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
what are results of the CT scan calcium scoring on angina patients?
CT the heart and if there is atherosclerosis in the arteries then the calcium will light up white - if there is significant calcium then this indicates angina
what are results of SPECT/myoview on angina patients?
- radio-labelled tracer injected into patient
- it’s taken up by the coronary arteries where there is good blood supply; this will light up
- where there is little blood supply these areas will not light up
- if there is no light after exercise then this is indicative of myocardial ischaemia
what is aspirin? what is its action, side effects and an example?
- antiplatelet effect in coronary arteries, thereby avoiding platelet thrombosis
- COX inhibitor; reduces prostaglandin synthesis including thromboxane A2 -> reduced platelet aggregation
- side effect: gastric ulceration
- e.g. salicylate
what are statins? what are their actions?
- HMG-CoA reductase inhibitors; reduces cholesterol produced by the liver
- reduce events and LDL-cholesterol
- anti-atherosclerotic
what is the process in PCI?
- dilating coronary atheromatous obstructions by inflating balloon within it
- insert balloon and stent, inflate balloon and remove it
- stent persists and keeps artery patent
- expanding plaque makes artery bigger
what is LIMA? when is it used?
Left Internal Mammary Artery
- used to bypass proximal stenosis (narrowing) in LAD coronary artery
what are features of a STEMI?
- occlusion of a coronary artery previously affected by atherosclerosis
- this causes full thickness damage of heart muscle
- can usually be diagnosed on ECG at presentation
- will produce a pathological Q wave some time after MI so also known as Q-wave infarction
what are features of unstable angina?
- angina of recent onset (less than 24hrs) or
- cardiac chest pain with crescendo pattern
- deterioration in previously stable angina, with symptoms frequently occurring at rest
- angina of increasing frequency or severity, occurs on minimal exertion or even at rest - form of acute coronary syndrome
what are features of NSTEMI?
- occurs by developing a complete occlusion of a minor or a partial occlusion of a major coronary artery previously affected by atherosclerosis
- is a retrospective diagnosis made after troponin results and sometimes other investigation results are available
- this causes partial thickness damage of heart muscle
- also known as a Non-Q wave infarction; will see ST depression and/or T wave inversion
what is the pathophysiology of UA/MI?
- rupture or erosion of the fibrous cap of a coronary artery plaque
- leading 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 is associated with an increased risk of rupture
- thrombus formation and the vasoconstriction produced by platelet release of serotonin and thromboxane A2 result in myocardial ischaemia due to
reduction of coronary blood flow
what is the difference between pathophysiology in UA and MI?
- in unstable angina the plaque has a necrotic centre and ulcerated cap and the thrombus results in partial occlusion
- in myocardial infarction the plaque also has a necrotic centre but the thrombus results in total occlusion
what is the process of coagulation?
- atheromatous plaque rupture results in platelets being exposed to ADP/thromboxaneA2/adrenaline/thrombin/collagen tissue factor
- this results in platelet activation/aggregation via IIb/IIIa glycoproteins binding to fibrinogen (enables platelets to adhere to each other = aggregation)
- then thrombin (already present in surroundings) is able to enzymatically convert fibrinogen to fibrin (insoluble) resulting in the formation of a fibrin mesh over platelet plug and the formation of a thrombotic clot
what are the types of antiplatelet agents?
- aspirin
- P2Y12 inhibitors (oral)
- glycoprotein IIb/IIIa antagonists (IV)
what are examples of P2Y12 inhibitors? what are some side effects?
clopidogrel, prasugrel and ticagrelor
- side effects: neutropenia, thrombocytopenia, increased risk of bleeding
- avoid if CABG planned
what are examples of glycoprotein IIb/IIIa antagonistst?
- only IV
- e.g. abciximab, triofiban, eptifbatide
- increases risk of major bleeding
what are examples of statins?
simvastatin, pravastatin, atorvastatin
what are examples of ACE inhibitors?
ramipril and lisonopril
what are ECG characteristics of NSTEMI?
ST depression and T wave inversion
what are the differential diagnoses of STEMI?
stable angina, unstable angina, NSTEMI, pneumonia, pneumothorax, oesophageal spasm, GORD, acute gastritis, pancreatitis, MSK chest pain
what is prehospital treatment of acute MI?
- aspirin 300mg chewable
- GTN (sublingual)
- morphine
what is hospital treatment of acute MI?
- IV morphine
- oxygen if sats below 95% or breathless
- beta blocker (atenolol)
- P2Y12 inhibitor (clopidogrel)
when is PCI given to acute STEMI patients? what is the alternative?
- all patients who present with an acute STEMI who can be transferred to a primary PCI centre within 120 minutes of first medical contact
- if not possible then give patient fibrinolysis and then transfer to PCI centre after infusion
what is fibrinolysis?
enhances the breakdown of occlusive thromboses by the activation of plasminogen to form plasmin
what is secondary prevention of acute STEMI?
- statins
- aspirin long term
- warfarin if large MI
- beta blockers
- ACE inhibitors
what are complications of MI?
- sudden death
- arrhythmias
- persistent pain
- heart failure
- mitral incompetence
- pericarditis
- cardiac rupture
- ventricular aneurysm
when does sudden death after MI occur?
often within hours due to ventricular fibrillation
when do arrhythmias after MI occur?
in first few days due to electrical instability following infarction, pump failure and excessive sympathetic stimulation
when does persistent pain after MI occur?
12 hours to a few days after due to progressive myocardial necrosis
why does heart failure occur after MI?
- when CO is insufficient to meet the body’s metabolic demands
- due to ventricular dysfunction following muscle necrosis also resulting in arrhythmias
when does mitral incompetence occur after MI?
- in first few days or later
- due to myocardial scarring preventing valve closure
why does pericarditis after MI occur?
due to transmural infarct resulting in inflammation of pericardium, more common in STEMI
why does cardiac rupture occur after MI?
- early rupture: shearing between mobile and immobile myocardium
- late rupture: due to weakening of wall following muscle necrosis and acute inflammation
why does ventricular aneurysm occur after MI?
due to stretching of newly formed collagenous scar tissue
what is the function of the pericardium? what does it consist of?
- acts as a protective covering for the heart
- consists of an outer fibrous pericardial sac and an inner serous pericardium
what are the layers of the heart from outside to inside?
pericardium, myocardium, endocardium
what is the inner serous pericardium made up of?
- inner visceral pericardium: single cell layer that’s adherent to the epicardium (myocytes), that lines the heart and great vessels, and its reflection
- outer parietal pericardium: mainly collagen and elastin fibres, with no cells, that lines the fibrous sac
- in between the layers is around 50ml of serous fluid that acts as a lubricant to allow the two surfaces to move over each other easily
what is inbetween the inner visceral pericardium and the outer parietal pericardium?
in between the layers is around 50ml of serous fluid that acts as a lubricant to allow the two surfaces to move over each other easily
what lies in/outside of the pericardium?
- great vessels lie in the pericardium; if the proximal segment (ascending) of the aorta is ruptured then it will bleed in into the pericardial space and result in a cardiac tamponade
- left atrium is mainly outside the pericardium
what happens if the ascending aorta is ruptured?
if the proximal segment (ascending) of the aorta is ruptured then it will bleed in into the pericardial space and result in a cardiac tamponade
what are the functions and actions of the pericardium?
- it promotes cardiac efficiency by limiting dilation, maintaining ventricular compliance and distributing hydrostatic forces
- aids atrial filling by creating a closed chamber, reduces external friction and acts as a barrier against infection and extension of malignancy
- anatomically fixes the heart to the sternum, diaphragm and costal cartilages
how is the pericardium similar to an elastic band?
initially stretchy but becomes stiff at higher tension, thus at low tension the pericardium has a small reserve volume
what happens if the small reserve volume of the pericardium is exceeded?
- if this volume is exceeded the pressure is translated to the cardiac chambers and thus puts pressure on the heart
- small amount of volume added to this space has dramatic effects on filling e.g a cardiac tamponade
what is the pressure in the pericardium?
very low
what happens in a chronic pericardial effusion?
in a chronic pericardial effusion, the pericardium adapts slowly by laying down elastin and collagen and becomes more elastic so there is a much slower tamponade (thus there is no collapse of the right atrium) since the pressure equalises - but the entrance of fluid making up the effusion must be slow
what is acute pericarditis?
acute inflammation of the pericardium; with or without effusion
what is the epidemiology of acute pericarditis?
- majority are idiopathic and most commonly seen in the young, previously healthy patient
- occurs in men more than women
- occurs in adults more than children
what are infectious causes of acute pericarditis?
viral (common):
• enteroviruses e.g. coxsackieviruses and echoviruses
• adenoviruses
• HIV
bacterial:
- Mycobacterium tuberculosis (other bacteria are rare)
fungal (very rare):
• Histoplasma spp. - most likely to be seen in
immunocompromised patient
what are non-infectious causes of acute pericarditis?
- autoimmune (common): • sjorgrens syndrome • rheumatoid arthritis • SLE - neoplastic; secondary metastatic tumours (common, above all is lung or breast cancer, and also leukaemia and lymphoma) - dressler’s syndrome - post cardiac injury syndromes - traumatic and iatrogenic - uraemia
what are trauma and iatrogenic causes of acute pericarditis?
early onset (rare):
- direct injury - penetrating thoracic injury or oesophageal perforation
- indirect injury - non-penetrating thoracic injury or
radiation
delayed onset (common):
- pericardial injury syndromes (common)
- iatrogenic trauma e.g. coronary percutaneous
intervention or pacemaker lead insertion
what is the pathophysiology of acute pericarditis?
- pericardium becomes acutely inflamed, with pericardial vascularisation and infiltration with polymorphonuclear leukocytes
- a fibrinous reaction frequently results in exudate and adhesions within the pericardial sac, and a serous or haemorrhagic effusion may develop
what is the clinical presentation of acute pericarditis?
- sharp retrosternal chest pain which is characteristically relieved by leaning forward
- pain may be worse on inspiration and radiate to the neck and shoulders
- dysponea
- cough
- hiccups due to phrenic involvement
- pericardial friction rub present on auscultation
- fever and lymphocytosis (increase in lymphocytes) if due to virus or bacteria
- tachycardia
what is the chest pain of acute pericarditis like?
- severe
- sharp and pleuritic (without constricting crushing character of ischaemic pain)
- rapid onset
- worse on inspiration or lying flat; relieved by sitting forward
- left anterior chest or epigastrium
- radiates to arm, more specifically the trapezius ridge (has co-innervation with the phrenic nerve), whereas a STEMI would be arms, jaw and teeth
what are differential diagnoses of acute pericarditis?
- angina
- MI
- pleuritic pain
- pulmonary infarction
- pneumonia, GI reflux, peritonitis and aortic dissection
how is acute pericarditis diagnosed on ECG?
- ECG is diagnostic
- widespread concave (upwards) saddle shaped ST elevation
- diffuse ST segment elevation - present in all leads (must exclude STEMI which would have ST segment elevation but will be limited to the infarcted area e.g. anterior or inferior)
- return towards baseline as inflammation subsides
- PR depression
how is acute pericarditis diagnosed with CXR?
