ACS Flashcards
- What is acute coronary syndrome?
ACS is a spectrum of conditions including myocardial infarction with or without ST-segment-
elevation (STEMI or NSTEMI), and unstable angina.
- What causes ACS?
What causes ACS?
- Result from the formation of a thrombus of an atheromatous plaque in a coronary artery
- Presentation and management has similarities but also important differences.
- How can a diagnosis of ACS be made?
Clinical presentations, biochemical cardiac markers and ECG changes
What is STEMI caused by?
ASTEMIis generally caused by acompleteandpersistentblockage of the artery resulting in
myocardial necrosis with ST-segment elevation on ECG.
What is NSTEMI and unstable angina caused by?
In NSTEMI and unstable angina a partial or intermittent blockage of the artery occurs, which
usually results in myocardial necrosis in NSTEMI but not in unstable angina
- What causes myocardial ischaemia?
Results from imbalance in myocardial oxygen demand and supply.
What leads to an increased myocardial oxygen demand and what leads to a decreased myocardial supply?
Increased myocardial oxygen demand:
* increase in heart rate and ventricular contractility;
* Increase afterload and preload
* hypertension, high cardiac output (myocardial hypertrophy)
Decreased myocardial oxygen supply:
* reduced coronary blood flow and blood oxygen carrying capacity
* thrombosis, vasospasm
What is an atheroma and what does it consists of?
An accumulation of degenerative material in the tunica intima of artery walls (inner wall)
The material consists of:
Macrophage
Lipids such as cholesterol and fatty acids
Calcium deposits
Fibrous connective tissue
Explain the molecular mechanism of plaque formation in the artery./ Explain the process of plaque formation.
LDLs enter dysfunctional endothelium which causes three responses:
1. Causes the releases of inflammatory cytokines and growth factors which activates adhesion molecules (VCAM1) to attract leucocytes and monocytes into the cell
2. LDLs get engulfed by oxidised macrophages
Foam cell accumulates and smooth muscle cells proliferate causing the formation of plaque.
Inflammatory cell infiltration, smooth
muscle cell death through apoptosis, and matrix degradation through proteolysis (by matrix metalloproteinases- MMPs) generate a vulnerable plaque with a thin fibrous cap and a lipid- rich necrotic core. Plaque rupture can cause thrombosis which might be sufficient to cause vessel occlusion (or blockage).
How does fatty streak formation occur?
Foam cells eventually die propagating inflammatory cytokines which cause smooth muscle cells to proliferate and migrate. As the endothelium is dysfunctional it cannot release nitric oxide to prevent the proliferation of smooth muscle cells.
Explain the sequences in progression of atherosclerosis.
initial lesion
fatty streak
intermediate lesion
atheroma
fibroatheroma
Complicated lesion
What is the major difference between stable angina and unstable angina?
Stable angina - symptoms present on exertion but not at rest due to partially occluded artery. At rest flow although reduced by stenosis may be sufficient to serve cardiac oxygen needs
- Whilst in unstable angina the symptoms still occurs at rest. Angina of increasing severity, duration or frequency and occurring at rest or with a lesser degree of exertion
Exertion activates what pathway of the nervous system?
Sympathetic NS
What effect does exertion have on the SNS?
Exertion activates sympathetic nervous system, increasing:
* Heart rate
* Force of contraction
* Blood pressure
What are the key features of angina?
Myocardial oxygen consumption is increased during exertion
Demand > Supply = myocardial ischemia
Symptoms persist until oxygen balance restored
Detection usually by: ECG (depressed ST segment), exercise stress test, Holter monitor
What are the features of unstable angina (acute coronary syndrome)?
Angina of increasing severity occurring at rest
medical emergency
usually caused by fissures or disruption of atherosclerotic plaque. Thrombus forms at the site of fissure further obstructing lumen and blood flow
What is the rare form of angina found in young adults?
Variant (Prinzmetal) Angina
How can angina be diagnosed?
Diagnostic examination:
* Electrocardiogram
* Exercise stress test/ECG
* Cardiac scintigraphy using thallium-201, cold spots indicate area or injury
* Coronary angiography- most direct means of detection
What are the common ECG patterns associated with myocardial ischemia?
Subendocardial - St depression (downward sloping), ST depression (horizontal), T wave inversion
Transmural Ischemia - ST elevation
How can Angina be managed?
