among various subgroups (gender, age, eGFR,
atrial fibrillation, heart failure, CAD, history of MI or hypertension), Abbreviations: AF = atrial fibrillation; HF = heart failure; CAD = Coronary artery
disease; AMI = acute myocardial infarction.

© 2016 American Medical Association. All rights reserved.

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016

 eFigure 2. ROC Curves for Troponin I Measured at Different Times

Presented are the ROC curves for troponin I measurement at baseline, after 1 and 3 hours.
AUC = Area under the ROC-Curve.

© 2016 American Medical Association. All rights reserved.

Downloaded From: http://cardiology.jamanetwork.com/ by cassie wati on 09/11/2016