Cardiovascular Flashcards
what is coronary atherosclerosis?
a complex inflammatory process characterised by the accumulation of lipid, macrophages and smooth muscle cells in intimal plaques in the large and medium-sized epicardial coronary arteries
what contributes to initial endothelial injury or dysfunction?
- mechanical shear stresses (e.g. from morbid hypertension)
- biochemical abnormalities (e.g. from elevated LDL, diabetes mellitus)
- immunological factors (e.g. free radicals from smoking)
- inflammation (e.g. infection e.g. Chlamydophilia pneumonia)
- genetic alteration
what happens in the development of atheroslerosis?
follows endothelial dysfunction, where increased permeability to and accumulation of oxidised lipoproteins, which are taken up by macrophages at focal sites within the endothelium to produce lipid-laden foam cells
how do foam cells form?
macrophages at focal sites take up oxidised lipoproteins, to produce lipid-laden foam cells
what are endothelial lesions seen as, macroscopically?
flat yellow dots or lines on the endothelium of the artery and are known as fatty streaks
what are fatty streaks?
yellow dots or lines on the endothelium of the artery formed by foam cells
what is the further development of fatty streaks in atherogenesis?
- fatty streak progresses with appearance of extracellular lipid within the endothelium (transitional plaque)
- release of cytokines e.g. PDGF and TGF-beta by monocytes, macrophages or the damaged endothelium promotes further accumulation of macrophages and smooth muscle cell migration and proliferation
how is a transitional plaque formed?
fatty streak progresses with appearance of extracellular lipid within the endothelium
what promotes accumulation of macrophages and smooth muscle cell migration and proliferation?
release of cytokines e.g. PDGF and TGF-beta by monocytes, macrophages or damaged endothelium
how does an advanced or raised fibrolipid plaque form?
- proliferation of smooth muscle with formation of a layer of cells covering the extraceullar lipid separates it from the adaptive smooth muscle thickening in the endothelium
- collagen is produced in larger and larger quantities by the smooth muscle
how does a complicated plaque form?
the advanced plaque may grow slowly and encroach on the lumen or become unstable, undergo thrombosis and produce an obstruction
what are different mechanisms responsible for thrombosis on the plaques?
- first process (superficial endothelial injury/endothelial denudation)
- second process (deep endothelial injury/plaque fissuring)
what occurs in the first process for thrombosis formation on the plaques?
superficial endothelial injury
- involves denudation of the endothelial covering over the plaque
- subendocardial connective tissue matrix is then exposed and platelet adhesion occurs because of reaction with collagen
- thrombus is adherent to the surface of the plaque
what occurs in the second process for thrombosis formation on the plaques?
deep endothelial fissuring
- involves an advanced plaque with a lipid core
- plaque cap tears (ulcerates, fissures or ruptures), allowing blood from the lumen to enter the inside of the plaque itself
- core with lamellar lipid surfaces, tissue factor (which triggers platelet adhesion and activation) produced by macrophages and exposed collagen, is highly thrombogenic
- thrombus forms within the plaque, expanding its volume and distorting its shape
- thrombosis may then extend into the lumen
what is contained in the plaque core?
- fat deposit
- foam cells
- lymphocytes
- phagocytes
- smooth muscle cells
what is the fibrous cap made of?
- ECM proteins including collagen (strength) and elastin (flexibility) laid down by SMC
- overlies lipid core and necrotic debris
what are fixed risk factors for coronary disease?
- age
- male sex
- positive family history
- deletion polymorphism in ACE gene (DD)
what are potentially changeable risk factors for coronary disease?
- hyperlipidaemia
- cigarette smoking
- hypertension
- diabetes mellitus
- lack of exercise
- blood coagulation factors; high fibrinogen, factor VII
- C-reactive protein
- homocysteinaemia
- personality
- obesity
- gout
- soft water
- drugs, e.g. contraceptive pill, nucleoside analogues, COX-2 inhibitors, rosiglitazone
- heavy alcohol consumption
what changes should be made to diet to reduce atherosclerotic disease?
- reduction in fat, esp. saturated fat intake
- reduction in salt intake
- increase in carbohydrate intake
- increase of fruit and vegetables by 50% to about 400g a day
how is distribution of atherosclerotic plaques affected by haemodynamic factors?
- changes in flow/turbulence e.g. at bifurcations, cause the artery to alter endothelial cell pattern
- wall thickness changes, leading to neointima
- altered gene expression in the key cell types
what is the response to injury hypothesis of atherosclerosis?
- initiated by an injury to the endothelial cells which leads to endothelial dysfunction
- signals sent to circulating leukocytes by chemoattractants which accumulate and migrate into the vessel wall
- chemoattractants are released from site of injury and a concentration-gradient is produced
- inflammation ensues
how can LDL ignite inflammation in the arterial wall?
can pass in and out of the arterial wall in excess, accumulates in arterial wall, undergoes oxidation and glycation
what mediates the adhesion step in atherogenesis?
- once initiated, chemoattractants are released from the endothelium and send signals to leukocytes
- chemoattractants are released from site of injury and a concentration-gradient is produced
what are the inflammatory cytokines found in plaques?
IL-1, IL-6, IL-8, IFN-gamma, TGF-beta, MCP-1, C reactive protein
what are the steps of leukocyte recruitment to vessel walls? what mediates this?
- capture
- rolling
- slow rolling
- firm adhesion
- transmigration
- selectins
- integrins
- chemoattractants
what do fatty streaks consist of?
lipid-laden macrophages (foam cells) and T lymphocytes within the intimal layer of the vessel wall
what are intermediate lesions composed of?
layers of:
- lipid laden macrophages (foam cells)
- vascular smooth muscle cells
- T lymphocytes
- adhesion and aggregation of platelets to the vessel wall
- isolated pools of extracellular lipid
adhesion and aggregation of platelets to the vessel wall (aspirin inhibits platelet aggregation)
what are the effects and structure of fibrous plaques/advanced lesions? what do they contain?
- impede blood flow
- prone to rupture
- covered by dense fibrous cap made of ECM proteins including collagen (strength) and elastin (flexibility) laid down by SMC that overlies lipid core and necrotic debris
- may be calcified
- contains smooth muscle cells, macrophages and foam cells and T lymphocytes
how does a fibrous plaque grow?
- constantly growing and receding
- fibrous cap has to be resorbed and redeposited in order to be maintained
what occurs in fibrous plaque rupture?
- if balance shifted in favour of inflammatory conditions (increased enzyme activity), the cap becomes weak and plaque ruptures
- basement membrane, collagen and necrotic tissue exposure as well as haemorrhage of vessels within the plaque
- thrombus (clot) formation and vessel occlusion
what occurs in fibrous plaque erosion?