- may demonstrate cardiomegaly in cases of effusion; if found then confirm with echocardiography
- often normal in idiopathic
- pneumonia is common with bacterial pericarditis
how is acute pericarditis diagnosed with FBC?
- slight increase in white cell count
- anti Neutrophil Antibody in young females - SLE
- troponin - elevation suggests myopericarditis
what is treatment of acute pericarditis?
- restrict physical activity until resolution of symptoms and see improvement in ECG and CRP
- treatment of underlying disorder
- NSAID e.g ibuprofen for two weeks or aspirin for two weeks
- systemic corticosteroids in resistant cases
- colchicine for 3 weeks however is limited by nausea and diarrhoea but does reduce recurrence
what is recurrent or relapsing pericarditis?
- about 20% of cases of acute pericarditis go on to develop idiopathic relapsing pericarditis
- this may occur within 6 weeks during weaning off NSAIDs or intermittently i.e. recurs more than 6 weeks after the initial presentation
what is treatment of recurrent or relapsing pericarditis?
- the first line treatment is oral NSAIDs e.g. ibuprofen
- colchicine has been proven to be more effective than aspirin alone
- in resistant cases, oral corticosteroids e.g. prednisolone may be effective, and in some patients, pericardiectomy (removal of part/most of the pericardium) may be appropriate
what is a pericardial effusion? when does it often occur?
- a pericardial effusion is an accumulation of fluid within the potential space of the serous pericardial sac
- it commonly accompanies an episode of acute pericarditis
- can be caused by hypothyroidism which rarely compromises ventricular function
what is a cardiac tamponade?
when a large volume of pericardial fluid collects in the potential space of the serous pericardial sac (often accumulated rapidly) leads to restricted diastolic ventricular filling, leading to marked reduction in the cardiac output/haemodynamic compromise
what are clinical presentations of pericardial effusion?
- symptoms of a pericardial effusion commonly reflect the underlying pericarditis
- soft and distant heart sounds
- apex beat obscured
- raised jugular venous pressure
- dysponea
what are clinical presentations of cardiac tamponade?
- high pulse but low blood pressure
- hypotension
- tachycardia
- high jugular venous pressure
- muffled 1st and 2nd heart sounds
- Kussmaul’s sign - rise in jugular venous pressure and increased neck vein distension during inspiration
- pulsus paradoxus - an exaggeration in the normal variation in pulse pressure seen with inspiration, such that there is a drop in systolic blood pressure
- reduced cardiac output
what is Kussmaul’s sign?
rise in jugular venous pressure and increased neck vein distension during inspiration
- sign of cardiac tamponade
what is pulsus paradoxus? what is it caused by?
- a fall in BP of more than 10mmHg on inspiration
- due to increased venous return to the right side of the heart during inspiration
- increased right ventricular volume occupies more space within the rigid pericardium and impairs left ventricular filling
- sign of cardiac tamponade
how is pleural effusion diagnosed with CXR, ECG and echocardiogram?
CXR:
• large globular heart
ECG:
• low-voltage QRS complexes
• sinus tachycardia
Echocardiogram:
• most useful for demonstrating effusion
• echo-free zone surrounding heart
what is Beck’s triad?
- falling blood pressure
- rising jugular venous pressure
- muffled heart sounds
how is cardiac tamponade diagnosed with CXR, ECG and echocardiogram?
CXR:
• big globular heart
Beck’s triad
ECG
- low voltage QRS
Echocardiogram:
• is diagnostic
• echo-free zone around heart
• late diastolic collapse of right atrium (because most of left atrium is outside pericardium)
• early diastolic collapse of right ventricle
what is treatment of pericardial effusion?
- underlying cause should be sought and treated if possible
- most pericardial effusions resolve spontaneously
- pericardial effusions may re-accumulate most often due to malignancy - this may require a pericardial fenestration (a window in the pericardium is created
to allow the slow release of fluid into the surrounding tissues)
what is a pericardial fenestration?
a window in the pericardium is created to allow the slow release of fluid into the surrounding tissues
- used in reccuring pleural effusion
what is treatment of cardiac tamponade?
- seek expert help
- requires urgent drainage via pericardiocentesis which will drain the fluid to relieve the pressure on the heart
- send fluid for culture, Ziehl-Nielsen stain and for cytology
what is the epidemiology of constrictive pericarditis?
- certain causes of pericarditis such as tuberculosis, bacterial infection and rheumatic heart disease result in the pericardium becoming thick, fibrous and calcified
- cause is often unknown and can occur after any pericarditis
- most cases are idiopathic or from intrapericardial haemorrhage during heart surgery
what causes of pericarditis cause it to become thick, fibrous and calcified?
tuberculosis, bacterial infection and rheumatic heart disease
what is the pathophysiology of constrictive pericarditis?
- in many cases, these pericardial changes do not cause any symptoms
- heart becomes encased within a rigid fibrotic pericardial sac which prevents adequate diastolic filling of the ventricles
why is constrictive pericarditis not immediately life-threatening?
as these changes are chronic, allowing the body time to compensate, this condition is not as immediately life-threatening as in cardiac tamponade, in which the circulation is more acutely embarrassed
what happens in the later stages of constrictive pericarditis?
the sub-endocardial layers of myocardium may undergo fibrosis, atrophy and calcification
what is the clinical presentation of constrictive pericarditis?
- Kussmaul’s sign - rise in jugular venous pressure and increased neck vein distension during inspiration
- pulsus paradoxus - an exaggeration in the normal variation in pulse pressure seen with inspiration, such that there is a drop in systolic blood pressure
- diffuse heart sounds
- ascites
- oedema
- right heart failure signs
- atrial dilatation
- AF
- pericardial knock on auscultation caused by rapid ventricular filling
- jugular venous distension
- hepatomegaly
how is constrictive pericarditis diagnosed with CXR, ECG, echocardiography?
CXR:
• small/normal heart with/without pericardial calcification
ECG:
• low-voltage QRS
Echocardiography:
• thickened, calcified pericardium
• small ventricular cavities with normal wall thickness
what is treatment of constrictive pericarditis?
complete resection of the pericardium - risky with high complication rate
what is cardiomyopathy?
group of diseases of the myocardium that affect the mechanical (hypertrophic, arrhythmogenic right ventricular, dilated and restrictive cardiomyopathy) or electrical function (conduction system disease and ion channelopathies, e.g. long QT syndrome) of the heart
what is the epidemiology of cardiomyopathy?
- all carry an arrhythmic risk
- can occur at younger ages
- restrictive cardiomyopathy is rare in childhood and has a poor outcome once symptoms develop
- in general they are inherited genetic conditions although there are some acquired ones
what are the 4 types of cardiomyopathy?
- hypertrophic
- dilated
- primary restricted
- arrythmogenic right ventricular
what are risk factors for cardiomyopathy?
- family history of cardiomyopathy
- high blood pressure
- obesity
- diabetes
- previous MI
what is hypertrophic cardiomyopathy?
- hypertrophic cardiomyopathy (HCM) is characterised by marked ventricular hypertrophy in the absence of abnormal loading conditions such as hypertension and valvular disease
- there is usually disproportionate involvement of the interventricular septum
- the hypertrophic non-compliant ventricles impair diastolic filling, so that stroke volume is reduced
- most cases are familial, autosomal dominant and caused by mutations in genes encoding sarcomeric proteins, e.g. troponin T and β-myosin
- it is the most common cause of sudden cardiac death in young people.
what is the epidemiology of hypertrophic cardiomyopathy?
- quite common, second most common cardiomyopathy (behind dilated)
- 1/500 people have it
- autosomal dominant - familial
- may present at any age
- most common cause of sudden cardiac death in the young
- HCM refers to otherwise unexplained primary cardiac hypertrophy
what is the pathophysiology of hypertrophic cardiomyopathy?
- caused by sarcomeric protein gene mutations e.g troponin T and B-myosin
- all in the absence of hypertension and valvular disease
- the hypertrophic, non-compliant ventricles impair diastolic filling resulting in reduced stroke volume and thus cardiac output
- another issue with thick powerful heart is that there is a disarray of cardiac myocytes so conduction is affected
what is the clinical presentation of hypertrophic cardiomyopathy?
- hypertrophy of the myocardium, particularly the intraventricular septum
- sudden death may be the first manifestation
- chest pain, angina, breathlessness, dysponea, dizziness, palpitations, syncope
- left ventricular outflow obstruction may be a feature
- cardiac arrhythmia
- ejection systolic murmur
- jerky carotid pulse
- pansystolic murmur of functional mitral regurgitation
what is the diagnosis of hypertrophic cardiomyopathy by an ECG?
ECG is abnormal and shows signs of left ventricular hypertrophy with progressive T wave inversion and deep Q waves
what is the diagnosis of hypertrophic cardiomyopathy by an echocardiogram?
shows ventricular hypertrophy and a small left ventricle cavity, and fibrosis
what is the diagnosis of hypertrophic cardiomyopathy by genetic analysis?
genetic analysis can confirm diagnosis since most cases are autosomal dominant and familial, and provide prognostic information
what is the treatment of hypertrophic cardiomyopathy?
- amiodarone - anti-arrythmatic medication, if at high risk of arrhythmia then can place an implantable cardiac defibrillator
- calcium channel blocker e.g. verampil
- beta-blocker e.g. atenolol
- vasodilators avoided because they may aggravate left ventricular outflow obstruction or cause refractory hypotension
- outflow tract gradients can be reduced by surgical resection or alcohol ablation of the septum, or by dual-chamber pacing
what is dilated cardiomyopathy?
dilated left ventricle which contracts poorly/has thin muscle
what is the epidemiology of dilated cardiomyopathy?
- most common cardiomyopathy
- autosomal dominant - familial
- can be caused by; ischaemia, alcohol, thyroid disorder or familial/genetic
what can dilated cardiomyopathy be caused by?
ischaemia, alcohol, thyroid disorder, familial/genetic
what is the pathophysiology of dilated cardiomyopathy?
- caused by cytoskeletal gene mutations
- left ventricle or right ventricle or all 4 chamber dilatation and thus dysfunction
- theory is that poorly generated contractile force leads to progressive dilatation of heart with some diffuse interstitial fibrosis
what is the clinical presentation of dilated cardiomyopathy?
- shortness of breath at first and fatigue
- dysponea
- heart failure since heart can’t contract
- arrhythmias
- thromboembolism
- sudden death
- increased jugular venous pressure
what is the diagnosis of dilated cardiomyopathy with CXR, ECG and echo?
• CXR: cardiac enlargement
• ECG: tachycardia, arrhythmia and T wave flattening
• echo: shows dilated ventricles with global hypokinesis
- cardiac MR may show other aetiologies of left ventricular dysfunction, e.g. previous MI
what is the treatment of dilated cardiomyopathy?
