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Block 5 – Cardiology Learning Objectives Arunan Sriravindrarajah The following lecture objectives were ordered thematically TABLE OF CONTENTS Anatomy ................................................................................................................................................................. 4 Thorax – Heart .............................................................................................................................................. 4 Thorax – Clinical Anatomy ........................................................................................................................ 6 Imaging ................................................................................................................................................................... 7 Thorax - Radiology ...................................................................................................................................... 7 Thorax – Radiology II – An Interactive Session............................................................................... 7 Cardiac Physiology .................................................................................................................................................. 8 The Heart as a Pump – The Cardiac Cycle ......................................................................................... 8 Cardiac Muscle Function ............................................................................................................................ 9 Control of Cardiac Output ....................................................................................................................... 10 Autonomic Cardiovascular Physiology and Pharmacology ......................................................... 11 Regulation of Blood Flow to Tissues ................................................................................................... 13 Medium to Long-Term Regulation of Blood Pressure ................................................................... 14 Muscle Weakness and Fatigue .............................................................................................................. 15 Cardiac Pathophysiology ...................................................................................................................................... 16 Pathophysiology of Clinical Features in the Heart ......................................................................... 16 Treatment of Heart Failure ..................................................................................................................... 18 Pathological Consequences of Heart Failure .................................................................................... 20 Lipids in Heart Disease ............................................................................................................................ 21 Clinical Features, Investigation and Treatment of Acute Coronary Syndrome (ACS) ..... 22 Treatment of Chronic Ischaemic Heart Disease ............................................................................. 23 Peripheral Vascular Disease (Investigation, Acute and Chronic Management) ................. 25 Cardiac Investigations ........................................................................................................................................... 26 Introduction to ECG .................................................................................................................................. 26 Investigating Coronary Disease and Cardiac Function ................................................................ 28 Diagnostic and Therapeutic Angiography ......................................................................................... 29 The ECG in Ischaemia .............................................................................................................................. 30 Valvular Heart Disease .......................................................................................................................................... 31 Abnormal Heart Valves ............................................................................................................................ 31 Infective Endocarditis ............................................................................................................................... 31 Medical, Percutaneous and Surgical Management of Valvular Heart Disease .................... 33 Genetics and Congenital Abnormalities ............................................................................................................... 34 Genes and Cardiovascular Disease ..................................................................................................... 34 Environment, Epigenetics and Foetal Programming ..................................................................... 35 1 Chromosomal Abnormalities .................................................................................................................. 36 Development of Heart and Cardiovascular System ...................................................................... 37 Circulatory Changes at Birth.................................................................................................................. 38 Introduction to Congenital Abnormalities of the Heart ............................................................... 39 Developmental Delay / Disability ......................................................................................................................... 41 Identifying Developmental Delay......................................................................................................... 41 Support and Medical Services for Down Syndrome ...................................................................... 41 Intellectual Disability Support and Families .................................................................................... 42 Arrhythmias .......................................................................................................................................................... 43 Supraventricular Arrhythmias and Bradyarrhythmias (Including AF, SVT) ......................... 43 Introduction to Ventricular Arrhythmias ........................................................................................... 44 Anti-Arrhythmic Drugs ............................................................................................................................. 45 Hypertension ........................................................................................................................................................ 46 Obesity-Related Hypertension .............................................................................................................. 46 End-Organ Damage in Hypertension .................................................................................................. 47 Pharmacology of Hypertension Management .................................................................................. 48 Clinical Examination and Investigation in Hypertension ............................................................. 49 Other..................................................................................................................................................................... 50 Introduction to Somatisation ................................................................................................................. 50 Pulmonary Hypertension ......................................................................................................................... 51 The Link between Depression and Cardiovascular Disease ....................................................... 53 PPD ....................................................................................................................................................................... 54 Professional Communication – How to Get Published .................................................................. 54 Seminars ............................................................................................................................................................... 56 Seminar – Exercise and the Heart ....................................................................................................... 56 Seminar – Cardiovascular Disease – A Population Medicine Perspective – The individual Within the Community ............................................................................................................................. 56 Seminar – Complementary Alternative Medicine........................................................................... 58 Seminar – Sensing Blood Flow ............................................................................................................. 60 Seminar – Cardiovascular Disease – A Population Medicine Perspective – Social and Systemic Responses ................................................................................................................................. 60 Seminar – Team Conference – Chest Pain ....................................................................................... 62 Seminar – Critical Appraisal of Systematic Reviews .................................................................... 64 Seminar – Investigation of Cardiac Abnormalities in Kids ......................................................... 64 Seminar – Normal ECG Demonstration ............................................................................................. 65 Seminar – Drugs in the Community ................................................................................................... 66 2 Seminar – Critical Appraisal of Intervention Studies ................................................................... 67 Seminar – ECG and Arrhythmias ......................................................................................................... 68 3 ANATOMY THORAX – HEART Detailed anatomical organisation and of the great vessels, pericardium and the structures of the heart, for example the electrical system, chambers, valves - There are four chambers of the heart – Right Atrium and Ventricle AND Left Atrium and Ventricle There are four valves in the heart – Tricuspid (RA to RV), Pulmonary (RV to Pulmonary Trunk), Mitral (LA to LV) and Aortic (LV to Aorta) o Only the Mitral Valve has 2 leaflets; the other 3 valves have three leaflets o Aortic and Pulmonary valve leaflets are referred to as ‘semi-lunar cusps’ (different in structure to the Tricuspid and Mitral Valves) It is important to understand that Pulmonary Circulation is low pressure, whilst the Systemic Circulation is high pressure o As a result, the Left Ventricle is much thicker than the Right Ventricle (to cope with the higher pressure) Systemic Hypertension will typically result in the Left Ventricle coping adequately by thickening (rather than having Left Ventricular Failure) o Conversely, the Right Ventricle is much thinner and cannot cope well with higher pressure in the Pulmonary Circulation (leading to Right Ventricular Failure) External Jugular Vein will typically drain into the Subclavian Vein, which will then together with the Internal Jugular Vein form the Brachiocephalic Vein, which drains into the Superior Vena Cava The Pulmonary Trunk (from the Right Ventricle) is anterior to the Aorta, though the right branch of the Pulmonary Trunk (i.e. Right Pulmonary Artery) will pass under the Arch of the Aorta to the Right Lung Right Ventricle is the most anterior chamber in anatomical position, whilst the Right Atrium is also an anterior chamber o The Left Atrium is the most posterior chamber in anatomical position, whilst the Left Ventricle wraps around both Anterior and Posterior aspects of the body in anatomical position Pericardium has a fibrous and serous component o The Fibrous Pericardium is easily visible as the ‘leathery’ outer layer o The Serous Pericardium can be divided into Parietal and Visceral layers (with Pericardial Cavity between these two serous pericardium layers) o Innervation of the Fibrous and Parietal Pericardium is via the Phrenic Nerve (C3,4,5), whilst innervations of the Visceral Pericardium is via the T1-T5 sympathetic nerves Innervation of Fibrous and Parietal Pericardium by Phrenic Nerve means that pathologies in these areas can result in referred pain towards the shoulder and jaw area (as this is also innervated by the Phrenic Nerve) Innervation of Visceral Pericardium by T1-5 Sympathetic Nerves means that pathologies in this area can result in referred pain towards the upper arm (as this is also innervated by the T1-5 Sympathetic Nerves) The Right Atrium can be divided into a two components: Muscular and Smooth o The ‘Crista Terminalis’ divides the Muscular (i.e. Pectinate Muscle) and Smooth parts, and will progress from the SVC to the IVC Other features of the Right Atrium include: o Coronary Sinus – this is where the Heart’s own blood supply drains (i.e. heart venous circulation will drain into Right Atrium via Coronary Sinus) o Foramen Ovale – this is a connection between the Right and Left Atrium, which exists embryologically This will close off as part of normal development leaving behind the Fossa Ovale Right Ventricle will initially begin as a smooth part beneath the Pulmonary Valve (Infundibulum) and then becomes muscular in nature o This transition between Smooth and Muscular components occurs at the Intra-Ventricular Septum (IVS) [which is a potential site of pathology] - - - - - - - 4 o - - - - - - - Unique features of the Right Ventricle include the presence of the Infundibulum and a greater quantity of Trabeculae Carnae (which mean ‘beams’) Trabeculae Carnae are the ridges in the ventricle wall that are distinct from the Papillary Muscle Tricuspid Valve (which is the valve in between the Right Atrium and Right Ventricle) is anchored to the Right Ventricle by the Chordae Tendinae (which itself is connected to the Papillary Muscle) o Each of the Leaflets will be associated with separate Chordae Tendinae, which are connected to an individual Papillary Muscle o Papillary Muscles originate from the Muscular component of the Right Ventricle o Moderator Band will connect the Papillary Muscle to the Intra-ventricular Septum (IVS) Note the Moderate Band is an anatomical feature of the Right Ventricle, but does NOT serve any clinical purpose Left Atrium will have four Pulmonary Veins drain into it from the Lungs (i.e. Right and Left Superior and Inferior Pulmonary Veins) o These Pulmonary Veins will insert into the back wall of the Left Atrium supplying oxygenated blood o Left Atrium will have a Left Atrial Appendage o Left Atrium is also smaller than the Right Atrium, but has thicker walls Left Ventricle has a similar general structure / anatomical features to the Right Ventricle; for example: o Mitral Valve has the same structure as the Tricuspid Valve (i.e. each leaflet anchored to the Left Ventricle by the Chordae Tendinae [which itself is connected to a Papillary Muscle]) o Trabeculae Carnae are also present o However, key differences are the Left Ventricle has thicker walls and less quantity of Trabeculae Carnae compared to the Right Ventricle The two Coronary Arteries will originate behind two of the three cusps (i.e. Left and Right Cusp) of the Aortic Valve (i.e. this area behind the cusps is known as the ‘Sinus of Valsalva’) The term ‘Aortic Root’ refers to the entire structure at the base of the Aorta (including the Aortic Valve) o The Sinotubular Junction is the point of division between the Aortic Root and the Ascending Aorta Coronary Arteries will arise from behind the cusps of the Aortic Valve and are on the outer surface of the heart o Left Coronary Artery will travel 1cm before branching into the Circumflex Artery and Anterior Interventricular Artery (also known as the Left Anterior Descending [LAD] Artery) Anterior Interventricular Artery (i.e. LAD) travels through the Anterior Interventricular Groove o Right Coronary Artery [RCA] will initially travel on the anterior aspect of the heart before progressing to the posterior aspect of the heart In 80% of patients, the Posterior Interventricular Artery (also known as the Posterior Descending Artery [PDA]) [which travels within the Posterior Interventricular Groove] will arise from the RCA However, in ~15% of patients, the Posterior Interventricular Artery will arise from the Circumflex Artery In the remaining ~5% of patients, the Posterior Interventricular Artery can arise from both the RCA and Circumflex Artery Coronary Sinus is a structure on the posterior aspect of the heart that collects blood from the venous supply of the heart (Great, Middle and Small Cardiac Veins) and drains into the Right Atrium o Great Cardiac Vein will run adjacent to the LAD Artery, whilst the Small Cardiac Vein will run adjacent to the RCA Artery [both on the anterior aspect of the heart] o Middle Cardiac Vein will run adjacent to the Posterior Interventricular Artery, whilst the Coronary Sinus flows into the Right Atrium [both of these are on the posterior aspect of the heart] SA Node is in the Superior Right Atrium near the SVC, whilst the AV Node is immediately superior to the junction between the Right Atrium and Right Ventricle o ‘Bundle of His’ refers to fibres from the AV Node that travel through the Intra-Ventricular Septum (IVS) 5 o ‘Purkinje Fibres’ are the microscopic network of fibres that travel from the IVS throughout both Ventricles that enable synchronous contraction The surface anatomy of the heart and clinical significance - The interventricular septum is mainly muscular but superiorly there is a small membranous portion which can be the site for a ventricular septal defect ~20% of people will have a Patent Foramen Ovale (i.e. that did not close off fully); this is typically not a significant problem as the quantity of blood that passes through this Patent Foramen Ovale is not significant o In contrast, an Atrial Septal Defect (ASD) at this location will involve significant quantities of blood passing through and is a significant problem Left Atrial Appendage serves no clinical purpose other than being a potential site for Thrombus o Atrial Fibrillation involves the Atrium beating out of synchronisation from the Ventricles o This can result in blood pooling in the Atrium in the appendage resulting in a clot o If this clot is pumped into the Systemic Circulation, this could travel to the brain and cause a stroke o Hence, patients with Atrial Fibrillation are typically given prophylactic anti-coagulants to prevent clotting o Note: Patients undergoing open-heart surgery / bypass surgery who may potentially be at risk of Atrial Fibrillation will commonly have their Left Atrial Appendage tied off (to prevent the risk of thrombus formation) Left Ventricle will adapt to a pressure load by hypertrophying (which reduced internal cavity size) and to a volume load by dilating Arch of Aorta will become more prominent as people age Left Ventricle will dilate and increase in size towards the left when there is Left Heart Failure Left Atrial enlargement may occur if there is a problem (e.g. Stenosis) with the Mitral Valve o This will result in the loss of curve between the Aortic Knuckle and Left Ventricle on a Chest X-Ray (instead there will be a straight line from the Aortic Knuckle to the Left Ventricle) Right Ventricle enlargement (e.g. due to Pulmonary Hypertension) will