- second most prevalent cause of coronary thrombosis
- lesions tend to be small early lesions
- fibrous cap doesn’t disrupt
- luminal surface underneath the clot may not have endothelium present, but is rich in smooth muscle cells
- may be a prominent lipid core
what increases HDL levels?
exercise, alcohol in moderation, not smoking and lowered TG
how is hyperlipidaemia treated? how does each treatment affect CAD risk?
statins
- 24-30% reduction in mortality primary and secondary prevention
- up to 50% reduction if dose of statin is titrated to achieve target LDL of <2.6mmol/L
fibrates
- reduction in CAD events in diabetics and patients with high TG and low HDL
diet
- Mediterranean diet leads to 75% reduction in CAD events in post MI patients
what are the priorities for CVD prevention in clinical practice?
- patients with established CAD, PVD and cerebrovascular atherosclerotic disease
- asymptomatic individuals who are at high risk of developing disease due to risk factors resulting in 10-year risk of 5% now for developing a fatal event (cholesterol >8mmol/L; LDL cholesterol >6mmol/L; BP>180/110mmHg)
- all diabetics
- close relatives of patients with early-onset atherosclerotic CV disease and asymptomatic individuals at high risk
what is an ECG?
- representation of the electrical events of the cardiac cycle
- each event has a distinctive waveform
- study of waveform can lead to greater insight into a patient’s cardiac pathophysiology
what can ECGs identify?
- arrhythmias
- myocardial ischaemia and infarction
- pericarditis
- chamber hypertrophy
- electrolyte disturbances
- drug toxicity (e.g. digoxin and drugs which prolong the QT interval)
what are the pacemakers of the heart and what are their intrinsic rates?
- SA node: dominant pacemaker with an intrinsic rate of 60-100bpm
- AV node: back up pacemaker with an intrinsic rate of 40-60bpm
- ventricular cells: back up pacemaker with an intrinsic rate of 20-45bpm
what is the standard calibration of an ECG?
25mm/s
0.1 mV/mm
how does direction of electrical impulses affect wave shape?
- impulse that travels towards the electrode produces an upright (positive) deflection
- when a depolarisation wave spreads away from the lead, there is downwards (negative) deflection
- shape of waveform in any lead depends on orientation of that lead to vector of depolarisation
what is the sequence of electrical impulse conduction in the heart?
SA node -> AV node -> bundle of His -> right and left bundle branches -> Purkinje fibres
what does the P wave represent? where is it seen and how long does it last?
atrial depolarisation
- seen in every lead apart from aVR
- 0.08-0.1s
what is the PR interval? how long should it last?
- interval between the start of the P wave and the start of the QRS complex (whether this is a Q wave or an R wave)
- time taken for excitation to pass from the sinus node, through the atrium, AV node and the His-Purkinje system to the ventricle
- determines whether impulse transmission from atria to ventricles is normal
- 0.12-0.22s
what is the PR segment?
- the isoelectric (flat) line between the end of the P wave and the start of the QRS complex
- baseline of the ECG curve
- reference line or isoelectric line
what does the QRS complex represent? how long should it last?
- reflects depolarisation of the ventricles
- <0.12s
- short QRS complex implies that the ventricles are depolarised rapidly, and that the electrical conduction system functions normally
- wide/broad QRS complexes indicate that ventricular depolarisation is slow
what is the ST segment? what does it represent?
between end of the QRS complex and the start of the T wave
- interval between depolarisation and repolarisation
how is deviated ST segment studied?
- ST segment depression implies that the ST segment is depressed below the level of the PR segment
- ST segment elevation: ST segment elevated above the level of the PR segment
- magnitude of deviation is measured as the height difference (mm) between the J point and the PR segment
- PR segment is reference level
what is the J point?
- measurement of ST-segment elevation and depression in most cases
- where ST segment starts
- point between QRS and ST segment
what is the J-60 point?
measurement of ST-segment depression in exercise stress testing
what does the T wave represent?
- reflects rapid repolarisation (recovery) of the ventricles
- transition from ST segment to T wave should be smooth
- normal T wave is somewhat asymmetric, with a steeper downward slope and first half more gradual
- amplitude rarely exceeds 10mm
what is the corrected QT duration in men and women?
men: <0.44s
women <0.46s
what is the U wave? when is it usually seen? what are characteristics of it?
- positive wave after the T wave; same direction as T wave
- related to after-depolarisations which follow repolarisation
- small, round, symmetrical and positive in lead II, amplitude <2mm
- occurs occasionally on the ECG
- its height (amplitude) is about 1/4th of the amplitude of the T wave
- most often seen in leads V2, V3 and V4
- people with prominent T waves display U waves more often, and it’s clearer during bradycardia
what does the QT duration represent?
- total duration of ventricular depolarisation (activation) and repolarisation (recovery)
- measured from start of QRS complex to end of T wave
- QT interval increases at slower heart rates and vice versa
- shorter at faster heart rates
what does each box on the ECG paper represent?
horizontally:
- one small box 0.04s
- one large box 0.20s (5 x small boxes) (5mm wide)
vertically:
- one large box 0.5mV
what do ECG leads measure? what are the types of leads used?
measure the difference in electrical potential between two points
- bipolar leads: two different points on the body
- unipolar leads: one point on the body and a virtual reference point with 0 electrical potential, located in the centre of the heart
how many leads does the standard ECG have? what are they called?
12 leads
- 3 standard limb leads
- 3 augmented limb leads
- 6 precordial leads
what are the different standard limb leads used in ECG?
I: negative (right arm) -> positive (left arm)
II: negative (right arm) -> positive (left leg)
III: negative (left arm) -> positive (left leg)
what are the degrees of the standard limb leads used in ECG?
I: 0
II: +60
III: +120
what are the degrees of the augmented limb leads?
aVL: -30
aVF: +90
aVR: -150
where are the precordial (chest) leads placed?
V1: fourth intercostal space, to right of sternum (septal)
V2: fourth intercostal space, to left of sternum (septal)
V3: between leads V2 and V3 (anterior)
V4: fifth intercostal space in mid-clavicular line (anterior)
V5: horizontally even with V4, in left anterior axillary line (lateral)
V6: horizontally even with V4 and V5 in the mid-axillary line (lateral)
what are the colours of the RA, LA, RL and LL leads?
RA: white
LA: black
LL: red
RL: green
what are are alternative placements of chest leads?
- right side chest leads
- V7, V8 and V9 on posterior chest wall
which ECG leads are inferior, lateral, septal and anterior?
row 1: I (lateral), aVR, V1 (septal), V4 (anterior)
row 2: II (inferior), aVL (lateral), V2 (septal), V5 (lateral)
row 3: III (inferior), aVF (inferior), V3 (anterior), V6 (lateral)
what are Chamberlain’s 10 rules of an ECG reading?
