Coronary Heart Disease Flashcards
How does coronary artery disease present?
Sudden cardiac death
Acute coronary syndrome
- Acute MI
- Unstable angina
Stable angina pectoris
Heart failure
Arrhythmia
These ^ are the conditions that count as coronary artery disease
Patients who present with sudden onset chest pain (in the emergency room) fall into two categories:
Myocardial Infarction
Progressive (Unstable) Angina
If you have coronary artery disease then this can lead to damage of the heart muscle leading to heart failure (pumping action is impaired)
If the damage to the heart muscle leads to scar tissue formation within the myocardium then this is an important substrate for the development of arrhythmia which, in turn, is the main substrate for sudden cardiac death
pidemiology – Determinants of Risk
Tobacco use, physical inactivity, harmful use of alcohol, unhealthy diet accounts results in:
– Hypertension
– Obesity
– Diabetes mellitus
– Hyperlipdaemia
o Responsible for ~80% of CHD
Global Burden of CVD
Functional Anatomy of Coronary Circulation
The big conduit arteries divide into smaller arterioles and these then divide into the myocardium to deliver oxygen and nutrients and remove toxic waste products
Epicardial coronary arteries are mainly …………………. vessels - dependent on arterial blood pressure
Arterioles …………….. in response to changes in blood pressure and they are subject to vasoconstriction and vasodilation due to the autonomic nervous system
Changes in capillary resistance is responsive to myocardial …………….. stimuli
Job of the coronary circulation:
List 2
Functional Anatomy of Coronary Circulation
The big conduit arteries divide into smaller arterioles and these then divide into the myocardium to deliver oxygen and nutrients and remove toxic waste products
Epicardial coronary arteries are mainly conductance vessels - dependent on arterial blood pressure
Arterioles dilate in response to changes in blood pressure and they are subject to vasoconstriction and vasodilation due to the autonomic nervous system
Changes in capillary resistance is responsive to myocardial metabolic stimuli
Job of the coronary circulation:
To make sure that over a wide range of perfusion pressures, flow remains constant - AUTOREGULATION
To make sure that coronary blood flow matches myocardial demand
Overall coronary resistance is divided 50% in the large arteries and 50% in the smaller arteries and capillaries
REMEMBER: the coronary arteries have an epicardial component and an intramyocardial component
Effect of Epicardial Stenosis of Resting Coronary Resistance and Flow
Usually the resistance in the smaller arteries in the myocardium and the larger arteries outside the myocardium is……………..
If you have stenosis in the epicardial compartment - the resistance in the epicardial component ……………….
This can be compensated to a degree by an …………….. in the diameter of the intramyocardial resistance vessels - thus …………… the resistance in the intramyocardial component to maintain flow
The bottom graph shows how coronary blood flow changes with percent stenosis
As we …………… the stenosis, the resting blood flow remains unchanged because of the response of the intramyocardial arterioles
After around 70% stenosis, the coronary blood flow decreases rapidly
Effect of Epicardial Stenosis of Resting Coronary Resistance and Flow
Usually the resistance in the smaller arteries in the myocardium and the larger arteries outside the myocardium is equal
If you have stenosis in the epicardial compartment - the resistance in the epicardial component INCREASES
This can be compensated to a degree by an increase in the diameter of the intramyocardial resistance vessels - thus decreasing the resistance in the intramyocardial component to maintain flow
The bottom graph shows how coronary blood flow changes with percent stenosis
As we increase the stenosis, the resting blood flow remains unchanged because of the response of the intramyocardial arterioles
After around 70% stenosis, the coronary blood flow decreases rapidly
Effect of Coronary Stenosis on Flow: Response to Vasodilators
In terms of ratio, what is Coronary Flow Reserve?
The coronary flow reserve is the ability of the coronary circulation to ……………
Effect of Coronary Stenosis on Flow: Response to Vasodilators
Lots of things can trigger a sympathetic stimulus which leads to an increase in heart rate and blood pressure hence leading to an increase in coronary flow
The ratio of resting blood flow: blood flow achieved under maximal stress is the CORONARY FLOW RESERVE
This ratio is on the y axis on the right
The coronary flow reserve is the ability of the coronary circulation to adapt to an increasing demand in the face of an increasing demand
Resting blood flow doesn’t tend to decrease until about 70% stenosis
In the graph on the RIGHT - we’re looking at the ability of the coronary circulation to dilate in the face of a narrowing coronary artery - you find that the ability to maintain the requisite amount of flow needed under stressful conditions starts to become impaired around 50% stenosis
This is what happens in people with stable coronary disease
Angina Pectoris
Where do you feel the pain when you have Angina Pectoris?