result in a more pronounced curve at the bottom right of the heart on a Chest X-Ray In Chest X-Rays of Heart Failure, lung markings are much more visible (due to the presence of fluid, as fluid backs up from the heart into the Interstitium [and eventually Alveoli] of the lung) o Upper Lobe Diversion will result in more pronounced / visible blood vessels in the upper lobes LAD Artery supplies most of the anterior aspect of the Left Ventricle, so infarct of this artery can damage up to ~25% of the Left Ventricle o In contrast, infarct of the Left Circumflex Artery (which supplies the lateral aspect of the Left Ventricle) will result in a smaller infarct area of the Left Ventricle and hence less damage o The RCA supplies both the Right Atrium and Right Ventricle as well as a small part of the inferior wall of the Left Ventricle, so infarct of the RCA can result in a small level of Left Ventricular dysfunction Infarct of the RCA can also cause Bradycardia, as this artery supplies the SA Node ~60% of the time and the AV node ~80% of the time - - - - - THORAX – CLINICAL ANATOMY Understand the major features of the clinical anatomy of the Thorax - Mitral Valve murmurs are more apparent / louder when the patient is rolled onto their left hand side, as the heart (and hence the Mitral Valve) is closer to the chest wall Aortic Stenosis and Mitral Regurgitation are the most common valvular abnormalities in Australia Treatment for Empyema (i.e. build-up of pus in the pleural space) would require a surgical procedure (i.e. decortication) to remove the Empyema (and the associated fibrous tissue) and to enable the lung to re-expand - 6 o - - - - - - Draining would likely be ineffective as this would not deal with the fibrous tissue surrounding the Empyema o Draining would result in the cavity remaining (which would re-fill with fluid and likely get reinfected once more) Thoracentesis will require avoiding the neurovascular structures to avoid any bleeding or pain o This is commonly performed under CT or Ultrasound guidance to ensure the needle is inserted appropriately o Air is typically drained apically (2nd intercostal space at the mid-clavicular line) whilst fluid is typically drained laterally (5th intercostal space at the mid-axillary line) Tumour in the apex of the right lung has the potential to irritate the Brachial Plexus (e.g. C8/T1 impingement) o Removal of tumours is this location can be quite difficult due to the presence of other important structures limiting access Oesophageal Hiatus (through the Diaphragm) is at the midline, though the oesophagus will travel towards the left-hand side of the body The Bronchi will divide into: o Primary (Main) Bronchi o Secondary (Lobar) Bronchi o Tertiary (Segmental) Bronchi Right Main Bronchus is typically a short, straightened structure o Foreign bodies aspirated will typically travel down this Right Main Bronchus (rather than the Left Main Bronchus) due to this anatomical difference The Left Bronchus can be distinguished from the Right Bronchus in a Bronchoscopy by the location of the Trachealis Muscle o Longitudinal Fibres of the Trachealis Muscles are at the posterior of the Trachea, and can be used to orient oneself Patient with a tumour around the Carina will typically present with Haemoptysis and Stridor (due to the physical obstruction of the tumour in the airways) Loss of border of the lesion / tumour in the Right Upper Zone in a Chest X-Ray is highly suspicious and may be suggestive of being a malignant tumour IMAGING THORAX - RADIOLOGY Understand the major structures of the thorax from radiographs - SVC and Brachiocephalic Veins are more anterior in the body (compared to the Aorta and Brachiocephalic Trunk which are relatively more posterior compared to these veins) Azygous Vein flows into the SVC near the junction of the Trachea and Right Bronchus on a Chest X-Ray Left Pulmonary Artery will travel behind the Left Bronchus, whilst the Right Pulmonary Artery will remain in front of the Right Bronchus - THORAX – RADIOLOGY II – AN INTERACTIVE SESSI ON TBA - Pneumothorax will be more easily visible on Chest X-Ray in full expiration (as the lung is more compressed and hence the lung markings [and hence absence of lung markings] are more visible) Lordotic X-Ray will move the Clavicles away from the Apices of the Lung; this will make it easier to view the Apices of the lung Lateral decubitus view (i.e. patient rolled onto their side) will make it easier to view fluid / foreign bodies in both the Thoracic and Abdominal cavities Radiological complications from an Asthma attack that may be visible on a Chest X-Ray are either a Pneumothorax or a Pneumomediastinum (i.e. air in the mediastinum) - 7 - - - - Acute Left Ventricular Failure will result in Acute Pulmonary Oedema this will be visible on a Chest X-Ray (i.e. Kerley B lines, increased opacification of lung fields, etc.) Pleural Effusion will be visible earlier on a lateral Chest X-Ray compared to a Frontal X-Ray (as ~50mL of fluid will be visible on a Lateral X-Ray whilst ~250mL of fluid are required to be visible on a Frontal X-Ray) Rib Fracture may not be easily visible on a Frontal X-Ray given the curved nature of ribs o If the clinical picture is indicative of a rib fracture (e.g. pain on inspiration following trauma to chest), then assume there is a rib fracture even if this cannot be identified on a Chest X-Ray Deviation of airway towards the side of concern suggests Atelectasis (i.e. collapse of lung), whilst deviation of airways away from the side of concern suggests Tension Pneumothorax (which should be a clinical rather than X-Ray diagnosis!) Flat Diaphragm suggests underlying COPD, whilst a Raised Diaphragm can result from a range of different factors (e.g. Phrenic Nerve Palsy, Hepatomegaly, etc.) Loss of contrast between borders of Heart and Diaphragm with respect to the lung suggests consolidation of the lung Prominence of the Hilum suggests congestion (which could indicate Left Ventricular failure) Rib fractures are most easily identified if they are on the lateral aspect of the rib (i.e. the sides of the body) Right Middle Lobe Consolidation will be indicated by the loss of the Right Heart border o In contrast, loss of diaphragm edge can be indicative of Lower Lobe Consolidation Pulmonary Oedema can be identified in a Chest X-Ray from widespread opacification across both lungs CARDIAC PHYSIOLOGY THE HEART AS A PUMP – THE CARDIAC CYCLE Understand the cardiac cycle, including its two major phases: o The flow of blood of around the body is determined by pressure generated by the pump action of the heart o The key to understanding valve abnormalities and the complex birth defects of the heart is a detailed understanding of the cardiac cycle - The heart is a pump whose function is to pump adequate amounts of blood to all tissues of the body o Supply to each group of cells should be matched to its needs o This will avoid both ischemia (if supply < demand) AND any unnecessary energy usage (if supply > demand) There are two major phases in the cardiac cycle: o Diastole (i.e. Filling Phase) – the heart will fill passively due to the pressure gradient from the Great Veins It is important the pressure in the Right Atrium during diastole is low enough so that it will fill passively from the Great Veins due to the pressure gradient (i.e. Filling Phase) Failure of the Right Atrium pressure to be lower than the Great Veins’ pressures during diastole will result in pathology o Systole (i.e. Ejection Phase) – the heart actively contracts and pumps blood through the body Ventricles are the key chambers responsible for the pump function of the heart o Ventricles have valves at input and output to ensure the flow of blood in the desired direction only The stimuli to contract the Heart is via intrinsic pacemaker regions (e.g. SA Node) rather than a nerve supply o This provides evolutionary advantage as the heart is more likely to continue to contract uninterrupted SA Node will fire spontaneously (~80 signals / minute) and create an Action Potential that is conducted across the Atrium in all directions o This signal is received by the AV Node, which will then conduct this signal to the Bundle of His (BOH) - - - - 8 - However, there is a time delay for the AV Node to conduct the electrical signal from the SA Node to the BOH Note: The AV Node and BOH also have the potential to fire spontaneously and each could act as a pacemaker in the heart (though it spontaneously fires at a slower rate [i.e. ~60 and ~40 signals / minute respectively] compared to the SA Node) o BOH will transmit the signal to the Purkinje Fibres, which are located in the inside of both Ventricles (at which point the electrical signal is transmitted from cell-to-cell within the Cardiac Muscle of the Ventricles) The transmission of the electrical signal via the BOH in the midline of the heart to each of the Ventricles enables the Ventricles to contract synchronously Spontaneous Firing of SA Node occurs as the SA Node electrical potential will spontaneously rise until it reaches a threshold that triggers an Action Potential (after which the electrical potential will spontaneously rise once more) o The rate of spontaneous increase in electrical potential (and hence heart rate) is regulated by the autonomic nervous system Understand the pressures and volume changes occurring in each chamber throughout the cardiac cycle and the way in which these lead to opening and closing of the valves o This facilitates understanding of the ECG, the heart sounds and the functional changes in many arrhythmias and at abnormally low and high heart rates o Note: The heart has four chamber and four valves - Slight increase in pressure in the Atrium once the Ventricle commences contraction is due to the closure of the Mitral Valve o This closure of the valve will increase the pressure within the Atrium o Pressure of Atrium will reduce once the Mitral Valve opens as there is opportunity for the remaining blood in the Atrium to flow into the Ventricle Pressure in Ventricle and Atrium will be the same when the Mitral Valve opens o The pressures will diverge once the Mitral Valve closes, with the pressure in the Ventricle rising very steeply (Isovolumic Contraction Phase) o The Aortic Valve will then open, resulting in a slower rise in pressure and reduction in volume of the Ventricle (Ejection Phase) o The closure of the Aortic Valve will result in a rapid reduction in the pressure of the Ventricle (Isovolumic Relaxation Phase) o The Mitral Valve will then re-open after the Ventricle Pressure falls to the level of the Atrial Pressure, resulting in the Ventricle to commence filling (Passive Filling Phase) The Atrial Filling Component Phase occurs at the conclusion of the Passive Filling Phase due to the contraction of the Atrium; this will only fill the heart a smart amount beyond the filling achieved in the Passive Filling Phase o Note: Pressures in the Right Heart are ~25% of the pressures in the Left Heart The minimum volume of the Heart is ~80mL (i.e. heart never completely empties of blood) - - CARDIAC MUSCLE FUNCT ION Understand the organisation, structure and function of cardiac muscle o All muscles are compromises between high speed and high force which are desirable but very costly metabolically and require complex control mechanisms which are more liable to damage o Cardiac muscle is specialised in a number of ways to meet the functional requirements of the heart - Myocytes (i.e. Cardiac Muscle Cells) are small cells (which enables rapid diffusion of Oxygen) and contain numerous mitochondria o This enables them to produce energy via Oxidative Phosphorylation; this enables the heart to be continuously active in a metabolically efficient manner that is not liable to fatigue 9 o - - - - - - Disadvantage is that there is a propensity for ischaemic damage (if there is a loss of oxygen supply), as well as a loss of force production (as there is a greater proportion of mitochondria instead of only being myofibrils) Myocytes are connected via end-to-end gap junctions o This results in low resistance between cells and enables current to pass from cell-to-cell o This allows rapid conduction of the AP from cell to cell (and across whole heart), which enables synchronous pumping of the heart Action potential is triggered by a depolarising current from the rapid, inward flow of Na+ ions (similar to nerve and muscles) o However, in contrast to Skeletal Muscle, there is additionally a slower, inward flow of Ca2+ ions this slow inflow prolongs the long plateau of the Action Potential (compared to Skeletal Muscle) to ~300ms Note: Calcium channel blocking drugs will reduce this inflow and slow the heart rate and contractility of the heart o Repolarising current will then occur from the efflux of K+ ions The prolonging of the Action Potential (through slow inward flow of Ca2+) is designed to prevent repetitive activity (i.e. tetany) which would prevent diastolic filling (and hence reduce cardiac output to zero) o Disadvantage of prolonged action potential is that it requires a careful balance between depolarising and repolarising currents; errors in this balance may result in arrhythmias Action potential will trigger the excitation-contraction coupling (i.e. conversion of electrical signal to mechanical response) via: o AP activates Calcium Current (i.e. ICa) and causes a small Calcium entry into the cell o Calcium binds to Sarcoplasmic Reticulum (SR) Calcium Release Channel within the cell and opens it (resulting in Calcium induced Calcium release [CICR]) o Large Calcium release from SR causes contraction of the cell o Relaxation (which enables diastolic filling) is caused by: Reuptake of Calcium into the SR by the SR Calcium pump Removal of Calcium from the cell by the Na+/Ca2+ exchanger on the cell surface There are complex mechanisms for varying calcium release within myocytes (e.g. in response to sympathetic triggers such as adrenaline) this enables the myocytes to vary output over a large range (through higher force and rate of contraction) o Furthermore, the development of multiple Calcium pumps in the myocyte ensures intracellular calcium is sufficiently low in diastole; this causes the heart to be extremely compliant during diastole and ensures adequate diastolic filling NOTE: The ‘Learning Objectives’ section of the Compass page for this lecture has a lot of relevant information (http://smp.sydney.edu.au/compass/teachingactivity/view/id/431) CONTROL OF CARDIAC OUTPUT Understand the mechanisms for varying cardiac output - Cardiac Output = Heart Rate x Stroke Volume = HR x (End Diastolic Volume – End Systolic Volume) The stimuli to contract the Heart (i.e. Heart Rate) is via intrinsic pacemaker regions (e.g. SA Node) Currents involved in the pacemaker function include: o If current – this will be triggered by hyperpolarisation (rather than depolarisation) and will contain a range of different cations (i.e. non-specific cation current) o Na/Ca exchanger – this will contribute current as it pumps in three Na+ ions for each Ca2+ ion pumped out o L-type Calcium current responsible for rising phase of the Action Potential (AP) Heart Rate can be increased through sympathetic activation (e.g. Adrenaline) o However, there is a maximum effective heart rate of ~180 due to the diastolic filling time (and hence diastolic filling) being inadequate if HR >180 Beta-blockers and Ca2+ Channel Blockers will reduce heart rate, but they are also negatively inotropic - - 10 o - - - - - Hence, they will not only reduce the heart rate but also reduce the stroke volume (by reducing the release of Calcium and the force of contraction) o Alternatively, Ivabradine is a non-inotropic agent that will slow the heart rate through blocking the If current End Systolic Volume is determined by the force of contraction (i.e. inotropic state) o Force of contraction in muscle contractile proteins can be increased via increasing the systolic Calcium ion concentration o Interventions to increase Calcium ion concentration include: Increased stimulation frequency Calcium enters with each Action Potential Increased extracellular Calcium Calcium entry is increased and Na/Ca exchanger is also affected by extracellular Calcium concentration Sympathetic stimulation (e.g. Noradrenaline released from sympathetic nerves) Cardiac Glycosides (e.g. Digoxin) blocks Na+ pump, which inhibits efflux of Calcium through Na/Ca exchanger o Interventions to reduce Calcium ion concentration include: Calcium channel blockers reduce Calcium entry and reduce Calcium release from Sarcoplasmic Reticulum Beta-blockers inhibit sympathetic activation End Diastolic Volume is determined by the central venous pressure (i.e. preload) o The greater the pressure, the larger the end diastolic volume However, increased central venous pressure (i.e. preload) stretches the cardiac muscle and causes increased force production by several mechanisms including increased sliding filament overlap and increased Ca2+ sensitivity of the contractile proteins o Consequently, the stretched heart has a greater Stroke Volume and a greater Cardiac Output o This is summarized as ‘Starling’s Law’ (i.e. Cardiac Output is dependent on Central Venous Pressure) Central Venous Pressure (i.e. preload) is regulated via: o Muscle Pump – muscle contractions will pump blood from the peripheral veins to the central veins; this increase in volume will increase CVP o Sympathetic Innervation of peripheral veins – this results in vasoconstriction, which will pump blood from the peripheral veins to the central veins; this increase in volume will increase CVP o Renin/Angiotensin/Aldosterone system – this increases sodium and water retention; this increase in volume will increase CVP Patient following moderate heart attack will have reduced Cardiac Output o The body may compensate fully for this by increasing the CVP (and hence increasing the Cardiac Output) This may be performed by increasing Na+ and water retention, which increases blood volume and hence increases CVP o However, in patients with severe heart attacks, Na+ and water retention will be insufficient to fully compensate for the reduction in Cardiac Output These patients will progressively increase their water retention resulting in severe Peripheral Oedema and Pulmonary Oedema (which will inhibit gas exchange / respiration) Afterload refers to the pressure into which the heart needs to pump (i.e. systemic arterial blood pressure) o The energy required by the heart is dependent on the stroke volume and the afterload o Cardiac output will fall at extremely high arterial blood pressures, as the heart is unable to generate sufficient energy to work at the level required to maintain SV at these pressures AUTONOMIC CARDIOVASCULAR PHYSIOLOGY AND PHARMACOLOGY Understand the principles of neurotransmission in autonomic efferent nerves, together with the concept of autonomic neuronal receptor 11 - - - - - - - Autonomic Nerves are those nerves that innervate anything other than skeletal muscle (which is innervated by Somatic Nerves) There are three components of the Autonomic Nervous System o Sympathetic System – these Nerve Fibres arise from either the Thoracic or Lumbar regions of the spinal cord (Intermediolateral [IML] component of the Spinal Cord) o Parasympathetic System – these Nerve Fibres arise from either the Brainstem or the Sacral region of the spinal cord o Enteric System – this is intrinsic to the gut The major neurotransmitters in the sympathetic and parasympathetic nervous systems are Noradrenaline, Adrenaline and Acetylcholine o The neurotransmitter