- heart failure and AF are treated in a conventional way
- cardiac resynchronisation therapy and ICDs are used in patients with NYHA III/IV grading
- severe cardiomyopathy treated with cardiac transplantation
what is the epidemiology/causes of restricted cardiomyopathy?
causes are amyloidosis, idiopathic, sarcoidosis, end-myocardial fibrosis
what is the pathophysiology of restricted cardiomyopathy?
- there is normal or decreased volume of both ventricles with bi-atrial enlargement, normal wall thickness, normal cardiac valves and impaired ventricular filing
- restrictive physiology
- poor dilation of the heart restricts its the ability of the heart to take on blood and pass it to the rest of the body
- rigid myocardium restricts diastolic ventricular filling
what is the clinical presentation of restricted cardiomyopathy?
- similar to constrictive pericarditis
- dysponea, fatigue and embolic symptoms
- elevated jugular venous pressure with diastolic collapse and elevation of venous pressure with inspiration
- hepatic enlargement, ascites and dependent oedema
- third and fourth heart sounds
what is the diagnosis of restricted cardiomyopathy?
- CXR, echo and ECG are abnormal but non-specific
- cardiac catheterisation helps to diagnose restrictive cardiomyopathy, and shows characteristic pressure changes
- endomyocardial biopsy may be taken during catheter procedure, providing histological diagnosis
what is the treatment of restricted cardiomyopathy?
- no specific treatment with poor prognosis
- patients die within a year
- can consider cardiac transplantation
what is the epidemiology of arrythmogenic right ventricular cardiomyopathy?
- progressive genetic cardiomyopathy characterised by progressive fatty and fibrous (fibro-adipose) replacement of right ventricular myocardium
- cause is unknown
- familial form is usually autosomal dominant with incomplete penetrance but can be recessive
what is arrythmogenic right ventricular cardiomyopathy?
progressive genetic cardiomyopathy characterised by progressive fatty and fibrous replacement of ventricular myocardium
what is the pathophysiology of arrythmogenic right ventricular cardiomyopathy?
- desmosome (normally holds cardiac cells together) gene mutation
- right ventricle replaced by fat and fibrous tissue
- muscle dies and replaced by fat as part of inflammatory process
what is the clinical presentation of arrythmogenic right ventricular cardiomyopathy?
- cardiac cells are held less together thus conduction issues
- arrhythmia is most common feature
- ventricular tachycardia
- sudden death in a young man
- syncope
- in late stages may be signs of right heart failure
what is diagnosis of arrythmogenic right ventricular cardiomyopathy?
- ECG usually normal but may show T wave inversion
- echo may also be normal but in advanced disease may show right ventricular dilation
- genetic testing is the gold standard
what is the treatment of arrythmogenic right ventricular cardiomyopathy?
- beta-blockers e.g. atenolol for patients with non-life-threatening arrhythmias
- amiodarone for symptomatic arrhythmias
- occasionally cardiac transplant indicated i.e. in cardiac failure or devastating arrhythmia
what is the epidemiology of structural/congenital heart defects?
• 1% of all live births have some form of cardiac defect - common
• vary from minor to incompatible with life ex-utero
• there is an overall male predominance
• although some individual lesions such as atrial septal defect and persistence ductus arteriosus occur more commonly in females
• usually due to misplaced structures or the arrest of the progression of normal
structure development
what are the causes of congenital heart disease?
- one child with defect increases the chance of the second child having another defect
- maternal prenatal rubella infection - persistent ductus arteriosus and pulmonary valvular and arterial stenosis
- maternal alcohol misuse - septal defects
- single genes associated e.g. Trisomy 21 (Down’s - septal, mitral and tricuspid valve defects)
- drugs e.g. Thalidomide, Amphetamines and Lithium
- diabetes of mother
- genetic abnormalities e.g. the familial form of arterial spatial defect and congenital heart block
what is central cyanosis?
occurs because of right-left shunting of blood or because of complete mixing of systemic and pulmonary blood flow resulting in poorly oxygenated blood entering the systemic circulation
what causes pulmonary hypertension?
- results from large left-to-right shunts
- the persistently raised pulmonary flow leads to the development of increased pulmonary artery vascular resistance and consequent pulmonary hypertension
- this resistance is due to the thickening of the vascular walls of the pulmonary arteries in response to the higher pressure
what is Eisenmenger’s reaction? what is it caused by?
- the increased pulmonary artery vascular resistance caused by pulmonary hypertension causes right ventricular pressure to increase and causes the reversal of a shunt to right-to-left resulting in the patient going blue i.e. cyanosis
- known as Eisenmenger’s complex specifically in relation to a ventricular-septal defect
what are features of syncope with congenital heart disease/septal defects?
- common when severe right or left ventricular outflow tract obstruction is present
- exertional syncope is associated with keeping central cyanosis and may occur in Fallot’s tetralogy
what is the clinical presentation of congenital heart disease/septal defects?
- central cyanosis
- pulmonary hypertension
- clubbing of the fingers (associated with prolonged cyanosis)
- growth retardation
- syncope
- adolescents and adults present with specific common problems related to the longstanding structural nature of these conditions
what may adolescents and adults with congenital heart disease present with?
- endocarditis - especially in small ventricular septal defects or bicuspid aortic valve
- calcification and stenosis of congenitally deformed valves e.g. bicuspid aortic valve
- atrial and ventricular arrhythmias
- sudden cardiac death
- right heart failure
- end-stage heart failure
what is the classification of congenital heart disease?
- acyanotic or cyanotic
- with or without shunts
what are some acyanotic congenital heart diseases with shunts?
- atrial septal defect
- ventricular septal defect
- patent ductus arteriosus
- partial anomalous venous drainage
what are some acyanotic congenital heart diseases without shunts?
- coarctation of the aorta
- congenital aortic stenosis
what are some cyanotic congenital heart diseases with shunts?
- Fallot’s tetralogy
- transposition of the great vessels
- severe Ebstein’s anomaly
what are some cyanotic congenital heart diseases without shunts?
- severe pulmonary stenosis
- tricuspid atresia
- pulmonary atresia
- hypoplastic left heart
what is the definition of hypertension?
- high BP
- clinical BP of 140/90mmHg or higher, based on at least two readings on separate occasions
- level of BP is abnormal when it is associated with a clear increase in morbidity and mortality from heart disease, stroke and renal failure; this level varies with age, sex, race and country
what is hypertension a major risk factor for?
- stroke - ischaemic and haemorrhagic
- myocardial infarction
- heart failure
- chronic renal disease - causes and is caused by hypertension
- cognitive decline
- premature death
how does hypertension affect the risk of atrial fibrillation?
increases the risk of atrial fibrillation which in turn increases the risk of stroke and emboli due to the fact that there is some stasis of blood in the fibrillating atria
resulting in thrombus formation that can easily lead to emboli
how is hypertension diagnosed?
people with suspected hypertension are offered ambulatory blood pressure monitoring (ABPM - over 24 hours) to confirm a diagnosis of hypertension
what are factors controlling BP and targets for BP control therapy?
- cardiac output x Peripheral resistance = BP, can target peripheral resistance to alter BP
- local vascular vasoconstrictor and vasodilator mediators
- interplay between RAAS and sympathetic nervous system (noradrenaline)
briefly describe the Renin-Angiotensin-Aldosterone system and how it relates to hypertension
- most drugs aim to block RAAS
- kidney senses low BP and renin is released from the
juxtaglomerular cells - renin converts angiotensinogen to angiotensin I
- ACE from the lungs converts angiotensin I to angiotensin II
- angiotensin II (extremely potent vasoconstrictor) stimulates aldosterone release resulting in increased Na+ and thus water reabsorption which leads to increased blood volume and thus blood pressure
- thus angiotensin II increases peripheral resistance and inhibitors target this
briefly describe the sympathetic nervous system and how it relates to hypertension?
- drop in BP also sends signals to the brain resulting in the release of noradrenaline resulting in vasoconstriction and increased contractility of the heart thus increasing peripheral resistance and
cardiac output and thus BP - sympathetic nervous system also results in renin release
what are the effects of angiotensin II?
- increased peripheral resistance
- increase cardiac output
- vascular growth (hyperplasia and hypertrophy)
- salt retention (aldosterone release and tubular sodium reabsorption)
what are the actions of noradrenaline?
- increased renin
- increased peripheral resistance
- increased cardiac output
what are 5 examples of ACE inhibitors?
- ramipril
- enalapril
- perindopril
- lisinopril
- trandolapril
what are the main adverse effects of ACE inhibitors related to?
- reduced angiotensin II formation
- increased kinin production
what are some adverse effects of ACE inhibitors due to reduced angiotensin II formation?
• first dose hypotension
• acute renal failure:
- if excess ACE inhibitor is given then kidney will detect drop and releases more renin and thus BP increases further which can lead to renal failure
• hyperkalaemia
• teratogenic effects in pregnancy - since angiotensin II is important for baby development
• leucopenia
• proteinuria
what are some adverse effects of ACE inhibitors due to increased kinin production?
• dry chronic cough:
- this is because ACE also breaks down bradykinin
(inflammatory mediator) so if you inhibit it then there will be increased bradykinin resulting in cough
• rash - due to increased bradykinin
• anaphylactoid reaction - due to increased bradykinin
what do ARBs act on?
AT-1 receptor (angiotensin receptor): selectively block these
what are 5 examples of angiotensin II receptor blockers (ARB)?
- candesartan
- losartan
- valsartan
- irbesartan
- telmisartan
what are main adverse effects/contraindications of angiotensin II receptor blockers (ARB)?
- symptomatic hypotension (especially volume deplete patients e.g. dehydrated and severe blood loss)
- hyperkalaemia
- potential renal dysfunction
- rash
- angio-oedema
- contraindicated in pregnancy
- generally very well tolerated
what are 5 examples of calcium channel blockers?
- amlodipine
- diltiazem
- verapamil
- nifedipine
- felodipine
- lacidipine
what is the action of calcium channel blockers?
- vasodilators
- dilatation of peripheral arterioles
- diltiazem and verapamil have effects on electrical conductivity
what are examples of dihydropyridines (CCB) and what are their actions?
dihydropyridines e.g. nifedipine, amlodipine, felodipine, lacidipine:
- preferentially affect vascular smooth muscle
- peripheral arterial vasodilators
what are examples of phenylalkylamines (CCB) and what are their actions?
phenylalkylamines e.g. verapamil:
- main effect is on heart
- reduce HR (negatively chronotropic) and force of
contraction of the heart (negatively inotropic)
what are examples of benzothiozepines (CCB) and what are their actions?
benzothiozepines e.g. diltiazem:
- intermediate heart/peripheral vascular effects
what are adverse effects of calcium channel blockers?
- due to peripheral vasodilation: • flushing • headache • oedema • palpitations - due to negatively chronotropic effects cardiac conduction defects: • bradycardia • atrioventricular block • postural hypotension - due to negatively inotropic effects: worsening of cardiac failure - verapamil causes constipation
what are 6 examples of beta-adrenoceptor blockers?
