myocardial Ischaemia

what is coronary artery disease

• reduced blood flow of coronary arteries 

• most common cause is atherosclerosis → build up of fatty plaques in the coronary artery walls

what happens when fatty plaque deposists in the coronary arteries (atherosclerosis) → add on gizmo

• become narrowed → restricts blood supply to heart resulting in Non-ST elevation Acute Coronary Syndrome (NSTEACS)

• NSTEACS are divided into

  • chronic coronary syndrome

  • acute coronary syndrome

what is myocardial ischaemia

• when myocardial cells don’t receive enough blood (oxygen)

• there is an imbalance between myocardial blood (oxygen) supply and demand

• if demand exceeds supply → irreversible damage and myocardial tissue death

what is atherosclerosis

when fatty deposits build up in the arteries, which causes them to narrow

stages from normal to progressive coronary artery disease

• Damage to artery wall (caused by smoking, diabetes, hypertension etc) → inflammation and build up of fatty plaques (atheroma) in walls of coronary arteries

• If the plaque ruptures → platelet activation, aggregation and thrombus formation

• thrombus can break loose and travel to other part of body (embolus)

coronary artery disease when atherosclerosis occurs leads to…

ischaemic heart disease (coronary artery disease, and is divided into 

• chronic coronary syndromes (CCS) → people are ‘stable’, symptoms are controlled/asymptomatic 

• acute coronary syndromes (ACS) → people are not stable, symptomatic due to sudden reduction in blood flow to heart 

what are the disease consequences of ischaemic heart disease causing myocardial ischaemia

how to distinguish between clinical symptoms of myocardial ischaemia

• ECG → ST elevation, ST depression, T wave inversion

• troponin T/ troponin I → protein released from cardiac cells when damaged

what is stable angina slide 11

• crushing sensation in the chest caused by they have narrow blood vessel and reduced blood flow to the heart (ischaemic pain)

• chest pain, tightness, indigestion type pain

• Associated with effort (exercise, cold, excitement) à demand exceeds supply

• Relieved by rest or medications

• Short lived

• predictable and reproducible 

how is supply and demand affected in stable angina 

• only really a problem when in high demand for oxygen, but supply is really low

• can occur during intense exercise and stress

• stenosis → narrowing as a result of fatty plaque build up in coronary arteries 

• stenosis prevents increased supply

what is acute coronary syndrome and the different spectrum of conditions

describes a spectrum of clinical syndromes including

• unstable angina → normal, inverted T waves (ST depression), troponins are normal 

• non-ST elevation myocardial infarction (NSTEMI) → normal, inverted T waves (ST depression), roponins are elevated 

• ST elevation myocardial infarction (STEMI) → hyperacute T waves (ST elevation), troponins are elevated

caused by thrombosis, leading to acute occlusion of a coronary artery , presenting as the spectrum of clinical syndromes

what are the symptoms of acute coronary syndrome

• Severe pain – chest, jaw, neck, back

• Breathlessness

• Nausea and vomiting

• Light-headedness

• Sweating

can be unpredictable and acute in onset 

• For some people the first major sign is cardiac arrest

how does myocardial infarction develop 

• proceeds in ‘wavefront’ from subendocardium to subepicardium

• Eventually transmural infarct is produced (24 hours), and cell death occurs by coagulation necrosis

• Further changes take place over days and weeks

• Neutrophils enter the infarct → scar tissue is developed (granulation)

• Ventricular remodelling → ventricles change in size, shape, and function in response to damage or disease

what are the complications of myocardial infarction

• heart failure

• arrhythmias

  • ventricular ectopic beats

  • ventricular tachycardia

  • ventricular fibrillation

  • supraventricular tachycardia

  • heart block 

• intracardiac thrombus

• cardiac rupture

• pericarditis 

how is ischaemic heart disease diagnosed and investigated

• coronary angiography (invasive) → catheter passed up to heart and coronary arteries, dye is injected and X-rays are taken 

• imaging → via CT coronary angiogram, cardiac MRI, echocardiogram 

• electrocardiogram (ECG) → distinguishes between NSTEACS/STEMI

• clinical history → symptom assessment 

• troponin blood test → detects sign of damage to heart cells 

how is acute ST elevation myocardial infarction (STEMI) managed

primary percutaneous coronary intervention (PPCI)