released from all Sympathetic and Parasympathetic preganglionic nerve terminals is Acetylcholine (hence these nerve fibres are described as cholinergic); these will act on Nicotinic Receptors o Most of the Sympathetic postganglionic nerve fibres release Noradrenaline (plus a small fraction of Adrenaline) and are described as Adrenergic fibres; these will act on Adrenoreceptors There are a few Sympathetic postganglionic nerve fibres that release Acetylcholine; these are described as sympathetic cholinergic fibres and will act on either Muscarinic or Nicotinic Receptors o The Parasympathetic postganglionic nerve fibres are cholinergic, releasing Acetylcholine from their terminals at the neuro-effector junction One preganglionic fibre may innervate up to 100 postganglionic neurons, whilst one postganglionic neuron may be innervated by multiple preganglionic fibres Neurotransmitters are released from the pre-synaptic terminal of the Axon and will impact upon the target (e.g. smooth muscle cell) to trigger a response / action Neuromodulators are substances that can potentiate and / or inhibit the effects of neurotransmitters o For example, Neuropeptide Y will inhibit the release of Noradrenaline (to prevent the depletion of Noradrenaline by preventing excessive secretion) whilst maintaining its effectiveness / impact (by potentiating its action on the smooth muscle cell) Preganglionic neurons are specific to a particular target / function (depending on the type of preganglionic neuron) (e.g. neuron A is specific to blood vessels vs. neuron B is specific to the heart) o There are also sub-populations within each major group (e.g. those neurons that innervate blood vessels in skin are separate from those neurons that innervate blood vessels in skeletal muscle) o These different sub-groups can be independently controlled by inputs from spinal afferents or descending inputs from brain nuclei o This specificity will enable the sympathetic nervous system to trigger only particular functions (rather than all functions at once) The various different receptors triggering sympathetic activity will each have different impacts on the different types of preganglionic neurons Heart receives innervations from both sympathetic and parasympathetic nerves o Sympathetic nervous system innervates the SA Node (and hence can increase heart rate) and the Atrial and Ventricular Myocardium (and hence can increase contractility) o Conversely, Vagus Nerve (i.e. parasympathetic nervous system) innervates the SA Node (and hence can decrease heart rate) and to a lesser extent the Atrial and Ventricular Myocardium (and hence can decrease contractility) Blood vessels diameter will be influenced by sympathetic innervations (resulting in vasodilation) o This will change the peripheral resistance and hence blood pressure o Note: There is minimal parasympathetic innervations of blood vessels; exception is particular Cerebral Vessels and Erectile Tissue Sympathetic vasoconstrictor nerves are tonically active (i.e. active at all time) o Hence, denervation will result in loss of vasoconstriction (and hence trigger vasodilation of the blood vessels) o The signal to remain tonically active arises from the brain, so high spinal / brain injury can also result in the loss of this vasoconstriction (and hence trigger vasodilation of the blood vessels) 12 - - o Note: The neurotransmitter is usually Noradrenaline (and hence these are adrenergic nerves) ‘Baroreceptor Reflex’ is the single most important reflex that regulates blood pressure in the shortterm o This reflex will maintain the blood pressure within normal limits in the short-term by adjusting the level of sympathetic stimulation to a range of different organs (e.g. heart, blood vessels, kidneys, etc.) o Other factors affecting sympathetic stimulation include stress / anxiety, circulating hormones, disease states (e.g. hypertension), ‘central command’ (e.g. during exercise), etc. Increased sympathetic nerve activity is associated with heart failure, hypertension and obesity NOTE: The ‘Content’ section of the Compass page for this lecture has a lot of relevant information (http://smp.sydney.edu.au/compass/teachingactivity/view/id/7088) REGULATION OF BLOOD FLOW TO TISSUES Understand the nervous and hormonal mechanisms designed to regulate the blood flow to tissues o The aim of the circulation it to provide every cell with appropriate amounts of oxygen, glucose, etc. and to remove waste products such as CO2, heat, etc. o Because the intrinsic metabolic rates of different tissues vary widely and because the metabolic rate can change dramatically with activity, this process requires a series of control mechanisms which regulate blood flow to each of the tissues - Arterial Blood Pressure is normally held constant by the Baroreceptor Reflex and the Sympathetic Nervous System o Largest pressure drop in the circulation occurs along arterioles hence, arterioles have the greatest resistance to flow o With tissues in parallel, flow to any tissue is inversely related to its resistance o Hence, Arteriolar resistance, which is set by the degree of constriction of smooth muscle in the arteriolar walls, determines tissue blood flow Extrinsic determinants of arteriolar smooth muscle constriction include: o Sympathetic stimulation of Alpha-adrenoreceptors causing vasoconstriction This is used for short term regulation of the BP Density of sympathetic innervations is high in low-priority organs (e.g. skin, GI tract) and low in high-priority organs (e.g. brain, heart) this means there is a greater capacity to reduce blood flow in the low-priority organs o Parasympathetic stimulation causing vasodilation In contrast to the tonically active sympathetic stimulation, parasympathetic activation only occurs under specific circumstances o Circulating hormones Adrenaline causes peripheral vasoconstriction through its impact on Alpha-1 adrenoreceptors but vasodilation through its impact on Beta-2 adrenoreceptors Angiotensin causes widespread vasoconstriction Vasopressin (i.e. ADH) causes widespread vasoconstriction Histamine caused vasodilation and increased capillary permeability Intrinsic determinants of arteriolar smooth muscle constriction include: o Basal Vascular Tone – this is caused by spontaneous vascular smooth muscle activity and stretch-induced activity (by the pressure of blood in the vessel) Reduction of this Basal Vascular Tone (e.g. via Nitrates) will result in vasodilation and increased flow o Vasodilator Metabolites (e.g. reduced oxygen, increased CO2, lactic acid, adenosine, etc.) – this can cause relaxation of vascular smooth muscle These play a key role in regulating the level of blood flow (via a negative feedback loop) - - 13 o These are the link between tissue metabolism and blood flow, and are the main mechanism of action for matching local blood flow to the needs of small groups of cells Endothelial-derived Factors – these various vasoactive factors affect underlying smooth muscle; examples include: Nitric Oxide (NO) – an endothelial-derived relaxing factor Endothelin – potent vasoconstrictor Prostaglandins – powerful local vasodilator MEDIUM TO LONG-TERM REGULATION OF B LOOD PRESSURE Understand the distinction between medium to long-term regulation, and short term regulation of arterial pressure - Short-term regulation of arterial pressure will involve temporary changes in response to different stimuli; for example, there is a diurnal variation in blood pressure where levels are low during late night / early morning (i.e. sleep time) and rise in the morning after waking up o Therefore, the recording of Blood Pressure and Heart Rate will vary based on the time of the day and hence it’s important to take this into consideration when assessing these vital signs o It may be preferable to measure Blood Pressure and Heart Rate over a 24-hour period when assessing whether a patient is hypertensive In contrast, medium to long-term regulation of arterial pressure involves changes in blood pressure due to chronic, continuous changes (e.g. changes in renal function) - List and describe the different mechanisms of medium to long-term regulation - The different mechanisms of medium to long-term regulation of blood pressure will each impact upon the kidneys; these include: o Renin / Angiotensin / Aldosterone system – this will impact total peripheral resistance and blood volume, both of which impacts blood pressure o Baroreceptor Reflex – this will stimulate sympathetic changes in the kidneys (e.g. increased Renin levels, increased sodium retention, increased renal vascular resistance) which will impact upon blood pressure Chronic re-setting of the Baroreceptor Reflex will change sympathetic activation of the kidneys and result in a change in the renal function curve; this will trigger a change in the long-term equilibrium blood pressure (e.g. hypertension) o Salt intake – this will increase sodium and water retention, which will increase blood pressure o Other mechanisms increasing Renal Sympathetic Activity (e.g. increased Leptin, activation of chemoreceptors, other circulating hormones, etc.) Discuss the role of hormones (particularly the renin-angiotensin-aldosterone system) - Hormones can influence blood pressure through their impact on the level of vasoconstriction / vasodilation, as well as their impact on fluid levels For example, the hormone Renin will be released from the kidneys in response to reduced arterial pressure in the kidneys o Renin will convert Angiotensinogen to Angiotensin I; this is converted via the Angiotensin Converting Enzyme (ACE) to Angiotensin II o Angiotensin II will impact upon a range of different targets such as: Brain – this triggers behavioural changes (e.g. drinking water) and a signal to release Vasopressin (i.e. ADH) Adrenal Cortex – this triggers release of Aldosterone Blood Vessels – this triggers vasoconstriction - 14 - Kidneys – this triggers (in addition to the Vasopressin and Aldosterone from the Brain and Adrenal Cortex respectively) the increased retention of Na+, which will result in an accompanying retention of water o The combined impact is the increase in total peripheral resistance and blood volume, both of which results in an increase in blood pressure Other hormones (e.g. Leptin) can trigger sympathetic stimulation of the kidneys, which will increase blood pressure (via increased Renin levels, increased sodium retention and increased renal vascular resistance) Discuss the interrelationship between arterial pressure and blood volume regulation - Reduction in arterial pressure will trigger the kidneys to release Renin o This will ultimately increase blood volume (via the Renin / Angiotensin / Aldosterone system), which will increase arterial pressure o Once arterial pressure increases to an appropriate level, the kidneys will no longer release additional Renin and hence the blood volume and arterial pressure will be maintained Discuss the crucial importance of the kidney in long-term regulation (with examples to illustrate how a change in renal function can lead to hypertension) - The position of the Renal Function Curve is critical to determining the equilibrium level of mean arterial pressure where fluid intake = fluid output o Changes in renal function will result in a change in the long-term equilibrium arterial pressure o For example, renal sympathetic nerve activity is increased in Essential Hypertension as this will shift the Renal Function Curve such that fluid intake and output will be equal at these higher arterial blood pressures Kidneys are also critical to the long-term regulation of blood pressure through their key role in the Renin-Angiotensin-Aldosterone system o The levels of Salt and Angiotensin II should be inversely related (in order to maintain arterial blood pressure at the equilibrium level) o As a result, failure of the Renin-Angiotensin-Aldosterone system will interfere with this ability to maintain the equilibrium arterial blood pressure - MUSCLE WEAKNESS AND FATIGUE Discuss the methods of measuring muscle force and fatigue, and some of the causes of muscle weakness - Methods of measuring muscle force include: o Simple clinical approaches (e.g. squeeze fingers, maximum force of biceps, eyelid droop [in Myasthenia Gravis], getting up from the floor [child] or chair [adult]) o Objective measurement (e.g. force transducer) Causes of muscle weakness include: o Loss of muscle mass due to: Old age (i.e. sarcopenia) Malnutrition Cancer or serious infection Immobility / disuse atrophy Muscular diseases (e.g. muscular dystrophy) o Perception of muscle weakness / fatigability (albeit without loss of muscle mass) (i.e. Chronic Fatigue Syndrome) o Spinal damage (e.g. trauma, tumour, demyelinating diseases) o Cortical damage (e.g. stroke, tumour) o Hormones (e.g. Corticosteroids) - 15 o o o Neuromuscular Junction problems (e.g. Myasthenia Gravis) Peripheral Motor Neuron problems (e.g. nerve damage) Fatigue; this may be caused by: Any process (e.g. inactivity / immobility) resulting in increased proportion of ‘fast’ fibres (which fatigue easier vs. ‘slow’ fibres) Inadequate blood / oxygen supply Abnormal muscle metabolism Any severe muscle wasting disease (as more effort is required from the remaining muscle fibres) Describe objective methods of measuring muscle force and fatigue (including methods of determining whether weakness is central, neuromuscular or in the muscle) - Objective methods of measuring muscle force include: o Force Transducer (to measure maximum force from a muscle group) o Surface Electromyogram (to assess nerve stimulation) o MRI (to assess muscle mass) Identification of the location of the weakness can be performed by stimulating the central upper motor neuron vs. peripheral nerve vs. muscle fibre directly o If stimulation of the peripheral nerve can trigger a force, then weakness is central o If stimulation of the muscle fibre can trigger a force, then weakness is either central and / or neuromuscular (i.e. upstream) o If stimulation of the muscle fibre CANNOT trigger a force, then weakness can be either central, neuromuscular and / or in the muscle - CARDIAC PATHOPHYSIOLOGY PATHOPHYSIOLOGY OF CLINICAL FEATURES IN THE HEART Define heart failure, including a description of the structural adaptations occurring in the heart and the systemic neurohumoral changes in heart failure o The role of cardiac dilatation and preload recruitment will be illustrated o Neurohumoral changes, including activation of the sympathetic nervous system and the renin-angiotensin system, will be described - Heart Failure is the mechanical failure of the heart to maintain systemic perfusion commensurate with the requirements of metabolising tissues o This can be acute heart failure or chronic heart failure o Alternatively, heart failure can be systolic (i.e. reduced systolic function) vs. diastolic (i.e. preserved systolic function) Chronic Heart Failure can result in structural adaptations in the heart such as Hypertrophy or Dilatation Ventricular Dysfunction will trigger a Neuroendocrine response o This Neuroendocrine Response will result in a positive feedback loop that further increases Ventricular Dysfunction (i.e. increased preload and / or afterload results in increased Ventricular Dysfunction) o For example, the Sympathetic Nervous System will be overactive in Heart Failure this results in increased Renin release, which will increase blood pressure (i.e. afterload) Natriuretic Peptides are released in response to increased preload and volume of shear stress o These peptides will cause Natriuresis (i.e. excretion of sodium in urine), vasodilation and the suppression of Renin and Endothelin (which are vasoconstrictors) o There are three classes of Natriuretic Peptides – A-type (release by Atrium), B-type (released by Ventricles) and C-type (released by Vascular Endothelium) - - 16 Understand the pathophysiology of heart failure - The primary effect of Heart Failure is on the heart and vascular system, though adverse effects also occur in other systems too (e.g. Respiratory, Renal, CNS, etc.) There are two distinct pathophysiologies of Heart Failure: o Heart Failure with Reduced Systolic Function (i.e. reduced Ejection Fraction) (HFrEF) o Heart Failure with Preserved Systolic Function (i.e. preserved Ejection Fraction) (HFpEF) HF with Preserved Systolic Function results from increased myocardial stiffness; this will inhibit appropriate relaxation (i.e. diastole) and hence result in decreased end diastolic volume / reduced stroke volume o This has both mechanical and metabolic components o A number of other mechanisms contribute to the pathophysiology, such as: Resting and exercise systolic dysfunction Impaired ventricular-vascular coupling Abnormal exercise and flow-mediated vasodilation Chronotropic incompetence (i.e. stiff heart requires longer to fill) Pulmonary arterial hypertension Causes of HF with Preserved Systolic Function include: o Acute Ischaemia (this limits the energy available to the heart, which inhibits Lusitropy [i.e. the ability of the heart to relax]) o Age o Hypertension o Aortic Stenosis o Hypertrophic Cardiomyopathy o Pericardial Disease o Sarcoid (and other infiltrative diseases) There are significant differences between patients with HF with Preserved Systolic Function compared to HF with Reduced Systolic Function in terms of co-morbidities o However, the survival prognosis of both groups are similar o In contrast, the treatment options for HF with Preserved Systolic Function are limited compared to HF with Reduced Systolic Function Diuretics is the main treatment available for HF with Preserved Systolic Function There is an increase in the slope of the pressure-volume curve for patients with HF with Preserved Systolic Function o This magnifies the change in LV Pressure following a change in Preload and / or Afterload Causes of Acute Heart Failure include: o Tachycardia o Pressure or Volume Overload (e.g. Hypertension, Pulmonary Embolism, Pregnancy) o Acute Valvular Failure (e.g. Endocarditis, Trauma, Valve Dysfunction) o Acute Myocyte Dysfunction (e.g. Ischaemia, Drugs, Toxins) o Acute Pericardial Disease (e.g. Pericarditis, Aortic Dissection) Clinical Manifestations of Acute Heart Failure include: o Symptoms (of Reduced Output Heart Failure) Fatigue / weakness Effort intolerance Cognitive impairment Sleep disturbance o Symptoms (of Congestive Output Heart Failure) Shortness of breath / Orthopnoea Peripheral oedema Sleep disturbance (e.g. Paroxysmal Nocturnal Dyspnoea) GIT symptoms (e.g. dyspepsia, abdominal swelling, etc.) o Physical Findings Peripheral Oedema Tachycardia Hypotension Peripheral cyanosis - - - - - - - 17 - - Vascular congestion (e.g. elevated JVP) Crepitations in the lungs Respiratory-related complications occur in Congestive Heart Failure (CHF) as gas exchange is impaired due to the lung containing excess fluid from the backfill from the heart this will increase the work required for breathing resulting in dyspnoea o These respiratory-related complications will also contribute to worsening heart failure by: Increasing respiratory muscle fatigue, which will increase the workload required by the heart (which worsens the heart failure) Triggering hyperventilation, which causes hypocapnia this results in reduced ventilatory drive, which will result in sleep apnoea / disruption (which worsens the heart failure) Main modes of death in heart failure will be: o Progressive Heart Failure o Sudden Death (especially due to VT / VF) o Stroke Understand the major principles of drug treatment for heart failure - Patients with