- bisoprolol
- carvedilol
- propranolol
- metoprolol
- atenolol (antagonist at beta-1 adrenoceptor)
- nadolol
how can beta blockers be used in asthma?
use blockers smartly e.g. use selective B-1 (but note selectivity is linked to dose so best to avoid in asthma) in asthma since if non-selective used then will block B-2 resulting in airway constriction and thus the worsening of asthma
what are the most selective and least selective beta blockers?
beta1 selective
- metoprolol
- bisoprolol
middle
- atenolol
beta1/beta2 (non selective)
- propranolol
- nadolol
- carvedilol
what are main adverse effects of beta-adrenoceptor blockers?
- fatigue
- weakness
- headache
- sleep disturbance/nightmares
- bradycardia
- hypotension
- cold peripheries
- erectile dysfunction
- bronchospasm
what is there worsening of in use of beta-adrenoceptor blockers?
- asthma or COPD by inducing bronchospasm
- PVD - claudication or raynauds
- heart failure if given in standard dose or acutely - give blockers in small doses and increase slowly
what are classes of diuretics?
- thiazides (cause Na+ and thus water loss in urine) and related drugs - act on distal tube - less potent, tend to end in ‘thiazide’
- loop diuretics (act on loop of Henle; more potent)
- potassium sparing diuretics
- aldosterone antagonists
what are 3 examples of thiazides (diuretics)?
- bendroflumethiazide
- hydrochlorothiazide
- chlorothalidone
what are 2 examples of loop diuretics?
- furosemide (blocks NKCC2 transporter)
- bumetanide
what are 2 examples of potassium-sparing diuretics?
- spironolactone
- eplerenone
what are the main adverse effects of diuretics?
- hypovolaemia (mainly loop diuretics e.g. furosemide)
- hypotension (mainly loop diuretics e.g. furosemide)
- hypokalaemia
- hyponatraemia
- hypomagnesaemia
- hypocalcaemia
- hyperuricaemia
- erectile dysfunction (mainly thiazides e.g. bendroflumethiazide)
- impaired glucose tolerance i.e. diabetes (mainly thiazides e.g. bendroflumethiazide)
what are other classes of antihypertensives?
- alpha-1 adrenoceptor blockers
- centrally acting anti-hypertensives (i.e. on the brain)
- direct renin inhibitors
what is 1 example of alpha-1 adrenoceptor blockers?
doxazosin
what are 2 examples of centrally acting anti-hypertensives?
- moxonidine
- methyldopa (can be used in pregnancy)
what is 1 example of direct renin inhibitors?
aliskiren
what is step 1 in anti-hypertensive therapy for under 55s/over 55s/Afro-Caribbeans?
under 55yrs: ACE-inhibitor or angiotensin II receptor blocker
over 55yrs/Afro-Caribbean any age: calcium channel blocker
what is step 2 in anti-hypertensive therapy?
ACEi/ARB + CCB
what is step 3 in anti-hypertensive therapy?
ACEi/ARB + CCB + thiazide-like diuretic
what is step 4 in anti-hypertensive therapy?
resistant hypertension; consider addition of:
- further diuretic therapy e.g. spironolactone
- high dose thiazide-like diuretic
- alpha blocker
- beta blocker
- others
what is symptomatic treatment of congestion in chronic heart failure?
diuretics, usually loop diuretics
what is disease influencing therapy (neurohumoral blockade) for chronic heart failure?
- inhibition of RAAS e.g. ACE-inhibitors and ARB’s
- inhibition of the sympathetic nervous system e.g. beta-blockers such as bisoprolol which are effective at blocking reflex sympathetic responses which stress the failing heart
what is first line treatment for chronic heart failure?
- ACE inhibitors e.g. ramipril and beta-blocker e.g. bisoprolol
- low dose and slow uptitration
what is second line treatment for chronic heart failure?
- aldosterone antagonists
- if ACE-inhibitor intolerant then give ARB’s (not as good as ACE-i) e.g. candesartan
- if ACE-I and ARB intolerant then give hydralazine/nitrate combination (peripheral vasodilators)
what stimulates cardiac natriuretic peptide release?
- stretching of atrial and ventricular muscle cells
- raised atrial or ventricular pressures
- volume overload
what are the main effects of cardiac natriuretic peptides?
• increased renal excretion of sodium and water
• relax vascular smooth muscle (except efferent arteriole of renal glomeruli to preserve filtration pressure in kidney whilst still removing Na+ and thus H2O thus no renal damage)
• increased vascular permeability
• inhibits the release or actions of:
- aldosterone, angiotensin II, endothelin (most potent
vasoconstrictor) and ADH
• counter-regulatory system to RAAS
what are natriuretic peptide levels like in heart failure?
raised natriuretic peptides in serum blood
what are cardiac natriuretic peptides metabolised by?
neural endopeptidase (NEP or neprilysin)
what is the pharmacological treatment of raised cardiac natriuretic peptides/heart failure?
- sacubitril: neprilysin inhibitor
- valsartan: ARB
- entresto: combination of sacubitril and valsartan; very effective in heart failure
what is entresto a combination of?
sacubitril and valsartan
- used in heart failure
what are the effects/actions of nitrates?
- arterial and venous dilators
- reduce preload and afterload
- lower BP
what are the indications for nitrates?
ischaemic heart disease (angina) and heart failure
what are 3 examples of nitrates?
- isosorbide mononitrate (long acting)
- GTN spray (sublingual spray, potent vasodilator, headache)
- GTN infusion
what are the main adverse effects of nitrates?
headache and GTN spray syncope as well as potential tolerance to the drug
what are 4 examples of lipid-lowering therapy/statins?
- simvastatin
- atorvastatin
- rosuvastatin
- pravastatin
what is first line treatment for chronic stable angina?
- beta blocker e.g. bisoprolol
* calcium channel blocker e.g. amlodipine
what are 3 examples of long acting nitrates?
- ivabradine
- nicorandil
- ranolazine
what are 3 examples of P2Y12 inhibitors?
- ticagrelor
- prasugrel
- clopidogrel
what are 3 examples of glycoprotein IIb/IIIa inhibitors (IV)?
- tirofiban
- eptifbatide
- abciximab
what are class 1 antiarrhythmic drugs?
sodium channel blocker e.g. flecainide
what are class 2 antiarrhythmic drugs?
beta-adrenoceptor blockers
what are class 3 antiarrhythmic drugs?
prolong the action potential
- amiodarone
- sotalol
- potential for significant side effects
what are class 4 antiarrhythmic drugs?
calcium channel blockers:
• verapamil (more effective than amlodipine since it doesn’t affect the calcium channel at rest)
• dilatizem
• amlodipine
what is digoxin? what is its action?
- antiarrythmic drug
- cardiac glycoside
- inhibits the Na/K pump
what is the main effect of digoxin on the heart?
- bradycardia (due to increased vagal parasympathetic tone)
- increased ectopic activity - can trigger extra heartbeats i.e. minor arrhythmias
- increased force of contraction (direct positive inotropic effect on heart muscle) by increased intracellular Ca2+
- slowing of AV conduction
what are the side effects of digoxin?
narrow therapeutic range; need to have precise amount to have desired effects otherwise get side effects:
- nausea, vomiting, diarrhoea and confusion
when is digoxin used?
- used in atrial fibrillation to reduce ventricular rate response
- used in severe heart failure as a positive inotropic (increases heart contractility)
what are adverse effects of amiodarone?
- QT prolongation
- polymorphic ventricular tachycardia
- interstitial pneumonitis
- abnormal liver function
- hyperthyroidism/hypothyroidism
- sun sensitivity
- slate grey skin discolouration
- optic neuropathy - effect optic nerve
- multiple drug interactions
- very large volume of distribution - gets into all tissues and can take up to 3 months to clear system
what drugs can result in QT prolongation?
amiodarone and sotalol; can be fatal
what is the definition of cardiac failure?
- the inability of the heart to deliver blood and thus O2 at a rate that is commensurate with the requirements of the metabolising tissues, despite normal or increased cardiac filling pressures
- is a syndrome of breathlessness, tiredness and fluid overload caused by a form of cardiac dysfunction; not a diagnosis on its own
- can result from any structural or functional cardiac disorder that impairs the hearts ability to function and meet the demands of supplying sufficient oxygen and nutrients to the metabolising body
what is the epidemiology of cardiac failure?
- 25-50% of patients die within 5 years of diagnosis
- 1-3% of the general population
- around 10% in patients over 65yrs
what are the main causes of cardiac failure?
- ischaemic heart disease (IHD)
- cardiomyopathy
- hypertension
what are the risk factors for cardiac failure?
- 65 and older
- African descent
- men
- obesity
- previous MI
what is the pathophysiology of cardiac failure?
- when the heart begins to fail, there are many systems involved that initiate physiological compensatory changes that try to maintain cardiac output and peripheral perfusion in order to negate the effects of the heart failure
- as heart failure progresses, these mechanisms are overwhelmed and become pathophysiological also known as decompensation
what are the mechanisms that lead to decompensation in cardiac failure?
- venous return (preload)
- outflow resistance (afterload)
- sympathetic system activation
- RAAS
what are symptoms of heart failure?
- breathlessness
- tiredness
- cold peripheries
- leg swelling
- increased weight
- exertional dyspnoea
- orthopnoea
- paroxysmal nocturnal dyspnoea
- fatigue
what are signs of heart failure?
- tachycardia
- displaced apex beat
- raised JVP
- added heart sounds/murmurs
- cardiomegaly with a displaced apex beat, third and fourth heart sounds
- bi-basal lung crackles
- pleural effusion
- ankle oedema
- ascites
- tender hepatomegaly
how does venous return (preload) lead to cardiac failure?
- myocardial failure leads to a reduction of the volume of blood ejected with each heart beat, and an increase in the volume of blood remaining after systole
- this increased diastolic volume stretches the myocardial fibres and myocardial contraction is restored since the stretching of myocardial fibres will increase its force of contraction
- in heart failure, the failing myocardium actually doesn’t contract as much in response to increased preload meaning cardiac output cannot be maintained and may decrease
what is outflow resistance (afterload)?
the load of resistance against which the ventricle contracts
what is the outflow resistance (afterload) made up of?
- pulmonary and systemic resistance
- physical characteristics of the vessel walls
- the volume of blood that is ejected
how does outflow resistance (afterload) cause cardiac failure?
- when there is an increase in afterload there is a increase in end-diastolic volume and a decrease in stroke volume and thus a decrease in cardiac output
- this results in a increase of end-diastolic volume and dilatation of the ventricle itself (the more the ventricle is dilated the harder it must work i.e. the more resistance there is to contract against) which further exacerbates the problem of afterload
how does sympathetic activation affect heart function?
increases the force of contraction of the heart which increases stroke volume as well as heart rate - both resulting in an increase in cardiac output
what are the effects of sympathetic system activation in cardiac failure?
- in heart failure there is chronic sympathetic activation which results in the receptors being acted on by the sympathetic system to down regulate
- resulting in there being less receptors to act on so the effect of sympathetic activation is diminished and cardiac output stops increasing
how is the RAAS involved in cardiac failure?