• an emergency procedure that rapidly opens blocked coronary artery with a balloon and implants a stent to restore blood flow

• usual first line approach if accessible within specified timeframe from onset symptoms

thrombolyis

• using a "clot-busting" drug to dissolve blood clots, restoring blood flow

• usual approach if PPCI can’t be achieved within specified timeframe from onset of symptoms

medical management

• no intervention

• decision of risk vs benefit

what is Percutaneous Coronary Intervention (PCI)

balloon inserted to widen vessel and stent deployed 

what is coronary artery bypass graft (CABG)

open heart surgery where vessel removed from another part of body and grafted to either side of the blockage to divert blood flow 

what is thrombolysis

• dissolution of a blood clot

• Allows reperfusion of ischaemic region

• Limits infarction size and reduces complications

• Can be used within 12 hours after infarction

• Complications include bleeding (haemorrhagic stroke)

what is the management of Non-ST-Segment Elevation Acute Coronary Syndrome (NSTEACS)

medical management → angiogram test leads to two options

• percutaneous coronary intervention → if accessible within specified time frame from onset of symptoms

• coronary artery bypass grafting (CABG) → usual approach if severe disease of three coronary arteries

what are the types of acute coronary syndrome 

• Type 1: Caused by plaque rupture – most commonly seen

• Type 2: Oxygen supply-demand imbalance without atherosclerosis

• Type 3: Sudden death with MI Symptoms

• Type 4: MI associated with stenting

• Type 5: MI associated with bypass grafts

what is variant angina (prinzmetal/coronary artery spasm)

• vasospasms reduces supply

• occurs at rest

• there is no underlying coronary artery disease

what is the treatment for stable angina

anti anginal medicines 

• reduce heart rate (in order to reduce demand and cardiac work)

  • beta blockers

  • ivabradine

  • rate limiting calcium chanel blockers

• widen narrowed coronary arteries

  • Coronary artery dilation improves blood flow to heart

  • Vein dilation decreases preload, reducing cardiac work, lowers blood pressure

  • nitrates

  • calcium channel blockers

  • nicorandil 

• ranolazine

what are beta blockers

examples

• bisoprolol

• atenolol

mechanism 

• Beta-selective adrenoceptor blocking agent → blocks action of adrenaline and noradrenaline on heart → reduces heart rate and the hearts demand for oxygen

• Dose adjusted to resting heart rate of 60 bpm (provided blood pressure ok) or maximum target dose

• No preference on which betablocker (licenced)

• Also lowers BP

• can’t be used for patients with asthma 

what are rate-limiting calcium channel blockers 

examples

• verapamil 

• diltiazem (rate-limiting)

mechanism 

• Calcium channel blockers with both cardiac and vascular effects

• Reduce heart rate and therefore oxygen demand of the heart

• Reduce force of heart contraction (negative inotropic effect)

• Vasodilation

• Will also lower BP

• Avoid use with betablockers

what are dihydropyridine calcium channel blockers

examples

• amlodipine

• felodipine

mechanism

• Calcium channel blockers with predominantly vascular effects (vasodilation)

• don’t affect rate

• can be used with beta blockers

• Vasodilation

  • Coronary artery dilation improves blood flow to heart

  • vein dilation decreases preload, reducing cardiac work

what are nitrates 

examples

• glyceryl trinitrate (GTN)

• isosorbide mononitrate (ISMN), isosorbide dinitrate 

mechanism 

• vasodilation via the release of nitric oxide (NO) 

• Endogenous production of NO is impaired by coronary artery disease, nitrates provide an exogenous source of NO

• Side effects – some related to vasodilation eg reduced blood pressure, lightheadedness, headaches

how does vasodilation via the release of nitric oxide occur (use of nitrates)

• Organic nitrates are metabolised to release NO

• NO activates soluble guanylate cyclase (sGC)

• sGC forms cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP)

• cGMP activates Protein Kinase G (PKG)

• PKG dephosphorylates myosin light chains and promotes sequestration of intracellular Ca²⁺

• Vascular smooth muscle is relaxed

what are the forms of nitrates for angina

• GTN sublingual spray or tablets

  • for Acute angina attacks

  • Quick onset and short time of action

• ISMN tablets –taken daily.