a dysfunctional / disadvantaged heart will have their prognosis improved by reducing the blood pressure (i.e. reducing afterload) o The appropriate level of blood pressure for such patients will be lower than normal (indeed, aim for the lowest blood pressure possible without adverse side-effects) Drug treatment for heart failure attempts to minimise the level of pre-load and / or afterload for patients o This will reduce the LV pressure required to maintain cardiac output / perfusion, and hence reduce the effort required from the heart (which reduces the symptoms of heart failure) - Understand the pharmacological actions of the most frequently used drugs - The main drugs for treatment of heart failure and their mechanisms of action are: o ACE Inhibitors / ARB (Angiotensin Receptor Blockers) – these will inhibit the Renin / Angiotensin / Aldosterone system in a manner that will reduce blood pressure (i.e. afterload) and blood volume (i.e. preload) o Beta-Blockers – these will reduce sympathetic activation of the heart, which will reduce the speed of cardiac remodelling such as hypertrophy (which results in loss of cardiac output) and / or dilatation (which results in congestion) o Diuretics – these will reduce blood volume and hence pre-load o Salt Restriction – this will reduce blood volume and hence pre-load o Inotropes (only used in end-stage heart failure as long-term usage increases mortality) – these will increase contractility of the heart and thus increase cardiac output TREATMENT OF HEART FAILURE Understand the different drug treatments in patients with heart failure - There is no proven therapy available for Diastolic Heart Failure (i.e. Preserved Systolic Function Heart Failure) Diuretics are the main treatment used for patients with this condition Management / treatment of Systolic Heart Failure will vary depending on whether it is Acute or Chronic Heart Failure; the particular management / treatments are: o Acute Heart Failure Treatment MONA (Morphine, Oxygen, Nitrates, Aspirin) Morphine provides pain relief Oxygen reduces dyspnoea and work of breathing Nitrates act as a vasodilator (decrease preload and afterload) Low-dose diuretic (e.g. Frusemide) this will reduce blood volume and hence preload - 18 - Inotropes (e.g. Dobutamine, Dopamine, etc.) this will augment contractility (though it will increase mortality if used long-term) Non-drug therapies (e.g. CPAP) o Chronic Heart Failure Treatment Lifestyle changes (e.g. fluid restriction, no salt added diet, reduction / cessation of alcohol) Diuretic (with patient to weight themselves daily and increase dosage of diuretics if higher levels of fluid are being retained) Blocking vasoconstrictive agents (e.g. Angiotensin, Noradrenaline, etc.) in order to achieve neurohormonal balance The different drugs available for treatment in chronic heart failure include: o ACE Inhibitors (e.g. Ramipril, Captopril, Enalapril) All the different ACE Inhibitors work exactly the same in treatment of heart failure ACE Inhibitors will be effective regardless of whether the patient is post-MI or with mild, moderate or severe heart failure ACE Inhibitors mechanism of action is to inhibit the Renin-Angiotensin-Aldosterone system (and hence prevents vasoconstriction and increased blood volume) Side effects / contraindications include hypotension, hyperkalaemia, angioedema, dry cough, renal impairment o Angiotensin Receptor Blocker (e.g. Candesartan, Valsartan) Same mechanism of action to ACE Inhibitors, but can be effective at reducing hospitalisations in patients that are intolerant to ACE Inhibitor o Aldosterone Antagonists (e.g. Eplerenone, Spironolactone) Spironolactone is a useful drug to treat severe heart failure, but there is a significant risk of hyperkalaemia and / or renal impairment (and gynaecomastia) Hence, renal function and potassium levels need to be closely monitored for patients using Spironolactone o Beta-Blockers (e.g. Carvedilol, Metoprolol Succinate, Bisoprolol, Nebivolol) This is the most effective treatment for reducing mortality from heart failure However, the method and timing of administration is critical to ensuring this benefit Provision of large doses of Beta-Blockers to patients in Acute Heart Failure will kill them In contrast, patient in the decompensating phase (i.e. post Acute Phase of Heart Failure) can be commenced slowly on a low dosage of Beta-blockers, with the dosage slowly increased Each of the Beta-blockers are different / unique and so the choice of Beta-blocker is important (as they may have very different impacts / outcomes) Ensure the Beta-blocker prescribed is appropriate for the patient given their condition and situation Side-effects include bronchoconstriction, bradycardia and hypotension The bronchoconstrictive effect of Non-selective Beta-Blockers can be significant, so it’s important to ensure patients are able to tolerate this, especially if they have a history of respiratory problems The scale of the mortality benefit from the use of Beta-Blockers in Heart Failure is such that doctors will always aim to be use Beta-Blockers if possible o Other potential treatments include: Fish Oil has been shown to deliver a 9% relative risk reduction in mortality in chronic heart failure patients Ivabradine is another drug that has shown some potential promise for treatment of heart failure; this works through slowing of the heart rate However, recent evidence has shown potentially higher mortality in patients with active Angina, so further research is needed to better understand the risks / benefits of this drug Angiotensin and Neprilysin inhibitor may potentially improve outcomes for heart failure patients via increased vasodilation 19 - - - - Beta-Blockers are the equivalent of ACE Inhibitors for first line therapy o However, ACE Inhibitors are the first line therapy prior to use of Beta-Blockers in Australia, as the PBS requires the use of ACE Inhibitors prior to the use of Beta-Blockers in order to be subsidised Note: Remember to only use those specific Beta Blockers that are effective (e.g. Carvedilol, Metoprolol Succinate, Bisoprolol, Nebivolol) o Aldosterone antagonists are now the third-line therapy o Some patients will not respond to ACE Inhibitors and instead need to be treated with Hydralazine and Nitrates o Note: Digoxin is an older inotropic drug that is sometimes used, though there is no evidence this will provide a mortality benefit Similarly, Aspirin / Warfarin are drugs that are sometimes used, though there is no evidence this will provide a mortality benefit Heart Failure may also trigger Sudden Death due to Arrhythmias o Many different medications that theoretically minimise Arrhythmias have been considered, but these have not shown benefits (and sometimes shown harms) from clinical trials of these medications o However, the MADIT study illustrated that implantation of a Defibrillator in patients with Ejection Fraction <35% will increase survival NSAIDs are contraindicated in patients with heart failure as they have the opposite effect of ACE Inhibitors (i.e. stimulate Renin-Angiotensin-Aldosterone system [and hence stimulate vasoconstriction and increased blood volume]) o Newer diabetic medication (e.g. Thiazolidinediones), antiarrhythmic agents and Metformin are also contraindicated in heart failure Statins are ineffective in the treatment of chronic heart failure PATHOLOGICAL CONSEQU ENCES OF HEART FAILU RE Understand the relationship between heart failure and reduced tissue perfusion - Congestive Heart Failure is: o The pathophysiologic state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolising tissues, despite adequate venous filling; and / or o The heart can only pump adequately when there is an abnormally elevated diastolic volume Heart failure due to Volume Overload will lead to Dilatation of the chambers, whilst heart failure due to Pressure Overload will lead to Hypertrophy of the chambers o Note: End-stage heart disease due to Pressure Overload will involve a decompensatory phase where the heart dilates Capability to fully perfuse Cardiac Myocytes will be reduced when the Cardiac Myocytes become thicker due to hypertrophy (as the nutrients / oxygen cannot reach the centre of the Myocyte) o This lack of perfusion will inhibit the ability of the Cardiac Myocyte to contract, ultimately resulting in reduction of the force of contraction Left Heart Failure will reduce the cardiac output in the systemic circulation, which will reduce perfusion o Left Heart Failure will also result in a backflow of blood into the pulmonary circulation o Right Heart Failure will result in systemic venous congestion (also due to the backflow of blood) - - - Understand the changes that develop in the tissues as a consequence of reduced perfusion - Left Heart Failure will increase the load of the Left Atrium, which will flow backwards resulting in Pulmonary Congestion 20 o - This triggers Pulmonary Hypertension, which increases the load / pressure on the Right Heart as it needs to pump against this higher pressure o Pulmonary congestion will also eventually trigger Pulmonary Fibrosis and the deposition of haemosiderin in the lungs (as RBCs enter alveoli where they are degraded by macrophages) o Note: The increased load on the Left Atrium also increases the risk of arrhythmia in the Left Atrium (i.e. Atrial Fibrillation) Left Heart Failure will also reduce perfusion to the kidneys; this will trigger the release of Renin, which increases sodium and water retention, and hence blood pressure Left and Right Heart Failure will result in damage to the effectiveness of the valves (e.g. regurgitation) due to the structural changes that result in response to heart failure Right Heart Failure will trigger systemic venous congestion, which will result in the back-up of blood resulting in Hepatic and Splenic Venous Congestion o This slows bloodflow through these organs and will inhibit perfusion of the centre of these organs this results in centrilobular necrosis of hepatocytes in the liver o Spleen will become grossly enlarged, which triggers the development of pale fibrous trabeculae within the Spleen this aims to limit the further enlargement of the spleen o Systemic Venous Congestion will also result in peripheral oedema, elevated JVP, ascites, etc. LIPIDS IN HEART DISE ASE Understand how lipoproteins may affect the formation of atherosclerotic plaques in the artery wall - Amphipathic Apo-lipoproteins can solubilise lipids and enable their transport through blood o This can lead to the transport of lipids to the artery wall forming an atherosclerotic plaque LDL, Lp(a), IDL and VLDL remnants are lipoproteins that are all directly Atherogenic (i.e. causing plaques) o All these lipoproteins are based on Apolipoprotein B100, which will aim to deliver these lipoproteins to an appropriate site o In contrast, HDL lipoproteins will transport cholesterol away from the artery wall towards the liver LDL particles will move into the Tunica Intima layer of the artery through a gradient-driven process (i.e. passive diffusion) o Once in the arterial wall, the LDL will undergo oxidation and become inflammatory Inflammation will increase the permeability of the endothelium, which exaggerates the influx of LDL, oxidation, etc. (i.e. self-fulfilling prophecy) o This will trigger the entry of Monocytes into the arterial wall, which convert to Macrophages The Macrophages will phagocytose these oxidised LDLs and eventually become so full of oxidised LDL that they become known as a ‘Foam Cell’ Damage to the artery wall is caused by the number of LDL particles rather than the total quantity of cholesterol o Hence, a greater quantity of smaller, dense LDL particles will cause more damage and increased CVD risk o High levels of Triglyceride will drive cholesterol ester transfer via CETP to/from LDL and HDL resulting in impairment of HDL and greater numbers of small, dense LDL Reduction in LDL will significant decrease CV events (even in patients without vascular disease) whilst having no significant increase in non-CVD o Statins will reduce circulating LDL by reducing LDL production within the cell this results in the cell absorbing more LDL from the bloodstream and hence lower circulating LDL There is a significantly increased risk of CV event above the threshold of ~60% of the Coronary Surface Covered Acute CVD events arise from inflamed lipid- rich ‘culprit’ lesions with a thin fibrous cap o Lipid modification can reduce inflammation and plaque lipid, which stabilises plaque lesions Accumulation of plaque in the vessel wall may result in the size of the overall vessel expanding outwards (rather than inwards and hence reducing the size of the lumen) - - - - - 21 o o As a result, a ‘clear’ angiogram may be present even in the presence of significant Atherosclerosis This type of plaque accumulation will be identified by Intravascular Ultrasound Understand the environmental and genetic factors that affect lipids - Changes in environmental factors (i.e. diet and exercise) are the main cause of the increased prevalence of heart disease o Genetics though will determine those people most susceptible and likely to suffer from heart disease given these environmental factors Environmental risk factors include: o Smoking o Hypertension o Diabetes o Dyslipidaemia o Obesity o Physical Inactivity o Low fruit and vegetable intake Genetic risk factors include: o Familial Hypercholesterolaemia o ATSI background Risk factors for heart disease tend to occur in multiples / clusters (as they are often associated) Atherosclerosis is proportional to the number and severity of classic risk factors - - - CLINICAL FEATURES, I NVESTIGATION AND TRE ATMENT OF ACUTE CORO NARY SYNDROME (ACS) TBA – New in 2014 - Acute Coronary Syndrome (ACS) typically implies a plaque rupture that will trigger a thrombus on the plaque o Plaque ruptures are extremely common, though most do not cause a clinical syndrome / symptoms o ACS can manifest in several different ways depending on the level of occlusion and the occurrence of emboli downstream; the different manifestations are: Unstable Angina – this implies no myocardial damage Non-Q Wave Myocardial Infarction (e.g. NSTEMI) – this implies a transient occlusion (although this is not always the case) Q Wave Myocardial Infarction (e.g. STEMI) – this implies a full thickness infarction of the myocytes downstream Symptoms of ACS include: o Abrupt onset / rapidly progressive angina o Chest Pain at rest o Diaphoresis (i.e. sweating) o Tachycardia o Dyspnoea / Acute Pulmonary Oedema o Cardiac Arrest / Ventricular Arrhythmia (which can result in syncope) Diagnosis of ACS based on: o Positive Troponin levels (i.e. high sensitivity, low specificity) Note: Renal impairment will affect the Troponin levels o ECG o Stress Testing o D-Dimer / CRP levels o CT Angiogram Differential Diagnosis for ACS will include: o Aortic Dissection (indicated if sudden onset, severe interscapular pain) - - - 22 - - - o Pulmonary Embolus (indicated if hypoxic, dyspnoea, tachycardia) o Pericarditis (indicated if positional, pleuritic pain) o Oesophageal (indicated if positional, responds to Antacid) o Musculoskeletal ( indicated if local tenderness, positional) Treatment of ACS involves: o PCI (Percutaneous Coronary Intervention [i.e. Coronary Angiography]) This is indicated for ALL ACS! There is a significant mortality advantage if PCI treatment for MI can be provided within 4 hours of onset of symptoms There is no benefit for having a ‘cooling off’ / waiting period prior to PCI after onset of ACS Note: If PCI is not available, then provide Thrombolysis o Beta-Blockers Beta-Blockers are prescribed to the patient at as high a dosage as possible without excessively reducing the heart rate (as Beta-Blockers have the side-effect of reducing heart rate) o Statins This will stabilise existing plaques, though there is a time-lag of ~3-6 months for this to occur o Anti-platelet Therapy (e.g. Aspirin, Clopidogrel, etc.) Treatment with a GPIIb/IIIa inhibitor (e.g. Abciximab) will be effective as this is the common pathway of platelet aggregation Aspirin and Clopidogrel / Prasugrel / Ticagrelor have complementary mechanisms and can be used together to maximise anti-platelet action o Antithrombotic Therapy (e.g. Heparin) ACS typically will involve multiple unstable plaques (rather than a single unstable plaque) o This increases the risk of further ischaemic events from these other plaques rupturing (even during the same admission) o As such, there may be an opportunity to provide treatment for these other plaques to minimise the risk of these other plaques rupturing Initial studies have shown there is a mortality benefit from conducting preventative PCI for these other plaques o Another study illustrated that the impact of subsequent plaque ruptures can be minimised (e.g. avoid mortality, avoid cardiac arrests, reduced frequency of infarcts, smaller infarcts) by continued treatment of the patient with anti-platelet therapy and Beta-blockers Continued treatment of the patient with anti-platelet therapy and Beta-blockers is particularly important in the ~3-6 months after an initial event as this is the time-lag required for Statins to stabilise existing plaques Heart bypass surgery is the gold standard treatment as it will provide a ‘cure’ for any plaque ruptures upstream of the graft o In contrast, PCI will only treat that individual plaque rupture (and NOT the remainder of plaques that are likely to exist) o Hence, heart bypass surgery will most benefit those patients who are most likely to suffer from progressive disease (e.g. diabetic patients, patients with family history of cardiovascular disease) TREATMENT OF CHRONIC ISCHAEMIC HEART DISE ASE Understand the different treatment modalities for improving the balance between myocardial oxygen demand and myocardial oxygen delivery o Consider the pharmacological approaches, as well as the use of surgical revascularisation procedures - Ischaemic Heart Disease is a life-long disease that can never be cured o One-off treatments such as Angioplasty or Heart Bypass does NOT cure this disease, but rather slows down the progression of the disease and / or alleviates symptoms 23 o - - - - - - - - Instead, a life-long treatment plan is needed to provide the optimal outcome for patients with Ischaemic Heart Disease Treatment of Ischaemic Heart Disease will focus upon: o Risk Factors Examples include cholesterol, smoking, diabetes, hypertension, obesity, etc. There are clear treatment targets for some of these risk factors, which can serve as a goalpost to measure progress / outcomes o Symptoms o Revascularisation Medications for Treatment of Ischaemic Heart Disease include: o Prognosis (‘SAAB’) Statin Aspirin ACE Inhibitor Beta-Blocker o Symptoms Nitrates (causes vasodilation, which reduces afterload) Beta-Blocker (inhibits sympathetic activation, which reduces heart rate) Calcium Antagonist (causes vasodilation, which reduces afterload) Statins will lower hepatic cholesterol production in cells via inhibition of HMGCoA Reductase, and hence lower LDL cholesterol levels in the bloodstream (as more LDL cholesterol is absorbed into the cells) o This lowering of LDL cholesterol levels in the bloodstream will result in increased removal of cholesterol from the plaques via the natural dynamic cholesterol transport system across the vessel wall o This reduces Atheroma progression and stabilises any existing plaques o The benefits from the use of Statins is proportional to the absolute level of risk in the patient, although there is still a benefit from continuing to lower