Name 3 ways it can be provoked?
Why is an inorganic nitrate vasodilator used to treat it?
Name 1 way it can be relieved?
Angina Pectoris
Clinical diagnosis based on the constellation of symptoms
It is a tight feeling in the chest which can diffuse across the jaw, shoulders, back or arms
It can be provoked by physical exertion, emotional stress or anxiety
Use of an inorganic nitrate vasodilator (e.g. glyceryl trinitrate) - the nitrates act as a vasodilator leading to reduced coronary resistance and increasing blood flow thus reversing the supply and demand imbalance
It can be relieved by rest
Myocardial Ischaemia
What is myocaridal ischaemia a mismatch between>
What is it a primary reduction in?
What is it an inability to do?
Mismatch betwwen myocardial ocygen supply and demand
Primary reduction in blood flow
Inanility to increase blood flow to match increased metabolic demand
Ischaemic Cascade
List in order the 5 components
Anatomical tests can be used to see if there are any narrowings
A catheter can be inserted into the radial or femoral artery and moved along to the left main coronary artery to identify the stenoses that you see
Computational fluid dynamics can be used to determine the degree to which flow is impaired
Non-invasive tests can involve giving stressing agents to create situations of increased oxygen demand
You can give inotropic agents (beta agonists), vasodilators or get the patient to exercise
Imaging techniques include: echocardiography, MRI or nuclear perfusion imaging
The term acute coronary syndrome (ACS) refers to any group of clinical symptoms compatible with acutemyocardial ischemia and includes unstable angina (UA), non—ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).
Mechanisms Underlysing MI
List 4 ways that can cause Myocardial cell death arising from interrupted blood flow to the heart ?
List two mechanisms of myocardial cell death
Mechanisms Underlysing MI
Myocardial cell death arising from interrupted blood flow to the heart
Coronary plaque rupture
Coronary plaque erosion
Coronary dissection
Calcific Nodule
Mechanisms of myocardial death
Oncosis (a form of accidental or passive cell death that is often considered a lethal injury)
Apoptosis
Thrombosis can occur even in the absence of plaque rupture
Plaque erosion could be sufficient to cause thrombus formation
What 3 factors is thrombosis development dependant on?
Thrombosis - Virchow’s Triad
Abnormal Vessel Wall
Abnormal Blood Flow
Abnormal Blood Constituents (hypercoagulability)
Development of thrombosis is dependent on these three factors
If you have an impaired endothelium then you have increased risk of thrombosis
Abnormal flow happens in the case of coronary artery stenosis
Thrombosis - Virchow’s Triad
Abnormal Vessel Wall- Name 3 things that can cause this
Abnormal Blood Flow - name 3 things that can cause this
Abnormal Blood Constituents- name 6 things that can cause this
List 3 features of white thrombs and three features of red thrombus?
Tissue Factor circulates in the blood: possible cellular sources
One of the key factors that triggers the coagulation cascade is ………….. …………..
Tissue factor can be made from the cellular constituents of the…………………. ……………. or by the ……………… ……………… ………………. itself
Circulating inflammatory cells can also act as a humoural source of tissue factor that can promote the atherosclerotic process
Tissue factors triggers a ……………. of factor activation leading to coronary thrombosis
Factor …… and Factor …… are important molecular targets
Tissue Factor circulates in the blood: possible cellular sources
One of the key factors that triggers the coagulation cascade is TISSUE FACTOR
Tissue factor can be made from the cellular constituents of the atherosclerotic plaque or by the ischaemic heart muscle itself
Circulating inflammatory cells can also act as a humoural source of tissue factor that can promote the atherosclerotic process
Tissue factors triggers a cascade of factor activation leading to coronary thrombosis
Factor 10a and Factor 2a are important molecular targets
Define Acute ocaridal Infarction
What are the three isoforms of Cardiac Troponin?
Which one of them are highly specific to cardiac muscle?
