Acute Coronary Syndrome: Angina and MI

Question 1

What is coronary artery disease (CAD)?

Answer 1

Any vascular disorder that occludes, narrows, or obstructs the CA

Question 2

What is the most common cause of CA?

Answer 2

Atherosclerosis: can affect arteries anywhere in the body

Question 3

What is acute coronary syndrome (ACS)?

Answer 3

Conditions associated with sudden reduced blood flow to the heart (Angina pectoris (stable or unstable) and AMI)
*Largest single cause of death and the most common cause of sudden death

Question 4

What are the risk factors (modifiable and non-modifiable) for ACS?

Answer 4

Risk Factors: same as for hypertension and atherosclerosis
• Non-modifiable risk factors: advanced age, gender, family history, ethnicity (Indigenous Australians are 2.6 times more likely to die from coronary heart disease (CHD) and stroke).
• Modifiable risk factors: alcohol, dyslipidaemia, smoking and T2DM

Question 5

What is Dyslipidaemia ?

Answer 5

Abnormal concentrations of serum lipoproteins (cholesterol, triglycerides, HDL)
• Cholesterol: essential for the manufacture and repair of plasma membranes (steroid hormones)
• Lipoproteins: very low-density lipoproteins (VLDL), LDL and HDL. HDL are essential for endothelial repair and decrease the chance of thrombosis
*An increase in serum concentration of LDL or low levels of HDL is a strong indicator of coronary risk (CHD and stroke)

Question 6

How does cigarette smoking effect the risk of developing ACS?

Answer 6

Nicotine stimulates release of catecholamines and affects CV function - increases the HR, vascular resistance and BP
• Catecholamines: stimulate release of free fatty acids (increase LDL and decrease HDL) - linked to an increase in inflammatory markers (C-reactive protein (CRP)) = linked to CAD
*Risks associated with CAD may decrease up to 50% in the first 12 months after cessation of smoking

Question 7

How does diabetes mellitus effect the risk of developing ACS?

Answer 7

Affects CV function through production of ROS = alter vascular cell function:
• Endothelial damage through non-enzymatic glycosylation
• Decrease in nitric oxide (vasodilator)
• Stimulating release of endothelin (vasoconstrictor)
• Thickening of the vessel wall
• Increasing inflammation (cellular proliferation, sclerotic changes)
**DM causes dyslipidaemia due to an alteration of hepatic lipoprotein synthesis and an increase in LDL oxidation

Question 8

What is acute myocardial infarction (AMI)?

Answer 8

Necrosis of myocardial tissue resulting from an acute, sudden decrease in coronary blood flow usually from a thrombotic total occlusion
• ~30% of MIs are not preceded by any anginal symptoms and may be the first indication of significant CHD

Question 9

What is Non-STEMI?

Answer 9

Subendocardial infarct involves the inner 30-50% of the ventricle; usually occurs due to chronic hypoperfusion

Question 10

What is STEMI?

Answer 10

Transmural infarct involves the full ventricular wall thickness = acute occlusion of a CA
• STEMI heart attack occurs as a result of a complete blockage in a CA = high risk of mortality and morbidity (disability). When an artery is partially blocked, severely reducing blood flow, a non-STEMI heart attack may occur

Question 11

• Left anterior descending artery occlusion =
  
  • Right coronary artery proximal occlusion =
  • Circumflex artery occlusion =

Answer 11

• Left anterior descending artery occlusion = infarct of apical, anterior and anteroseptal walls of the left ventricle (anterior infarct)
  
  • Right coronary artery proximal occlusion = infarct of the posterior region of the left ventricle part of the interventricular septum (inferior infarct)
  • Circumflex artery occlusion = left lateral infarct

Question 12

What is the pathophysiology of MI?