cholesterol levels even if the patient has a normal level of cholesterol Aspirin is effective at reducing the risk of ischaemia by reducing the risk of thrombus formation on a ruptured plaque (which would then cause occlusion, ischaemia and potentially myocardial infarct) o Thienopyridines (e.g. Clopidogrel, Prasugrel) are a different anti-platelet therapy that may be used as an alternative or supplement to Aspirin o Clopidogrel AND Aspirin use is indicated for patients with events on Aspirin, and is effective for prevention of coronary stent thrombosis, especially drug eluting stents o Overall, anti-platelet therapy is a critical component of the treatment plan for all patients suffering or at-risk of ischaemic heart disease ACE Inhibitors are effective at improving outcomes of patients with clinical heart failure (e.g. Ventricular Scar), asymptomatic impairment of LV function or known cardiovascular disease and normal LV function o The mechanism of action of ACE Inhibitors is the inhibition of the Renin-AngiotensinAldosterone system; this reduces blood pressure and vascular fibrosis (which is promoted by Aldosterone) Beta-blockers will block the Beta-Adrenergic receptors and hence inhibit the sympathetic nervous response o This will reduce the heart rate and blood pressure of the patient, and hence the amount of work required from the heart o Reduction in heart rate increases diastole time (i.e. time for oxygen supply to heart) as well as reducing myocardial demand Nitrates are effective by stimulating vasodilation (particularly in the veins), which reduces venous return to the heart o Reduction in venous return (i.e. preload) will reduce the stroke volume and hence the work required from the heart Calcium Antagonists are potent vasodilators (both venous and arterial); this will reduce blood pressure, but also contribute to ankle oedema 24 o - - However, they also have negative inotropic and chronotropic effects and should NOT be used if there is Left Ventricular dysfunction or peripheral oedema There is a synergistic benefit from taking multiple different medications for cardiovascular disease (as they each have different mechanisms of action, which increases the impact of the other medications) Revascularisation will be indicated when there is: o Symptoms not controlled by medical therapy o Prognostic benefit (e.g. Left Main Artery or 3 vessel involvement) o Continued ischaemia after acute coronary syndrome o Ischaemic myocardial dysfunction and heart failure Revascularisation is generally performed via an Angioplasty o This often involves inserting and expanding a balloon catheter at the ischaemic vessel to restore blood flow (a stent may be inserted too at the time to keep the vessel open) o Anti-platelet therapy is critical when inserting a stent (as occurrence of Stent Thrombosis will often be fatal) o Alternatively, a Coronary Artery Bypass Graft (CABG) can be performed Arterial Grafts are preferable as the material used for the Coronary Artery Graft compared to Vein Grafts Vein Grafts have a higher risk of clotting / stenosing compared to Arterial Grafts (and hence will have a lower lifespan) PERIPHERAL VASCULAR DISEASE (INVESTIGATI ON, ACUTE AND CHRONI C MANAGEMENT) Understand the non-operative and operative management of patients with intermittent claudication - Intermittent Claudication will involve adequate circulation at rest, but the arterial occlusion preventing the augmentation of flow needed for exercise o As a result, anaerobic metabolism will occur, which results in acidic products and pain o The level at which the pain occurs is always below the level of the arterial occlusion Measurement of peripheral pressure (initial, post-exercise, post-rest) can provide an understanding of the level of the occlusion in the periphery Intermittent Claudication is generally benign (~85% manage without operation), with 5% at risk of amputation o ~85% of patients with Claudication develop collateral arteries that will circumvent the arterial occlusion Exercise will stimulate development of these collateral arteries Collateral Arteries will disappear / close-down following opening of the occluded artery (i.e. post-balloon) as they are no longer needed For patients needing surgery, options include: o Arterial Bypass Graft Upper Limb Veins are preferable to synthetic material for Grafts Outcomes from synthetic graft can be improved by attaching a small amount of vein to either side of the occluded artery and then inserting the synthetic material between them o Balloon Angioplasty (including Stenting) o Endarterectomy (i.e. physically shelling out the plaque) This is preferred vs. stenting for Carotid Artery disease Treatment with an exercise program has a superior outcome for patients with Claudication compared to Angioplasty o Angioplasty provides a short-term benefit but exercise produces superior long-term outcomes Angioplasty with Stenting is preferable than Angioplasty alone, though the incremental benefit is small and inconsistent Endoluminal Aneurysm Grafts have increased in prevalence in the past 20 years and is the most popular technique for repairing an Aortic Aneurysm - - - - 25 o o This technique enables aneurysm repair on a wider range of patients (who otherwise would be contraindicated for Open Aneurysm Grafts) Furthermore, this technique delivers a more rapid recovery compared to Open Aneurysm Grafts Understand the difference between acute and chronic limb ischaemia - Acute Limb Ischaemia results from acute trauma such as road accident, stabbing, glass injury or iatrogenic causes In contrast, Chronic Limb Ischaemia will result from long-term trauma such as atherosclerotic or diabetic driven stenosis, occlusion or aneurysm When fixing Acute Trauma, the Orthopaedic Surgeon will ideally fix the bones first and then the Vascular Surgeon will fix the blood vessels afterwards o This will mean the Vascular Surgeon knows exactly how long the vessel graft needs to be (as otherwise a graft that is too short may have problems if the bone is only fixed afterwards) - CARDIAC INVESTIGATIO NS INTRODUCTION TO ECG Understand the basic concepts underlying recording of electrocardiograms - Electrocardiograms (ECGs) records the electrical activity of the heart (depolarisation and repolarisation of the myocardium) o The surface of the heart is viewed from 12 different angles (in a 12-lead ECG) 10 electrodes are places on the patient, with a ‘lead’ referring to the signals transmitted between two electrodes (which enables 12 leads from 10 electrodes); these are divided between: o 4 Limb Electrodes (i.e. Right Arm, Left Arm, Right Leg (earth) and Left Leg); these are placed at: RA, LA = Lateral aspect of anterior side of the arms (avoid bony prominences and hairy areas) RL, LL = Medial aspect of the legs (avoid bony prominences and hairy areas) o 6 Precordial Electrodes (and Leads) (i.e. V1, V2, V3, V4, V5, V6); these are placed at: V1 = 4th Intercostal Space Right Sternal Edge V2 = 4th Intercostal Space Left Sternal Edge V3 = In-between V2 and V4 V4 = 5th Intercostal Space Mid-Clavicular Line V5 = Horizontal from V4 on the Anterior Axillary Line V6 = Horizontal from V4 on the Mid-Axillary Line Normal ECG will have a ‘PQRST’ aspects / waves in the recording o P wave reflects Atrial depolarisation (i.e. Systole) o QRS interval reflects the Ventricular depolarisation (i.e. Systole) o T wave reflects Ventricular repolarisation Complexes will look different in each lead as the same electrical impulse is oriented at a different angle (and hence will have a different strength) for each lead o QRS Complex of Lead I should be positive; if this is negative, this typically indicates the Limb Leads have been incorrectly placed in opposite directions (i.e. back-to-front) Interpretation of an ECG will involve following a system; this system is: o Rate Calculate by dividing 300 by the number of big boxes between two adjacent R waves to calculate the rate Alternatively, count the number of waves across the horizontal length of the ECG (i.e. on the Rhythm strip) and multiply this by 6 to calculate the rate o Rhythm Are there normal P waves present prior to every QRS complex? - - - - 26 o Is the QRS complex narrow vs. wide (i.e. is QRS > 0.12 seconds?) Are there any delays in conduction (e.g. Heart Block, Bundle Branch Block) First Degree Heart Block = PR Interval > 0.2 seconds Second Degree Type 1 (i.e. Wenkebach) Heart Block = Increasing PR interval followed by a missed QRS complex (with this cycle then repeated) Second Degree Type 2 Heart Block = P wave sometimes having an associated QRS complex and other times not having an associated QRS complex Third Degree (i.e. Complete) Heart Block = No relationship between the P wave (which occurs regularly) and the QRS Complex o The QRS complex is due to as escape rhythm from somewhere beyond the AV Node o This is an indication for the provision of a pacemaker to the patient Right Bundle Branch Block o The delay in the signal reaching the Right Ventricle in a Right Bundle Branch Block results in a delayed R wave in V1 (i.e. RSR wave [‘M’ shape]) Left Bundle Branch Block o The delay in the signal reaching the Left Ventricle in a Left Bundle Branch Block results in a delayed R wave in V6 (i.e. RSR wave [‘M’ shape]) Other Rhythm abnormalities include: Ectopic Beats o Junctional Ectopic Beat will occur around the AV Node and result in an unexpected very narrow QRS complex WITHOUT a preceding P Wave o Atrial Ectopic Beat will involve an unexpected P Wave followed by a QRS complex o Ventricular Ectopic Beat will involve a wider than normal QRS complex Atrial Fibrillation o Absence of P waves and irregular QRS waves is a classic sign of Atrial Fibrillation Atrial Flutter o This will involve regular QRS waves interspersed with a series of P waves (i.e. ‘sawtooth’ pattern of P waves) o Patients with Heart Rate of 150 that is very constant are likely to have Atrial Flutter (though the flutter P Waves are more difficult to identify at this speed) Supraventricular Tachycardia o This will involve a very narrow QRS complex tachycardia and the absence of P Waves Ventricular Tachycardia o This will involve a regular, very wide QRS complex tachycardia and the absence of P Waves Ventricular Fibrillation o This will involve a rapid, disordered / irregular series of QRS complexes Axis o Normal Axis will involve positive QRS complex in Lead I and aVF Right Axis Deviation will involve positive QRS complex in Lead aVF, but a negative QRS complex in Lead I Left Axis Deviation will involve positive QRS complex in Lead I, but a negative QRS complex in Lead aVF Hypertrophy 27 o Left Atrial Hypertrophy’ will be identified by a later depolarisation of the Left Atrium (which is identified in the ECG as a double peak in the P Wave) Right Atrial Hypertrophy will be identified in the ECG by a higher amplitude P Wave in the leads facing the Right Atrium Right Ventricular Hypertrophy will involve a larger amplitude QRS complex and an ST depression in the leads facing the right (e.g. Lead V1) Left Ventricular Hypertrophy will be identified if the sum of the S wave depth in Lead V1 and R wave amplitude in either V5 or V6 is greater than 35mm (or 7 big boxes) Ischaemia ST Elevation indicative of infarction ST Depression indicative of Ischaemia (OR reciprocal ST depression to an ST Elevation Infarction in the leads facing the other direction) INVESTIGATING CORONA RY DISEASE AND CARDI AC FUNCTION Understand the major methods of investigating cardiac pump function, with reference to the anatomy of the heart and normal values for intracardiac volumes and pressures - The major methods for investigating cardiac function are: o Radiology (i.e. X-Ray, Angiography, CT) o Cardiac MRI o Ultrasound (e.g. Echocardiography, Intravascular Ultrasound, etc.) o Nuclear Imaging Cardiac Catheterisation (i.e. Angiography) involves invasive arterial / venous access with pressure measurement and injection of contrast to visualise cardiac chambers and vessels o The movement of the chambers of the heart (and hence function) can be visualised o Pressure gradient can be measured (which together with cardiac output can be used to calculate the size of each of the Valve areas) o The size of the chambers can be assessed (and hence whether there is dilatation) Nuclear imaging includes a range of techniques such as Blood Pool Studies, Nuclear Stress Tests (i.e. Thallium + Sestamibi) and PET Scans - - Discuss the relative benefits and indications of each method - The key dimensions to consider when determining the appropriate method of investigation are: o Invasive vs. Non-invasive o Functional vs. Anatomical The following methods are available, and their benefits / indications are: o Plain X-Ray Advantages – Cheap, non-invasive Disadvantages – Limited information on function and chamber size, limited understanding of cause of pathology o Cardiac Catheterisation (i.e. Angiography) Advantages – Provides information on both anatomy and function, multiple investigations possible, accurate data, enables treatment in same procedure Disadvantages – Expensive, invasive (which risks complications such as a Stroke or MI), provides no information regarding the vessel / chamber wall (hence Atherosclerotic Plaques will not be identified unless there is stenosis) o Cardiac CT Advantages – Non-invasive, images Aorta and Pulmonary Vessels as well as Coronary Arteries Disadvantages – Radiation exposure, lower resolution, unable to interpret calcified vessels, respiratory and cardiac movement artifacts - 28 o o o Note: Key advantage of CT Scan is that will enable rapid identification of Coronary Disease, Pulmonary Embolus and /or Aortic Dissection (i.e. the three medical emergencies possible from the clinical sign of chest pain) Cardiac MRI Advantages – Non-invasive, information on myocardial viability and pathology, images Aorta and Pulmonary Vessels, assesses Ventricular function Disadvantages – Expensive, limited access, respiratory and cardiac movement artifacts, lower resolution for Coronary Arteries Echocardiogram Advantages – Provides information on both anatomy and function (e.g. visualise blood flow through heart [and hence any valvular abnormalities], measure volumes of heart, identify vegetations or thrombus, etc.), cheap, non-invasive Disadvantages – Investigator dependent, some patients difficult to study (e.g. Obese patients), no information regarding Coronary Arteries Nuclear Studies Advantages – Understand differences in perfusion across heart, assesses metabolic activity, measures volumes Disadvantages – Radiation exposure, expensive DIAGNOSTIC AND THERA PEUTIC ANGIOGRAPHY Understand the range of vascular pathologies for which angiography provides diagnostic and therapeutic options - PCI (Percutaneous Coronary Intervention) is indicated in: o STEMI o Left Main Coronary Artery Disease o Three-Vessel Coronary Artery Disease o Acute Coronary Syndromes o Symptomatic control of Angina o Note: Exception is diabetic patients with multi-vessel disease and / or patients with complex and extensive disease they have better outcomes with a CABG (i.e. Bypass) rather than PCI Complications of PCI include: o Stroke o Myocardial Infarction (~1%) o Coronary Damage requiring emergency CABG o Allergic response to contrast o In-stent Restenosis (hence use drug-eluting stents that release anti-proliferative drugs) o Stent Thrombosis (hence treat with anti-platelet drugs such as Aspirin + Clopidogrel) Non-coronary percutaneous cardiac interventions include closure devices (which can block ASD, VSD, PDA, PFO, etc.) and valve replacements o This enables replacement of the Aortic Valve in patients that otherwise are too ill for openheart surgery o The TAVI study indicated a significant improvement in mortality after 24 months in this group of patients who underwent Percutaneous Aortic Valve Replacement rather than the optimal medical treatment only Percutaneous Alcohol Septal Ablation involves inserting 100% alcohol into the hypertrophied area of the septum, which will trigger an infarct in this area o This will result in the reduction of the size of that part of the septum o This is important as the hypertrophied septum will then no longer be an obstruction within the heart (which enables a reduction in the pressure in the Left Ventricle) Non-cardiac interventions have less evidence / data supporting their usage (as there is an absence of clinical trials in this area) o Internal Carotid Artery Stent is a possible option to reduce the risk of stroke in patients with previous TIA (though surgical removal of the Atheroma has been shown to deliver superior outcomes) - - - - 29 o Aorto-Iliac and Renal Artery Stenting have been shown to have the same outcomes as surgical intervention to remove the Atheroma in these areas THE ECG IN ISCHAEMIA Understand the mechanisms which underlie the genesis of myocardial ischemia - Ischaemia occurs with interruption of Coronary Artery bloodflow this causes a reduction in oxygen and nutrient delivery to the myocardium o Infarction of heart tissue will commence further away from the Coronary Artery (i.e. deep within the heart in the Endocardium) before then approaching towards the Epicardium (where the Coronary Arteries are located) o Total transmural infarction will occur within ~6-12 hours of the occlusion Time = Muscle; the quicker the obstruction can be removed (and perfusion returned), the less damage that will occur to the heart ECGs are now conducted within the Ambulance to speed up the process of reviewing patients and getting them revascularised Mechanisms for Ischaemia can be: o Acute (e.g. thrombotic occlusion after plaque rupture, embolic event, etc.) o Chronic (e.g. stable plaque with gradually narrowing lumen) STEMI will involve a total-occlusion of the Coronary Artery, whilst NSTEMI will involve partial occlusion o Hence, NSTEMI treatment can be more conservative (i.e. initial Heparin and anti-platelets rather than immediate PCI) - - Explain the characteristic changes on the surface ECG which allow one to diagnose myocardial ischemia o Acute myocardial ischemia in turn has a number of cellular and metabolic consequences, leading to changes in the ionic milieu of the cardiac myocyte, and therefore to the action potential. o This results in characteristic changes on the surface ECG - Characteristic changes in an ECG indicating acute myocardial infarction are: o T-wave changes (i.e. T-wave inversion, tall peaked T-wave, depressed ST segment) these indicate Ischaemia Peaked T-waves (>6mm in limb leads / >12mm in precordial leads OR > 2/3 height of R-wave) will occur initially, but inverted T-waves will occur within a short time of infarction (i.e. ~2 hours) Downsloping or Horizontal ST Depression is much more specific for ischaemia compared to Upsloping ST Depression o ST changes (i.e. elevated ST segment) these indicate injury to the tissue o Q-wave changes (e.g. Q-wave size > 1/3 size of R-wave) these indicate tissue infarction (i.e. death) o Note: ECG changes need to be present in at least 2 contiguous leads to be material (otherwise the changes are likely due to another reason) o Note: New Left Bundle Branch Block can be an indicator of Myocardial Infarct Differential diagnosis for ST depression include: o Reciprocal ST depression o Digoxin effect o Hypokalemia / low magnesium Differential diagnosis for ST elevation include: o Ventricular hypertrophy o Ventricular aneurysm o Hyperkalemia o Pericarditis - - 30 - - Pericarditis will involve widespread ST Elevation across all the leads (except aVR) in contrast to Myocardial Infarction where the