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

Disclosures

• Swiss National Science Foundation

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• 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

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

Background: Early diagnosis of AMI

0h 1h 2h 3h 4h 5h 6h 7h

ECG

1.Rule-in

2.Rule-out

cTn cTn

ESC 2011: hs-cTn hs-cTn

TRAPID-AMI: hs-cTnT hs-cTnT

APACE: hs-cTnT 1h-algorithm

Reichlin T, et al. Arch Intern Med 2012

600 ptsNPV 100%95% CI 99-100%

150 ptsPPV 76%95% CI 69-82%

Mmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmm

APACE: hs-cTnT 1h-algorithm

Reichlin T, et al. Arch Intern Med 2012

Aim of TRAPID-AMI: to prospectively validate the hs-cTnT 1h-algorithm

491 Patients (56%)NPV 100%95% CI 99-100%

169 Patients (19%)PPV 76%95% CI 69-82%

212 Patients (24%)Prevalence of AMI 9%

12 sites on 3 continents

• 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

Methods II

• 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

Methods III

Results

Results

95% CI 98.2-99.7% 95% CI 70.4-83.0%

Subgroups:

Results

0.1%

• 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

Limitations

• 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.

Conclusions