Pathophysiology and treatment of Ischaemic heart disease

Question 1

list, in order of increasing severity, the types of acute coronary syndromes

Answer 1

1. stable angina
2. unstable angina
3. NSTEMI
4. STEMI

Question 2

How does stable angina develop

Answer 2

1. angina pain develops when there is increased demand in the setting of a stable athersclerotic plaque
2. the vessel is unable to dilate enough to allow adequate blood flow to meet the myocardial demand

Question 3

how does unstable angina occur

Answer 3

1. the plaque ruptures and a thrombus forms around the ruptured plaque, causing partial occlusion of the vessel

Question 4

how does an NSTEMI occur

Answer 4

1. the plaque rupture and thrombus formation causes partial occlusion to the vessel
2. results in injury and infarct to the subendocardial myocardium

Question 5

how does a STEMI occur

Answer 5

1. characterised by complete occlusion of the blood vessel lumen
2. results in transmural injury and infarct to the myocardium, which is reflected by ECG changes and a rise in troponin

Question 6

define ischaemic heart disease

Answer 6

narrowing of the lumen of the coronary arteries resulting in an imbalance between the supply of oxygen and the myocardial demand
- resulting in myocardial ischaemia and chest pain

Question 7

what are involved in the regulation of coronary blood flow

Answer 7

1. adenosine
2. beta agonists
3. acid
4. EDRF- nitric oxide
   - endothelium derived relaxing factor

Question 8

describe the process of atherogenesis

Answer 8

1. damage to endothelium- LDLs, tobacco smoke, diabetes, hypertension
2. activation of toll receptors initiate inflammatory response
3. monocytes drawn into intima by TNFa, MCP and VCAM-1, ICAM
4. LDLs enter the endothelium and become oxidised
5. monocytes mature into macrophages and engulf cholesterol and turn into foam cells and secrete other inflammatory mediators (IL-1, TGF)
6. attract and stimulate smooth muscles to proliferate
7. fatty streaks develop into soft plaques, then hard plaques
8. foam cells release tissue factor (thrombogenic)
9. necrotic core and lipid core also thrombogenic
10. thrombus that kills

Question 9

what determines when the plaque ruptures

Answer 9

the combination of the development of the plaque and the degree of inflammation

Question 10

give examples of risk factors of IHD

Answer 10

smoking, diabetes, hypertension, hypercholesterolaemia

- other potential markers that relate to cardiovascular risk (C reactive protein, Il-6)

Question 11

give examples of the causes of stable angina

Answer 11

1. atherosclerosis
2. hypotension
3. lung infection
4. valve problems
5. heart failure
6. anaemia

Question 12

what is Prinzmetals or invariant angina

Answer 12

1. spontaneous or irregular spasms of coronary vessels

2. mechanisms: stress/exercise, cold, cocaine, decongestants, triptans

Question 13

what are the symptoms of stable/prinzemetals angina

Answer 13

• pain
• tachycardia
• nausea and sweating

Question 14

how can angina be diagnosed

Answer 14

1. exercise ECG
2. echocardiography
3. coronary angiography

Question 15

how can angina be treated

Answer 15

1. mixture of drug therapy and non pharmacological intervention
   - reduce body weight, smoking and stress
2. drug treatment designed to decrease work done by the heart and increase blood supply
3. prevent progression of disease

Question 16

what is reflex tachycardia

Answer 16

1. side effect caused by treatment of stable angina
2. due to activation of sympathetic nervous system
   - if treatment causes reflex tachycardia, should look to block effects of sympathetic nervous system using a beta blocker
   - eg. bisoprolol.