ST Elevation will only occur in some of the leads Furthermore, there is likely to be a ‘U-shaped’ ST Elevation o Brugada Syndrome The different leads provide an indication of the different directions of the heart; these are: o Septal Leads – V1, V2 o Anterior Leads – V3, V4 o Lateral Leads – I, aVL, V5, V6 o Inferior – II, III, aVF Note: Patient may have a normal ECG and still be having a Myocardial Infarction (which will be apparent from the clinical findings) o In these circumstances, re-perform the ECG every 10 minutes as the Myocardial Infarction may have occurred but is not yet showing on the ECG VALVULAR HEART DISEASE ABNORMAL HEART VALVE S Understand the microbiological aspects of acute rheumatic fever (ARF) and their prevention - Acute Rheumatic Fever is an acute, often recurrent, immunological inflammatory disorder which follows an upper respiratory tract infection due to Group A Streptococci (GAS) o Upper Respiratory Tract / Pharyngeal GAS Infection (i.e. Throat Infection) can result in cross reactivity in the inflammatory response between the Group A Streptococcus and SelfAntigens o As a result, the immune system will react to self-antigens in the heart resulting in Acute Rheumatic Fever o The interval between the GAS infection and the occurrence of Acute Rheumatic Fever is ~1-5 weeks There is no bacteria in the heart during Acute Rheumatic Fever but rather it is caused by immunopathology Prevention of upper respiratory tract infections of Group A Streptococci (GAS) will enable the prevention of Acute Rheumatic Fever Note: Repeated or severe episodes of acute rheumatic fever lead to chronic rheumatic heart disease (which causes permanent damage to valves) - Examine the relationship between rheumatic fever (especially when recurrent) and various valvular abnormalities which may interfere with normal cardiac function - Rheumatic Heart Disease can cause chronic inflammation this will lead to fibrotic thickening of valves, which reduces the valve orifice resulting in a stenosis of the valve o Alternatively, Rheumatic Heart Disease can cause fusion of commissures between Valve leaflets / cusps, which will also reduce the valve orifice resulting in a stenosis of the valve o The Mitral Valve is the valve most commonly stenosed by Rheumatic Heart Disease Rheumatic Heart Disease may also damage the Chordae Tendinae o This will result in valve incompetence, leading to regurgitation (e.g. Mitral Regurgitation) - INFECTIVE ENDOCARDIT IS Understand general pathogenesis of bacterial endocarditis - Bacterial Endocarditis will involve microorganisms from the mouth or IV drug use lodging on a damaged valve 31 o o - The bacteria will embed itself in the valve and proliferate The bacteria will destroy the valve on which they form as well as potentially releasing Septic Emboli into the body (which can reach other organs such as the brain or kidney) Bacteria are more likely to latch onto abnormal endovascular sites (e.g. pre-existing damaged heart valve) Distinguish key host and microbial factors - Hosts with pre-existing illnesses / diseases are more likely to be immunodeficient and susceptible to additional infections o Organs with pre-existing dysfunction are more likely to fail when suffering from Septicaemia Some organisms are more likely to adhere to endothelial surfaces (and hence cause Infective Endocarditis) (e.g. Streptococcus mutans) o Gram negative bacteria tend to be more aggressive and increase the likelihood of requiring a valve replacement o Skin bacteria (e.g. Staphylococcus aureus, Pseudomonas aeruginosa, etc.) are more likely to cause infection on prosthetic valves - Understand the biofilm infection concept - Bacteria can form a biofilm, which involves a group of microorganism cells sticking together o Biofilms are involved in a variety of microbial infections in the body o Biofilms are more difficult to eliminate compared to free-standing bacteria as they are more resistant to antibiotics Understand the general clinical features of endocarditis and their genesis - General clinical features of Endocarditis include: o Immune complex disease or nephritis (due to chronic antigenaemia [especially Sub-Acute Endocarditis]) o Splenomegaly (due to Reticuloendothelial hyperplasia) o Embolic phenomena Endocarditis may result in Septicaemia (if it showers septic emboli through the body), which will have significant adverse effects throughout the body - Understand the cardiac-specific features of endocarditis - Endocarditis can result in vegetation on the Valves and significant valve damage o This damage can result in Valvular Regurgitation o Nightmare scenario is Endocarditis destroying the Aortic Valve this would require immediate / urgent Aortic Valve replacement! Endocarditis will also result in ECG abnormalities (e.g. Axis Deviation and Bundle Branch Blocks) Distinguish clearly between the syndromes of acute and subacute bacterial endocarditis in terms of predisposing factors, microbial pathogenesis and characteristic clinical features - Syndromes of acute and subacute bacterial endocarditis will depend on: o Predisposing Factors (e.g. host resistance) o Virulence of micro-organism o Duration, frequency and intensity of infection Acute Bacterial Endocarditis usually involves a particularly virulent organism (e.g. Staphylococcus Aureus, Pseudomonas Aeruginosa) o This is an emergency as the valve is under significant attack from the infection this may require immediate Cardiothoracic surgery! - 32 - - - Subacute Bacterial Endocarditis (SBE) is typically from a relatively trivial bacteraemia (e.g. mouth organisms such as Viridian Streptococcus or Streptococcus Mutans) that is unable to cause an infection in a normal person o However, these bacteria will latch onto abnormal endovascular sites (e.g. pre-existing damaged heart valve) resulting in SBE o The more abnormal the endovascular site, the more likely it will be a site of an SBE infection Clinical Features of ABE include: o Hypotension o Vasodilation o Murmurs Clinical Features of SBE include: o Fever o Murmur o Constitutional Symptoms (e.g. nausea, lethargy, weight loss) o Emboli o Splenomegaly Understand the general principles of investigation and management - Investigation will require taking a blood culture to identify the precise microorganism causing the infection (which then enables the narrow tailoring of antibiotic treatment) o Endovascular foci infection is much more likely to be detected from a blood culture compared to Extravascular foci infection o This is due to the Extravascular foci infection being walled off from the blood, and so the infection is only released into the blood intermittently Hence, the blood for the blood culture needs to be taken at a specific time to be able to detect the infection As a result, repeated blood cultures over 24 hours may be required to identify the cause of Extravascular foci infection Full Blood Count will also be useful to confirm the presence of inflammatory markers (e.g. elevated CRP, Neutrophilia, etc.) Echocardiogram is a useful investigation as this can demonstrate the presence of vegetation on the valves o Echocardiogram will not identify microscopic infection of the heart valve, but only macroscopic damage o As such, negative Echocardiogram does NOT exclude Endocarditis o Positive Echocardiogram can help identify emergency / severe cases of Endocarditis and hence confirm the urgency / need for a valve replacement (or other surgical intervention) Slow-growing bacteria can live for extended periods of time (by shutting down their metabolic activity) and hence prolonged treatment is required to fully cure / eliminate the bacteria o Cessation of treatment will enable the bacteria to survive and potentially switch to a rapidly dividing / metabolising state that will cause significant symptomatic infection There is a time lag of >16 hours to be able to specifically identify the species of bacteria affecting the patient o Treatment decisions are made without knowledge of the specific species of bacteria; these decisions are made based on knowledge of the common species of bacteria that cause Endocarditis - - - MEDICAL, PERCUTANEOU S AND SURGICAL MANAGEMENT OF VALVULAR HEART DISEASE Understand the factors that contribute to the surgical management of valvular heart disease, in particular when to intervene, the interventional options and the choices of the options - Intervention for Valvular Heart Disease is indicated when there is: 33 - - - o Significant symptoms; and / or o Risk to life Interventional Options for Valvular Heart Disease are: o Valve Conservation Valve reconstruction and repair (i.e. of leaflets, Chordae Tendinae, Papillary Muscles, Valve Annulus) Valvotomy (i.e. splitting open valve) this can be performed percutaneously or via an open operation o Valve Replacement Heterograft (e.g. porcine valve, bovine valve) Mechanical Prosthesis Homograft (i.e. from human cadaver) Factors influencing choice of Interventional Option: o Valve anatomy (e.g. stenosis vs. regurgitation vs. mixed) o Cause of valvular disease o Patient age This affects the risk of the operation (e.g. may only be able to perform percutaneous replacement rather than surgical replacement) This will also affect the expected lifetime required for the replacement valve (as Tissue Valves will need to be replaced earlier compared to Mechanical Prosthetic Valves) o Availability of grafts o Patient preference / lifestyle o Possibility of coagulant control (as lifelong anticoagulation is required for Mechanical Prosthetic Valves) o Co-morbidities NOTE: The ‘Learning Objectives’ section of the Compass page for this lecture has a lot of relevant information (http://smp.sydney.edu.au/compass/teachingactivity/view/id/7217) GENETICS AND CONGENITAL ABNORMALITIES GENES AND CARDIOVASCULAR DISEASE Highlight the widespread impact of genetics in cardiovascular disease, with a specific focus on cardiomyopathies and primary arrhythmogenic disorders of the heart - There are particular genes that will directly cause CV Disease o There are currently ~45 different CV conditions (e.g. Marfan, Hypertrophic Cardiomyopathy, Long QT Syndrome, etc.) that are directly caused by an underlying genetic abnormality Given most genetic cardiomyopathies are autosomal dominant, the whole family will require examination o Examining rest of the family is CRITICAL!!! other members of the family are highly likely to be at risk! o Family history may also provide a better understanding of the risk for the individual patient (e.g. higher risk if there was a previous Sudden Death in the family) o Genetic testing will enable prediction of genetic abnormalities causing CV disease o Genetic counselling is very important for families where there is genetic cardiomyopathies There is significant clinical heterogeneity (i.e. there are different clinical manifestations of the same condition) and genetic heterogeneity (i.e. there are multiple different genetic mutations that can cause the same condition) in these genetic cardiomyopathies Sudden Cardiac Death is caused either by Structural or Arrhythmogenic causes o ~50% of young people who die from Sudden Cardiac Death have no symptoms prior to the initial collapse that results in death - - - 34 o - - - - - - Sudden death triggers can include contact sports, high-adrenaline / extreme activities (e.g. bungee jumping), sudden noises (e.g. alarm clocks), energy drinks, stressful events (e.g. knock-out sporting matches), etc. Implantable Cardioverter-Defibrillator will deliver an electric shock to the patient if the heart goes into a rhythm that could lead to sudden death (e.g. VT, VF) o This undoubtedly saves lives, although it is only implanted into higher-risk patients (given the excessive cost of implanting this device in all patients) Examples of Structural Diseases causing Sudden Cardiac Death include: o Hypertrophic Cardiomyopathy – this is a disease of the sarcomeres in the heart It is the main cause of Sudden Cardiac Death in US athletes There are >1,000 mutations in at least 13 genes responsible for this disease o Familial Dilated Cardiomyopathy – this is a disease of the cytoskeleton Abnormalities in several different genes can potentially result in this disease o Arrhythmogenic RV Cardiomyopathy – this is a disease of the Desmosome Junctions between myocytes Pathology involves fatty infiltration of the Right Ventricle leading to fat, fibrosis and necrosis This is associated with people undertaking endurance triathlons / competitions (e.g. hours of training) o LV Noncompaction – this involves a failure of the LV to compact as part of normal development and instead the LV remains spongy Most Arrhythmogenic causes of Sudden Cardiac Death (e.g. Long QT Syndrome) are caused by Ion Channelopathies o ~95% of these Ion Channelopathies involve either Sodium, Potassium or Calcium channels Some of the genes resulting in Long QT Syndrome are associated with other genetic conditions (e.g. SIDS, Brugada Syndrome, etc.) It is now mandatory in Australia for a blood sample to be taken from any young person (i.e. <40 years) who dies in case it is needed for future testing o For example, a Molecular Autopsy can be performed on this sample to identify any underlying genetic abnormalities / conditions that may explain why they died o Molecular Autopsy has helped identify an underlying cause in ~33% of those patients where there previously was no identified underlying cause of the Sudden Cardiac Death (which itself was ~33% of Sudden Cardiac Death cases) Each of the different gene mutations resulting in a condition (e.g. Long QT Syndrome) will have different triggers and different optimal treatments o Similarly, the risk level will vary depending on the particular genes involved Advances in genetic technology will enable more accessible, cheaper and more comprehensive genetic assessment ENVIRONMENT, EPIGENETICS AND FOETAL PROGRAMMING TBA - Epigenetics do NOT involves differences / changes in DNA, but other functional modifications that can potentially be inherited (e.g. DNA Methylation, Histone modifications, etc.) o However, these functional modifications are NOT guaranteed to be inherited These epigenetic changes can be triggered by the environment / conditions facing the person o ‘Foetal Origins of Disease Hypothesis’ states organisms make predictive, adaptive responses in anticipation of perceived impending environmental situations, and that this process begins in-utero Examples of epigenetic changes include: o Low birth weight or impaired foetal growth (IUGR) – this is associated with many adverse health outcomes (e.g. hypertension, diabetes, CVD, etc.) This is presumed to occur due to the foetal compensatory responses in-utero that increase foetal survival, BUT result in adverse long-term effects - - 35 o - Exposure to maternal diabetes – this is associated with CVD, diabetes, obesity and cancer (irrespective of birth weight) o Other factors affecting outcomes include maternal and paternal obesity and diet, maternal smoking and maternal preeclampsia There is some evidence that adults born with impaired foetal growth can have their CVD risk reduced by dietary supplementation (with Omega-3 PUFA [Polyunsaturated Fatty Acids]) Recent data suggests that early life experience (e.g. healthy diet, normal weight) can help to ameliorate deleterious changes CHROMOSOMAL ABNORMALITIES Understand the cytogenetic mechanisms responsible for Down Syndrome and the mechanisms that produce Trisomy 21 - Down Syndrome (i.e. Trisomy 21) results from there being 3 copies of the Chromosome 21 (rather than 2 copies) o Chromosome 21 is the smallest of the 23 different chromosomes o This may explain why Chromosome 21 is the most common chromosome that can occur three times (rather than the normal two times) and still be a live birth (as other Chromosomes that occur three times will be too mutated resulting in a miscarriage) The risk of having a child with Trisomy 21 increases with maternal age o In contrast, there is no relationship between paternal age and Trisomy 21 Trisomies are observed in a significant proportion of spontaneous abortions Trisomy 21 can result from: o Full Trisomy (~95%) o Chromosome Translocation (~4%) o Mosaicism (~1%) o Other (<1%) Full Trisomy will result from meiotic or mitotic non-disjunction events o Errors in Meiosis that lead to Trisomy 21 are usually (~95% of the time) maternal in origin Nondisjunction at Meiosis I is more likely to occur for maternal origin of dysfunction compared to Nondisjunction at Meiosis II In contrast, nondisjunction at Meiosis II is more likely to occur for paternal origin of dysfunction compared to Nondisjunction at Meiosis I o These are two mechanisms through which Full Trisomy of chromosomes can occur Chromosome Translocations can involve: o Reciprocal Translocation This involves the swap of part of the Chromosome between two different Chromosomes This can result in balanced translocation (i.e. normal number of genes), though the gametes will have unbalanced translocation (i.e. partial trisomy and monosomy) Partial Trisomy can be detected via FISH o Robertsonian Translocation This involves fusion of the whole long arms of two acrocentric chromosomes (chromosomes with the centromere near the very end) Note: The two short arms will also fuse together, but may be lost o Insertional Translocation This involves a part of one chromosome being inserted into another chromosome (without any reciprocal exchange) - - - Define the meaning of translocation and mosaicism - ‘Translocation’ refers to rearrangement of parts of the chromosomes between nonhomologous chromosomes ‘Mosaicism’ refers to the presence of two or more different genotypes in one individual (i.e. not every cell in the body has the same DNA content) - 36 o o This can occur by chance during early embryogenesis This can result in partial Trisomy 21 Note: ‘High-performing’ Down Syndrome individuals generally have mosaicism DEVELOPMENT OF HEART AND CARDIOVASCULAR SYSTE M Understand the major events that occur during the embryological development of the heart (in particular the various partitioning processes) - The heart forms very early in the mesoderm within the trilaminar embryonic disc as a simple paired tube inside the forming pericardial cavity o These paired tubes will fuse to form a single primitive heart tube o The heart begins to beat at about 22-23 days, with blood flow beginning in the 4th week The single heart tube is then partitioned into 4 chambers with a systemic outflow on the left and a pulmonary outflow on the right o Septation of the heart into separate chambers occurs as the embryonic / foetal circulation is different to the neonatal circulation, several defects of heart septation may only become apparent on this transition to the neonatal circulation Blood passes the nonfunctioning lungs via 2 temporary ‘shunts’ (i.e. Foramen Ovale and Ductus Arteriosus) The three key differences in foetal circulation are the presence of the: o Foramen Ovale (opening between Left and Right Atrium) o Ductus Arteriosus (connection between Pulmonary Trunk and Descending Aorta) o Ductus Venosum (connection from Umbilical Vein to Inferior Vena Cava [hence enabling placental blood to bypass the liver]) o Note: Failure of these three differences to close will result in a congenital heart defect Foramen Ovale should close soon after birth once Left Atrium pressure > Right Atrium pressure Ductus Arteriosus should constrict/close soon after birth Ductus Venosum should constrict/close within one week of birth After birth, the lungs will inflate and the resistance to blood flow in