Myocardial Infarction:Blood tests for diagnosis

Dr Esmé HitchcockCHEMICAL PATHOLOGIST

Myocardial Infarction

Oxygen starvation & cell death

of heart muscle, caused by

interrupted blood supply due to

occlusion of a coronary artery.

Occlusion of blood vessel

Atheroma

= Accumulation of cells, lipids and calcium in artery walls

Thrombosis

= Blood clot, obstructing blood flow

Atherothrombosis

Lab tests in Atherothrombosis

Lipid accumulation

Plaque destabilization

Rupture & Thrombosis

Ischaemia & Necrosis

Myocardial dysfunction

ProBNPTroponins

CK-MB

HomocysteineUs-CRPLipogram

ApoB & A1

Acute Coronary Syndrome

Incomplete occlusion Complete occlusion

Irreversible cell damage biochem markers

Unstable Angina

MI without ECG changes

MI with ECG changes

Biochemical markers

• Molecules released into blood from damaged heart tissue.

• Cardiac Markers:– CK-MB mass

– Troponin T or Troponin I– gold standard for detecting myocardial damage

CK-MB mass

• Muscle enzyme– Highest concentration in heart

– Small amounts in skeletal muscle

• Relative early marker– Starts to rise 3-6 h after MI

– Back to normal in 3-4 days

• Not entirely Cardiac Specific:– May rise with significant amount of skeletal muscle damage

Troponin

• Forms part of the protein complex that regulates muscle contraction.

Striated muscle

Muscle fibers

Myofibrils

Myofilaments

Thin filament

Troponin ITroponin C

Troponin T

Troponin release during MI

I

TI

IT

T

T

Bound Tn TIC

IC

T

Free TnI(3-4%)

Free TnT(6-8%)

Cytoplasm

Trop T

1d

2d 3d 4d 5d12h 14d

Decision limit

Trop I

Degradation of bound Tn complexes

I

T

Myocyte

Troponin I

• Highly Sensitive– Detects smaller amounts of

myocardial damage than CK-MB mass.– Starts to rise within 4 hours after

the event.

• Large diagnostic window period– Remains elevated 4 - 10d after AMI

• Unequalled Cardiac Specificity – Cardiac Tn differ completely from skeletal muscle

Tn. – Specific for myocardium, but not for ischaemia

• Troponin can also be raised by:CW Hamm. ESC Guidelines – EHJ 2011;32:2999-3054

CI

T

Nonthrombotic causes of Tn

• Demand ischaemia– Tachy- / bradyarrhythmias– LV hypertrophy– Hypotension / Hypertension– Hypovolaemia– Anaemia, GI bleed– Aortic dissection– Severe aortic valve disease– Coronary vasospasm– Stroke / Subarachnoid haemorrhage– Sepsis / Critically ill / ARDS– Cardiomyopathy

• Myocardial strain– Congestive heart failure– Pulm embolism– Pulm hypertension– COPD– Strenuous exercise

• Direct damage– Trauma / Surgery– Myocarditis, Pericarditis– Infiltrative disorders– ChemoRx / Toxins

• Other– Renal insufficiency– Burns >30% of body surface

Jeremias et al. Ann Intern Med 2005;142:786-791 Daubert et al. Vasc Health Risk Management 30 Jul 2010

Thygesen et al. EHJ 2010;31:2197-2206

False positives

• Analytical false positives– Interference

• Fibrin, cellular matter• Rheumatoid factor• Immune complexes (Macro-Tn)• Auto-antibodies• Heterophilic Ab

Jaffe et al. Cardiovasc Toxicol 2001;1:87-92 Roongsritong et al. Chest 2004;125:1877-84

Interpretation of Cardiac Markers

• Important to know time of onset of chest pain.• Consider other causes of raised levels.• Normal initial results do not exclude MI• Serial sampling required to confirm • Always to be interpreted in conjunction with clinical

picture and ECG findings– Troponin specific for heart, but not for ischaemia!

Agewall et al. Eur Heart Journal 2011;32:404-411

Troponin level

Criteria for diagnosis of MI

• Ischaemic symptoms• Characteristic ECG changes• Imaging evidence of viable myocardial loss• ID of intracoronary thrombus by angiography

Detection of rise &/or fall of biochemical markers of myocardial cell death, with at least one value above the upper reference limit and with at least one of the following:

In pts with characteristic ECG changes – Dx of AMI can be made and Rx initiated without biochemical marker results.

The term MI should be used when there is evidence of myocardial cell death in a clinical setting consistent with acute myocardial ischaemia.

Thygesen et al. Circulation. 2012;126:2020-2035

SA Consensus Development

• Many Non-ACS causes of raised Tn, therefore should not be interpreted in isolation. Dx requires:– Careful clinical evaluation, particularly chest pain characteristics– Risk assessment with GRACE- or TIMI risk score– Accurate ECG interpretation

• Dx of STEMI made by ECG. Rx should not be delayed until biomarker assay completed.

• Normal hs-Tn at 6h after onset of chest pain, rules out MI• Hs-Tn > WHO cut-off, rules in MI• Serial sampling 3h apart, to distinguish acute from chronic

cardiomyocyte damage• Algorithm - Dynamic change in Tn needed for Dx.

RM Jardine. – SA Heart J 2012;9:210-215

RM Jardine. – SA Heart J 2012;9:210-215

Thank you