Answer 12

• Inadequate supply of oxygen = hypoxia = stimulates anaerobic metabolism and decreases ATP production = increases lactic acid, pyruvate, H+ and low cellular pH
  
  • ^ stimulates the release of inflammatory mediators and ROS = changes to the sodium-potassium pump = intracellular accumulation of sodium and calcium, loss of potassium and release of lysosomal enzymes = alter membrane permeability
  • All of these changes alter membrane potential, cause cell lysis (death) and lead to arrhythmias and failure of contraction
  • Ischaemic myocytes release catecholamines = serious ANS dysfunction, an increase BGL, free fatty acids and glycerol

Question 13

What are the clinical manifestations of MI?

Answer 13

• A classic AMI presents with severe, ‘crushing’ central pain, radiation to the left arm, jaw and through to the back
  
  • Usually associated with profound apprehension (some may present with mild or absent pain)
  • Typically, pain is sudden in onset, persisting for at least 15-20 minutes, unrelieved by rest or sublingual nitrates
  • Syncope, sweating, clamminess, nausea/vomiting, dyspnoea, mild pyrexia (>38°C) may persist for 2-3 days
  • Ventricular arrhythmia (tachycardia/fibrillation) in the first 24 hours which is linked to sudden death

Question 14

What are the diagnostics associated with MI?

Answer 14

• ECG: recording of cardiac electrical activity; does not directly measure the mechanical function of the heart (acute PO may have a normal ECG; abnormal ECG may have normal cardiac function)
  
  • Biochemical (cardiac) markers: troponin, CRP, CK
  • Chest X-ray: rule out other causes of pain

Question 15

Creatinine Kinase (as a biochemical marker)

Answer 15

• Ratio of Creatinine Kinase (CK) total: CK-MB
  
  • Determine probability of further infarctions after a recent infarction
  • Early rise in this ratio may be indicative of successful reperfusion
  • Assayed 0, 6, 12, 18 and 24 hours after prolonged pain and if further episodes

Question 16

Troponin (as a biochemical marker)

Answer 16

• Specific to cardiac muscle; located on the thin filament of contractile apparatus in both skeletal and cardiac muscle
• ‘Gold standard’ for serum evaluation of MI/ischaemia; using highly sensitive assays
• Early marker for MI (2-4 hr after onset of symptoms) and stays elevated in the blood for over a week post infarct
• Recommended timing of samples: obtain the 1st sample at admission to ED and the 2nd sample at 2-3 hours later
○ Normal troponin results (0 and 3 hours after admission to ED) do not rule out ACS where there is a high clinical suspicion
○ Further troponin testing may be indicated at 6 or 12 hours post-admission to the ED
○ Slowly evolving AMIs may not elevate troponin until >12 hours after admission

Question 17

What is the immediate assessment of chest pain?

Answer 17

• ABCD
• Brief Hx and physical assessment - Vitals and Oxygen saturation
• ECG, CXR
• Blood: biochemical markers, U&E, FBE, coagulation
*STEMI: thrombolysis or angioplasty - Time from onset of chest pain (<6 h, max of 12 h); recent surgery/ cerebrovascular accident (CVA)
*Non-STEMI: pharmacological/ medical management

Question 18

What is the immediate treatment of chest pain?

Answer 18

morphine,oxygen,nitrates,aspirin, rest and reassurance

Question 19

Thrombolytic agents used in MI

Answer 19

• Convert plasminogen to plasmin = catalyses or breaks down the fibrin clot = help dissolve the embolus but can cause bleeding and transient hypotension
• Contraindicated for use in active bleeding, recent major surgery (<1 month), trauma, risk of intracranial haemorrhage, history of stroke (haemorrhage) or ischaemic stroke within a year, intracranial neoplasm and intracranial aneurysm
• Administered IV within 12 hours of onset of chest pain; typically in ED and followed up by transfer to the cardiac care unit (CCU)
• Post-administration: avoid IM injections and other invasive procedures during IV therapy; monitor for hypotension and treat accordingly. If severe bleeding occurs, stop the infusion and treat
E.g. alteplase and reteplase (-ase)