the lungs decreases o This will cause blood to flow via the Pulmonary Circulation (rather than the Ductus Arteriosus) - - - Consider how abnormalities of the normal partitioning processes can cause congenital heart defects and the effect that these can have on the circulation - Abnormalities of the normal development process can result in congenital heart defects such as: o Patent Ductus Arteriosus o Coarctation of Aorta o Atrial Septal Defects (ASD) o Ventricular Septal Defects (VSD) o Atrioventricular Septal Defects (AVSD) o Tetralogy of Fallot o Transposition of the Great Vessels Atrial Septal Defects may not produce any clinically relevant problems; however, significant defects will produce a left-to-right shunt, which can ultimately cause increases in Pulmonary Pressure / Pulmonary Hypertension o Alternatively, venous embolism may travel through this septal defect and enter the arterial circulation (which can then potentially lodge in the brain causing a Stroke) o Ventricular Septal Defects can also produce a left-to-right shunt, which can ultimately cause increases in Pulmonary Pressure / Pulmonary Hypertension Patent Ductus Arteriosus will result in oxygenated blood from the Left Heart re-entering the Pulmonary Circulation o This will increase the pulmonary pressures (resulting in Pulmonary Hypertension) and make breathing more difficult (resulting in dyspnoea) - - 37 o - Furthermore, the effective cardiac output to the systemic circulation is reduced due to this diversion of blood Transposition of the Great Vessels will result in two circulations in parallel this will result in death without surgery, as deoxygenated blood cannot be oxygenated resulting in a lack of oxygen supply to tissue CIRCULATORY CHANGES AT BIRTH Understand the normal changes in the circulation that occur at birth, to enable transition from foetal to postnatal life - Normal changes to circulation that occur at birth are: o Foramen Ovale should close soon after birth once Left Atrium pressure > Right Atrium pressure o Ductus Arteriosus should constrict/close soon after birth o Ductus Venosum should constrict/close within one week of birth After birth, there is a reduction in Pulmonary Vascular Resistance (due to the lungs breathing, the fluid in the lungs being expelled and an increase in pulmonary vasodilating hormones) and an increase in Systemic Vascular Resistance (as the low resistance placenta is removed from the circulation) o This results in blood flowing via the Pulmonary Circulation rather than via the Ductus Arteriosus (which can then functionally close within ~10-15 hours of birth) o This also increases flow to the Left Atrium; this will increase Left Atrium pressure such that the Foramen Ovale functionally closes o Ductus Venosum closure commences shortly after birth due to cessation of umbilical venous return - Understand the conditions that interfere with this normal transition - Causes of difficult transition of circulation include: o Normal transition complicated by premature delivery (which can result in Patent Ductus Arteriosus) o Delay in transition in infant with normal cardiovascular system o Normal transition in infant with abnormal cardiovascular system (who relies on a Patent Ductus Arteriosus for survival) Abnormal transition can result in: o Cyanosis (i.e. ‘blue baby’) o Respiratory distress o Cardiac failure o Shock Examples of conditions interfering with the normal transition include: o Patent Ductus Arteriosus This will result in pulmonary congestion this can lead to Pulmonary Haemorrhage, which will impair gas exchange (which can result in death!) Alternatively, this can result in insufficient blood supply to the brain, resulting in poorer developmental outcomes o Persistent Foetal Circulation This involves failure of systemic and pulmonary circulation resistance to convert from the foetal to the normal postnatal resistance This results in continued blood flow through the Foramen Ovale and a lack of oxygenation of blood Examples of abnormal cardiovascular system conditions that rely on a Patent Ductus Arteriosus for survival include: o Pulmonary Atresia This involves the Pulmonary Outflow Tract / Pulmonary Trunk being absent or completely stenosed (preventing blood from the Right Heart reaching the lungs to be oxygenated) - - - 38 o o o o Patent Ductus Arteriosus provides a pathway for blood to be oxygenated Transposition of Great Arteries This results in two circulations in parallel this will result in death without surgery as deoxygenated blood cannot be oxygenated, resulting in a lack of oxygen supply to tissue Patent Ductus Arteriosus provides a pathway for blood to be oxygenated Aortic Atresia This involves the Left Ventricular Outflow Tract being absent Oxygenated blood will back up from the Left Heart back into the Pulmonary Circulation and back into the Pulmonary Arteries Patent Ductus Arteriosus provides a pathway for oxygenated blood to reach the systemic circulation Coarctation of Aorta Narrowing of Aorta will restrict blood flow to the lower half of the body However, Patent Ductus Arteriosus will ensure appropriate perfusion to lower half of body Note: Prostaglandin E1 is infused after birth for these infants, as this will re-open the Ductus Arteriosus INTRODUCTION TO CONGENITAL ABNORMALITIES OF THE HEART TBD – New in 2014 - Medical aspects of congenital heart disease include: o Cyanosis (which is related to Acne, Osteoporosis, Gout and Gall Stones) o Haemodynamics o Electrophysiology o Endocarditis Psychosocial aspects of Congenital Heart Disease include: o Employment o Insurance o Contraception o Exercise / sport o Social development o Intellectual development The most common types of Congenital Heart Disease (which account for ~85% of Congenital Heart Diseases) are: o Ventricular Septal Defect (VSD) o Atrial Septal Defect (ASD) o Patent Ductus Arteriosus (PDA) o Aortic Stenosis o Pulmonary Stenosis o Aortic Coarctation o Transposition of the Great Arteries o Tetralogy of Fallot Ventricular Septal Defect will result in higher pressures and oxygen saturation in the Right Ventricle Eisenmenger VSD involves the blood shunting from the right-to-left ventricle due to the Pulmonary Resistance increasing to above the Systemic Resistance o The Pulmonary Vessels will adapt to the higher pressures from the Right Ventricle (due to the VSD) by developing higher resistance o Once the Pulmonary Resistance is greater than the Systemic Resistance, blood will find it easier to travel from the Right Ventricle to the Left Ventricle (rather than to the Pulmonary Trunk) o This will ultimately result in deoxygenated blood being pumped from the Left Ventricle into the Systemic Circulation (which will trigger Cyanosis and Polycythaemia) - - - 39 - - - - - - - - - Central Atrial Septal Defect (i.e. defect in the centre of the Atrium wall) can be closed percutaneously by threading a catheter through the defect and releasing a twin-disc device that clamps a single disc down on either side of the Septal Defect (i.e. in both the Right and Left Atrium) and blocks the hole o However, this technique can only be used on central defects and NOT on defects close to other structures, as the device / discs need to be able to clamp down in the space around the hole (to ensure the hole in completely blocked) Atrial Septal Defect will result in blood flow from the Left to Right Heart (as Left Heart Pressure is higher) o This can result in Right Heart dilatation due to the excessive volume and pressures in these chambers (which can cause Atrial Fibrillation, Pulmonary Hypertension and / or Right Heart Failure) Patent Ductus Arteriosus can be resolved / closed off percutaneously by placing a disc on either side of the Patent Ductus Arteriosus o This uncorrected defect will result in blood flow from the Aorta to the Pulmonary Trunk o This will trigger a continuous murmur (as there is continual rapid flow from the Aorta to the Pulmonary Trunk) o This will also trigger greater volume load into the Pulmonary Trunk, Left Atrium and Left Ventricle (but NOT Right Heart) Patients with Bicuspid Aortic Valve are more likely to have Aortic Stenosis, Aortic Regurgitation and / or dilatation of the Aorta (which may eventually result in Aortic Rupture / Dissection) Patients with an Aneurysm later in life following an Aortic Coarctation Repair are at risk of Sudden Death o These patients will need treatment of this aneurysm to avoid this risk Tetralogy of Fallot will involve the following four features: o Right Ventricular Outflow Obstruction (e.g. Pulmonary Trunk Stenosis) o Right Ventricular Hypertrophy o Ventricular Septal Defect o Aortic Override (over the Right Ventricle) o Note: The four features of Tetralogy of Fallot occur due to the Infundibular Septum being directed anteriorly rather than inferiorly Blalock-Taussig Operation / Shunt increases pulmonary blood flow for palliation in duct dependent (i.e. Patent Ductus Arteriosus) cyanotic heart defects o This operation involves connecting the Subclavian Artery to the Pulmonary Trunk / Arteries o This operation will relive cyanosis in patients (mainly infants) whilst they await corrective or palliative surgery Patients with congenital heart defects are more likely to suffer from arrhythmias due to: o Scars on the heart from the operation to correct the congenital heart defect (which will increase electrical instability) o Dilated chambers (due to the congenital defect), which are irritated electrically Transposition of the Great Vessels results in two circulations in parallel o This is palliated with a Balloon Atrial Septostomy (which creates a connection between the two parallel circulations), whilst definitive treatment involves an ‘Arterial Switch’ Tricuspid Atresia results in a hypoplastic or absent Right Ventricle this results in the heart being unable to properly oxygenate the rest of the body (as it cannot pump the blood into the Pulmonary Circulation) o Treatment can include Total Cavopulmonary Connection, which involves diverting venous blood from the IVC / SVC directly to the Pulmonary Arteries (i.e. circumvent the Right Atrium) 40 DEVELOPMENTAL DELAY / DISABILITY IDENTIFYING DEVELOPM ENTAL DELAY Understand the range of normal development in children, together with major deviations from the normal pattern that cause the greatest concern - ‘Development Delay’ is defined as when a child does not reach developmental milestones at the expected age (i.e. performance 2 standard deviations below age-appropriate norm), allowing for normal variability o This delay should be persistent rather than temporary / one-off (e.g. due to an illness in the child) o Indigenous children are more than twice as likely to be developmentally vulnerable (i.e. 43% of Indigenous children vs. 22% of Non-Indigenous children) o Males are more likely to be vulnerable Domains for development are: o Gross Motor o Fine Motor o Speech and Language o Cognitive o Social / Emotional o Self-help If developmental delay is only is a single domain, consider whether there is a localised issue driving this rather than being a true developmental delay (e.g. MSK condition inhibiting fine motor skills) o However, single domain developmental delay (e.g. speech / language) may be an early sign of a more global developmental delay o Be VERY concerned if there is any regression in developmental progress!!! Screening tools when used longitudinally improve detection of developmental delay by 3-4 times and will correctly detect almost all children (compared to clinical judgment alone) Screening for developmental delay is NOT a one-off but rather an ongoing process of ‘Developmental Surveillance’ o Other risk factors should also be considered in this Developmental Surveillance program An approach to assessing children suspected of developmental delay includes: o Taking a History from Parents – this can provide additional information on the functional capabilities of the child (as the child may not be exhibiting their full capabilities in the examination room) o Examining for Risk Factors (e.g. failure to thrive, congenital abnormalities, sensory problems, environment for child, etc.) Common causes of developmental delay in developing countries are: o Malnutrition o Inadequate stimulation or learning opportunities o Iodine deficiency o Iron deficiency anaemia o Note: Absence of attachment to a consistent caregiver can have significant negative effects on brain development and cognitive functioning - - - - - SUPPORT AND MEDICAL SERVICES FOR DOWN SY NDROME Understand the common medical conditions associated with Down Syndrome - Common medical conditions associated with Down Syndrome includes: o Congenital Heart Disease / Abnormalities (e.g. AVSD, PDA, etc.) o GIT Malformations (e.g. Duodenal Atresia) o Ocular / Vision disorders (prevalence ~60%) o Hearing impairment (which will magnify any developmental delay by having a marked inhibitory effect on language development) o Hypothyroidism 41 o o o o o o o o o o o o o Atlanto-Axial Instability (which can lead to neck pain, gait abnormality, etc.) Obstructive Sleep Apnoea Childhood Leukaemia and Testicular Cancer Infertility Coeliac Disease Obesity Poor Oral Health Osteoporosis Autoimmune disorders (e.g. Vitiligo, Alopecia) Skin Disorders (e.g. Hyperkeratosis) Respiratory Infections Psychiatric Disorders Alzheimer’s Disease (earlier onset vis-à-vis general population) Understand the importance of providing a thorough medical, developmental and educational assessment - A thorough medical, developmental and educational assessment is important as this will identify areas of need for people with Down Syndrome and ensure appropriate support is provided to maximise their development, health and independence o This will help foster autonomy and maximise inclusion in the community for people with Down Syndrome o Ongoing support is often required for individuals and their families, though most people with Down Syndrome live in the community (rather than within institutions) Remember to check / screen for particular health conditions regularly (even if there is no complaint from the patient [as Down Syndrome patient may not have the skills to communicate any health problems]) o There is often ‘Diagnostic Overshadowing’ (i.e. doctor being distracted by the intellectual disability and not diagnosing other medical conditions present) which increases the importance of pro-active screening Preventative healthcare is also important given the high prevalence of various medical conditions in people with Down Syndrome - - INTELLECTUAL DISABILITY SUPPORT AND FAMI LIES Understand the range of support mechanisms for families of children that have intellectual disability - ‘Intellectual disability’ refers to deficits in intellectual function (e.g. reasoning, problem solving) AND deficits in adaptive functioning (e.g. social participation, independent living) that had its onset in the developmental period o Severity of intellectual disability is based on functioning in Conceptual (e.g. language, literacy, money, time, etc.), Social (e.g. interpersonal skills, ability to follow rules / laws, etc.) and Practical (e.g. ADLs, travel / transportation, etc.) domains Current approach to support is that it should be provided based on the needs of the individual o The specific support needed will change across the lifespan of the individual The support mechanisms available for families of children that have an intellectual disability include: o Coordination of services (e.g. GP, Disability Case Manager, etc.) o Advisors on schooling o Respite care o Financial support (e.g. NDIS, Carer Allowance, Taxi Subsidy, Disability Support Pension) o Support groups / sibling groups o Prenatal diagnosis support (e.g. explain the full circumstances of the life of a child with an Intellectual Disability [e.g. Down Syndrome] and the impact on their parents / siblings lives too) - 42 ARRHYTHMIAS SUPRAVENTRICULAR ARR HYTHMIAS AND BRADYAR RHYTHMIAS (INCLUDING AF, SVT) TBD – New in 2014 - The key mechanisms for Arrhythmia are: o Abnormal Automaticity o Re-Entry (this is the most frequently encountered mechanism of Arrhythmia) o Triggered Activity After Depolarisation Increased automaticity results in a part of the Atrium (other than the SA Node) firing off an additional electrical signal this additional signal causes the Ectopic Beat Re-entry refers to the ability of an electrical wave of depolarisation to go down a pathway and return back through an alternative pathway to allow a circuit of electrical activation to form; this requires: o Two alternative electrical pathways o Unidirectional block in one of the above pathways o Critical zone of ‘slow’ conduction (which enables depolarised tissue sufficient time to repolarise in preparation for the next depolarisation [which will then sustain the Arrhythmia]) Supraventricular Arrhythmias will include: o Atrial Ectopic Beats Mechanism – Automaticity, Re-entry Diagnosis – ECG Implications – Benign in absence of heart disease Symptoms – ‘Missed beat’, cough Treatment – Generally nil as this is benign Beta-blockers can be used if needed (assuming ectopic due to adrenergic input) Otherwise, avoid triggers (e.g. caffeine, alcohol, stress) o Supraventricular Tachycardia Mechanism – AV Junctional Re-Entrant Tachycardia (70%), Accessory Pathway (25%), Automatic Focal (5%) Symptoms – Rapid palpitations, dizziness, sudden onset / abrupt offset, sweating, chest pain, pulsing in neck / throat Treatment – Vagal manoeuvres (e.g. coughing, Carotid massage, Valsalva manoeuvre), drug therapy (e.g. Adenosine, Verapamil IV, Sotalol, Flecainide), cardioversion, Catheter Ablation (preferred long-term treatment option Ablation involves delivery of radiofrequency energy that cauterises cardiac tissue (which prevents transmission of electrical signals via this tissue) this is a very effective treatment (cure rate of ~95%) Note: Wolff-Parkinson-White (WPW) Syndrome is a specific type of Supraventricular Tachycardia involving an accessory pathway; this is characterised by a short PR interval, SVT and Delta waves (i.e. slurred upstroke of QRS complex) Note: Ectopic Atrial Tachycardia is a specific type of Supraventricular Tachycardia involving ectopic beats from the Atrium; treatment can involve Flecanaide (extremely effective), Sotalol or Cardiac Ablation o Atrial Flutter Mechanism – Single re-entry circuit (typically in Right Atrium) Symptoms – Palpitations, light-headedness, flutters Treatment – Cardiac Ablation, Anticoagulation, Drug Therapy (e.g. Flecanaide, Verapamil, Sotalol, Amiodarone) o Atrial Fibrillation Mechanism – Multiple re-entry circuits (typically with a foci near the Pulmonary Veins) - - 43 Risk factors – Age (>50), Hypertension, Heart Failure, Ischaemic Heart Disease, Valvular Heart Disease, Obesity, Diabetes, Thyroid Disease, Obstructive Sleep Apnoea Triggers – Endurance training / sports, respiratory disease, dehydration, spicy foods, inflammation, GORD (Gastro-Oesophageal Reflux Disease) Symptoms – Palpitations, dyspnoea, fatigue, dizziness, syncope, angina Implications – 5x Stroke Risk, 2x Mortality, Heart Failure, reduced quality of life, reduced exercise tolerance Treatment – Slow heart rate (e.g. via drug therapy [e.g. Flecanaide, Sotalol, Amiodarone], cardioversion, pacemaker), treat symptoms, prevent stroke / anticoagulation (e.g. Warfarin, Aspirin) INTRODUCTION TO VENT RICULAR ARRHYTHMIAS Describe disturbances of rhythm arising in the ventricles of the heart, how they are classified, their mechanisms and effects, and how they may be diagnosed and treated - Depolarisation / repolarisation of Ventricular