Ischaemic heart disease

IHD

▪ Ischaemia: insufficient blood supply (oxygen and nutrients supply), due to CAD or increased demand of oxygen or nutrients that can’t be satisfied.

The cardiac muscle of the myocardium doesn’t extract oxygen and nutrients from the blood that is flowing through the atrium into the ventricles. Heart muscle cells depend on its own blood supply via the coronary arteries

Coronary circulation

• left coronary arteries divide into two branches

• the bigger the artery that is affected the worse the ischaemia

Ischaemic heart disease causes

Reduction of blood supply

• Atherosclerosis

• Embolus

• Vessel inflammation

• Vasospasm of coronary arteries

Increased demand

• tachycardia

• left ventricle hypertrophy - ventricle wall becomes thicker so more and bigger cells require oxygen

• exertion due to exercise

Atherosclerosis

• Formation of plaque in the coronary arteries reduces the vessel lumen and therefore the blood flow

Modifiable and non-modifiable risk factors

Modifiable

• hypercholesterolaemia

• HT

• diabetes

• diet

• sedentarism

• obesity

• smoking

• alcohol

• stress

Non - modifiable

• age

• genetics

• gender

• ethnicity

IHD classification

Angina (angina pectoris)

• Partial reduction in the blood flow

• Stable or unstable

• usually does not result in permanent damage of the myocardium

Myocardial infarction - heart attack

• prolonged or complete blockage of the blood flow

• necrosis of cardiac muscle cells and replaced by scar formation which is more fibrous so cannot pump

• permanent damage

• heart function becomes reduced

Symptoms depend on rate at which blood flow is reduced

STEMI AND NSTEMI are prolonged ischaemia or full blockage of the blood flow - cardiac muscle cells die

IHD - Stable angina

• Atheroma in coronary artery reducing the blood flow

• Stable: plaque with fibrous cap that prevents rupture

• flow is reduced but nothing else happens

• No ECG changes

• Intense chest paint

  • Physical exertion - increased demand of oxygen

  • Emotional stress - increased demand of oxygen

• symptoms relieved by rest

IHD – Unstable angina

• Rupture of the surface of an atheroma → platelet plug & thrombus formation. Break in lining causes haemostasis

• Unstable: unpredictable, fast progression, can happen at any time regardless if there is oxygen demand or not

• Normal ECG or subtle changes

• Intense chest paint

  • Mild exercise

  • At rest

• Symptoms not relieved by rest

• urgent treatment

  • avoid progression to MI

IHD - STEMI AND NSTEMI

• Rupture of the surface of an atheroma (both are usually a consequence of atherosclerotic plaque that breaks from the vessel) → platelet plug & thrombus formation

• Cardiac muscle cells die: MI (myocardial infarction) → troponin

• MI can also happen as a result of coronary artery dissection, for e.g. in accident or dure to spasm because of cocaine consumption or emotional stress

• if troponin is found then that means cardiac cells are dying

IHD - Molecular mechanisms of MI

Cardiomyocytes are dependant on oxygen to produce ATP in a process called oxidative phosphorylation. If oxygen is reduced then cellular metabolism switches to glycolysis resulting in build up of lactate and hydrogen ions. This lowers the pH affecting ion transport in the cell membrane, leading to increased calcium ions in cell, oxidative stress due to the production of R.O.S. Furthermore contractility of cells is reduced as there is less ATP being formed. This induces cell death by apoptosis or necrosis. Therefore there is contractile dysfunction, decreasing CO, and potentially leading to death

Release of extracellular compounds can cause arrythmias and ventricular fibrillation which decrease CO, leading to death

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Graph

Troponin

As cardiac muscle cells die the plasma membrane becomes leaky, and release cellular components to the blood stream which can be measured and used as a diagnostic tool

• most important is troponin which is a protein that is essential for the contraction of cardiac muscle

• in angina troponin levels are normal as cells aren't dying

• cardiac protein, CKMB, myoglobin,

ECG

Stable angina pharmacology

• Symptom relief (pain)

  • Short-acting nitrates

• symptom control

  • beta blocker OR calcium channel blocker

  • beta blacker AND calcium channel blocker

  • alternative medications : long acting nitrates, nicorandil, ranolazine, ivabradine

  • beta blocker OR CCB AND alternative medications

• comorbidity treatment as plaque will not disappear but need to prevent unstable angina

  • HT

  • Diabetes

  • hyperlipidaemia

• preventative treatment

  • aspirin - deals with oxygen demand by either supplying more or decreasing demand

Nitrates

Short-acting nitrates: GTN spray (glyceryl trinitrate)

• Sublingual or transdermal administration

• Rapid onset and short action duration

Long acting nitrates : isosorbide mononitrate

• oral administration

• slower onset of action

Vasodilators : metabolised with release of nitric oxide that induces vasodilation, reduces cardiac work by reducing preload and afterload. Also improves circulation.

tolerance can be reversed by drug free period

Nitrates being metabolised activates guanine cyclase increasing formation of cGMP. This activates protein kinase G leading to cascade which causes phosphorylation of the myosin light chain

Beta-blockers (Beta1-adrenergic receptor blockers)

• Decrease cardiac output

• Β1-adrenergic receptors are primarily found in the heart

• Their activation increases the rate and strength of cardiac contraction

• Drugs inactivating them:

  • ↓ HR

  • ↓ Stroke volume

  • ↓ CO

  • therefore reducing oxygen demand at myocardium

Calcium channel blockers

• Decrease entry of Ca2+ into vascular smooth/cardiac muscle cells

• Calcium is needed for both cardiac and smooth muscle contraction

• Dihydropyridines: affect blood vessels, anti-hypertensive properties

  • ↓ contraction:

  • ↑ vasodilation, ↓Peripheral resistance

  • ↓ afterload, ↓ cardiac work

• Non - dihydropyridines: affect heart, anti- arrhythmic properties

  • decrease contraction and HR

  • Decrease oxygen demand

****mechanism of action

Nicorandil

• Nitrate like action

  • vasodilation

  • increased coronary flow

  • decreased preload

• k+ATP channel activator

  • hyperpolarisation of plasma membrane, reducing electrical activity

    • vasodilation

Ranolazine

• affects Sodium levels → ↓ intracellular calcium

• reduces force of contraction without affecting HR

• decreased myocardial oxygen demand

Ivabradine

• decreases heart rate through affecting ion channels in the sinoatrial node

• affects first step in conduction system of the heart

Aspirin

• antiplatelet drug

• irreversibly inhibits COX1

  • blocking formation of thromboxane A2 inhibiting formation platelet plug and therefore blood clots

Prophylactic treatment in angina: Prevention of clot formation

Other drugs

Fibrinolytic drugs

• Alteplase, streptokinase (plasminogen → plasmin: breaks down fibrin)

Antiplatelet drugs

• aspirin

• prasugrel/Clopidogrel/Ticagrelor (ADP-mediated platelet aggregation inhibitors, target the ADP receptor in platelets)

Others

• antithrombotic drugs (heparin)

• analgesics (morphine) for pain

Secondary prevention

Dual antiplatelet therapy

• Aspirin + Clopidogrel/Prasugrel/Ticagrelor

Beta blocker

ACE inhibitor

Statin

PPI

GTN spray