Ultra-Sensitive Cardiac Troponin I for Rapid Rule-out and ... · PDF fileUltra-Sensitive...
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Ultra-Sensitive Cardiac Troponin I for Rapid Rule-out and Rule-in of Myocardial Infarction Raphael Twerenbold, MD Singulex BioRemarkable Symposium - London, September 7-8 th , 2017
Transcript of Ultra-Sensitive Cardiac Troponin I for Rapid Rule-out and ... · PDF fileUltra-Sensitive...
Ultra-Sensitive Cardiac Troponin Ifor Rapid Rule-out and Rule-inof Myocardial InfarctionRaphael Twerenbold, MD
Singulex BioRemarkable Symposium - London, September 7-8th, 2017
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bottleopener
knifescrewdriver
(phillips head)saw
(wood)rasp
pliers
scissors
magnifier
awlcorkscrew
saw(metal)
bottleopener
screwdriver(slotted head)
diagnosis of MI
risk predictionin acute setting
diagnosis of MI
diagnosis ofunstable angina
exclusion ofcardiac disesases
risk predictionin general population
individual wellnesstest
diagnosisof stable CAD
risk predictionin acute setting
cardiac toxicityduring chemotherapy
Aims
I. to assess the diagnostic accuracy of the Singulex us-cTnI for theearly diagnosis of myocardial infarction (MI).
II. to compare Singulex us-cTnI with Abbott hs-cTnI.
III. to derive and internally validate a 0/1-hour algorithm usingSingulex us-cTnI for the rapid triage of patients with suspectedNSTEMI.
Roffi M, et al. EHJ 2016; 37, 267-315. / Pickering J, et al. Circulation 2016; 134: 1532-1541.
Methods - APACE§ Population: - unselected patients presenting to the ED with symptoms suggestive of MI- chest pain onset / peak within last 12 hours- 13 centers in five European countries- STEMI excluded
Barcelona del MarBarcelona Clínic
Brno
Zabrze
GenuaMadrid
USB Basel
Schlieren
USZ Zurich
Lucerne
Liestal
Bottmingen
Olten
Methods
§ Final diagnosis: centrally adjudicated by two independent cardiologists 90 days after index admission (including data on cardiac imaging, coronary angiography and serial hs-cTnT).
§ Investigational biomarker: Ultra-sensitive cardiac Troponin I (us-cTnI) measured with the Singulex Clarity® analyzer in blood samples drawn at ED presentation and during serial sampling (1h, 2h, 3h, 6h).
Results§ 2601 patients,
§ Median age 61 years, 68% male sex, 36% early presenters (≤3h after CPO)
§ Distribution of goldstandard diagnoses:
17%
10%
14%54%
5%
NSTEMI
UA
Cardiac, not coronary
non-cardiac
unknown
Results§ us-cTnI concentrations according to diagnostic group
Samples number All patients NSTEMI wo NSTEMI p-value
Troponin levels – ng/L
at presentation n=2601 1.53 (0.69-5.76) 46.69 (10.94-240.11) 1.17 (0.60-2.69) <0.001
after 1h n=2079 1.60 (0.74-6.42) 67.37 (14.59-331.89) 1.23 (0.64-2.66) <0.001
after 2h n=1698 1.62 (0.74-6.32) 80.11 (16.56-291.90) 1.29 (0.66-2.79) <0.001
after 3h n=690 1.69 (0.78-6.52) 90.67 (21.53-351.82) 1.38 (0.71-2.78) <0.001
after 6h n=396 1.89 (0.89-11.52) 105.19 (24.45-500.05) 1.50 (0.80-3.30) <0.001
Absolute troponin changes – ng/L
change 0h/1h n=2079 0.23 (0.08-1.15) 15.57 (3.27-67.53) 0.18 (0.06-0.50) <0.001
change 0h/2h n=1698 0.29 (0.10-1.40) 29.34 (4.84-112.85) 0.21 (0.08-0.61) <0.001
change 0h/3h n=690 0.32 (0.11-1.45) 35.10 (6.95-166.63) 0.24 (0.10-0.73) <0.001
change 0h/6h n=396 0.46 (0.14-3.26) 54.37 (16.47-224.61) 0.30 (0.12-1.04) <0.001
Results – Diagnostic Accuracy of us-cTnI for NSTEMI0h-sample
(n=2348)1h-change
(n=1794)Combination
(n=1794)
Abbott hs-cTnI: 0.92 (0.91-0.93)Singulex us-cTnI: 0.93 (0.92-0.95)
p=0.002Abbott hs-cTnI: 0.92 (0.90-0.93)Singulex us-cTnI: 0.92 (0.90-0.94)
p=0.430
100 - Specificity100806040200
Sens
i tivi
ty
100
80
60
40
20
0
Abbott hs-cTnI: 0.93 (0.91-0.94)Singulex us-cTnI: 0.93 (0.92-0.95)
p=0.188
Results – Diagnostic Accuracy for NSTEMI in Early Presenters0h-sample
(n=832)1h-change
(n=646)Combination
(n=646)
100 - Specificity100806040200
Sens
itiv i
ty
100
80
60
40
20
0
Abbott hs-cTnI: 0.90 (0.88-0.93)Singulex us-cTnI: 0.92 (0.90-0.94)
p=0.079Abbott hs-cTnI: 0.93 (0.91-0.95)Singulex us-cTnI: 0.93 (0.91-0.95)
p=0.580Abbott hs-cTnI: 0.93 (0.90-0.95)Singulex us-cTnI: 0.94 (0.91-0.96)
p=0.246
100 - Specificity100806040200
Sens
i tivi
ty
100
80
60
40
20
0
Results – Diagnostic Performance of the 0/1h Algorithm
Suspected NSTEMI
OtherBaseline very low*
Baseline lowAND
No 1h-changeOR Baseline
very high OR Relevant 1h-change
n=160 Proportion: 15% (13-17)PPV: 73.6% (67.2-79.2)
n=303Proportion: 29% (26-32)
n=578Proportion: 56% (53-58)NPV: 99.5% (98.4-99.8)
* only if chest pain onset>3h prior ED presentation.
RULE-INOBSERVERULE-OUT
Confidential - unpublished, preliminary data
n=1041
Results – Prognostic Performance of the 0/1h Algorithm
Confidential - unpublished, preliminary data
Log-rank 30 days, p-value <0.001
Log-rank 720 daysp-value <0.001
Rule-in groupObserve groupRule-out groupSu
rviv
al
Follow-up Time, days
97.8%
89.3%
86.7%
99.8%
99.1%97.3%
only 2 deaths within 30 days in rule-out group (1 for aortic dissection & 1 for cancer)
Take home messages
The Singulex Clarity us-cTnI assay performs:
I. excellent in the early diagnosis of MI (also in early presenters)
II. comparable to Abbott hs-cTnI
The 0/1h-algorithm using us-cTnI provides:
III. excellent safety (NPV≈99.5%)
IV. high efficacy (>70%)
V. powerful risk prediction