- PR interval should be 120 to 200 milliseconds or 3 to 5 little squares
- width of QRS complex should not exceed 110ms, less than 3 little squares
- QRS complex should be dominantly upright in leads I and II
- QRS and T waves tend to have the same direction in the limb leads
- all waves are negative in lead aVR
- R wave must grow from V1 to at least V4; S wave must grow from V1 to at least V3 and disappear in V6
- ST segment should start isoelectric except in V1 and V2 where it may be elevated
- P waves should be upright in I, II, and V2 to V6
- there should be no Q wave or only a small less than 0.04s in width in I, II, V2 to V6
- T wave must be upright in I, II, V2 to V6
what are characteristics of the P wave in an ECG reading?
- always positive in lead I and II
- always negative in lead aVR
- < 3 small squares in duration
- < 2.5 small squares in amplitude
- commonly biphasic in lead V1
- best seen in lead II
what is a feature of right atrial enlargement on an ECG reading?
tall (>2.5mm), pointed P waves (P pulmonale)
what is a feature of left atrial enlargement on an ECG reading?
notched/bifid P wave (P mitrale) in limb leads
what is a feature of WPW syndrome on an ECG reading?
Wolff-Parkinson-White syndrome
- short PR interval (<0.2s)
- accessory pathway (bundle of Kent) allows early activation of the ventricle (delta wave and short PR interval)
what is a feature of first degree heart block on an ECG reading?
long PR interval (>0.2s)
what do short and long PR intervals on an ECG reading indicate?
short: Wolff-Parkinson-White syndrome
long: first degree heart block
what are features of QRS complexes on an ECG reading?
- non-pathological Q waves may present in I, III, aVL, V5 and V6; small and narrow
- R wave in lead V6 is smaller than V5
- depth of S wave should not exceed 30mm
- pathological Q wave: >2mm deep and >1mm wide or 25% amplitude of the subsequent R wave (except in aVR and V1); indicate MI
what are characteristics of left ventricular hypertrophy on an ECG reading?
Sokolow and Lyon criteria
- increases voltage-induced depolarisation of the free wall of the left ventricle
- deep S waves (>30mm) in V1 and V2
- tall R waves (>25mm) in V5 or V6
- R wave of 11-13mm or more in lead aVL
- sum of R wave in left ventricular leads and the S wave in the right ventricular leads exceeds 40mm
- ST-segment depression
- T wave flattening or inversion in left ventricular leads
what are features of an abnormal T wave?
symmetrical, tall, peaked, biphasic or inverted
- usually follows the direction of the QRS deflection
where is the QT interval measured? why?
measured in lead aVL as this lead does not have prominent U waves
what are characteristics of the QT interval? how does it compare to HR?
- total depolarisation and repolarisation of the ventricles
- QT decreases when HR increases
- for HR = 70bpm, QT <0.40s
- should be 0.35-0.45s
- should not be more than half of the interval between adjacent R waves (R-R)
what are the two methods of determining the heart rate from an ECG reading?
- rule of 300/1500
- 10 second rule
what is the QRS axis? what do abnormalities suggest?
- represents overall direction of the heart’s electrical activity
- abnormalities hint at ventricular enlargement and conduction blocks (i.e. hemiblocks)
what are the values for normal and abnormal QRS axes?
normal: -30 to +90
left axis deviation: -30 to -90
right axis deviation: +90 to +180
what are approaches to determining the QRS axis?
- quadrant approach
- equiphasic approach
when does myocardial ischaemia occur?
imbalance between the heart’s supply of oxygen (and other essential myocardial nutrients) and the myocardial demand for these substances
what are causes of mechanical obstruction that can reduce coronary blood flow to a region of the myocardium?
- atheroma
- thrombosis
- spasm
- embolus
- coronary ostial stenosis
- coronary arteritis
what are causes of decreased flow of oxygenated blood to the myocardium?
- anaemia
- carboxyhaemoglobulinaemia
- hypotension causing decreased coronary perfusion pressure
why may an increased demand for oxygen occur?
increase in cardiac output (e.g. thyrotoxicosis) or myocardial hypertrophy (e.g. from aortic stenosis or hypertension)
- aortic stenosis
- valvular disease
- arrhythmia
when does myocardial ischaemia most commonly occur?
due to obstructive CAD in form of coronary atherosclerosis
- variations in the tone of smooth muscle in the wall of a coronary artery may add another element of dynamic or variable obstruction
what is the epidemiology of CAD?
- largest single cause of death in the UK and many parts of the world
- over the last decade, mortality in the UK has decreased
- sudden cardiac death is a common feature of CAD
- more common in men
what is the chest pain in angina described as?
- heavy, tight or gripping
- pain is cental/retrosternal and may radiate to the jaw and/or arms
- can range from a mild ache to a most severe pain that provokes sweating and fear
what is classical or exertional angina pectoris characterised by?
- constricting discomfort in the front of the chest, arms, neck, jaw
- provoked by physical exertion, esp. after meals and in cold, windy weather or by anger or excitement
- relieved (within minutes) with rest or glyceryl trinitrate
- may disappear with continued exertion
- pain may radiate to one or both arms, the neck, jaw or teeth
- may be dyspnoea, nausea, sweatiness and faintness
what is typical angina vs atypical angina vs non-anginal chest pain?
typical angina: all three features of classical/exertional angina pectoris
atypical angina: two out of three features of classical/exertional angina pectoris
non-anginal chest pain: one or less features
when is angina considered stable?
when it is not a new symptom and when there is no change in the frequency or severity of attacks
what is unstable angina?
angina of recent onset (<24hrs) or a deterioration in previous stable angina with symptoms frequently occurring at rest, i.e. acute coronary syndrome
what is refractory angina?
patients with severe coronary disease in whom revascularisation is not possible and angina is not controlled by medical therapy
what is variant (Prinzmetal’s) angina?
angina that occurs without provocation, usually at rest, due to coronary artery spasm
- more frequent in women
- ST elevation on ECG during pain
- provocation tests may be needed for diagnosis
what is cardiac syndrome X? who does it usually affect?
- refers to patients with good history of angina, positive exercise test and angiographically normal coronary arteries
- heterogenous group
- more common in women
- good prognosis, symptomatic, difficult to treat
- abnormal metabolic response to stress
what is the examination for angina?
- usually no abnormal findings in angina
- 4th heart sound may be heard
- signs to suggest anaemia, thyrotoxicosis, or hyperlipidaemia (e.g. lipid arcus, xanthelasma, tendon xanthoma should be sought
- exclude aortic stenosis as possible cause
- take BP
why should an ECG be done when assessing angina? what would be found?
- to exclude an acute coronary syndrome
- often normal between attacks
- evidence of old MI, left ventricular hypertrophy or LBBB may be present
- during an attack, transient ST depression, T wave inversion or other changes of the shape of the T wave may appear
how is diagnosis of stable angina made?
clinical assessment alone or combined with anatomical (cardiac catheterisation or CT coronary angiography) or functional imaging (SPECT, stress-echocardiography, stress-MRI)
what is the treatment of stable angina?