Question 17

what do beta blockers inhibit

Answer 17

inhibit renin release from kidney and so inhibit RAAS

• decrease frequency and force of contraction
• so decrease cardiac output

Question 18

how do Ca2+ channel antagonists have an effect on cardiac workload

Answer 18

1. reduce frequency and force of contraction
2. increase dilation of arterioles
   - leading to reduced cardiac workload

Question 19

how can Calcium channel blockers reduce heart rate

Answer 19

can reduce heart rate by blocking L type channels in the SA and AV nodes

• this will slow the rate of depolarisation and therefore reduce the rate of action potential generation
• they also decrease the force of contraction of the ventricles by reducing calcium entry through L type channels

Question 20

what is ivabradine

Answer 20

blocks the pacemaker current (Ih/f) in the nodal tissue of the heart

Question 21

what are the side effects of ivabradine

Answer 21

phosphenes, blurred vision, dizziness

Question 22

what does a blockade of Ih/f result in

Answer 22

1. ivabradine will reduce Na+ entry through If channels and slow rate of depolarisation of the SA node cells
   - reducing firing frequency and therefore heart rate
   - won’t directly alter the force of contraction of the heart

Question 23

give examples of alternatives that can be used instead of ivabradine

Answer 23

1. long acting nitrates- isosorbide mononitrate
   - decrease preload
2. nicorandil
3. ranolazine

Question 24

what can be used for secondary prevention of IHD

Answer 24

1. aspirin- prevents platelet activation/aggregation
2. ACE inhibitors- useful for diabetics
3. statins- decreases inflammation and reduce cholesterol levels

Question 25

how can blood pressure be controlled

Answer 25

may be controlled by beta blocker/CCB or ACE inhibitor | - if not, add in additional agents as required

Question 26

what surgical interventions can be used in IHD

Answer 26

1. percutaneous transluminal angioplasty 2. coronary bypass graft 3. stents

Question 27

why are nitrates useful in treatment of stable angina

Answer 27

1. nitrates can dilate venous smooth muscle 2. this decreases end diastolic volume, reduces stroke volume and therefore cardiac workload 3. nitrates can also dilate some of the collateral coronary blood vessels 4. can also have an effect on the arterioles, decreasing total peripheral resistance - therefore decreasing after load and the work done by the heart

Question 28

what is the molecular mechanism by which cardiac selective calcium channel blockers are useful in treating angina

Answer 28

1. CCBs will slow the frequency of the heart beat by blocking L type channels in the SA node 2. they will also slow conduction velocity and increase the refractory period of AV nodal cells by blocking L type calcium channels - this reduces ventricular rate 3. they decrease the force of contraction of ventricular muscle by blocking L type calcium channels

Question 29

why are ACE inhibitors useful for secondary prevention

Answer 29

1. they decrease workload of the heart by: - dilating veins and reducing EDV and therefore decreasing stroke volume - dilating arterioles and reducing total peripheral resistance and therefore decreasing after load

Question 30

why are statins useful in treating stable angina

Answer 30

1. decrease serum LDL cholesterol 2. also have anti inflammatory actions 3. may decrease reactive oxygen species 4. improve NO production by the endothelium and so cause vasodilation

Question 31

why is ivabradine useful in treatment of angina

Answer 31

1. blocks If 2. slows the depolarisation of the nodal cells 3. reduces automaticity in the SA node 4. increases the refractory period in the AV node 5. reduces the work done by the heart

Question 32

why can a patient suffering a MI present with tachycardia, sweating and cold clammy skin

Answer 32

1. this is caused through a combination of anxiety brought on by the pain associated with an MI and also the response to a reduction in cardiac output and therefore blood pressure 2. in both cases, the sympathetic nervous system is activated either through anxiety or to try to maintain blood pressure in the face of decreased CO - leads to tachycardia as BP= CO X TPR

Question 33

why is morphine given as pain relief to someone having an MI

Answer 33

1. morphine will reduce the pain associated with the MI 2. this will decrease stress and anxiety and reduce the stimulation of the sympathetic nervous system 3. morphine can also dilate some coronary blood vessels - so has the ability to increase oxygen supply to the heart muscle

Question 34

why might you have pulmonary congestion if you are having an MI

Answer 34

1. reduced cardiac output will activate the sympathetic nervous system 2. this will increase EDV 3. weak left ventricle will not be able to clear all of the blood so it will back up in the atria 4. this increases the pressure in the pulmonary capillaries preventing fluid from being reabsorbed 5. this fluid passes into alveoli causing congestion