ED Journal Club: T. Reichlin et al. Utility of Absolute and Relative Changes in Cardiac Troponin

Concentrations in the Early Diagnosis of Acute Myocardial Infarction. Circulation. 2011;124:136-145

Novel high-sensitivity Troponin AssaysEBM topic: ROC curvesSeptember 19st 2011

Farooq Khan MDCM PGY3 FRCP-EM

McGill University

Rohit Mohindra MDPGY1 FRCP-EM

McGill University

Causes of Troponin elevation in the absence of significant CAD

• SIRS/Sepsis (supply/demand)• Acute/chronic heart failure• Pulmonary embolism• Peri/myocarditis• ESRD• Cardiotoxic drugs• Infiltrative disorders• Recent defibrillation• Blunt myocardial contusion• Recent cardiac transplant

Early Diagnosis of Myocardial Infarction with Sensitive Cardiac Troponin Assays

Tobias Reichlin, et alN Engl J Med 2009; 361:858-867August 27, 2009

Sensitive Troponin I Assay in Early Diagnosis of Acute Myocardial InfarctionTill Keller, M.D., et alN Engl J Med 2009; 361:868-877August 27, 2009

Diagnosing Acute Coronary Syndromes, Biomerieux Diagnostics

Troponin I ELISA, Labmaster Ltd. Finland

ESC/ACCF/AHA/WHF Universal Definition of MI

• Detection of rise and/or fall of cardiac biomarkers (preferably troponin) with at least one value above the 99th percentile of the upper reference limit (URL) together with evidence of myocardial ischaemia with at least one of the following:

• Symptoms of ischaemia;• ECG changes indicative of new ischaemia (new ST-T

changes or new left bundle branch block [LBBB]);• Development of pathological Q waves in the ECG; • Imaging evidence of new loss of viable myocardium or

new regional wall motion abnormality.

Early Detection of disease | Biomarkers, Pictures of the future, Fall 2008

Box 1.

Babuin L , Jaffe A S CMAJ 2005;173:1191-1202

©2005 by Canadian Medical Association

Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarctionThe Joint European Society of Cardiology/ American College of Cardiology CommitteeJACC Volume 36, Issue 3, Sept 2000

T. Reichlin et al. Utility of Absolute and Relative Changes in Cardiac

Troponin Concentrations in the Early Diagnosis of AcuteMyocardial Infarction. Circulation. 2011;124:136-145.

What is the diagnostic dilemma?

• As stated by the authors? • But also implied ... ?

How did they decide to study this question?

• Type of study?• Inclusion/Exclusion criteria?

Does it seem appropriate?

Where the results of the study valid?

• How many patients enrolled?• Followed?

Any differences between AMI and non-AMI patients?

• Is this important?• Why?

What was the reference standard ?

• Was this appropriate? • Was there blinding?

Was the end-point reasonable?

Was the diagnostic test evaluated in an appropriate spectrum of patients ?

• As well, was there an second, independent validation of the results?

Was the reference standard applied regardless of the result of the

diagnostic test?

• Why is this important?

Was the decision to perform the diagnostic test influenced by the result of the

reference standard?

• How could this affect the results?

Conclusion: Are the results valid?

But now ... are they clinically important?

• How will we determine this?

First. What is a ROC?

MissesHits

HitsySensitivit

alarmsFalserejectionsCorrect

rejectionsCorrectySpecificit

__

_

http://www-psych.stanford.edu/~lera/psych115s/notes/signal/

Next: don’t forget the likelihood ratio

Was there confounding?

• If so, did the authors address this?

Was there confounding?

What does “tropinin negative” mean, based on the results?

• What population might this important in?

Case Study

• 57 year old male • Brought by EMS from work• CC: severe chest pain since 7am

Hx + PEx

• Severe retrosternal chest pain since 7am

• Radiates to left shoulder and jaw

• No change with position• Past Hx of smoking• On Lipitor for past year

• Vitals: HR 110, RR 20, BP 110/50, SpO2 97% Gluc 7.2 GCS 15

• Looks pale diaphoretic• Heart sounds normal• Chest clear• Abdomen soft, non-

tender

Investigations & Management?

Results of Investigations

• CBC – N• Lytes, Cr – N • Troponin #1 = “negative” < 0.010 μg/L• EKG – Sinus tachycardia • CXR – no significant pathology seen

Now what?

Sensitive cTn

• Baseline sensitive troponin is 0.015 μg/L • Next sensitive troponin is 0.030 μg/L at 2

hours• What is your decision now?

How does this compare what is currently available?

Swiss Med Wkly. 2011;141:w13202

Can we conclude that the results from the study are clinically important?

Finally, can we apply these results to our patients?

Photo Credit: Pierre Obendrauf , The Gazette

Are we able to estimate our pre-test probability for disease?

• Are the study patients similar to our own?• Have the disease possibilities or probabilities

have changed since the evidence was gathered from the study?

Would the consequences of the test help your patient?

Will the resulting post-test probabilities affect your management and help your

patient?

• Could it move you across a test-treatment threshold?

• Would your patient be a willing partner in carrying it out?

Is the diagnostic test available, affordable, accurate, and precise in

our setting?

• Is the cost of the new technology worth the benefit of early detection?

Is this practice changing for us?