- information, lifestyle modification
- short-acting nitrates
- secondary prevention
-> beta blocker or calcium channel blocker
what happens if a patient does not tolerate beta blocker or calcium channel blocker (in angina) or it is contraindicated?
- long acting nitrate (isosorbide mononitrate)
- ivabradine (It current inhibitor ivabradine)
- nicorandil (potassium channel activator)
- ranolazine (sodium channel inhibitor)
what happens if patients are symptomatic on 2 anti-anginals?
consider revascularisation -> PCI or CABG
PCI
- single vessel disease
- multi-vessel <65yrs
- suitable anatomy
CABG
- unsuitable anatomy
- multivessel >65yrs
- diabetes
what is PCI?
percutaneous coronary intervention
- process of dilating a coronary artery stenosis using an inflatable balloon
- metallic stent introduced into the arterial circulation via femoral, radial or brachial artery
what are favourable lesions for PCI?
discrete, soft lesion in a straight vessel without involving a bifurcation
what are unfavourable lesions for PCI?
occluded vessels, stenoses that are calcified, tortuous, long or involve a bifurcation
what are complications of PCI?
- bleeding
- haematoma
- dissection and pseudoaneurysm from the arterial puncture site (use of radial artery may reduce the risks)
- acute MI (2%)
- stroke (0.4%)
- death (1%)
what can reduce thrombotic complications?
- use of heparin or direct thrombin inhibitor bivalrudin together with antiplatelet agents, aspirin and the thienopyridine clopidogrel
- in high risk ACS or diabetic patients the antiplatelet GPIIb/IIIa antagonists (tirofiban, eptifibratide and abciximab) are used
- coated stents lined with substances reducing coronary artery restenosis
what are different types of stent?
Cypher stent
Xience V stent
Taxus stent
what does the Cypher stent contain?
sirolimus, which is an immunosuppressant agent that reduces cellular proliferation
what does the Xience V stent contain?
everolimus, which is a derivative of sirolimus
what does the Taxus stent contain?
paclitaxel, which is a mitotic inhibitor drug that inhibits neointima formation
what does inadequate endothelialisation of the stent lead to?
exposure of thrombus stimulating surface when the patient discontinues clopidogrel therapy, leading to recommendation that patients take prolonged dual therapy (aspirin and clopidogrel) and avoid discontinuing therapy within 6-12 months of implantation
what is CABG?
coronary artery bypass grafting
- autologous veins or arteries are anastomosed to the ascending aorta and to the native coronary arteries distal to the area of stenosis
how can improved graft survival be obtained for CABG?
with in situ internal mammary and gastroepiploic arteries grafted onto the stenosed coronary artery
what is PTCA? how is it done?
percutaneous transluminal coronary angioplasty
- coronary angiography demonstrates occluded coronary artery
- a soft wire passed through the guide catheter reopens the artery but a severe stenosis remains
- balloon is inflated to dilate the stenosis
- coronary artery is reopened with good antegrade flow
what are methods of relief of coronary obstruction?
- coronary artery vein bypass grafting (CAVBG)
- internal mammary arterial implantation (IMA)
what is the treatment for intractable angina?
some patients remain symptomatic despite medication and are unsuitable for revascularisation; need a pain management programme
what types of pharmacological therapy is used in stable angina?
- vasodilators
- beta blockers
- calcium channel blockers
- second line anti-anginal drugs
- secondary prevention
what do acute coronary syndromes (ACS) include?
- ST-elevation myocardial infarction (STEMI)
- non-ST-elevation myocardial infarction (NSTEMI)
- unstable angina (UA)
what is the difference between UA and NSTEMI?
in NSTEMI, there is occluding thrombus, which leads to myocardial necrosis and a rise in serum troponins or CK-MB
when does myocardial infarction occur?
when cardiac myocytes die due to prolonged myocardial ischaemia
how can MI be diagnosed?
- appropriate clinical history
- 12 lead ECG
- elevated biochemical markers: troponin I and T, CK-MB
- three types of MIs
what is type 1 MI?
spontaneous MI with ischaemia due to a primary coronary event, e.g. plaque erosion/rupture, fissuring or dissection
what is type 2 MI?
Mi secondary to ischaemia due to increased oxygen demand or decreased supply, e.g. coronary spasm, coronary embolism, anaemia, arrhythmias, hypertension, or hypotension
what is type 3,4,5 MI?
diagnosis of MI in sudden cardiac death, after PCI and after CABG, respectively
what is the pathophysiology of acute coronary syndrome?
- common mechanism to all ACS is rupture or erosion of the fibrous cap of a coronary artery plaque
- leads to platelet aggregation and adhesion, localised thrombosis, vasoconstriction and distal thrombus embolisation
- presence of a rich lipid pool within the plaque and a thin fibrous cap are associated with an increased risk of rupture
- thrombus formation and the vasoconstriction produced by platelet release of serotonin and thromboxane A2, results in myocardial ischaemia due to reduction of coronary blood flow
what does rupture/erosion of the fibrous cap of a coronary artery plaque lead to?
leads to platelet aggregation and adhesion, localised thrombosis, vasoconstriction and distal thrombus embolisation
what platelet products induce vasoconstriction?
serotonin and thromboxane A2
what are risk factors for ACS?
- age >65
- more than three CAD risk factors: hypertension, hyperlipidaemia, family history, diabetes, smoking
- known coronary artery disease (coronary angiography stenosis >50%)
- aspirin use in last 7 days
- severe angina (more than two episodes of rest pain in 24hrs)
- ST elevation on ECG (horizontal ST depression or transient ST elevation >1mm)
- elevated cardiac markers (CK-MB or troponin)
what is clinical presentation of ACS?
- new onset of chest pain
- chest pain at rest
- deterioration of pre-existing angina
- atypical features e.g. indigestion, pleuritic chest pain or dyspnoea
what can physical examination detect in ACS?
- alternative diagnoses e.g. aortic dissection, PE or peptic ulceration
- adverse clinical signs e.g. hypotension, basal crackles, fourth heart sounds and cardiac murmurs
what are ECG signs of ACS?
- may be normal
- ST depression and T wave inversion are highly suggestive for an ACS, esp. if associated with anginal chest pain
- should be repeated when in pain
- continuous ST-segment monitoring is recommended
- STEMI: complete occlusion of coronary vessel results in persistent ST elevation or LBBB
- transient ST elevation seen with coronary vasospasm of Prinzmetal’s angina
what are biochemical markers for ACS?
- cardiac troponin complex
- creatine-kinase-MB
- myoglobin
what is the cardiac troponin complex? how is it used as a biochemical marker for ACS?
