1. Troponins: a selective review… July 4th, 2002 ECG/Lab rounds Rob Hall PGY3

2. What is Troponin? Regulatory protein (NOT enzyme) found on contractile apparatus of striated muscle Initiates sliding of thin and thick filaments Troponin C, T, I Cardiac and skeletal muscle forms are genetically different ----> assays use an antibody specific for cardiac form

3. CONTEXT 45yo male + intermittent chest pain Troponin < 0.03 at…….. –2hr –4hr –6hr –10hr When is maximal sensitivity reached?

4. EBELL June 2000 Systematic review of Troponins and MI Prospective studies Physician determining dx of AMI blinded AMI defined as per WHO criteria –History + ECG + CKMB Sensitivity reported from onset of pain (not presentation)

5. EBELL 2000

6. Problems –Were the exact same assays used? –? Methodology of combining data from several studies?

7. TROPONIN T AND SENSITIVITY Troponin should NOT determine disposition Sensitivity will depend on cutoffs for normal General Numbers to remember –6 -----------------> 60% sensitive –8 -----------------> 80% sensitive –10 -----------------> 90% sensitive

8. TROPONIN AND SPECIFICITY Why does troponin sensitivity max out at 90% –Gold Standard definition of AMI is based on Hx + ECG + CKMB What does the patient with +ve troponin and -ve CKMB represent?

9. Troponin +ve and CKMB -ve Troponin is released from reversible ischemia of myocardial cells UNSTABLE ANGINA Troponin is released from microinfarction (irreversible) MYOCARDIAL INFARCTION

10. Troponin +ve and CKMB -ve Unstable angina vs small MI? WHO CARES -------------> Troponin +ve and CKMB -ve do WORSE and thus should be treated aggressively

11. Troponin +ve and CKMB -ve Hamm NEJM 1997 Anhman NEJM 1996 FRISC (Eur Heart Journal 1997) FRISC (NEJM 2000) Anhman NEJM 2000 INCREASED RATES OF CV EVENTS AND MORTALITY AT 30 DAYS

12. Doesn’t really sound like ACS but Troponin +ve…... Myocarditis Pericarditis Severe CHF Hypertensive crisis Trauma Post arrythmias Post CV surgery Post angioplasty Post cardioversion Post CPR Infiltrative cardiomyopathy Cardiotoxic drugs (chemotherapy) RENAL FAILURE PULMONARY EMBOLISM

13. TROPONINS AND RENAL FAILURE Dialysis patient with CP and troponin 0.3 Troponins are elevated in dialysis patients Debate in the literature whether the troponin level is predictive of poor outcome Frankel 1995 –70% of CRF patients on dialysis will have troponin level > 0.1

14. TROPONINS AND RENAL FAILURE Why are troponin levels elevated? –Decreased clearance –Chronic ongoing ischemia/microinfarction –Uremic pericarditis –Re-expression of cTnT in muscles due to myopathy –UNKNOWN

15. CHRONIC RENAL FAILURE but NOT ON DIALYSIS Chest pain + Troponin 0.15 –Scr 150 –Scr 250 Frankel 1995 –Elevated troponins in 3/10 patients with Scr > 300 and no evidence of MI –Small, no long term follow up ESSENTIALLY UNKNOWN

16. CASE 75yo male, dementia Chest pain: ? Pressure ? Sharp ? Pleuritic Known CAD PE RF: immobilization in nursing home Exam not helpful (Sat 90% RA) ECG = sinus tach CXR clear Troponin = 0.2

17. TROPONIN and PULMONARY EMBOLISM Giannitsis, Circulation 2000 –56 Consecutive patients with PE –PE dx by angio, high probability V/Q, TEE –Troponin > 0.1 in 32% of patients with massive (hypotensive) or moderate-severe presentations (RV dysfunction on TEE) –No troponin elevation in small PE

18. TROPONIN and PULMONARY EMBOLISM Elevated Troponin in Submassive PE: Douketis, Arch Int Med Jan 2002 Prospective, N=24 PE dx by angio, high prob V/Q, or non- diagnostic V/Q + DVT on ultrasound Excluded –BP 150

19. TROPONIN and PULMONARY EMBOLISM Elevated Troponin in Submassive PE: Douketis, Arch Int Med Jan 2002 20% had elevated troponins > 0.4 Small study BUT ………… DON’T FORGET ABOUT PE IN CHEST PAIN AND +VE TROPONIN

20. TAKE HOME POINTS Sensitivity not great until 8 - 10 hrs Troponin +ve, CKMB -ve predicts poor outcomes There are many causes of a false +ve troponin Renal Failure: dialysis (? Non-dialysis pts) Pulmonary Embolism: big and small