9. Acute Coronary Syndrome Flashcards
Define acute coronary syndrome
Set of signs + symptoms/conditions brought on by decreased blood flow in coronary arteries to heart muscle
Describe the hearts blood supply
Heart requires blood to supply O2
Coronary arteries supply blood to heart muscle
Describe the pathophysiology + complications of coronary artery disease
Build up of cholesterol + calcium on walls of blood vessel forms plaques (atheroma)
- process = atherosclerosis
The plaques narrow the lumen + reduce blood supply to the heart muscle = ischemia
Plaques can rupture leading to formation of clots (thrombus) which block the vessel
- complete lack of blood supply to heart = infarction leading to muscle death
How is an MI classified?
MI is currently classified according to WHO criteria
2/3 of;
- ischemic symptoms
- ECG changes
- increased serum biomarkers
What is the typical patient work up in ED for ACS?
ACS symptoms lead to an initial ECG;
- ST elevation/new left bundle branch block = start immediate treatment
- no ST elevation = still undifferentiated from unstable angina
Cardiac markers are used to differentiate MI and unstable angina but take longer
What are the clinical features of ACS?
Chest pain is most common; - radiating to left should/left angle of jaw - crushing/central Nausea + vomiting Breathlessness (dyspnea) Dyspepsia Others; atypical presentation (no pain) - common in women, elderly, DM
What proportions of chest pain patients are diagnosed with MI?
Only a small proportion; STEMI 10% NSTEMI 10% Unstable angina 14% Other/non-AMI 66%
What are the 3 clinical manifestations commonly associated with ACS?
- STEMI
- NSTEMI
- Unstable angina
Classified by ECG appearance + cardiac markers
What is the difference between ischemia +infarction? How does this relate to cardiac biomarkers?
Ischemia = only symptoms + reversible muscle damage Infarction = muscle death, irreversible damage
Cardiac enzymes + macromolecules used as markers are only released on cell death = markers of myocardial injury
What are ideal characteristics of a cardiac biomarker?
Diagnostically;
- high sensitivity (detect MI)
- high specificity (absent in non-cardiac injury)
- rapid release to detectable concentration
- long t1/2
- correlates efficiently with extent of MI
Analytically;
- high sensitivity (lower detect limit)
- high specificity (less interference)
- easy
- inexpensive
- rapid
List the types of cardiac markers used
Diagnostic markers;
ENZYME;
- creatine kinase (CK) + subforms
- lactic dehydrogenase
PROTEIN;
- troponin
- myoglobin
- fatty acid binding protein
Prognostic + risk stratification markers;
- CRP (acute phase protein - inflamm)
- MPO (myeloperoxidase - coronary art disease)
- homocysteine (risk of future CVD)
- troponin
Describe troponin + its relevance as a cardiac biomarker
Tpn is a complex of 3 regulatory proteins;
- TpnC
- TpnI
- TpnT
It is integral to muscle contraction in skeletal + cardiac muscle (not smooth);
- different types in each
- skeletal TnC subunit = 4x Ca+ binding sites
- cardiac TnC subunit = 3x Ca+ binding sites
Tpn subunits are used as cardiac biomarkers;
- TpnI + T used
- TpnI is more specific as some TpnT in skeletal muscle
How does troponin level change during cardiac injury?