- made up of three distinct proteins (I, T, C) situated with tropomyosin on thin actin filament
- cardiac troponins are not detectable in normal people, so monoclonal antibody tests to cardiac specific troponin I and T are sensitive markers of myocyte necrosis
- if initial troponin assay is negative, it should be repeated 6-12hrs after admission
- serum levels increase within 3-12hrs from the onset of chest pain and peak at 24-48hrs
- fall back to normal after 5-14days
- can act as prognostic indicator
what are the actions of the cardiac troponins?
- troponin T binds the complex to tropomyosin and helps position it on actin, and together with the rest of the tropomyosin complex, modulates contraction of striated muscle
- troponin C binds calcium during excitation-contraction coupling
- troponin I inhibits the myosin binding site on the actin
how is CK-MB used as a biomarker for ACS?
- creatine-kinase-MB
- previously the standard marker for myocyte death
- there is presence of low levels of CK-MB in the serum of normal individuals and patients with skeletal muscle damage
- can be used to determine to determine reinfarction as levels drop back to normal after 36-72hrs
how is myoglobin used as a biomarker for ACS?
- rapid diagnosis of an ACS as levels become elevated very early in MI
- presence of myoglobin in skeletal muscle; poor specificity for ACS
what is the management of low-risk NSTEMI/UA patients?
oral aspirin, clopidogrel, beta blockers and nitrates
what tests are used as first line investigation for NSTEMI/UA?
- exercise test (negative result has good prognosis and early positive test should lead to invasive strategy)
- baseline ECG
- dobutamine stress ECG
- myocardial perfusion scintigraphy
what drug treatments are used in ACS?
- myocardial oxygenation
- antiplatelet
- antithrombin
- glycoprotein IIb/IIIa inhibitors
- analgesia (diamorphine or morphine)
- myocardial energy consumption (atenolol and metoprolol)
- coronary vasodilation (GTN)
- plaque stabilisation/ventricular remodelling (HMG-CoA reductase inhibitors and ACEi)
what does rupture of the atheromatous plaque lead to? how does this affect platelets?
- exposes circulating platelets to ADP, thromboxane A2, epinephrine, thrombin and collagen tissue factor
- causes platelet activation, with thrombin as a potent stimulant
- platelet activation stimulates the expression of glycoprotein IIb/IIIa receptors on platelet surface
- receptors bridge fibrinogen between adjacent platelets, causing platelet aggregates
what is the action of aspirin as an antiplatelet agent? what is its dose?
- blocks formation of thomboxane A2, and so prevents platelet aggregation
- 150-300mg chewable or soluble aspirin, then 75-150mg orally daily
- caution if active peptic ulceration
- used in combination with ticagrelor
what is the action of clopidogrel as an antiplatelet agent? what is its dose?
- thienopyridine
- inhibits ADP-dependent activation of the GPIIb/IIIa complex that allows platelet aggregates to form
- prodrug that requires conversion by hepatic CYP450 enzymes to an active moiety
- active drug binds irreversibly to the P2Y12 receptor on platelet membranes and inhibits the ADP-dependent pathway of platelet activation
- increased risk of bleeding
- 300mg orally loading dose, then 75mg OD
what are the actions of activated GPIIb/IIIa receptor antagonists?
- powerful inhibitors of platelet aggregation
- receptors usually bind to fibrinogen, initiating platelet aggregation
what is the action of abciximab as a GPIIb/IIIa receptor antagonist for ACS? what is its dose?
- monoclonal antibody that binds strongly and has a long half life
- indicated if coronary intervention likely within 24hrs
what is the action of eptifibatide as a GPIIb/IIIa receptor antagonist for ACS? what is its dose?
- indicated in high-risk patients managed without coronary intervention or during PCI
- cyclic peptide that selectively inhibits GPIIb/IIIa receptors
- short half life, wears out in 2-4hrs
what is the action of tirofiban as a GPIIb/IIIa receptor antagonist for ACS? what is its dose?
- small non-peptide that rapidly blocks the GPIIb/IIIa receptors
- reversible in 4-6hrs
- indicated in high-risk patients managed without coronary intervention or during PCI
what is the action of bivalrudin as an antithrombin for ACS? what is its dose?
- direct thrombin inhibitor that reversibly binds to thrombin and inhibits clot-bound thrombin
what is the action of fondaparinux as an antithrombin for ACS? what is its dose?
- synthetic pentasaccharide that selectively binds to antithrombin, which inactivates factor Xa resulting in strong inhibition of thrombin generation and clot formation
- does not inactivate thrombin and has no effect on platelets
what is the action of rivaroxaban as an antithrombin for ACS? what is its dose?
- risk of bleeding
- factor Xa inhibitor
- effective in reducing the risk of further cardiac events
what is the action of beta blockers for ACS?
- anti-ischaemia agents
- for patients with no contraindications (asthma, AV-block, acute pulmonary oedema)
- administered IV or orally
- reduce myocardial ischaemia by blocking circulating catecholamines
- reduce HR and BP, reducing myocardial oxygen consumption
what are some plaque stabilising/remodelling drugs? what is their action in ACS?
- HMG-CoA reductase inhibitor drugs (statins) and ACE inhibitors
- may produce plaque stabilisation, improve vascular and myocardial remodelling, and reduce future CV events
- starting drugs whilst patient is still in hospital increases the likelihood of them receiving secondary drug therapy
what is the pathophysiology of a STEMI?
- rupture or erosion of a vulnerable coronary artery plaque can produce a prolonged occlusion of a coronary artery leading to myocardial necrosis within 15-30 minutes
- subendocardial myocardium is initially affected
- with continued ischaemia the infarct zone extends through to the subepicardial myocardium, producing a transmural Q wave MI
- early reperfusion may salvage regions of the myocardium, reducing future mortality and morbidity
what are risk factors for STEMI?
- age >65yrs
- age >75yrs
- history of angina, hypertension or diabetes
- systolic BP <100
- HR >100
- Killip II-IV
- weight >67kg
- anterior MI or LBBB
- delay to treatment >4hrs
what are symptoms and signs of a STEMI?
- any patient presenting with severe chest pain more than 20mins may have an MI
- pain does not usually respond to sublingual GTN, and opiate analgesia is required
- pain may radiate to left arm, neck or jaw
- symptoms may be atypical and include dyspnoea, fatigue, pre-syncope or syncope (esp. in elderly/diabetics)
- pale and clammy, marked sweating
- thready pulse with significant hypotension, bradycardia or tachycardia
- pain described as substernal pressure, squeezing, aching, burning or even sharp pain
- breathlessness, fatigue, distress
which leads show ST elevation in small and extensive anterior STEMI?
- small: V3-V4
- extensive: V2-V5
which leads show ST elevation in anteroseptal STEMI?
V1-V3
which leads show ST elevation in anterolateral STEMI?