Question 20

Antiplatelets used in MI

Answer 20

• Inhibit platelet aggregation = reduce risk of clot formation on stent
  
  • Aspirin: low dose standard therapy; inhibit platelet aggregation by irreversibly inhibiting COX
  • Clopidogrel: binds to the platelet P2Y12 receptor and inhibits platelet aggregation
  • All have side effects including bleeding and thrombocytopenia

Question 21

Anticoagulants used in MI

Answer 21

Heparin, Warfarin, Rivaroxaban

Question 22

Heparin

Answer 22

forms a complex with antithrombin III, inactivates clotting factors IIa (thrombin) and Xa to prevent further clots (does not dissolve current clots)
• Low-molecular-weight heparin (LMWH) and danaparoid have a much greater effect on factor Xa than on thrombin
• Danaparoid is a more selective inhibitor of factor Xa than LMWHs
• High dose for treatment and lose dose for prevention
• Adverse effects: bleeding, bruising and pain at injection site, hyperkalaemia, mild reversible thrombocytopenia (not necessarily indicate increased risk for severe thrombocytopenia)
• Monitor activated partial thromboplastin time (aPTT) aiming for levels around 1.5-2.5 times more than the normal measurement. Measure ~6 hours after a bolus dose and then adjust for IV infusion
• LMWH (no need to monitor aPPT) are smaller in size and have the same anticoagulant activity (affect only factor Xa)
○ Adverse effects: haemorrhage, gut-bleeding, bruising and pain at the injection site

Clinical considerations include:
	• Standard heparin: monitor aPTT (normal 25-40 sec)
	• LMWH: longer half-life, safer and no need to monitor aPTT
	• Report signs of bleeding

Question 23

Warfarin

Answer 23

• Inhibits epoxide reductase = depleting vitamin K from the liver = interfering with hepatic synthesis of vitamin K-dependent clotting factors X, IX, VII and II = prevent a new thrombus forming
  
  • Loading dose of 5-10 mg for two days = then adjusted according to the International Normalised Ratio (INR) test. The daily maintenance dose range is 1-10 mg
  • Interacts with herbal medicines, excessive amounts of green leafy vegetables and numerous other drugs
  • Adverse effects: bleeding; alopecia (rare), fever, rash and hepatic dysfunction

Question 24

Rivaroxaban: (Orally)

Answer 24

• Overtaking warfarin in younger patients with AF, acute VTE and prevention
• Includes selective inhibition of Xa = blocking thrombin production and formation (no human data for pregnancy)
Adverse effects: bleeding, itch, peripheral oedema and muscle spasm

Question 25

Explain a Percutaneous transluminal coronary angioplasty (PTCA)

Answer 25

STENTING
• Percutaneous insertion of a miniature balloon and stent via a guide wire into the atheromatous coronary artery (may be performed on two or more arteries)
• Intracoronary stenting is commonly performed to reduce closure and maintain vessel patency post-plasty
**Must be faithful to post-plasty medications such as antiplatelets and statins

Question 26

What is a Coronary Artery Bypass Graft Surgery (CABG)?

Answer 26

• Anastomosis of a grafted blood vessel on to native CAs, bypassing atheromatous narrowing
• Donor graft vessels are taken from the internal mammary artery or radial artery
• Requires sternal opening, with the patient’s circulatory function usually supported by a ‘cardiopulmonary bypass’ machine

Question 27

What are some significant tests and studies regarding MI?

Answer 27

Echocardiography:
• Used in STEMI = provide information on the site and extent, complications of MI and ventricular function
• Used in atypical chest pain

Exercise Testing: increases the cardiac workload and is performed in controlled setting in the assessment of:
• ST/T wave changes
• HR and BP
• Symptoms and arrhythmias

Nuclear Medicine Studies:
Myocardial perfusion imaging (MPI): single-photon emission computerised tomography (SPECT) and positron emission tomography (PET). They use a radioactive substance called a tracer: Thallium-201 &Technetium-99m

Question 28

• Complications of MI (STEMI and NSTEMI) usually occur within – hours but complications may occur anytime in the first week (3)

Answer 28

Complications of MI (STEMI and NSTEMI) usually occur within 24 hours but complications may occur anytime in the first week:
• Cardiogenic shock (inadequate tissue perfusion due to cardiac dysfunction)
• Acute heart failure (acute damage of the heart to the point that it’s unable to supply enough blood to the organs of the body)
• Right ventricular infarction (atherosclerotic proximal occlusion of the right coronary artery)

Question 29

What is angina pectoris?