• Intravenous

Chronic nitrate use produces tolerance → timing of doses is important

• Reasons for nitrate tolerance are not entirely known but likely to involve a physiologic compensation of   having high levels of nitric oxygen.

what is ivabradine

a pacemaker current inhibitor

mechanism

• Blocks the pacemaker sodium and potassium currents (I_f or ‘funny current’) that go through the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the heart that controls depolarization of the sinoatrial node reducing heart rate and therefore oxygen demand of the heart

• Doesn’t lower BP

• Sinus rhythm

• May cause visual disturbance due to retinal I_f

what is nicorandil

a vasodilator drug

mechanism 

• Combined NO donor and activator of K+ channels

• NO release leads elevation in cGMP and activation of K+ channels

• Effect is hyperpolarisation (K+ leaves cells) with coronary artery vasodilation and improved blood flow

• Side effect: ulceration → formation of a break in the skin or a mucous membrane, leading to a sore where tissue has broken down and disintegrate

what is ranolazine

for chronic angina

• Mechanism not fully understood:

  • Reduces the work of the heart by reducing the late sodium current in the cardiac action potential

  • Effect is a reduction in calcium entry which reduces wall tension and improves blood flow via the coronary arteries.

  • Reduce ionic imbalances that can occur in ischaemia

• Marketed as no change in HR or BP

• Drug interactions eg carbamazepine, clarithromycin, phenytoin

summary of treatment guidelines for anti anginals

what is the initial management for acute coronary syndromes (STEMI, NSTEMI, unstable angina)

• Medications to prevent further platelet aggregation → aspirin/ clopidogrel/ ticagrelor  (loading doses)

• Medicines to treat the pain → morphine is a vasodilator and reduces preload, and to a lesser extent afterload)

  • If ongoing chest pain then can give nitrates (usually GTN sublingual)

• If low oxygen saturations and breathless → can be given oxygen

• If nauseous → give antiemetic

what is the treatment for ST-elevation myocardial infarction (STEMI)

• Primary PCI or Thrombolysis → Antithrombin, glycoprotein IIb/IIIa antagonists

• If not suitable then manage as for NSTEACS

what is the treatment for NSETEMI/Unstable angina (NSTEACS)

antithrombin therapy → fondaparinux SC 2.5mg daily

summary of early management of STEMI

summary of early management treatment of NSETEMI/Unstable angina

what is the secondary prevention after acute coronary syndrome 

• antiplatelets 

• ACE inhibitors

• betablockers

• statins 

how are antiplatelets as secondary prevention after ACS

• Reduce platelet aggregation in ACS

• Dual antiplatelets for12 months following ACS or PCI then review (usually reduce to single antiplatelet)

• Bleeding risks with dual antiplatelets

  • To reduce the risk → co-prescribe PPIs for those at high risk on antiplatelets

Interaction between clopidogrel and omeprazole/esomeprazole MHRA alert → shouldn’t be co-prescribed

how are ACE inhibitors used as secondary prevention after ACS

• cardioprotective (preservation of the heart)

• Reduce afterload , improve ejection fraction, may improve endothelial function, limit remodelling and infarct expansion

• Reduce mortality

• need to titrate doses

mechanism on different lecture

how are betablockers used as secondary prevention after ACS

• Cardioprotective ((preservation of the heart))

• Reduce heart rate, prevent overworking of heart

• Reduce myocardial oxygen demand (prevent angina)

• Reduce incidence of arrythmias

• Some beneficial in reduced left ventricular dysfunction (see HF lectures)

• Reduce mortality

• need to titrate doses

how are statins used as secondary prevention after ACS

• High intensity

• e.g. Atorvastatin 80mg daily

• Effects additional to cholesterol lowering

• Can have effects on inflammation, thrombogenesis and the blood vessels

• Reduce mortality and further events

• Some side effects include rhabdomyolysis, liver effects , MHRA → rare myasthenia gravis

(mechanism of action in other lecture)

summary of medical management for secondary prevention

summary of cardiac rehabilitation and secondary prevention (NICE)

what is triple A + B + C for secodnary prevention