Lifestyle
-increased oily fish consumptions - contain Ogmega-3-oils which decrease triglycerides and therefore lower cholesterol
- 5 fruit and veg
- stop smoking - increases plaque in blood vessels
- limit alcohol consumption
- weight reduction if obese or overweight
Therapeutic drugs
- Organic Nitrates - symptomatic relief —Isosorbide mononitrate
- Betablockers - decreased heart workload –Bisoprolol
- Calcium antagonists -Amlodipine
antithrombotic
- Antiplatelets
- Anti-coagulants
What is the treatment for the following conditions: vasospasm, fixed stenosis, thrombosis,
high heart rate, increased afterload, and increased preload?
vasospasm: Calcium channel blockers, beta blockers, and nitrates
fixed stenosis: angioplasty, stents, Calcium channel blockers, beta blockers, and nitrates
thrombosis: thrombolytics and anti-coagulants
high heart rate: Calcium channel blockers, beta blockers,
increased afterload: Calcium channel blockers, beta blockers, and antihypertensive
increased preload: Calcium channel blockers, beta blockers and ranolazine
What is the drug therapy treatment for people with stable angina?
short acting nitrate for immediate relief of angina
An everyday drug from Calcium channel blockers or beta blockers
If that does not control the symptoms switch to whatever you did not give them or combine CCB with BB
When can organic nitrates (esters of nitric acid) be used and explain the pharmacodynamics of each nitrate?
Only effective for symptomatic relief
Sublingual glyceryl trinitrate: rapid symptomatic relief of angina, but its effect lasts only for
20 to 30 minutes (spray or tablet)
* transdermal GTN: linked to tolerance (therefore only wear 8 -12 hours/day)
* Isosorbide dinitrate is active sublingually; infrequent users; effect is slower in onset and
lasts for hours
* active metabolite Isosorbide mononitrate
* All prevent the pain from angina attacks, and decreases oesophageal spasms associated with
attacks
Explain the mechanism of action of organic nitrates
Mechanism of action of nitrates. Organic nitrates have the chemical structure RNO 2 . The nitro group is reduced to form NO in by a mitochondrial enzyme (aldehyde dehydrogenase-
2). Free nitrite is released, which is converted to NO. NO activates guanylyl cyclase (GC) by interacting with its heme group. Activated GC converts GTP to cGMP. cGMP activates a phosphatase which dephosphorylates myosin light chains, resulting in decreased interaction between actin & myosin filaments, and relaxation. cGMP is normally short lived due to metabolism by intracellular phosphodiesterase (PDE). Drugs such as sildenafil can inhibit
PDE, resulting in a potentially dangerous intensification of the vaso-relaxant effect of
nitrates.
Causes decreased venodilation which causes reduction in preload. This results in less myocardial work and therefore oxygen consumption.
Also reduces vasospasm in arteries
What contributes to the therapeutic effects of nitrates?
Which of the following is not a dihydropyridine: nifedipine, verapamil or amlodipine?
Verapamil as it is a non-dihydropyridine
Explain the mechanism of action of calcium channel blockers.
blocks calcium flux into the cell
Explain the rationale for antiplatelet therapy
Plaques represent thrombogenic surfaces and rupture of a plaque exposes collagen matrix
to which platelets bind and aggregate
- Activation of aggregated platelets leads to release of vasoactive agents, activation of the
coagulation cascade, and subsequent thrombus formation which can cause further
reduction in lumen size
- aspirin is used for antiplatelet therapy
What other considerations must we consider?
aspirin 75mg given to people with stable angina - take risk of bleeding and comorbidities.
ACE inhibitors for people with stable angina and diabetes (remember avoid in Black patients)
offer statins in line with cardiovascular disease
offer treatments for high blood pressure -antihypertensive
What does NICE guideline recommend if therapy is contraindicated/ resistance to therapy?
give long acting nitrate or ivabradine, or ranozaline, or nicorandil
How does Ivabradine work?
Slows the heart rate by reducing cardiac pacemaker activity and allowing more blood to flow into the myocardium.
negative chronotropic (affect the rate at which the cardiac muscle fibers contract) drug with no effect inotropic effect (does not affect the amount of force that the cardiac fibers contract with).
How does nicorandil work?
has a nitrate vasodilator effect and is given if GTN is not
dilates the large coronary arteries
How does ranolazine work?
Inhibits inward NA current.
Prevents diastolic stiffness and allows myocardial blood flow
The sodium channels allow sodium transport from outside the cell to the inside of the myocyte, this determines QT interval. Process is blocked by action potential
What is microvascular angina/ cardiac syndrome X?
spasms in the small blood vessels reducing blood flow to the heart
