Troponins: a selective review…

July 4th, 2002

ECG/Lab rounds

Rob Hall PGY3

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

CONTEXT

• 45yo male + intermittent chest pain

• Troponin < 0.03 at……..– 2hr– 4hr– 6hr– 10hr

• When is maximal sensitivity reached?

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)

EBELL 2000

01020

3040

5060

7080

90100

0 2hr 4hr 6hr 8hr 10hr 12hr

0.10.23-D Column 3

EBELL 2000

• Problems– Were the exact same assays used?– ? Methodology of combining data from several

studies?

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

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?

Troponin +ve and CKMB -ve

• Troponin is released from reversible ischemia of myocardial cells

• UNSTABLE ANGINA

• Troponin is released from microinfarction (irreversible)

• MYOCARDIAL INFARCTION

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

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

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

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

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

CHRONIC RENAL FAILURE butNOT 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

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

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

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 < 90, cardiogenic shock, ventilated patients,

documented CAD, CHF, CM, Scr > 150

TROPONIN andPULMONARY 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

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