Answer 29

Transient chest discomfort
• Occurs as a result of reversible MI (50% of the lumen occluded)
○ Typically induced by increased myocardial oxygen demand during exercise, stress and environmental extremes
○ Inadequate coronary blood flow causes hypoxia - causes a build-up of lactic acid, potassium and inflammatory substances (kinins, adenosine) resulting in pain
• Most common type of heart disease in developed countries

Question 30

What is stable angina?

Answer 30

visceral pain arising from the autonomic fibres at the level of C8-T4
• Can be induced by factors which increase myocardial oxygen demand: exercise, stress, temperature extremes (cold) and large meals

Question 31

What are the clinical manifestations of stable angina?

Answer 31

○ Characteristic dull central pain/ pressure/ tightness/ discomfort in the chest, with or without radiation to lower jaw, neck and arms (left > right side)
○ Dyspnoea, diaphoresis, light-headedness, palpitations and nausea can occur
○ Pale and anxious and the pain subsides with rest nitrates in 5-10 minutes

Question 32

What is Prinzmetal Angina?

Answer 32

(Coronary Spasm): usually reversible myocardial ischaemia that occurs unpredictably and most commonly at rest (night)
• Chest pain is erratic in onset
• Caused by vasospasms of one or more major CAs with or without associated atherosclerosis
• *Pathology is not well understood: altered Ca2+ channel function in the arterial smooth muscle; endothelial dysfunction (5-hydroxytryptamine (5-HT), histamine, endothelin, thromboxane); SNS hyperactivity; decreased NO activity, elevated serum CRP and IL-6 levels

Question 33

What is silent ischemia?

Answer 33

episodes of myocardial ischaemia without chest pain or with non-specific symptoms (fatigue, shortness of breath)
• May occur in patients who have episodes of symptomatic angina or in individuals during mental stress
• More common in females
• Pathology is poorly understood; could possibly relate to dysfunction in the sympathetic afferent nerve fibres supplying the myocardium (more prevalent in people with DM). Screening for silent ischaemia can be completed using nuclear medicine studies

Question 34

What is unstable angina?

Answer 34

‘pre-infarction’ or ‘crescendo angina’
• Serious, intermediate state between stable angina and MI (MI is not necessarily inevitable - but may ensue unless advanced interventions occur
• Pathophysiology and the precise mechanism(s) is unknown
• Typically occurs near an occluded atherosclerotic vessel by either fibrous or a complicated plaque
• Precipitated by local vasoconstrictive factors (endothelin, thromboxane A2) = sub-intimal haemorrhage/platelet aggregation/thrombus formation/rupture/spasm

Question 35

What are the clinical manifestations of unstable angina?

Answer 35

• Significant worsening of usual anginal symptoms usually occurring on less exertion or occurring at rest
  
  • Change in severity of pain duration/radiation
  • May not be relieved by usual interventions i.e. GTN, rest or both
  • In some cases, it may first present as CHD

Question 36

What are the diagnostics of angina?

Answer 36

• Electrocardiogram (ECG)
• Chest X-ray
• Blood tests: creatine kinase myocardial band (CK-MB); troponin; full blood examination (FBE); urea and electrolytes (U&Es); fasting blood glucose (FPG) and lipids
• Echocardiogram
• Angiogram
• Exercise stress test

Question 37

What is the pharmacological aim for angina?