- results in increased Na+ reabsorption and thus water
reabsorption and release of ADH which stimulates water retention -> increased volume of the blood -> increased blood pressure and venous pressure which increases pre-load and increases the stretching of the heart and force of contraction, and stroke volume and cardiac output - fall in cardiac output and increased sympathetic tone -> diminished renal perfusion, activation of the RAAS and fluid retention
- salt and water retention increases venous pressure and maintains stroke volume
- peripheral and pulmonary congestion causes oedema and dyspnoea
- with increased force of contraction the cardiac
myocytes require more energy and more blood - in heart failure there will be no increase in blood and thus the cardiac myocytes will die resulting in decreased force of contraction and decreased stroke volume and cardiac output
what is systolic heart failure? what is it caused by?
- inability of the ventricle to contract normally resulting in a decrease in cardiac output
- caused by ischaemic heart disease, myocardial infarction and cardiomyopathy
what is diastolic heart failure?
inability of the ventricles to relax and fill fully, thereby
decreasing stroke volume and cardiac output
what are the causes of diastolic heart failure?
- hypertrophy due to chronic hypertension of the ventricles and increased afterload, resulting in less space for blood to fill in and decreased cardiac output
- aortic stenosis which increases afterload and decreases cardiac output
what is acute heart failure?
often used exclusively to mean new onset or decompensation of chronic heart failure characterised by pulmonary and/or peripheral oedema with or without signs of peripheral hypotension
what are the 3 cardinal symptoms of heart failure?
SOB, fatigue and ankle swelling (non specific)
what is the clinical presentation of cardiac failure?
- three cardinal symptoms
- dyspnoea especially when lying flat (orthopnoea)
- cold peripheries
- raised jugular venous pressure (JVP)
- murmurs and displaced apex beat
- cyanosis
- hypotension
- peripheral or pulmonary oedema due to back flow resulting from the
decreased cardiac output - tachycardia
- third and fourth heart sounds
- ascites
- bi-basal crackles
what is class I of the NYHA classification of cardiac failure?
no limitation (asymptomatic) - exercise -> no fatigue, dyspnoea or palpitations
what is class II of the NYHA classification of cardiac failure?
slight limitation (mild HF)
- comfortable at rest
- normal activity -> fatigue, dyspnoea and palpitations
what is class III of the NYHA classfication of cardiac failure?
marked limitation (moderate HF)
- comfortable at rest
- less gentle activity -> fatigue, dyspnoea and palpitations
what is class IV of the NYHA classification of cardiac failure?
inability to carry out any physical activity without discomfort (severe HF)
- symptoms occur at rest
- exacerbated by physical activity
how is heart failure diagnosed with blood tests?
brain natriuretic peptide (BNP)
- increased in patients with heart failure
- levels correlate with ventricular wall stress and the severity of heart failure
- normal plasma concentrations (<100pg/mL exclude heart failure)
FBC, liver biochemistry, blood glucose, U+E, thyroid function tests
how is heart failure diagnosed with CXR?
- cardiac enlargement and features of left ventricular failure
- alveolar oedema
- cardiomegaly
- dilated upper lobe vessels of lungs
- effusions (pleural)
how is heart failure diagnosed with ECG?
- shows underlying causes; ischaemia, left ventricular hypertrophy in hypertension or arrhythmia
- if ECG and BNP normal then heart failure is unlikely
- if both abnormal then go to echocardiogram
how is heart failure diagnosed with echo?
- assess ventricular systolic and diastolic function and may reveal the aetiology of heart failure
- look for regional wall motion abnormalities, valvular disease and cardiomyopathies
- look for sign of MI
- ejection fraction of <0.45 is usually accepted as evidence for systolic dysfunction
what is the overall treatment of heart failure?
- lifestyle changes
- diuretics
- ACE inhibitors
- beta blockers
- digoxin
- inotropes
- revascularisation (when some viable myocardium remains; PCI)
- surgery (mitral valve repair, aortic or mitral valve replacement)
- heart transplant in the young
- cardiac resynchronisation
what diuretics are used to treat heart failure? why?
- promote sodium and thus water loss thereby reducing ventricular filling pressure (preload) decreasing systemic and pulmonary congestion
- generally provide symptomatic relief
- loop diuretic - furosemide
- thiazide diuretic - bendroflumethiazide (inhibit sodium reabsorption in the distal convoluted tubule)
- aldosterone antagonists
what is the epidemiology of hypertension?
- often symptomless so screening is vital
- major risk factor for CVD
- remains under diagnosed, under treated and poorly controlled in the UK
- prevalence is in those older than 35
- more common in men
what are values for Stage 1 hypertension?
- more than or equal to 140/90mmHg clinic BP
- daytime average ambulatory blood pressure monitoring (ABPM - 24hr BP monitor) or home blood pressure monitoring (HBPM); greater than or equal to 135/85mmHg
what are the values for Stage 2 hypertension?
- more than or equal to 160/100mmHg clinic BP
- daytime average ABPM or HBPM greater than or equal to 150/95mmHg
what are the values for severe hypertension?
- clinical systolic BP greater than or equal to 180mmHg and/or diastolic BP greater than or equal to 110mmHg
- start immediate anti-hypertensive drug treatment
how can hypertension be classified?
- hypertension can be classified according to whether the cause is unknown ‘essential (primary or idiopathic) hypertension’ or is known ‘secondary hypertension’
- most cases are classified as essential
what is essential hypertension? what can it be caused by?
• primary cause unknown • accounts for the majority of cases • multifactorial involving: - genetic susceptibility - excessive sympathetic nervous system activity - abnormalities of Na+/K+ membrane transport - high salt intake - abnormalities in RAAS
what is secondary hypertension?
- cause is known
- commonly caused by renal disease or pregnancy
- other potential underlying conditions include; endocrine causes, coarctation of the aorta and drug therapy
what endocrine disorders can cause secondary hypertension?
- Cushing’s syndrome
- Conn’s syndrome
- pheochromocytoma
- adrenal hyperplasia
- acromegaly
how does Cushing’s syndrome cause secondary hypertension?
hypersecretion of corticosteroids (which enhance adrenalines resulting in a vasoconstrictive effect) is
associated with systemic hypertension
how does pheochromocytoma cause secondary hypertension?
adrenal tumour that secretescatecholamines (resulting in the stimulation of alpha-adrenergic receptors resulting in vasoconstriction, increased cardiac contractility and the stimulation of beta-adrenergic receptors resulting in an increase in heart rate and contractility) can cause hypertension
how does coarctation of the aorta cause secondary hypertension?
- raised blood pressure will be detected in either arm, but NOT in the legs
- the femoral pulse is often delayed relative to the radial
- undetected or untreated patients die from cardiac failure, hypertensive cerebral haemorrhage or dissecting aneurysm
- hypertension due to decreased renal perfusion, delayed pulses in the legs, mid-late systolic murmur and rib notching on X ray
how can drugs cause secondary hypertension?
- corticosteroids e.g. prednisolone
- cyclosporin
- erythropoietin
- some types of the contraceptive pill
- NSAIDs
- vasopressin
alcohol, amphetamines, ecstasy and cocaine are also causes of hypertension
what are the risk factors for hypertension?
- age - risk increases as you age
- race - hypertension is more common in blacks
- family history - hypertension runs in families
- overweight and obese
- little exercise
- smoking
- too much salt in diet
- alcohol
- diabetes
- stress
what is the pathophysiology of vascular changes caused by hypertension?
• hypertension accelerates atherosclerosis
• also causes the thickening of the media of muscular arteries
• smaller arteries and arterioles are especially affected in hypertension
• the resulting endothelial cell dysfunction is associated with impaired nitric oxide-mediated vasodilatation and enhanced secretion of
vasoconstrictors including endothelins and prostaglandins
what is the pathophysiology of kidney changes caused by hypertension?
kidney size is often reduced and small vessels show intimal thickening and medial hypertrophy and the numbers of sclerotic glomeruli are increased
what are features of malignant hypertension?
• characteristic features are a markedly raised diastolic blood pressure, usually over 120mmHg and seen in progressive renal disease
• quite rare
• renal vascular changes are prominent and there is usually evidence of acute haemorrhage and papilloedema (optic disc swelling caused by
increased intercranial pressure)
• can occur in previously fit individuals, often black males in their 30s-40s
what are consequences of malignant hypertension?
- cardiac failure with left ventricular hypertrophy and dilatation
- blurred vision due to papilloedema and retinal haemorrhages
- haematuria and renal failure due to fibrinoid necrosis of glomeruli
- severe headache and cerebral haemorrhage
- fibrinoid necrosis of the vessel wall -> end organ damage in the kidneys (haematuria, proteinuria, progressive kidney disease), brain (cerebral oedema and haemorrhage), retina (flame-shaped haemorrhages, cotton wool spots, hard exudates and papilloedema) and CVS (acute heart failure and aortic dissection)
how is hypertension diagnosed?
urinalysis:
• for protein, albumin:creatine ratio and haematuria
blood tests: • serum creatinine • eGFR • glucose (to assess diabetes risk) • UandE
fundoscopy/opthalmoscopy:
• looking for retinal haemorrhage or papilloedema
ECG
- to detect left ventricular hypertrophy or myocardial ischaemia; use echo to further detect this
serum lipids
what is the ACD pathway for hypertension treatment?
A: ACE-inhibitor e.g. ramipril or enalapril, or ARB (use if ACEi is contraindicated e.g. due to cough) e.g. candesartan or losartan
C: CCB e.g. nifedipine or amlodipine
D: diuretics e.g. bendroflumethiazide (thiazide, distal tube; less potent) or furosemide (loop diuretic, loop of Henle; more potent)
- beta blockers are not first line of treatment for hypertension but consider in young people if intolerant of ACEi/ARB
- statins are also given to reduce the overall cardiovascular risk burden
what are the drugs used in the treatment of hypertension in patients under 55yrs old?
ramipril/candesartan
+ nifedipine
+ bendroflumethiazide
+ furosemide
what are the drugs used in the treatment of hypertension in patients over 55/black/Afro-Caribbean origin?
ramipril/candesartan + nifedipine
+ bendroflumethiazide
+ furosemide
what is the definition of a cardiac arrhythmia?
an abnormality of the cardiac rhythm
- 24hr ambulatory ECG and event recorders are used to detect paryoxysmal arrhythmias
what can arrhythmias cause?
- sudden death
- syncope
- heart failure
- chest pain
- dizziness
- palpitations
- no symptoms at all
what are features of bradycardia?
- heart rate is slow (less than 60bpm during the day and less than 50bpm at night)
- usually asymptomatic unless the rate is very slow
- slower heart rates are more likely to cause symptomatic arrhythmias
- normal in athletes owing to increased vagal tone and thus parasympathetic activity
what are features of tachycardia?
- heart rate is fast (more than 100bpm)
* more symptomatic when the arrhythmia is fast and sustained
what are tachycardias subdivided into?