V4-V6, I, aVL
which leads show ST elevation in lateral STEMI?
I, aVL, V5-V6
which leads show ST elevation in inferior STEMI?
II, III, aVF
which leads show ST elevation in posterior STEMI?
ST depression V1-V3
dominant R wave
ST elevation V5-V6
which leads show ST elevation in subendocardial STEMI?
any lead
which leads show ST elevation in right ventricle STEMI?
VR4
what is the ECG evolution of the STEMI?
first few minutes: T waves become tall, pointed and upright and there is ST segment elevation
hours afterwards: T waves invert, R wave voltage decreases and Q waves develop
days afterwards: ST segment returns to normal; T wave is still abnormal; Q wave remains
weeks/months afterwards: T wave may return to upright but Q wave remains
what investigations should be done for a STEMI?
- blood samples taken for cardiac troponin I or T levels (will be increased)
- FBC, serum electrolytes. glucose and lipid profile
- myoglobin (increased)
- transthoracic ECG (TTE) may confirm an MI (wall motion abnormalities are detectable early in STEMI
- TTE may detect alternative diagnoses e.g. aortic dissection, pericarditis or PE
what is A+E treatment for STEMI?
- aspirin 150-300mg chewed and clopidogrel 300mg oral gel
- sublingual GTN 0.3-1mg. repeat
- nasal cannula 2-4L/min if hypoxia is present
- brief history/risk factors, examination
- IV access + blood for markers (+ FBC, biochemistry, lipids, glucose)
- 12 lead ECG
- IV opiate and antiemetic
- beta blocker (if no contraindication) for ongoing chest pain, hypertension, tachycardia
- if primary PCI available, give GPIIb/IIIa inhibitor; alternatively, give thrombolysis
what is the action of fibrinolytic agents?
enhance the breakdown of occlusive thromboses by activation of plasminogen to form plasmin
- still used if PCI is unavailable
what are examples of fibrinolytic agents?
r-PA (reteplase), TNK-t-PA (tenecteplase), streptokinase
what are absolute contraindications to thrombolysis?
- haemorrhagic stroke or stroke of unknown origin at any time
- ischaemic stroke in preceding 6 months
- CNS damage or neoplasma
- recent major trauma/surgery/head injury (within preceding 3 weeks)
- GI bleeding within last month
- known bleeding disorder - aortic dissection
what are relative contraindications to thrombolysis?
- TIA in preceding 6 months
- oral anticoagulant therapy
- pregnancy or within 1 week postpartum
- non-compressible punctures
- traumatic resus
- refractory hypertension (systolic >180)
- advanced liver disease
- infective endocarditis
what are complications of myocardial infarction?
- heart failure
- myocardial rupture and aneurysmal dilatation
- heart block
- rupture of interventricular septum
- pericarditis
- thromboembolism
- ventricular aneurysm
- ventricular septal defect
- mitral regurgitation
- cardiac arrhythmias
- conduction disturbances
- post-MI pericarditis and Dressler’s syndrome
what is the Killip classification?
used to assess patients with heart failure post-MI
what are characteristics of Killip I, II, III and IV categories?
Killip I: no crackles and no third heart sound
Killip II: crackles in <50% of the lung fields or a third heart sound
Killip III: crackles in >50% of the lung fields
Killip IV: cardiogenic shock
what is involved in post-ACS lifestyle modification?
- Mediterranean-style diet
- > 7g omega-3 fatty acids/week from oily fish or >1g daily of omega-3-acid ethyl esters
- safe alcohol consumption
- exercise 20-30mins a day
- stop smoking
- overweight and obese patients encouraged to get healthy
- hypertension treated to 140/90 or 130/80 if CKD/diabetes
- diabetics treated to maintain HbA1c <7%
what is post-ACS drug therapy and assessment?
- aspirin 75-100mg/day
- second anti-platelet agent
- beta blocker to maintain heart rate <60bpm
- ACE inhibitors
- high intensity statins
- clopidogrel 75mg/day for 9-12 months in moderate-high-risk patients with NST-ACS
- aldosterone antagonist for patients post-MI with clinical evidence of heart failure and left ventricular ejection fraction <40%
what is the commonest cause of angina?
ischaemia
what are predisposing factors to ischaemic heart disease?
- age
- male
- smoking
- family history
- diabetes mellitus
- hyperlipidaemia
- hypertension
- kidney disease
- obesity
- physical inactivity
- stress
- history of premature CHD/IHD
what are exacerbating factors for supply in ischameic heart disease?
- anaemia
- hypoxaemia
- polycynthemia
- hypothermia
- hypovolaemia
- hypervolaemia
what are exacerbating factors for demand in ischaemic heart disease?
- hypertension
- tachyarrhythmia
- valvular heart disease
- hyperthyroidism
- hypertrophic cardiomyopathy
what are environmental factors in angina?
- cold weather
- heavy meals
- emotional distress
how can blood supply be limited?
- impairment of blood flow by proximal arterial stenosis
- increased distal resistance e.g. left ventricular hypertrophy
- reduced oxygen-carrying capacity of blood e.g. anaemia
what is Poiseuille’s equation?
deltaP = (8uLQ)/(pi x r^4)
- deltaP = pressure loss
- L = length of pipe
- u/mew = dynamic viscosity
- Q = volumetric flow rate
- r = radius
- d = diameter
what is the incidence and prevalence of angina?
incidence
- men 35/100000/yr
- women 20/100000/yr
prevalence
- men 5% (5000/100000)
- women 4 (4000/100000)
what is considered in the history of ischaemic heart disease?
- personal details
- presenting complaint
- history of PC + risk factors
- past medical history
- drug history, allergies
- family history
- social history
- systematic enquiry
what are differential diagnoses of chest pain?
- myocardial ischaemia
- pericarditis/myocarditis
- pulmonary embolism/pleurisy
- chest infection/pleurisy
- dissection of the aorta
- GORD
- musculoskeletal
- psychological
what are the effects of beta blockers on the heart?
decreased HR (negative chronotropic) and decreased LV contractility (negative inotropic) -> decreased CO -> decreased O2 demand
- decreased cardiac output
- reduce force of contraction of heart
- act on B1 receptors in the heart as part of the adrenergic sympathetic pathway
- B1 activation -> Gs -> cAMP to ATP -> contraction
what are the side effects of beta blockers?
- tiredness, nightmares
- erectile dysfunction
- cold hands and feet
- bradycardia
what are contraindications of beta blockers?
- severe bronchospasm; asthma
- hypotension
- bradyarrythmias
- verapamil, diltiazem, amiodarone, digoxin
- Prinzmetal’s angina
- untreated heart failure
- severe heart block
- excessive bradycardia
what are the effects of nitrates on the heart? what is a side effect?
