1. for the TRAPID-AMI Investigators
Multicenter evaluation of a 1h-algorithm in the diagnosis of myocardial infarction using high-sensitivity cardiac Troponin T
Christian Mueller, Evangelos Giannitsis, Michael Christ, Jorge Ordóñez-Llanos, Christopher R. deFilippi, James K. McCord, Richard Body, Mauro Panteghini, Tomas Jernberg, Mario Plebani, Franck Verschuren, John K. French, Robert H. Christenson, Silvia Weiser, Garnet Bendig, Peter Dilba, Bertil Lindahl,
for the TRAPID-AMI Investigators
High sensitivity cardiac Troponin T assay for RAPID rule-out of Acute Myocardial Infarction
Sponsored by 1

2. Disclosures
Swiss National Science Foundation . ..

3. Background: Early diagnosis of AMI
Critical for timely initiation of evidence based therapies, but still an unmet need in many patients
Delayed “rule-in”  morbidity + mortality 
Delayed “rule-out”  time in ED + costs  patient anxiety 
3 key tools: History incl. chest pain characteristics
ECG
cTn
Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

4. Background: Early diagnosis of AMI
Critical for timely initiation of evidence based therapies, but still an unmet need in many patients
Delayed “rule-in”  morbidity + mortality 
Delayed “rule-out”  time in ED + costs  patient anxiety 
3 key tools: History incl. chest pain characteristics
ECG
hs-cTn
Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

5. Rule-in Rule-out 0h 1h 2h 3h 4h 5h 6h 7h ECG cTn cTn
ESC 2011: hs-cTn hs-cTn
TRAPID-AMI: hs-cTnT
hs-cTnT

6. APACE: hs-cTnT 1h-algorithm
Mmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmm
600 pts
NPV 100%
95% CI %
150 pts
PPV 76%
95% CI 69-82%
Reichlin T, et al. Arch Intern Med 2012

7. APACE: hs-cTnT 1h-algorithm
491 Patients (56%)
NPV 100%
95% CI %
212 Patients (24%)
Prevalence of AMI 9%
169 Patients (19%)
PPV 76%
95% CI 69-82%
Aim of TRAPID-AMI:
to prospectively validate the hs-cTnT 1h-algorithm
Reichlin T, et al. Arch Intern Med 2012

8. 12 sites on 3 continents

9. Methods II TRAPID-AMI ≈ APACE Prospective diagnostic study in the ED
Inclusion: acute chest pain suggestive of AMI
onset < 6h (<12h in APACE)
written informed consent
First blood draw <45min since presentation
Exclusion: terminal kidney failure on dialysis
Trauma
DC or defibrillation prior to inclusion
CABG <1month or AMI <3 weeks
Blinded measurement of hs-cTnT at 0h+1h
Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

10. Methods III
Final diagnosis: central adjudication by two independent cardiologists according to the universial definition of MI using all information including serial cTnI-ultra (hs-cTnT in APACE)
Primary endpoint: NPV for AMI
Secondary endpoints: PPV for AMI, ….
Follow-up: 30d mortality
Sample size calculation: based on APACE
761 patients in rule-out zone, 1233 patients overall
Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

11. Results Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

12. Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

14. Results 95% CI 98.2-99.7% 95% CI 70.4-83.0% Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924
95% CI %
95% CI %

15. Subgroups: Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

16. Results 0.1% Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924
0.1%

17. Limitations
ED patients vs general practitioner (pre-test probability)
Observational diagnostic study. Physicians were blinded to the investigational hs-cTnT results and patients were not managed based on these results.
May underestimate the true NPV of the hs-cTnT 1h- algo due to enrichment with early presenters
Performance in patients on dialysis is unknown
Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924

18. Conclusions
The hs-cTnT 1h-algorithm performs well for early rule-out as well as rule-in of AMI.
Effectiveness (% rule-out/in) and safety (NPV & 30d- mortality in rule-out, PPV in rule-in ≈ APACE.
Clinical implication: Used in conjunction with all other clinical information including ECG, the hs-cTnT 1h-algorithm will be a safe and effective approach to substantially reduce time to diagnosis in ≈75% of acute chest pain patients.
Einthoven aus Holland
Nobelpreis für Physiologie und Medizin 1924