ACUTE CORONARY SYNDROME


DEFINITION
Acute coronary syndromes are:
Unstable angina.
Non-STEMI.
STEMI.
- and additional Peri-op MI notes
See also
- preoperative cardiac assessment
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INCIDENCE
Most common killer in Western society.

Risk factors
Refer atherosclerosis.
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AETIOLOGY
Coronary artery disease
90% of patients with IHD have fixed obstructions
- most of these have at least one >75% cross-sectional lesion
--> most are in the first few cms of the LAD and LCX, and entire RCA
--> sometimes secondary epicardial branches are affected, eg diagonal, obtuse marginal.

Other causes
Rarely spasm or emboli
- refer angina pectoris card for rare causes.

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BIOLOGICAL BEHAVIOUR

Pathogenesis

ACS result from the rupture / ulceration of or haemorrhage into vulnerable unstable plaques.
--> exposes the highly thrombogenic fatty centre.
--> platelet adhesion, aggregation & activation
--> thrombus formation and vasospasm
Rupture may be initiated by adrenergic surge.
- unstable plaques are usually non-uniform, have a large soft core, many macrophages & a thin cap.
- often these are 50-75% lesions that have been previously asymptomatic, because:
--> bigger lesions tend to be occlusive so exposed to less mechanical stress
--> larger occlusions also promote greater collateral flow so are partially protective.
Which acute coronary syndrome results depends on nature and occlusiveness of thrombus.
- note that thrombi may also embolise.

Role of vasoconstriction
Vasoconstriction is stimulated at sites of atheroma & thrombus by:
- circulating adrenergics
- locally-released platelet contents
- impaired release of relaxing factors (surrounding endothelium is dysfunctional)
- surrounding perivascular inflammatory cells (eg mast cells) releasing mediators.

Thrombus Composition

Clotting cascade:
Extrinsic or intrinsic pathway activated.
Both activate Factor X -> Xa.
Xa activates IIa -> Thrombin.
Thrombin activates Fibrinogen -> Fibrin.

Clinicopathological correlation
Thrombin rich thrombi are 'jelly-like'.
- They sludge up artery, allowing only some blood to reach myocardium.
- Tend to cause Non-STEMIs.
- Using antifibrin drugs may actually promotes thrombin release.
Fibrin rich thrombi are 'rock-like'.
- If large, allow no blood to the myocardium.
- Cause STEMIs.
- Use antifibrin drugs on these.

Pathophysiology
Myocardium is obligate aerobic tissue.
Balance of supply vs demand.

Supply factors

Arterial saturations (fixed)
Coronary flow (in a normal heart, arteriolar tone changes to allow greater flow)
Myocardial O2 extraction (fixed at around 75%).
- remember the subendocardium is most at-risk of poor supply.

Demand Factors

Heart rate
Wall tension
Muscle mass
Myocardial contractility (inotropic state).

Natural History

Within seconds anaeorbic metabolism starts to produce noxious by-products
Within one minute there is marked loss of contractile function
In 20-40 minutes there is irreversible cell damage
- apoptosis plays a role in ischaemic myocardial cell death.
In 3-12 hours infarction is usually completing (longer if excellent collaterals present).
--> at any time arrhythmia may supervene.
--> during this time intervention is critical and successful.

Within 4 hrs, angiography shows thrombosed coronary in ~90% of cases
- by 12-24 hrs, this falls to 60%
--> hence some thrombus lysis or spasm relaxation naturally occurs.

Classification
Depending on the above factors, a spectrum of possible constituent diseases of the acute coronary syndromes.
Spectrum:
Unstable angina
- a disrupted plaque with superimposed thrombus and possibly vasospasm
Non-STEMI and STEMI.
- note that in most subendocardial infarcts (which may cross zones of coronary flow) there is reduction in coronary flow but no acute plaque disruption or superimposed thrombosis.
- although if a potential transmural is treated before completion, the subendocardium will be most affected.

Pathology
Transmural infarcts ecompass nearly the entire perfusion zone (apart from a 0.1mm rin of preserved myocardium)

Frequency of Infarct by Area:

40-50% LAD: anterior LV & apex, anterior septum.
30-40% RCA: inferior / posterior wall, post septum, RV occasionally
15-20% LCX: lateral LV except apex.