- venodilators
- dilate arterioles -> decreased BP -> decreased afterload
- dilates systemic veins -> decreased venous return -> decreased preload
- coronary arteries dilate
- reduced work of heart and O2 demand
- profuse headache immediately after use
what are the effects of calcium channel blockers on the heart? what is an example of one?
e. g. verapamil
- dilate arteries -> flushing, postural hypotension and swollen ankles
- decreased BP -> decreased afterload
- coronary arteries dilate
- decreased oxygen demand
- decreased work (negative inotropic and decreased LV contraction) (negative chronotropic and decreased HR)
what are advantages and disadvantages of PCI?
- less invasive
- convenient
- repeatable
- acceptable
- risk stent thrombosis
- risk restenosis
- can’t deal with complex disease
- dual antiplatelet therapy
what are advantages and disadvantages of CABG?
- good prognosis
- deals with complex disease
- invasive
- risk of stroke, bleeding
- can’t do if frail, comorbid
- one time treatment
- length of stay
- time for recovery
what is clinical classification of unstable angina?
- cardiac chest pain at rest
- cardiac chest pain with crescendo pattern
- new onset angina
- diagnosis: history, ECG, troponin (no significant rise)
what are some uncommon causes of ACS?
- coronary vasospasm without plaque rupture
- drug abuse (amphetamines, cocaine)
- dissection of coronary artery related to defects of the vessel connective tissue
- thoracic aortic dissection
what diseases other than ACS is troponin positive in?
- Gram negative sepsis
- pulmonary embolism
- myocarditis
- heart failure
- arrhythmias
- cytotoxic drugs
what mediates initial adhesion, rolling and stable adhesion and activation/aggregation of platelets?
initial adhesion
- GPIb/VWF
rolling
- GPIb/VWF
- alpha2beta1/collagen
stable adhesion and activation/aggregation
- GPVI
- GPIIb/IIIa
what are the different receptors on platelets that lead to platelet activation? what do they bind to?
- PAR1 and PAR4 bind to thrombin
- TPalpha binds to thromboxane A2
- GPVI binds to collagen
- 5HT2A binds 5HT
- P2Y1 binds ADP
- P2X1 binds ATP
what does platelet activation lead to?
- shape change AND
- alpha(IIb)beta(3) binds fibrinogen, which activates it and enhances adhesion and leads to platelet-platelet interactions
- thrombin generation
- alpha and dense granule secretion
what does alpha granule secretion lead to?
coagulation and inflammation
what are the contents of platelet alpha granules?
- IGF1, PDGF, TGFbeta, platelet factor 4
- clotting proteins (e.g. thrombospondin, fibronectin, factor V, vWF)
- P-selectin and CD63
what does platelet dense granule secretion lead to?
contributes to platelet activation
what are the contents of platelet dense granules?
ADP, ATP, ionised calcium, serotonin
why may some patients have no obstructive CAD?
- actual diagnosis not ACS
- plaque rupture without significant stenosis and resolution of obstructive thrombus by time of angiography
- stress induced (Tako-Tsubo) cardiomyopathy without obstructive CAD
what factors affect response to clopidogrel?
- dose
- age
- weight
- disease states including diabetes mellitus and CKD
- drug-drug interactions e.g. omeprazole and strong CYP 3A inhibitors
- CYP2C19 loss of function alleles
what is an alternative mechanism of ticagrelor action?
- inhibition of adenosine uptake via the ENT-1 pathway
- adenosine -> vasodilation, cardioprotection, antiplatelet, immunomodulation
- adenosine kinase catalyses AMP -> adenosine
what are adverse effects of ticagrelor that are common to all P2Y12 inhibitors?
- bleeding
- rash
- GI disturbance
what is the main mechanism of ticagrelor action?
an oral reversibly binding P2Y12 antagonist
what are idiosyncratic adverse effects of ticagrelor?
- dyspnoea: usually mild and well tolerated, but if not it may require switching to prasugrel or clopidogrel
- ventricular pauses: usually sinoatrial pauses, may resolve with continued treatment
what are common sites for venous thrombosis?
leg and pelvis
what is superficial thrombosis?
- commonly involves saphenous veins and often associated with varicosities
- axillary vein may be involved, due to trauma
- local superficial inflammation of the vein wall, with secondary thrombosis
- clinical picture: painful, tender cord-like structure with associated redness and swelling
what is treatment of superficial thrombosis?
rest, elevation of limb and analgesics
what is a DVT?
deep vein thrombosis
- any inflammation of the vein wall is secondary to this
- commonly occurs after immobilisation, but can occur in normal people
- in 50% of patients after prostatectomy or after a cerebral vascular event
- 10% of patients with an MI have DVT
what are clinical features of DVT?
- may be asymptomatic, presenting with features of PE
- pain in the calf with swelling, redness and engorged superficial veins
- warm
- ankle oedema
- calf tenderness
- superficial venous distension
- Homan’s sign (pain in calf on dorsiflexion of foot)
- complete occlusion -> cyanotic discolouration of limb and severe oedema, can lead to venous gangrene
- PE more frequent from iliofemoral thrombosis and rare with thrombosis confined to veins below the knee
what is Homan’s sign?
pain in calf on dorsiflexon of foot
what is investigation of DVT?
- clinical diagnosis is unreliable
- diagnosis sensitivity of 80% combined with D-dimer level
- confirmation of iliofemoral thrombosis made with B mode venous compression, ultrasonography or Doppler ultrasound with a sensitivity and specificity over 90%
- below knee thromboses detected reliably only by venography with non-invasive techniques, ultrasound, fibrinogen scanning and impedance plethysmography; sensitivity of 70%
- venogram is performed by injecting a vein in foot with contrast, which detects all thrombi present
how is a venogram performed?
venogram is performed by injecting a vein in foot with contrast, which detects all thrombi present
what is the aim of treatment of DVT?
to prevent PE; all patients with thrombi above the knee must be anticoagulated
what is treatment of DVT?
- anticoagulation of below-knee thrombi recommended for 6 weeks, as 30% of patients have an extension of the clot proximally
- bed rest advised until fully anticoagulated
- mobilised, with elastic/compression stocking giving graduated pressure over the leg
- low molecular weight heparin
- thrombolytic therapy
how is low molecular weight heparin used to treat DVT?
- have replaced unfractioned heparin as they’re more effective, do not require monitoring and less risk of bleeding
- can be treated at home
- warfarin started immediately and the heparin stopped when INR is in target range
- 3 months warfarin
- recurrent DVTs need permanent anticoagulents
- target INR should be 2.5
how is thrombolytic therapy used to treat DVT?
occasionally used for patient with a large iliofemoral thrombosis
what are risk factors for venous thromboembolism?