- supraventricular tachycardias - arise from the atrium or the AV junction
- ventricular tachycardias - arise from the ventricles
what are the conduction pathways of the heart (sinus rhythm)?
SAN → action potential → muscle cells of atria →
depolarisation of the AVN → slow → interventricular septum → Bundle of His → right and left bundle branches → free walls of both ventricles → Purkinje cells → ventricular myocardial cells
where is the SAN found?
at the junction between the SVC and right atrium
where is the AVN found?
in the lower interatrial septum
what is the purpose of the slow spread of the action potential between the AVN and ventricles?
to allow for the complete contraction of the atria before the ventricles are excited
what is the modulation of sinus node function? what problems can it lead to?
- the normal cardiac pacemaker is the sinoatrial node and it depolarises spontaneously
- the rate of SAN discharge is modulated by the autonomic nervous system
- normally, the parasympathetic system predominates, resulting in slowing of the spontaneous discharge rate
- a reduction of parasympathetic tone or an increase in sympathetic stimulation leads to tachycardia
- conversely, increased parasympathetic tone or decreased sympathetic stimulation produces bradycardia
- sinus rate in women is slightly faster than in men
what is a normal sinus rhythm characterised by on an ECG?
P waves that are upright in leads I and II, but inverted in cavity leads aVR and V1
what is sinus arrhythmia? what is it characterised by?
- fluctuations of autonomic tone result in changes of the sinus discharge rate
- during inspiration: parasympathetic tone falls and the heart rate quickens
- during expiration: parasympathetic tone increases and so heart rate falls
- this variation is normal especially in children and young adults
what is atrial fibrillation?
a chaotic irregular atrial rhythm at 300-600bpm; the AV node responds intermittently, hence an irregular ventricular rate
what is the epidemiology of atrial fibrillation?
- most common sustained cardiac arrhythmia
- males more than females
- around 5-15% of patients over age of 75
- can either be paroxysmal (stopping spontaneously within 7 days) or persistent (continues without intervention)
- atrial activity is chaotic and mechanically ineffective
what is the clinical classification of atrial fibrillation?
- acute: onset within the previous 48 hours
- paroxysmal: stops spontaneously within 7 days
- recurrent: two or more episodes
- persistent: continuous for more than 7 days and not self terminating
- permanent
what are the causes of atrial fibrillation?
- idiopathic (5-10%)
- any condition that results in raised atrial pressure, increased atrial muscle mass, atrial fibrosis, or inflammation and infiltration of the atrium may cause atrial fibrillation
- hypertension (most common in developed world)
- heart failure (most common in developed world)
- coronary artery disease
- valvular heart disease; especially mitral stenosis
- cardiac surgery (1/3rd of patients after surgery)
- cardiomyopathy (rare cause)
- rheumatic heart disease
- acute excess alcohol intoxication
what are risk factors for atrial fibrillation?
- older than 60
- diabetes
- high blood pressure
- coronary artery disease
- prior MI
- structural heart disease (valve problems or congenital defects)
what is the pathophysiology of atrial fibrillation? what does the ventricular response rate depend on?
- atrial fibrillation (AF) is maintained by continuous, rapid (300-600/min) activation of the atria by multiple meandering re-entry wavelets
- these are often driven by rapidly depolarising automatic foci, located predominantly within the pulmonary veins
- AV node conducts a proportion of the atrial impulses to produce an irregular ventricular response -> irregularly irregular pulse
- the atria respond electrically at this rate but there is no coordinated mechanical depolarisation and only a proportion of the impulses are conducted to the ventricles
- cardiac output drops by 10-20% as the ventricles are not primed reliably by the atria
what is the clinical presentation of atrial fibrillation?
- symptoms are highly variable
- may be asymptomatic
- palpitations
- dyspnoea and or chest pains following the onset of atrial fibrillation
- fatigue
- apical pulse rate is greater than the radial rate
- 1st heart sound is of variable intensity
what are differential diagnoses of atrial fibrillation?
- atrial flutter
- supraventricular tachyarrhythmias
how is atrial fibrillation diagnosed with ECG?
- absent P waves, only a fine oscillation of the baseline (so-called fibrillation or f waves)
- irregular and rapid QRS complex
what is acute management of atrial fibrillation?
- used in haemodynamically unstable patients
- when AF is due to an acute precipitating event, such as alcohol toxicity, chest infection or hyperthyroidism, the provoking cause should be treated
- immediate heparinisation
- cardioversion with a synchronised DC shock
- if cardioversion fails or AF recurs, IV amiodarone is given before another attempt
- ventricular rate control (by drugs that block the AV node)
how is rate control used for long term and stable patient management of atrial fibrillation? what is its aim?
- rate control aims to reduce HR at rest and during exercise, but the patient remains in AF
- AV nodal slowing agents plus oral anticoagulation
- beta-blocker e.g. bisoprolol
- calcium channel blocker e.g. verapamil or diltiazem
- if above fails then try digoxin and then consider amiodarone
how is rhythm control used for long term and stable patient management of atrial fibrillation?
- for younger, <65yrs, highly symptomatic and physically active patients, with heart failure and recent onset AF (<48hrs)
- cardioversion to sinus rhythm and use Beta-blockers e.g. bisoprolol to suppress arrhythmia
- can use pharmacological cardioversion e.g. flecainide, sotalol, propafenone if no structural heart defect or use IV amiodarone instead if there is structural heart disease
- appropriate anti-coagulation
- catheter ablation techniques in patients not responding to antiarrhythmic drugs
what is used to calculate the stroke risk and need for anticoagulation in atrial fibrillation?
CHA2DS2-VASc score
what is the CHA2DS2-VASc score? how is it used in atrial fibrillaiton?
- congestive heart failure (1 point)
- hypertension (1 point)
- a2ge greater or equal to 75 (2 points)
- diabetes mellitus (1 point)
- s2troke/TIA/thromboembolism (2 points)
- vascular disease (aorta, coronary or peripheral arteries) (1 point)
- age 65-74 (1 point)
- S(c)ex category: female (1 point)
- If score is 1 then it merits consideration of anticoagulation and/or aspirin
- If score is 2 and above then oral anticoagulation is required
- score of 0 should not require any antithrombotic prophylaxis
used to calculate stroke risk and need for anticoagulation in AF
what is the definition of atrial flutter?
usually an organised atrial rhythm with an atrial rate typically between 250-350bpm; ventricular rate of 150bpm
what is the epidemiology of atrial flutter?
- often associated with atrial fibrillation and frequently require a similar initial therapeutic approach
- either paroxysmal or persistent
- much less common than atrial flutter
- more common in men
- prevalence increases with age
what are causes of atrial flutter?
- idiopathic (30%)
- coronary heart disease
- obesity
- hypertension
- heart failure
- COPD
- pericarditis
- acute excess alcohol intoxication
what are symptoms for atrial flutter?
- palpitations
- breathlessness
- chest pain
- dizziness
- syncope
- fatigue
what are differential diagnoses of atrial flutter?
- atrial fibrillation
- supraventricular tachyarrhythmias
how is atrial flutter diagnosed with an ECG?
• definitive diagnosis
• regular sawtooth-like atrial flutter waves (F waves) between QRS complexes due to continuous atrial depolarisation
• note if F waves are not visible then they may be able to be unmasked by
by slowing atrioventricular conduction by carotid sinus massage or IV adenosine (AV nodal blocker)
what is the treatment of atrial flutter?
- electrical cardioversion but anticoagulate before e.g low molecular weight heparin e.g. enoxaparin or dalteparin if acute, i.e. atrial flutter started less than 48 hours ago
- catheter ablation; creating a conduction block to try an restore rhythm and block offending re-entrant wave
- IV amiodarone to restore sinus rhythm and use a beta-blocker e.g. bisoprolol to suppress further arrhythmias
- the treatment of atrial flutter is similar to AF, except that most cases of flutter can be cured by radiofrequency catheter ablation of the re-entry circuit
what are the three forms of atrioventricular block?
- first degree AV block
- second degree AV block
- third degree AV block
what are features of first-degree AV block?
- this is prolongation of the PR interval to greater than 0.22 seconds on the ECG
- no change in HR
- every atrial depolarisation is followed by conduction to the ventricles but with delay
- asymptomatic; no treatment
what are causes of first-degree AV block?
- hypokalaemia
- myocarditis
- inferior MI
- atrioventricular node (AVN) blocking drugs e.g. beta blockers, calcium channel blockers and digoxin
what are features of second-degree AV block?
- occurs when some P waves conduct and other do not
- occurs when some atrial impulses fail to reach the ventricles
- acute MI may produce second degree heart block
- Mobitz I and II
what is Mobitz I block?
- also known as the Wenckebach block phenomenon
- caused by AV node block
- a progressive PR interval prolongation until beat is ‘dropped’ and P wave fails to conduct i.e. excitation completely fails to pass through the AVN/bundle of His
- absent QRS after the P wave
- the PR interval before the blocked P wave is much longer than the PR interval after the blocked P wave
- PR interval then returns to normal and cycle repeats itself
what are causes of Mobitz I block?
- atrioventricular node (AVN) blocking drugs e.g. beta blockers (Bisoprolol), calcium channel blockers (Verapamil) and Digoxin
- inferior MI
what are symptoms/treatment of Mobitz I block?
- results in light headedness, dizziness and syncope
* does not require a pacemaker unless it’s poorly tolerated
what is Mobitz II block?
- due to a block at an infra-nodal level so the QRS is widened and QRS complexes are dropped without PR prolongation
- PR interval is constant and QRS interval is dropped
- failure of conduction through the His-Purkinje system
- ratio of non-conducted P waves to QRS complexes is usually specified, e.g. 2:1 Mobitz II block is 2 P waves for every QRS complex
what are causes of Mobitz II block?
- anterior MI
- mitral valve surgery
- SLE and Lyme disease
- rheumatic fever
what are symptoms/treatment of Mobitz II block?
- results in shortness of breath, postural hypotension and chest pain
- high risk of developing sudden complete AV heart block and a pacemaker should be inserted
what is third degree heart block?
- complete AV block
- complete heart block occurs when all atrial activity fails to conduct to the ventricles; complete dissociation between atrial and ventricular activity
- ventricular contractions are sustained by spontaneous escape rhythm which originates below the block
- P waves are completely independent of QRS complex
what are causes of third degree heart block?
- structural heart disease e.g. transposition of great vessels
- ischaemic heart disease e.g. acute MI
- hypertension
- endocarditis or Lyme disease
what are types of escape rhythm in third degree heart block?
- narrow-complex escape rhythm
- broad complex escape rhythm
what are features of narrow-complex escape rhythm in third degree heart block?
- QRS complex less than 0.12 seconds
- implies block originates in the His bundle and thus the region of block lies more proximally in the AV node
- recent-onset, narrow-complex AV block that has transient causes that may respond to IV atropine
- chronic narrow-complex AV block requires permanent pacemaker if it is symptomatic
what are features of broad-complex escape rhythm in third degree heart block?