This troponin is released as a result of ………………. …………….. during myocardial ischaemia
So, troponin …. and …. can be related to cardiac cell death
What is the principle biomarker for myocardial infarction?
Cardiac Troponin
Cardiac troponin (cTn) is part of the thin filament of the sarcomere
There are THREE isoforms: I, T and C
Troponin I and T are highly specific to cardiac muscle
This troponin is released as a result of proteolytic cleavage during myocardial ischaemia
So, troponin I and T can be related to cardiac cell death
After the onset of symptoms, cardiac troponin levels rise and then fall after a period of time
Troponin can be detected for 2 weeks after MI
Troponin is the principle biomarker for myocardial infarction
Acute Coronary Syndromes
What is the problem in the coronary arteries of patients who have ST-Elevation Myocardial Infarction (STEMI) ?
What is the problem in the coronary arteries of patients who have NSTEMI (Non-ST-elevation myocardial infarction)?
There are TWO types of acute coronary syndrome:
Those who present with ST elevation have complete blockage of a coronary artery due to an occlusive thrombus- go straight to emergency
No ST elevation - partial occlusion which embolises distally into the microcirculation resulting in myocardial cell death and troponin elevation- ST depression or changes in T wave or normal ECG
What is Primary Percutaneous Coronary Intervention (PPCI) for ST Elevation Acute Coronary Syndrome (STEACS) ?
A guide wire is passed through the coronary thrombus and over the wire a balloon is passed and a stent is deployed which allows recanalisation of the vessel
This can be done in 10 mins
You want to get to the blocked vessel as soon as possible
Where does the myocardial necrosis zone start?
Define Subendocardial Infarction?
Define Transmural Myocardial Infarction?
Development of Infarction
The myocardial necrosis zone will start at the inner layers of the myocardium and progress as a wave front to spread through the entire extent of the myocardium if the coronary artery wasn’t quickly recanalised
The subendocardium is particularly under threat because this is the main work horse of the heart
The arterial inflow is on the outer surface of the heart and it runs through the myocardium to get to the endocardium
Intramyocardial pressures are GREATER that subepicardial pressures and this threatens to increase the difference between supply and demand
So the subendocardium gets hit worst and first when there is an occlusion
This then spreads and becomes a transmural myocardial infarction
Subendocardial infarction- If the heart attack damage is restricted just to the inner layers of the heart
Transmural myocardial infarction- The heart muscle damage ecompasses the entire thickness of the heart muscle wall
Reperfusion Injury
The act of opening an artery can be associated with damage to the heart muscle - reperfusion injury
If we occlude an artery and don’t recanalise it, 70% of the heart muscle will die
If we were to reperfuse it, you could reduce the amount of heart muscle death to around 40%
The act of reperfusion can be responsible for part of this 40% heart muscle death - if we use a number of strategies to attenuate this reperfusion injury process, we can reduce the extent of the heart attack even further
Post-MI Left Ventricular Remodelling
Remodelling of the Post-MI Left Ventricle involves 3 things?
What is it accompanied with an increase in?
Post-MI Left Ventricular Remodelling
Depending on the size and location of the damage you can get adverse left ventricular remodelling
This remodelling involves an expansion of the heat muscle, thinning of the scar and impairment of heart function
It is accompanied with an increased risk of heart failure and arrhythmias
You want to try and attenuate this process as much as possible in the management of MI
This can be done by treating people early to reduce the extent of the ischaemic damage and by treating with therapies that intervene with the mechanism of remodelling
Mechanisms Underlying Left Ventricular Remodelling
Why does the LV dialate Post MI?
What happens to the Non-infarcted myocardium ?
Mechanisms Underlying Left Ventricular Remodelling
Infarct thinning, elongation, expansion
Left Ventricular Dilation
INCREASED wall tension
Dilation allows maintenance of cardiac output
Non-infarcted myocardium
Left ventricular hypertrophy and myofilament dysfunction
Altered eletromechanical coupling
Myocardial fibrosis
Apoptosis
Inflammation
Which of the following are determinants of myocardial oxygen demand
– Heart rate
– Blood pressure
– Myocardial wall tension
– All of the above
– None of the above
– All of the above
Which of the following are recognised mechanisms of coronary plaque instability in an acute coronary syndrome?
– Plaque erosion
– Plaque rupture
– Dissection
– Calcific nodule
– All of the above
– All of the above