Evolution of a myocardial infarction:
Time
Gross Features
Microscopy
0 - 1/2hr
None
EM = swelling
1/2 - 4 hrs
None
EM = Sarcolemma disrupted
4 - 12 hrs
Some mottling
Coag necrosis starting, oedema, wavy fibres
12 - 24 hrs
Dark Mottling
Necrotic, pyknosis, neuts arriving.
1 - 3 days
Mottline and yellow-tan centre
Necrotic, no nuclei, neuts dense
3 - 7 days
Hyperaemic border, soft centre
Disintegrating, macrophages at borders
7 - 10 days
Yellow, tan and soft, red-tan margins
Necrosis eaten away, granulating margins
10 - 14 days
Red-gray depressed borders
Granulating & new vessels & collagen.
2 - 8 wks
Gray-white scar
More collagen, less cells
>2 months
Scar complete
Dense collagen scar
- triphenyltetrazolium chloride is a dye used to impart a colour to normal myocardium
--> it is very difficult otherwise to tell an acute infarct at autopsy.
- it is possible to age a scar once completely formed.

Effect of reperfusion
The infarct becomes haemorrhagic due to leaky injured vasculature.
Irreversibly-injured cells die with 'contraction-bands' as more calcium exposure after reperfusion.
- there is also some reperfusion injury from free radicals.

Ventricular remodelling
Both necrotic and normal myocardium undergo change:
- thinning, healing, hypertrophy, dilation.
- this adaptation can be counter-productive as it reduces EF, and can lead to aneurysm formation.

Complications of Infarction
- depend on site, size, thickness.
1. Contractile dysfunction & cardiogenic shock

2. Arrhythmia
3. Rupture

- of ventricle wall, septum or papillary muscles
4. Pericarditis
- fibrinous or fibrohaemorrhagic at day 2-3.
5. Infarct extension
6. Expansion
- the weak necrotic area can stretch, dilating the infarct region
7. Mural thrombus
- and thromboembolism
8. Ventricular aneurism (late)
- paradoxical bulging during systole
- lead to thrombi, arrhythmias, HF but rarely rupture.
9. Progressive late failure

--> overal mortality in first year is 30%
- then 3-4% per year amog survivors.
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MANIFESTATIONS
All are accompanied by angina.

MI Stats
(NB - older definition, so hard to relate to new understanding).
40% of patients die outside hospital.
- most die of arrhythmias.
Preventable deaths, if someone knew CPR / had defib available.
- 15% die in hospital.
- 10-15% more in first year.
- 2-5% each subsequent year.

Poor Prognostic Factors
Cardiac factors:
- left ventricular dysfunction.
- disease severity.
- extent of ischaemia at rest & with exercise.
Other factors:
- advanced age.
- congestive heart failure.
- diabetes.
- associated cerebral & peripheral vascular disease.
- renal dysfunction.
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INVESTIGATIONS
Goes together with management.
See troponin notes.
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MANAGEMENT

Immediate Tx
MONA greets all patients:
Morphine (+ Maxalon).
Oxygen.
Nitrates (release vasospasm around a 'hot' lesion, as well as decreasing preload).
Aspirin - 300mg chewed, stat.
Also insert a line, especially in case of arrhythmias.

Immediate investigations
Are crucial for Risk Stratification of these pts.
ECG.
- may be normal for first while
- t-waves peak in seconds
- ST changes occur in hours
- q waves take hours / days
- t-wave inversion takes hours / days
Trop T
- see cardiac markers for detail
More subtle stratification also must account for risk factors - eg diabetes, lipid profile, smoking &c.

Other Immediate Investigations
Full blood count.
Electrolytes - particularly K+
Lipids, glucose, creatinine, &c.

Classification

Theoretical basis
As above, thrombus composition determines extent of myocardial ischaemia.
And treatments further depend on this composition.
3 parts of a thrombus are possible targets:
--> Platelets - inhibited by aspirin.
--> Thrombin - broken down by heparin.
--> Fibrin - broken down by thrombolysis (tPA / strepkinase).
Hence thrombin rich clots get heparin, fibrin rich clots get thrombolysis.

Unstable angina
No trop rise
No ST elevation.
Possibly other ischaemic changes.

Non-STEMI
Trop +ve.
No ST elevation.
ECG - ischaemic changes.

STEMI
Trop +ve.
ST elevation.
1mm or more in 1 or more limb leads.
OR 2mm or more in 1 or more precordial limb leads.
OR new LBBB.

Management
Refer specific cards above.

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