B = below His
• QRS complex is greater than 0.12 seconds
• implies block originates below the bundle of His and thus the region of block lies more distally in the His-Purkinje system
• slow HR (<40 bpm)
• unreliable
• dizziness and blackouts often occur (Stokes-Adams attacks)
• permanent pacemaker implantation is recommended
what is treatment of third degree heart block?
- depends on aetiology
- one option is a permanent pacemaker
- IV atropine
what is bundle branch block?
- usually asymptomatic
- the His bundle gives rise to the right and left bundle branches
- the left branch subdivides into the anterior and posterior divisions of the left bundle
what is incomplete bundle branch block?
bundle branch conduction delay results in the slight widening of the QRS complex (up to 0.11 seconds)
what is complete bundle branch block?
- associated with a wider QRS complex (larger than 0.12 seconds) with an abnormal pattern
- usually asymptomatic
- shape of the QRS depends on whether the right or the left bundle is blocked
what are causes of right bundle branch block?
- can occur in normal healthy individuals
- pulmonary embolism
- right ventricular hypertrophy
- ischaemic heart disease
- congenital heart disease e.g. atrial/ventricular septal defect and tetralogy of Fallot
what happens in right bundle branch block?
- right bundle no longer conducts, meaning that the two ventricles do not get impulses at the same time, and instead spread from left to right
- sequential spread of an impulse (i.e. first left ventricle and then the right) resulting in secondary R wave (RSR’) in V1 and slurred S wave in V5 and V6; seen as deep S wave in leads V5 and V6 and as a tall late R wave in lead V1
- produces the late activation of the right ventricle
what are features of right bundle branch block on ECG and on auscultation?
- looks like maRRow
- maRRow = right bundle branch block
- MarroW:
• M - QRS looks like an M in lead V1
• W - QRS looks like W in V5 and V6 - seen as deep S wave in leads I, V1, V5 and V6 and as a tall late (slurred) R wave in lead V1
- causes wide physiological splitting of the second heart sound
what are causes of left bundle branch block?
- indicates underlying cardiac pathology
- hypertension
- severe CAD
- ischaemic heart disease
- aortic valve disease
- following cardiac surgery
what happens in left bundle branch block?
- produces the late activation of the left ventricle
- secondary R wave (RSR’) in left ventricular leads (I, AVL, V4, V5, V6) and a deep slurred S waves in V1 and V2
- since the left bundle branch conduction is normally responsible for the initial ventricular activation, left bundle branch block also produce abnormal Q waves
what are features of left bundle branch block on ECG and on auscultation?
- looks like wiLLiam
- wiLLiam = left bundle branch block
- WilliaM:
• W - QRS looks like a W in leads V1 and V2
• M - QRS looks like an M in leads V4-V6 - seen as deep S wave in lead V1 and a tall late R wave in leads I, aVL, V4, V5 and V6
- causes reverse splitting of the second heart sound
what are causes of sinus tachycardia?
- fever
- anaemia
- anxiety
- exercise
- pain
- heart failure
- pulmonary embolism
- thyrotoxicosis
- hypovolaemia
- drugs
what is treatment of sinus tachycardia?
- treating underlying causes
- beta blockers
what are types of paroxysmal supraventricular tachycardias (SVTs)?
AV nodal re-entrant tachycardia (AVNRT) and AV re-entrant tachycardia (AVRT)
what is the epidemiology of atrioventricular junctional tachycardias?
- AV nodal re-entrant tachycardia (AVNRT) and AV re-entrant tachycardia (AVRT) are usually referred to as paroxysmal supraventricular tachycardias (SVTs)
- they are often seen in young patients with no or little structural heart disease
- first presentation is commonly between ages 12-30
- in these tachycardias the AV node is an essential component
what is the epidemiology of atrioventricular nodal re-entrant tachycardia (AVNRT)?
- most common type of SVT
- twice as common in women as in men
- strikes suddenly without obvious provocation but there are some risk factors
- an attack may stop spontaneously or may continue indefinitely until medical intervention
what are risk factors of atrioventricular nodal re-entrant tachycardia (AVNRT)?
- exertion
- emotional stress
- coffee
- tea
- alcohol
how many pathways are there within the AV node in AVNRT? what are they?
2
• one has a short effective refractory period (the window of time where cells cannot be excited again after they have already been excited) and slow conduction
• one has a longer effective refractory period and fast conduction
what is a refractory period?
the window of time where cells cannot be excited again after they have already been excited
what is the pathophysiology of AVNRT?
- in sinus rhythm, the atrial impulse that depolarises the ventricles usually conducts through the fast pathway
- if the atrial impulse occurs early e.g. atrial premature beat when the fast pathway is still refractory then the slow pathway takes over in propagating the atrial impulses to the ventricles
- by the time the impulse has been propagated to the ventricles the fast pathway has finished its refractory period and is once again able to transmit impulses
- the same impulse that was carried by the slow pathway can be transmitted to the ventricles but also travel back up the fast pathway which by that time would be out of its refractory period
- by that time the slow pathway would have recovered from its refractory period so the signal will be able to go back down the slow pathway again
- this sets up a reentrant loop at the AV node and the loop sends signals through the AV node at a much faster rate than a normal pacemaker would -> tachyarrhythmia with 100-250 bpm
- it travels back through the fast pathway, which has already recovered its excitability, thereby initiating the slow-fast AVNRT in which the atria contract slowly in one cycle and then fast in the next
what is the clinical presentation of AVNRT?
- rapid regular palpitations with abrupt onset and sudden termination
- chest pain and breathlessness
- neck pulsations
- polyuria (due to the realise of atrial natriuretic peptide in response to increased atrial pressures during the tachycardia)
how is AVNRT diagnosed on ECG?
- QRS complex is usually of normal shape because the ventricles are activated in the normal way
- sometimes the QRS complex is wide, due to a rate-related BBB, and it may be difficult to distinguish from ventricular tachycardia
- P waves are either not visible or are seen immediately before (normal) or after the QRS complex due to simultaneous atrial and ventricular activation
what is the accessory circuit in AVRT?
- large circuit involving the AV node, the bundle of His, the ventricle and an abnormal connection of myocardial fibres from the ventricle back to the atrium
- this ‘abnormal connection’ is called the accessory pathway or bypass tract and results from an incomplete separation of the atria and the ventricles during fetal development
- connects the atria and ventricles and is capable of antegrade or retrograde conduction or both
- each part of the circuit is activated sequentially, so atrial activation occurs after ventricular activation and the P wave is clearly seen between the QRS and T wave
what are the two pathways in AVRT?
normal AV circuit and accessory circuit which both transmit impulses from the atria and the ventricles
how can impulses travel in the accessory pathway in AVRT?
impulse can travel from atria to ventricle (anterograde) or from ventricle back to atria (retrograde)
what is an example of AVRT?
Wolff-Parkinson-White (WPW) syndrome; an aberrant pathway syndrome
what occurs in AVRT?
- atrial activation occurs after ventricular activation
- patients are prone to atrial fibrillations and sometime ventricular fibrillation
what is the pathophysiology of Wolff-Parkinson-White syndrome?
- there is normal AV conduction but also an accessory pathway
- so when the SAN depolarises the impulse can travel to the AVN via the atria as well as to the accessory pathway
- if the accessory pathway conducts from the atrium to the ventricle during sinus rhythm, the electrical impulse can conduct quickly over this abnormal connection to depolarise part of the ventricles abnormally; this is pre-excitation
how is pre-excitation/early depolarisation in an AVRT reflected on an ECG?
- short PR interval
- wide QRS complex that begins as a slurred start to the QRS, known as a delta wave
- QRS is narrow
what is the pathophysiology of AVRT?
- normal AV conduction and an accessory pathway
- SAN depolarises -> impulse travels to AVN via atria and to the accessory pathway
- pre-excitation
- pre-excitation does not result in AVRT and doesn’t result in tachyarrhythmia
- premature beat from SAN will travel -> AVN and if accessory pathway is in refractory period it can’t transmit the signal
- impulse travels down via AVN, down interventricular septum through the bundle of His and LBB/RBB and into free walls of both ventricles via Purkinje cells until it meets the accessory pathway
- accessory pathway is out of its refractory period and can conduct the impulse back to the atria
- once in the atria the impulse can travel back to the AVN, setting up a reentry circuit; the signal goes around and around -> tachycardia
what is pre-excitation in AVRT?
if the accessory pathway conducts from the atrium to the ventricle during sinus rhythm, the electrical impulse can conduct QUICKLY over this abnormal connection to depolarise part of the ventricles
ABNORMALLY; this is known as pre-excitation
what is the clinical presentation of AVRT?
- rapid regular palpitations
- severe dizziness
- dysponea
- central chest pain
- syncope
- exertion, coffee, tea or alcohol may aggravate the arrhythmia
what is the treatment for AVRT and AVNRT?
- patients presenting with haemodynamic instability (hypotension and pulmonary oedema) require emergency cardioversion
- if stable then vagal manoeuvres
- if manoeuvres unsuccessful then IV adenosine; causes complete heart block for a fraction of a second and is highly effective at terminating AVNRT and AVRT
- surgery
what vagal manoeuvres are used to treat AVRT and AVNRT?
increases vagal stimulation of the sinus node
• breath-holding
• right carotid sinus massage (contraindicated in carotid bruit)
• Valsalva manoeuvre - several seconds after the release of the strain, the resulting intense vagal effect may terminate the AVNRT or AVRT
what surgery is used to treat AVRT and AVNRT?
- radiofrequency catheter ablation of the accessory pathway in AVRT, successful in 95% of cases
- modification of the slow pathway in AVNRT
what does the term ventricular tachyarrhythmias encompass?
- ventricular ectopics
- ventricular tachycardia
- sustained ventricular tachycardia (SVT)
- ventricular fibrillation
- some of these conditions are cardiac channelopathies; these are congenital disorders that are caused by mutations that affect the function of cardiac ion channels and hence the electrical activity of the heart, these include:
• long QT syndrome
what are cardiac channelopathies?
congenital disorders that are caused by mutations that affect the function of cardiac ion channels and hence the electrical activity of the heart
- e.g. long QT syndrome
what are ventricular ectopics?
- premature ventricular contraction
- these are asymptomatic or patients complain of extra beats, missed beats or heavy beats
what is the pathophysiology of ventricular ectopics?
- patient complains of extra beats, missed beats or heavy beats
- if the ectopics are frequent then left ventricular dysfunction may develop
- these premature beats have a broad (greater than 0.12 seconds) and bizarre QRS complex because they arise from an abnormal (ectopic) site in the
ventricular myocardium - following a premature beat, there is usually a complete compensatory pause because the AV node or ventricle is refractory to the next sinus impulse; resulting in missed beat
- can provoke ventricular fibrillation; potentially fatal
what is the clinical presentation of ventricular ectopics?
- may be uncomfortable especially when frequent
- pulse is irregular owing to the premature beats
- usually are asymptomatic
- can feel faint or dizzy
how is ventricular ectopics diagnosed on ECG?
widened QRS complex with a bizarre configuration; greater than 0.12 seconds
what is the treatment of ventricular ectopics?