- active cancer or cancer treatment
- age >60yrs
- critical care admission
- dehydration
- known thrombophilias
- obesity
- comorbidities e.g. heart disease, metabolic, endocrine or respiratory pathologies, acute infectious diseases, inflammatory conditions
- personal history or first-degree relative with a history of VTE
- use of HRT or oestrogen containing oral contraceptive
- varicose veins with phlebitis
- pregnancy/childbirth
- thrombophilia
- plasminogen deficiency
what are risk factors for bleeding in DVT?
- active bleeding
- acquired bleeding disorders e.g. acute liver failure
- concurrent use of anticoagulents
- lumbar puncture/epidural/spinal anaesthesia within previous 4hrs or expected within 12hrs
- acute stroke
- thrombocytopenia
- uncontrolled systolic hypertension
- untreated inherited bleeding disorders
what is prognosis for DVT?
- destruction of deep vein valves produces clinically painful, swollen limb made worse by standing, accompanied by oedema and sometimes venous eczema
- occurs in half of patients with clinically symptomatic DVT
- elastic support stockings required for life
what are the NICE guidelines on the assessment and prevention of venous thromboembolism (VTE) in patients admitted to hospital?
- all patients assessed on admission to hospital
- patients at risk if reduced mobility for >3 days or if mobility reduced and have a >1 risk factor for VTE
when are surgical and trauma patients at risk of VTE?
- surgical procedure with combined anaesthetic and surgery of >90min
- if admitted with acute inflammatory or intraabdominal condition
- if significantly reduced mobility
- if >1 risk factor for CTE
what is pulmonary embolism?
- thombus, usually formed in systemic veins or rarely in the right heart, may disoldge and embolise into the pulmonary arterial system
- common and potentially lethal condition
where do clots that cause pulmonary embolism come from?
pelvic and abdominal veins, femoral DVT or axillary thrombosis (not as common)
what is Virchow’s triad?
three broad categories of factors that are throught to contribute to thrombosis:
- stasis of blood flow
- endothelial injury
- hypercoagulability
what are other sources of pulmonary emboli, other than clots?
tumour, fat (long bone fractures), amniotic fluid and foreign material during IV drug use
what are risk factors for thrombophilia?
- antithrombin deficiency
- protein C or S deficiency
- factor V Leiden
- resistance to activated protein C
- prothrombin gene variant
- hyperhomocysteinaemia
- antiphospholipid antibody/lupus anticoagulant
what is a thrombus?
a solid mass formed in the circulation from the constituents of the blood during life
- fragments of thrombi (emboli) may break off and block vessel downstream
what is an arterial thrombosis?
- tends to form at areas of turbulent blood flow e.g. bifurcation
- platelets adhere to damaged vascular endothelium and aggregate in response to ADP and TXA2 to form white thrombus
- growth of platelet thrombus is limited at its margins by PGI2 and NO
- plaque rupture -> exposure of blood containing factor VIIa to tissue factor within the plaque, triggering blood coagulation and thrombus formation
- > complete occlusion or embolisation
what is tachycardia?
increased heart rate
what is bradycardia?
decreased heart rate
what is dextrocardia?
heart on the right side of chest instead of left
what is an acute anterolateral myocardial infarction?
ST segments are raised in anterior (V3-V4) and lateral (V5-V6) leads
what is an acute inferior MI?
ST segments are raised in inferior (II, III, aVF) leads
where is atrial repolarisation seen on an ECG?
usually not evident on an ECG since it occurs at the same time as the QRS complex, so it’s hidden
where is the left ventricle palpated?
palpated in the 5th left intercostal space and mid-clavicular line, responsible for the apex beat
what is stroke volume?
the volume of blood ejected from each ventricle during systole
what is cardiac output? how is it calculated?
the volume of blood each ventricle pumps as a function of time (litres per minute)
- cardiac output (L/min) = stroke volume (L) x heart rate (bpm)
what is total peripheral resistance?
the total resistance to flow in systemic blood vessels from beginning of aorta to vena cava; arterioles provide the most resistance
what is preload?
the volume of blood in the left ventricle which stretches the cardiac myocytes before left ventricular contraction - how much blood is in the ventricles before it pumps (end-diastolic volume).
- when veins dilate, it results in a decrease in preload (since by dilating veins the venous return decreases).
what is afterload?
the pressure the left ventricle must overcome to eject blood during
contraction
- dilated arteries = decrease in afterload
what is contractility?
- force of contraction and the change in fibre length; how hard the heart pumps
- when muscle contracts myofibrils stay the same length but the sarcomere shortens; force of heart contraction that is independent of
sarcomere length
what is elasticity?
myocardial ability to recover normal shape after systolic stress
what is diastolic dispensibility?
the pressure required to fill the ventricle to the same
diastolic volume
what is compliance?
how easily the heart chamber expands when filled with blood
what is Starlings law?
- force of contraction is proportional to the end diastolic length of cardiac muscle fibre; the more the ventricle fills, the harder it contracts
- at rest the cardiac muscle is not at optimal length; below optimal length means the force of contraction is decreased/inefficient
what does increased venous return lead to?
increased venous return -> increased end diastolic volume -> increased preload -> increased sarcomere stretch -> increased force of contraction thus -> increased stroke volume and force of contractions
how does standing affect venous return? what does this lead to?
- decreases venous return due to gravity thus, cardiac output decreases
- causes a drop in blood pressure
- stimulates baroreceptors to increase blood pressure
what are the different heart sounds and what do they mean?
S1: mitral and tricuspid valve closure
S2: aortic and pulmonary valve closure
S3: in early diastole during rapid ventricular filling; normal in children and pregnant women; associated with mitral regurgitation and heart failure
S4: gallop, in late diastole, produced by blood being forced into a stiff hypertrophic ventricle; associated with left ventricular hypertrophy
what is angina? what relieves/exacerbates it?
chest pain or discomfort as a result of reversible myocardial ischaemia
- implies narrowing of one or more coronary arteries
- exacerbated by exertion and relieved by rest
what stimulates inflammation in atherosclerosis?
- plaque encroaches upon the lumen and runs the risk of haemorrhage or exposure of tissue HLA-DR antigens which might stimulate T cell accumulation
- drives an inflammatory reaction against part of the plaque contents
what are complications of an atherosclerotic plaque?
ulceration, fissuring, calcification and aneurysm change
what are complications of plaque rupture?
- acute occlusion due to thrombus
- chronic narrowing of vessel lumen with healing of the local thrombus
- aneurysm change
- embolism of thrombus and/or plaque lipid content
what are results of an ECG on angina?
- often normal
- may show ST depression
- flat or inverted T waves
- look for signs of past MI
what are results of a treadmill test/exercise ECG on angina patients?
- put ECG on patient, then make them run on treadmill uphill
- monitor how long patient is able to exercise for
- if you see ST segment depression then this is a sign of late-stage ischaemia
- many patients unsuitable e.g. can’t walk, very unfit, young females and bundle branch block
