Myocardial Infarction: Blood tests for diagnosis Dr Esmé Hitchcock CHEMICAL 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 ProBNP Troponins CK-MB HomocysteineUs-CRPLipogram ApoB & A1

Acute Coronary Syndrome Incomplete occlusionComplete 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 I Troponin C Troponin T

Troponin release during MI I T I I T T T Bound Tn TIC I C T Free TnI (3-4%) Free TnT (6-8%) Cytoplasm Trop T 1d 2d 3d 4d 5d 12h 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 d 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: C I 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: Daubert et al. Vasc Health Risk Management 30 Jul 2010 Thygesen et al. EHJ 2010;31:

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:

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: 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:

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:

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