- reassure patient
- give beta-blockers e.g. Bisoprolol if symptomatic
what is ventricular tachycardia?
pulse of more than 100bpm with a least 3 irregular heart beats in row
what is the epidemiology of ventricular tachycardia?
commonly found in patients with structurally normal hearts (known as idiopathic ventricular tachycardia), in these cases it is usually a benign condition with an
excellent long-term prognosis
• occasionally it is pathological and known as Gallavardin’s tachycardia and if untreated may lead to cardiomyopathy
what is the pathophysiology of ventricular tachycardia?
- there is rapid ventricular beating leading to inadequate filling of ventricles since there is less time to fill
- results in decreased cardiac output and thus a decrease in the amount of oxygenated blood that is circulated around the body
what are symptoms of ventricular tachycardia?
- breathlessness (lack of lung perfusion)
- chest pain (lack of heart perfusion)
- palpitations
- light headed or dizzy (lack of brain perfusion)
what is sustained ventricular tachycardia?
ventricular tachycardia for longer than 30 seconds
what are symptoms of sustained ventricular tachycardia?
- dizziness (pre-syncope)
- syncope
- hypotension
- cardiac arrest
- pulse rate between 120-220 bpm
how is sustained ventricular tachycardia diagnosed on ECG?
- rapid ventricular rhythm
- broad and abnormal QRS complex (greater than 0.14 seconds)
- with BBB, there is a broad complex tachycardia, which can be differentiated from VT on ECG criteria
what is the treatment of sustained ventricular tachycardia?
- haemodynamically unstable (e.g. hypotensive or pulmonary oedema): emergency electrical cardioversion
- stable: IV beta blocker e.g. Esmolol and IV Amiodarone
- prevented by use of beta blockers and implantable cardiac defibrillator
what is ventricular fibrillation?
involves very rapid and irregular ventricular activation with no mechanical effect i.e no CO
what is the clinical and ECG presentation of ventricular fibrillation?
- patient is pulseless and becomes unconscious and respiration ceases
- ECG shows shapeless, rapid oscillations and there is no hint of organised complexes
- usually caused by a ventricular ectopic beat
what is treatment of ventricular fibrillation?
- only effective treatment is electrical defibrillaton
- survivors are at increased risk of sudden death so long term, implantable cardioverter-defibrillators are the first-line therapy
what is long QT syndrome?
describes an ECG where the ventricular repolarisation/QT interval is greatly prolonged
what are congenital causes of long QT syndrome?
- Jervell-Lange-Nielsen syndrome (autosomal recessive); mutation in cardiac potassium and sodium-channel genes
- Romano-Ward syndrome (autosomal dominant)
what are acquired causes of long QT syndrome?
- hypokalaemia
- hypocalcaemia
- hypomagnesamia
- drugs; Amiodarone and Tricyclic antidepressants e.g. Amitriptyline, phenothiazines and macrolide antibiotics
- bradycardia
- acute MI
- diabetes
what is clinical and ECG presentation of long QT syndrome?
- syncope
- palpitations
- due to polymorphic ventricular tachycardia that usually terminate spontaneously but may degenerate to ventricular fibrillation
- polymorphic VT: torsades de pointes, rapid irregular sharp QRS complexes that continuously change from an upright to an inverted position on the ECG
- ECG shows prolonged QT interval
what is treatment for long QT syndrome?
- treat underlying cause
- if acquired long QT then give IV isoprenaline (contraindicated for congenital long QT)
what is the definition of an aneurysm?
an aneurysm is defined if there is a permanent localised dilatation of the artery to twice the normal diameter
what are true aneurysms? what arteries are most frequently involved?
- abnormal dilatations that involve all layers of the arterial wall
- types: saccular and fusiform
- arteries most frequently involved are:
• abdominal aorta (most common)
• iliac, popliteal and femoral arteries
• thoracic aorta
what is the normal diameter of the aorta?
around 2cm; increases with age
what are false aneurysms?
- also known as pseudoaneurysm
- involves the collection of blood in the outer layer only (adventitia) which communicates with the lumen e.g after trauma from a femoral artery puncture
what is the epidemiology of abdominal aortic aneurysm (AAA)?
- most commonly occur BELOW the renal arteries (infra-renal)
- incidence increases with age
- AAA’s are present in 5% of the population above 60
- more common in men than women
- most result from a degenerative process and present in elderly men
- some are due to connective tissue disease
what is an abdominal aortic aneurysm? where do they most commonly occur?
- classified as an aortic diameter exceeding 3cm
- most commonly occur below the renal arteries (intra-renal)
what are causes and risk factors of abdominal aortic aneurysm?
- most have no specific identifiable causes
- severe atherosclerotic damage
- family history
- tobacco smoking
- male
- increasing age
- hypertension
- COPD
- trauma
- hyperlipidaemia
what is the pathophysiology of abdominal aortic aneurysm?
- degradation of the elastic lamellae resulting in leukocyte infiltrate causing
enhanced proteolysis and smooth muscle cell loss - the dilatation affects all three layers of the vascular tunic
- if it doesn’t then it is a pseudoaneurysm
what are clinical presentations of unruptured AAA?
- often asymptomatic and only picked up via a routing abdominal examination or plain X-ray
- pain in abdomen, back, loin or groin
- pulsatile abdominal swelling (less pronounced)
what are clinical presentations of ruptured AAA?
- rupture is more likely if there is; increased BP, female, smoker, strong family history
- intermittent or continuous abdominal pain (radiates to the back, iliac fossas or groin)
- pulsatile abdominal swelling (more pronounced)
- collapse
- hypotension
- tachycardia
- profound anaemia
- sudden death
when is rupture of an abdominal aortic aneurysm more likely?
- increased BP
- female
- smoker
- strong family history
what is differential diagnosis of abdominal aortic aneurysm?
- GI bleed
- ischaemic bowel
- MSK pain
- perforated GI ulcer
- pyelonephritis
- appendicitis
how is abdominal aortic aneurysm diagnosed?
- abdominal ultrasound - can assess aorta to degree of 3mm
- CT and/or MRI angiography scans
what is treatment of abdominal aortic aneurysm?
- small aneurysms below 5.5cm are generally just monitored
- treat underlying causes
- modify risk factors e.g. smoking and diet
- smoking cessation
- vigorous BP control
- lowering of lipid in blood
- surgical replacement of the aneurysmal segment with a prosthetic graft indicated for a symptomatic aneurysm or large asymptomatic aneurysm (>5.5cm)
- in patients who are poor surgical risks, endovascular repair with insertion of an aortic stent is being increasingly employed
what surgery can be used to treat abdominal aortic aneurysm?
- patients tend to do better if aneurysm is symptomatic, larger than 5.5cm and expanding yearly
- open surgical repair
- endovascular repair - stent inserted via femoral or iliac arteries
what is the normal size of the mid-descending thoracic aorta?
26-28mm
what is the epidemiology of thoracic abdominal aneurysm?
- the ascending, arch or descending thoracic aorta may become aneurysmal
- ascending thoraco-abdominal aneurysms occur most commonly in patients
with Marfan syndrome or hypertension - descending or arch TAAs occur secondary to atherosclerosis and are now rarely due to syphilis
what are causes of thoracic abdominal aneurysm?
• genetic link; in some families it is an autosomal dominant trait
• usual causes are cystic medial necrosis and atherosclerosis
• certain connective tissue disorders:
- Marfan’s syndrome
- Ehlers-danlos syndrome
- Loeys-dietz syndrome
• mycotic aneurysm is endocarditis
• aortic dissection
• weight lifting, cocaine and amphetamine use; perhaps due to the large rise in BP when undertaking these activities
what are connective tissue disorders that can cause thoracic abdominal aneurysm?
- Marfan’s syndrome
- Ehlers-danlos syndrome
- Loeys-dietz syndrome
what are risk factors for thoracic abdominal aneurysm?
- hypertension
- increasing age
- smoking
- bicuspid or unicuspid aortic valves
- atherosclerosis
- COPD
- renal failure
- previous aortic aneurysm repair
what is the pathophysiology of thoracic abdominal aneurysm?
- involves inflammation, proteolysis and reduced survival of the smooth muscle cells in the aortic wall
- once the aorta reaches a crucial diameter (around 6cm in the ascending and 7cm in the descending) it loses all distensibility so that a rise in BP to around 200mmHg can exceed the arterial wall strength and may trigger dissection or rupture
what is the clinical presentation of thoracic abdominal aneurysm?
- most TAA’s are asymptomatic
- may be diagnosed incidentally e.g. on routing CXR or cardiological investigation or if complicated by dissection, rupture or other complications
- pain in chest, neck, upper back, mid-back or epigastrium
- cause pressure on local structures (causing back pain, dysphagia and cough)
- aortic regurgitation
- fever if there is infective cause
- symptoms due to compression of local structures
- acute pain
- collapse, shock and sudden death
- cardiac tamponade
- haemoptysis
what is the differential diagnosis of thoracic abdominal aneurysm?
- thoracic back pain
- arterial ischaemia
- collapse
- MI
how is thoracic abdominal aneurysm diagnosed?
- CT or MRI used for assessment of TAA
- aortography may be helpful for assessing the position of the key branches in relation to the aneurysm
- transoesophageal echocardiography can be useful for identifying aortic dissection
- ultrasound
what is the treatment of thoracic abdominal aneurysm?
- immediate urgent surgery is required for ruptured TAA
- symptomatic TAA’s merit surgery regardless of size
- regular monitoring by CT or MRI every 6 months
- rigorous BP control using beta-blockers e.g. Bisoprolol
- smoking cessation
- treat underlying cause
what happens in aortic dissection?
- aortic dissection begins with a tear in the intima (inner wall)
- blood then penetrates the diseased medial layer and flows between the layers of the aorta, forcing the layers apart resulting in dissection; creates a false lumen
- a medical emergency that can lead to death
what is the epidemiology of aortic dissection?
- most common emergency affecting the aorta
- affects men more than females
- most common between the ages of 50-70 and is rare below 40
- very rare in children
how is aortic dissection classified?
can be classified according to the timing of diagnosis from the origin of symptoms:
• acute - less than 2 weeks
• subacute - 2-8 weeks
• chronic - more than 8 weeks
what are the causes of aortic dissection?
- inherited
- degenerative
- atherosclerotic
- inflammatory
- trauma e.g. shearing stresses in a road traffic accident (RTA)
what plane do chest leads assess?
look at the heart in a horizontal plane
what plane to limb leads assess?
look at the heart in a vertical plane
what are the unipolar limb leads?
aVR, aVL, aVF
what are the bipolar limb leads?
I, II and III
what does right ventricular hypertrophy look like on an ECG?
tall R waves in right ventricular leads
what are complications of hypertrophic cardiomyopathy?
- sudden death
- atrial and ventricular arrhythmias
- thromboembolism
- infective endocarditis
- heart failure