Pathophysiology of myocardial ischaemia and Acute Coronary Syndromes (ACS)

PATHOPHYSIOLOGY OF MYOCARDIAL ISCHAEMIA AND ACUTE CORONARY

SYNDROMES (ACS)Rick Allen

Acute coronary syndromes include: Unstable angina Acute myocardial infarction Sudden cardiac death

Basics of pathophysiology Stable atherosclerotic plaque unstable

atherothrombotic lesion Rupture, superficial erosion deep haemorrhage,

ulceration, fissuring. Change results in the formation of a thrombis

which causes partial or complete occlusion of the vessel

Angina Stable

↑ myocardial O2 demand > ability of stenosed coronary art. to deliver.

Due to ↑ physical activity, emotional excitement or ↑ workload.

Prinzmetal Caused by vasospasm. May be no/minor

athersclerotic presence Unstable

plaque rupture partially occlusive thrombosis + vasoconstriction severe but transient ↓ in coronary blood flow.

Thromboemboli can micro infarcts. Occurs with low exercise or at rest.

Angina The ischaemic episode can last from 15s

up to 15 minutes, meaning that no (/minimal?) myocyte necrosis occurs.

Myocardial Infarction Acute plaque change

platelet adherence to exposed collagen/necrotic plaque contents, combine to form microthrombi

platelets release mediators causing vasospasm

TF release act. Coagulation cascade, ↑ thrombus

occludes lumen.

Myocardial Infarction Other causes

Vasospasm : platelet loitering or cocaine use Emboli: from LA due to AF, left sided mural

thrombosis, infective endocarditis vegitation, right sided source via patent foramen ovale

Low systemic BP: e.g. shock, ↓ perfusion Vasculitis, vascular dissection Haematological issues like sickle cell causing

occlusion

Myocardial Infarction Reversible:

Aerobic metabolism stops no ATP production and accumulation of toxic metabolites (lactic acid)

Loss of contractility in 60 secs. This can cause death prior to the production of an infarct.

Irreversible: Leaky cell membrane intracellular

components leak into cardiac interstitium microvasculature and lymph.

>1hr, damage to microvasculature Permanent myocardium damage 2 - 4hrs.

Progression of Infarct Begins as subendocardial (dependent on

cause) and then moves as a wavefront transmurally

The inner 1/3 is the least perfused region and is therefore the most susceptible. Regionally isolated if thrombus is lysed early Circumferential in prolonged, severe ↓

systemic BP (shock + non-critical stenosis) Transmural infarct gives ST elevation,

subendcardial does not

Factors Determining Morphology

Location, severity, rate of development of coronary obstructions

Size of vascular bed perfused by occluded artery

Duration of occlusion Metabolic/O2 needs of myocardium at risk. Collateral vessels Presence, site, severity of vascular spasm HR, rhythm, blood oxygenation.

**Necrosis is complete in 6hrs, longer if collaterals are present**

Time Macroscopic features

Microscopic features

0-30mins None None30mins – 4hr None None… border fibres wavy?

4hrs – 12 hrs

(12 – 24 hrs)

Dark mottling Haemorrhage, oedema, early coagulative necrosis (wavy myofibrils, more space b/n cells, cells shrink and become more dense/ darker)

1 - 3 days Mottling with yellow-tan infarct centre

Neutrophil infiltration, coagulation necrosis (myofibrils lose nuclei)

3 - 7 days Hyperemic border, central yellow-tan softening

Macrophages performing phagocytosis at border. Dying neutrophils

10 – 14 days Red-gray infarct borders

Granulation tissue (angiogenesis + collagen)

2 – 8 weeks Grey-white scar, progressive from border to the core of infarct

↑ collagen deposition, ↓ cellularity

> 2 months Scarring complete Dense collagenous scar

Sudden Cardiac Death atherosclerotic lesion disrupted plaque

regional myocardial ischaemia fatal ventricular arrythmia

Can be the first clinical presentation of IHD AMI is the most common trigger for fatal

arrhythmias (e.g. VF, asystole)

Injury can affect the conduction system and create electrochemical cardiac instability.

Fatal arrhythmias are usually caused by electrical instability distant from the conduction system – arrythmogenic foci are often located adjacent to scars of old MI’s.

Non-atherosclerotic causes include

Pulmonary HTN Congenital abnormalities Aortic valve stenosis Mitral valve prolapsed Myocarditis Dilated or hypertrophic cardiomyopathy Cardiac hypertrophy Genetic (channel or proteins which assist

the channels functioning are faulty, often leading to long QT intervals.)

Dilation of Ventricles Dilated cardiomyopathy

Genetic Myocarditis (sometimes due to viruses) Alcohol and other toxins Childbirth (↑ volume?)

Ventricular remodelling Response to injury or changes in loading Adaptive

References Robbins and Cotran