Answer 37

restore the imbalance between myocardial oxygen supply and demand
• In early AMI: restore myocardial oxygen supply
• Chronic management of CHD: reduce myocardial oxygen demand
• In acute care settings: oxygen administered and titrated to augment PaO2and SaO2and optimise oxygen delivery to the myocardium

Question 38

What is the management of stable angina?

Answer 38

• Aspirin andAnti-anginal therapy
• β-AdrenergicBlocker andBlood Pressure (ACEI)
• Cigarette smoking andCholesterol
• Diet andDiabetes
• Education andExercise

Question 39

What is chest pain management?

Answer 39

1. STOP activity
   
   2. Rest and lie down
   3. Take ½ - 1 GTN tab or 1 spray (under the tongue) and wait 5 minutes
   4. If no relief, take another ½ - 1 tablet/spray under the tongue and wait 5 minutes
   5. If still no relief, call an ambulance and state that you are experiencing prolonged chest pain
      
      6. If pain relieved with GTN <10 minutes, still seek medical review

Question 40

What is the use of aspirin and anti-anginal therapy?

Answer 40

Aspirin:
○ Used for prophylaxis at doses of 75-150 mg/day
○ Inhibit COX enzyme = reduce synthesis of thromboxane A2 (platelet stickiness and vasoconstriction) = inhibit platelet aggregation
○ Adverse effects: GI irritation, asymptomatic blood loss and increased bleeding time

Anti-Anginal Therapy:
○ Taken up by endothelial cells = smooth muscle relaxation and vasodilation (predominantly as a venodilator) = reduce venous return and preload = reduction in myocardial oxygen requirements
○ Dosage:
- Sublingual tablets: 300-600 mcg every 3-4 minutes; until pain is resolved, to a maximum of 1800 mcg – if no relief; call help/ambulance
- Lingual aerosol 400-800 mcg, repeat after 5 minutes, if necessary, to a maximum of 3 sprays.
- Transdermal patch for sustained release; angina prophylaxis.
○ Adverse effects: dizziness, headache, hypotension, flushing, tachycardia headache, flushing, palpitations, orthostatic hypotension, fainting and peripheral oedema. Concurrent alcohol use may also enhance orthostatic hypotension
E.g. glyceryl trinitrate, isosorbide dinitrate and isosorbide mononitrate

Question 41

What is the use of cardio-selective beta blockers and BP control medications?

Answer 41

Cardio-selective Beta 1-blockers:
○ Reduce frequency of angina, prolong exercise capacity and decrease the risk of adverse cardiac events and mortality
○ Competitively blocking beta-receptors in the heart, peripheral vasculature, bronchi, pancreas, uterus, kidney, brain and liver
○ Decrease the HR, alter conduction velocity, myocardial contractility and decrease CO
○ Common adverse effects: bradycardia, hypotension, orthostatic hypotension, transient worsening of HF, nausea, diarrhoea, bronchospasm, dyspnoea, cold extremities, exacerbation of Raynaud’s phenomenon, fatigue, dizziness, abnormal vision, and alteration of glucose and lipid metabolism
E.g. Atenolol (25-100 mg/day) and metoprolol (50-300 mg/day)

Blood Pressure Control:
○ ACE Inhibitors/second generation AT1 receptor blockers = prevent remodelling and reduce mortality following an AMI
○ Block conversion of angiotensin I to angiotensin II and inhibit the breakdown of bradykinin = reduce vasoconstriction, sodium retention and aldosterone release
○ Adverse effects: hypotension, headache, dizziness, cough, hyperkalaemia, fatigue, nausea and renal impairment
E.g. captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril and trandolapril

Question 42

How does cholesterol and cigarette smoking relate to angina managemnent?

Answer 42

Cigarette Smoking:
○ 5As framework for smoking cessation is a well-recognised behavioural strategy addressing a patient’s addiction. This can be used in conjunction with nicotine replacement therapy and possibly other forms of treatments

Cholesterol: (-statins)
○ Statins are the first line in lipid-lowering treatment (apart from diet) for the reduction of CVD risk
E.g. atorvastatin, rosuvastatin and simvastatin