myocardial infarction: blood tests for diagnosis dr esmé hitchcock chemical pathologist
TRANSCRIPT
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