Damage to cardiac muscle releases Tpn;
- levels raise 3-12hrs after onset of chest pain
- levels peak 12-24hr
Elevations in TpnI + T can persist for up to 10 days post-MI
- good for retrospective diagnosis of AMI
Detectable levels indicate chronic disease even if not an AMI
Describe the use of TpnI as a cardiac biomarker
TpnI has only 1 isoform - cardiac isoform found only in cardiac muscle
Highly bound to tropomyosin complex in sarcomere
<5% in cytosol
N, C terminus + central portion;
- different Abs measure different terminus (6 assays)
- strong binding to TpnC subunit may affect measurement
- also affected by other protein kinases + fibrinogen levels
Describe the use of TpnT as a cardiac biomarker
TpnT has 4 isoforms: fetal skeletal tissue + cardiac tpn isoform is used
Muscle injury, myopathy + renal failure cause reexpression of cTnT in muscles
- possible false positive with 1st gen assay in renal failure
Patent regulations mean only 1 manufacturer for assays
- Roche Boeringer
List the different generations of Tpn assays used for cardiac biomarker testing
ASSAYS; 1st gen; - 1 step ELISA - 2% cross reactivity to skTnT - detection limit: 0.04ug/L
2nd gen;
- no cross reactivity to skTnT
- linearity problems
- detection limit: 0.0123ug/L
3rd gen;
- higher level of precision at lower end
- detection limit: <0.01ug/L
4th gen;
- detection limit: 0.028ug/L (10%CV)
5th gen;
- high sensitivity assays
Describe the 2 big turning points in Tpn assay use for cardiac assessment
In 2000: 1st Tpn assays replaced cardiac marker panels (CK, CKMB, myoglobin) for routine use
- specific for myocardial injury measured >=12h after onset of chest pain
- limitation: poor sensitivity in 1st few hours after onset
In 2007: worldwide task force recommended use of high sensitivity Tpn assay for cardiac assessment
- requires assay to detect hs-Tn at the 99th %ile of an apparently healthy reference population with 10% variability
This led to a change in the definition of MI to hs-Tn >99th %ile (hsTnT >14ng/L) with clinical features
- LOD was lowered vs the previous TnI std
Describe the hsTnT assay now in use
Allows detection of cTnT at 99th %ile of ref pop with 10% CV
- LOD: 0.002ug/L or 2ng/L
Advantages;
- no significant interference with skTnT/I
- earlier detection for newly admitted patients
- earlier rule in/rule out of MI
- identifies more AMI patients
- improved risk stratification in AMI
- prediction of long term prognosis in non-ACS
Disadvantages;
- reduced clinical specificity
How has hs-Tpn changed treatment for NSTEMI patients?
NSTEMI guidelines 2011 by European Society of Cardiology (ESC) for acute chest pain;
- use hs-Tn upper limit of normal in combo with symptoms to determine if discharge, retest, ddx or invasive management required
2015 ESC released new guidelines for NSTEMI patients;
- advocate use of hs-Tpn assays in evaluating suspected ACS
- supports use of 1hr algorithm on basis of several multicentre prospective validation studies leading on from initial single centre pilot study
List the other causes of increased Tpn in absence of overt IHD
Congestive heart failure (acute + chronic)
Pulmonary embolism
Severe pulmonary hypertension
Rhabdomyolysis with cardiac injury
Inflammatory diseases e.g. myocarditis
Critically ill patients - esp respiratory failure, sepsis
Renal failure
Cardiac contusion or other trauma inc surgery, ablation, pacing, etc
Aortic dissection
Aortic valve disease
Hypertrophic cardiomyopathy
Tachy/bradyarrhythmias or heart block
Acute neuro disease inc stroke, subarachnoid hemorrhage
Drug toxicity/toxins
What other preanalytical factors affect a Tpn result?
Fibrin clots HAMA Abs Rheumatoid factor Macroimmune complexes Elevated ALP Hemolysis, lipemia, icterus Heparin
Describe CK + its use as a cardiac biomarker
Creatine Kinase = muscle enzyme present in different tissues + cells
Mainly in 3 isoforms (other than mitochondrial form);
- CKMM = sk muscle
- CKMB = cardiac
- CKBB = brain
Measured by lab photometry Total CK = CKMM + CKMB (BB not normally detected) - CKMB normally <10% of total - 10-30% = diagnostic of MI - >30% = macroenzymes + CKBB
CKMB raises 4-6 hours post infarct + reaches baseline again in 48 hours
- short time means useful in diag re-infarction (common in AMI pts)
- Tpn levels will not have dropped in time