Muscle will involve Na+, K+ and Ca2+ channels Depolarisation will occur due to a gradual leakage of current until the threshold is achieved to trigger depolarisation o The heart rate (i.e. rate of depolarisation) can be decreased by increasing the threshold potential and / or lowering the resting membrane potential (and vice versa) o Anti-arrhythmic drugs commonly will adjust the threshold and / or resting membrane potentials and hence impact upon the rhythm Cardiac Myocytes have an elongated action potential phase compared to Skeletal Muscle Cells (during which it is refractory and cannot be re-stimulated) o This prevents rapidly repeated / continual contraction of the heart, which ensures there is a diastole phase (and hence the presence of blood in the Ventricles to pump in the systole phase) The different ventricular arrhythmias are: o Bradycardia This results from either the failure to generate an impulse (i.e. sinus node dysfunction) or a block in conduction (i.e. at the AV Node or Purkinje Fibres) o Tachycardia This can result from tachyarrhythmias conducted from the Atrium (e.g. Atrial Flutter, Sinus Tachycardia, Supraventricular Tachycardia) Alternatively, this can arise from the ventricles themselves (e.g. focus, re-entrant tachycardia, ventricular fibrillation, Torsades des Pointes) o Ventricular Bigeminy This refers to the presence of an ectopic beat every 2nd beat The second beat (i.e. ectopic beat) will produce less output / pressure as there has been insufficient time to fill the Ventricle fully prior to the ventricular contraction This will result in a weak pulse character for this ectopic beat Furthermore, there will be a gap until the next normal beat due to this Ectopic Beat interfering with the normal sinus rhythm This extra diastole time will cause the heart to overfill and contract harder (due to the Frank-Starling Law) resulting in a more forceful beat (which can be experienced as a palpitation) o Note: If unsure whether patient has VT or SVT, always assume VT and treat accordingly!!! (as this is the conservative choice and will avoid unnecessary mortality!) Treatments for Arrhythmias are: o Bradycardia Atropine (inhibit parasympathetic stimulation) Adrenaline (increases sympathetic stimulation) Pacing - - - 44 o - - - - Tachycardia Medications (e.g. Sotalol, Amiodarone, Flecanaide, etc.) Cardioversion Cardiac Ablation Implantable Defibrillators Mechanisms of Tachycardia’s are: o Increased Automaticity o Re-entry o Triggered Automaticity An infarction / myocarditis / cardiomyopathy, sarcoid, etc. causing a scar may leave small amounts of functioning tissue present through which an electrical signal can travel (albeit in a different pathway) o This preserved tissue amongst the infarcted tissue may lead to the formation of re-entry circuits ‘Triggered Automaticity’ refers to the slight depolarisation that occurs after stimulation of the heart (i.e. ‘delayed depolarisation’) being sufficient to reach the threshold potential and trigger a full depolarisation / additional ventricular contraction (leading to an Arrhythmia) o The more rapid the heart rate, the larger the delayed depolarisation o ‘Triggered Automaticity’ is more common in the outflow tract arrhythmias and as a result of certain drug toxicities Wolff-Parkinson-White (WPW) Syndrome is an arrhythmia resulting from an accessory Atrioventricular pathway in the lateral side of the Atrium and Ventricle (known as the Bundle of Kent) It is not uncommon for a patient with a Supraventricular Tachycardia to have large levels of ST Depression (i.e. sign of ischaemia) Channelopathies are genetic alterations in membrane channel function that predispose a person to potentially fatal arrhythmias (e.g. Long QT Syndrome, Brugada Syndrome, etc.) ANTI-ARRHYTHMIC DRUGS TBA - There are four classes of Anti-Arrhythmic Drugs; these are: o Class I – Drugs that block voltage-sensitive Na+ channels (e.g. Quinidine [Class 1A], Lignocaine [Class 1B], Flecainide [Class 1C]) These drugs reduce both the slope of depolarisation and the peak of the action potential Different sub-types of Class I drugs will increase (1A), decrease (1B) or have no effect (1C) on the action potential duration and effective refractory period The degree of blockage produced is greater if the channel is more frequently activated Note: Na+ Channel blockers may be proarrhythmic and trigger AF, Re-entry and Ventricular Arrhythmias o Class II – Beta-adrenoreceptor antagonists (e.g. Metoprolol, Propranolol) These drugs block sympathetic activity This will increase the Effective Refractory Period of AV Node (and hence is effective to prevent Supraventricular Tachycardia) Effect is to reduce heart rate and conduction o Class III – Drugs that prolong the Action Potential Duration (e.g. Amiodarone, Sotalol) These drugs delay repolarisation by blocking K+ channels Effect is to increase Action Potential Duration and Effective Refractory Period (and hence is effective against re-entrant tachycardia) However, all drugs that prolong QT interval have a proarrhythmic effect (and can cause VT!) o Class IV – Calcium channel antagonists (e.g. Verapamil) These drugs block L-type Ca2+ channels and hence inhibits action potential propagation These drugs are most effective at the SA and AV Nodes 45 - - Effect is to reduce heart rate and conduction (and hence is effective to prevent Supraventricular Tachycardia) Reduced Ca2+ also reduces risk of Triggered Automaticity and hence ectopic beats Clinical uses of different classes of drugs are: o Class IA – Ventricular Arrhythmias, prevention of paroxysmal AF o Class IB – Treatment and prevention of VT and VF during and immediately after MI (but not long-term) o Class IC – Prevention of paroxysmal AF, prevent recurrent tachyarrhythmias associated with WPW Syndrome o Class II – Reduce mortality after MI o Class III - Prevent tachyarrhythmias associated with WPW Syndrome, prevent refractory AF and other SVTs o Class IV – Prevent SVTs, reduce ventricular rate in AF patients (but NOT WPW patients) Blocking the AV Node in WPW patients with AF is contraindicated as this may result in the rapid, uncontrolled electrical currents from the Atrium being transmitted to the Ventricles via the Bundle of Kent rather than via the AV Node If this occurs, the rapid, uncontrolled electrical signals will be transmitted from the Atrium to the Ventricles unfiltered this may trigger VT or VF! In contrast, rapid, uncontrolled electrical signals transmitted via the AV Node to the Ventricles will NOT cause VT or VF, as the presence of the refractory period of the AV Node prevents excessive stimulation of the Ventricles Adenosine is a drug that will produce a transient AV block that will terminate SVT (though can induce AF in ~15% of patients) Ivabradine is drug that will reduce heart rate through its effect on the SA node; this reduced cardiac workload and oxygen demand and may be used to treat stable angina HYPERTENSION OBESITY-RELATED HYPERTENSION Discuss the current understanding of the contribution of obesity to hypertension - Obesity can be defined as body fat of > 25% in men and > 35% in women o BMI is a convenient surrogate marker for obesity such that obesity is presumed if BMI > 30 Hypertension is defined by the WHO as Arterial Blood Pressure > 140/90 The normal Systolic Blood pressure level will rise with age, due to increased arterial stiffness with age o Increased arterial stiffness will increase systemic vascular resistance AND reflectionaugmentation (which are both components of Central Blood Pressure) o Note: Reflection-Augmentation refers to the augmentation (i.e. increase) of Central Aortic Pressure by a reflected pulse wave Higher weight is associated with higher blood pressure (i.e. Obesity is associated with Hypertension); mechanisms linking the two are: o Overactivity of the sympathetic nervous system People with central adiposity (i.e. high abdominal visceral fat) will have higher sympathetic nervous activity compared to other people with the same BMI but less central adiposity Leptin is increased in obesity and has the effect of increasing sympathetic stimulation Obstructive Sleep Apnoea is associated with obesity and has the effect of increasing peripheral sympathetic activity Insulin is increased in obesity and has the effect of increasing sympathetic stimulation - - 46 o - - Adipose Tissue triggers increased Renin secretion (via increased sympathetic activity), which results in Sodium and water retention this increases blood volume and hence results in Hypertension o Metabolic Syndrome (which includes diabetes, dyslipidemia, central obesity) is increased in obese patients these factors are linked to hypertension o Renal Mechanism (as the number of glomeruli in obese patients will decrease over time) this results in a progressive reduction in renal function such that the equilibrium blood pressure increases (i.e. hypertension) to maintain equilibrium between fluid intake and output Obesity is associated with increased intravascular volume and pressure and therefore eccentric Left Ventricular Hypertrophy (i.e. dilatation) (which causes volume overload) o In contrast, hypertension in lean subjects is associated with concentric Left Ventricular hypertrophy (which causes pressure overload) o Obesity and hypertension leads to pressure AND volume overload this is a potentially synergistically adverse combination A sensible combination diet (i.e. balanced diet) will result in a larger reduction in blood pressure compared to a fruits and vegetable diet only END-ORGAN DAMAGE IN HYPERTENSION Discuss the end organ damage caused by benign and malignant systemic hypertension - Benign Hypertension is defined as systemic hypertension (i.e. Arterial BP > 140/90) that has been stable for years Malignant Hypertension is defined as Arterial BP > 200/120 over ~1-2 years; this will be lead to: o Severe headaches, shortness of breath and / or chest pain o Severe organ damage (e.g. stroke, haemorrhage, heart attack) Benign Hypertension may result in: o Left Ventricle Hypertrophy (eventually resulting in Left Heart Failure) Hypertrophied Cardiac Myocytes will increase the distance between the peripheral Cardiac Myocytes and the blood vessel This will reduce perfusion of these Cardiac Myocytes resulting in their necrosis and replacement with fibrous tissue Fibrosis increases the rigidity of the heart wall (which will exacerbate the developing heart failure as it cannot relax and fill properly) Fibrosis also increases the risk of developing Arrhythmias, as fibrous tissue is an insulator and increases the likelihood of developing re-entry circuits o Right Ventricle Hypertrophy Left Heart failure will result in Pulmonary Congestion / Hypertension This increases the pressure against which the Right Ventricle needs to pump this will result in Right Ventricle Hypertrophy o Replacement of smooth muscle in Arterioles with Eosinophillic Hyaline, which will narrow the lumen o Replacement of smooth muscle in Arteries with Fibrous Tissue, which increases the risk of Atherosclerosis o Renal damage (e.g. hypertensive nephrosclerosis, atherosclerosis) This will exacerbate hypertension via Renin release However, renal function is seldom compromised by hypertension alone (unless there is another renal disease present) o Cerebral complications, such as: Increased risk of cerebral infarction due to Atherosclerosis (i.e. stroke) Increased risk of intercerebral haemorrhage (due to degradation of penetrating arteries) Increased risk of rupture of Berry Aneurysms in Circle of Willis o Atherosclerosis throughout the body (which increases the risk of ischaemia) - - 47 o - Aortic Valve damage (due to Aortic Dissection [which can be triggered by Atherosclerosis, which results in Hypertension] progressing to the Aortic Valve) Malignant Hypertension may result in: o Myocardial infarction o Cerebral infarction (i.e. stroke) o Haemorrhage o Papilloedema PHARMACOLOGY OF HYPERTENSION MANAGEMENT Discuss the underlying pathophysiology of hypertension - Blood pressure is a continuum, whereby higher blood pressure is associated with higher risk of Stroke / Coronary Heart Disease o The threshold level at which ‘Hypertension’ is diagnosed is a relatively arbitrary level o The key purpose of these thresholds is to determine when it is worth it to provide a treatment o However, the limitation of arbitrary thresholds is that almost everyone will fall in the ‘needs treatment’ range Current approach to whether it is worth treating blood pressure is whether there are other risk factors present - Discuss the different classes of anti-hypertensive drugs and their mechanism of action - BP = CO x Total Peripheral Resistance o Peripheral Vascular Resistance is typically the main element targeted when attempting to treat Blood Pressure o In contrast, we typically avoid attempting to change cardiac output as a means of changing blood pressure The different classes of anti-hypertensive drugs are: o ACE Inhibitors These drugs end in the suffix ‘-pril’ Mechanism of action involves inhibition of the Renin / Angiotensin / Aldosterone system (by reducing synthesis of Angiotensin II) This results in vasodilation and a reduction in blood volume (as less Aldosterone is released) both these will decrease blood pressure Side effects include hyperkalaemia (due to reduced Aldosterone), worsened renal function if already impaired, dry cough, foetal malformations o Angiotensin II Receptor Blockers (ARB) These drugs end in the suffix ‘-sartan’ Mechanism of action involves inhibition of the Renin / Angiotensin / Aldosterone system (by reducing synthesis of Angiotensin II) Only difference between ACE Inhibitors and Angiotensin II Antagonists are that ACE Inhibitors will have a side-effect impact upon the Bradykinin system Angiotensin II Antagonists and ACE Inhibitors have a similar effect / impact on blood pressure The side effects are also similar (except for no dry cough in Angiotensin II Antagonists) o Calcium Channel Blockers Mechanism of action involves blocking voltage dependent Ca2+ channels this will result in vasodilation This consists of either Dihydropyridines (these drugs end in the suffix ‘-dipine’) and Non-dihydropyridines (e.g. Verapamil, Diltiazem) Dihydropyridines are more commonly used for hypertension - 48 - - - - Non-dihydropyridines are more commonly used for ischaemic heart disease (as they also block Ca2+ channels in the heart, which will inhibit the SA and AV Node, and hence inhibit heart rate) Side effects include peripheral oedema, reflex tachycardia [i.e. increase in heart rate in response to hypotension], headache, constipation (and decreased cardiac output / bradycardia for Non-dihydropyridines) o Diuretics (e.g. Thiazides, Loop Diuretics, etc.) Mechanism of action involves blocking Na+ re-absorption in the kidneys (which results in reduced water retention and hence lower blood volume / blood pressure) Different diuretics will have their effect in different areas of the Loop Each of these different locations have different ion transporters, so each diuretic will have a different impact upon electrolyte levels (e.g. Magnesium, Calcium, Potassium) Furthermore, each of the types of diuretics can be used concurrently to increase the diuretic effect as their precise mechanism of action is different Side-effects include Gout, Hypokalemia, Hypercalcaemia, Hypomagnesaemia and Hyperglycemia (these are all due to the increased Na+ in the urine up-regulating or down-regulating absorption or secretion of these other ions in the kidneys too) o Beta-Blockers These drugs end in the suffix ‘-lol’ Mechanism of action involves blocking Beta-adrenoreceptors and hence inhibiting the sympathetic response Inhibition of Beta receptors prevent the release of Renin (which will hence reduce vasoconstriction and blood volume, hence reduce blood pressure) Blocking of Beta receptors will also result in a reduction in heart rate and contractility in the event of sympathetic stimulation Unlike other drugs, there is significant variation / diversity within the class of Betablockers Not all beta-blockers are the same, as they may have different target receptors or special attributes (e.g. partial agonist, local anaesthetic, etc.) Side-effects include Bradycardia, muscle fatigue / tiredness, cold hands / feet (due to reduction in cardiac output to peripheries), bronchospasm There are a range of drugs that can result in Hypertension; these include NSAIDs and Cyclosporin (both of which ‘damage’ the kidneys and triggered increased Renin release) o Additionally, Corticosteroids and the Oral Contraceptive Pill will increase blood pressure through its interaction with Aldosterone Drug combinations are common in treatment of hypertension, as each individual anti-hypertensive medication only has limited effectiveness (i.e. each drug reduces BP by ~6-7mmHg only) o Multiple anti-hypertensive medications may be needed in ~50-75% of patients to achieve the reduction in blood pressure needed for their situation The choice of which particular drug to use to treat hypertension will be influenced by the other conditions / morbidities affecting the patient o Different anti-hypertensive drugs have different mechanisms of actions that may be beneficial (or contraindicated) for particular co-morbidities Lifestyle modifications such as smoking cessation, salt-restriction and weight control have a significantly bigger impact in reducing the risk of mortality / morbidity (as they are also a key risk factor in several other diseases too!) CLINICAL EXAMINATION AND INVESTIGATION IN HYPERTENSION Discuss the significance and meaning of hypertension and that it is a symptom of underlying disease o Hypertension is often one outcome of a long chain of pathological conditions and their elucidation can lead to useful therapy - Hypertension is defined as Arterial Blood Pressure > 140/90 (with optimal blood pressure <120/80) 49 o - This threshold is an arbitrary threshold, as there is a continuous relationship between increased blood pressure and adverse cardiovascular events Hypertension may be a manifestation of one or more underlying mechanisms or types of disease, rather than being a disease entity in its own right Understand the different risk factors associated with hypertension - Risk Factors for Hypertension include: o Age o Adverse lifestyle (e.g. smoking, obesity, high salt intake) o Family history of metabolic syndrome, hypertension, renal disease, heart disease and /or peripheral vascular disease o Specific diseases, such as: Sleep Apnoea Coarctation of the Aorta Renal disease Endocrine syndromes Genetic conditions o Pregnancy o Medications (e.g. NSAIDS, Steroids, Alcohol, Oral Contraceptive Pill) Examine the assessment of: o Structural, functional and biochemical aspects of each item in the causal sequence; and o End-organ damage resulting both from the hypertension itself and from its causal factors - Assessment will involve: o History o Physical Examination (particularly the renal, endocrine, cardiac, vascular and neurological systems) o Investigations (e.g. Full Blood Count + Biochemistry [e.g. EUC / GFR, LFT, Glucose, Lipids], Urinalysis, Chest X-Ray, Echocardiogram) Other potential tests that can be performed include 24-hour urine, nuclear medicine, hormones, autoimmune profile and imaging with CT / Ultrasound Specific causative diseases may also be specifically investigated for (e.g. Coarctation of the Aorta, Cushing’s Syndrome, etc.) OTHER INTRODUCTION TO SOMATISATION Introduce the concept of somatisation via an understanding of the mindbody problem - a philosophical dilemma that ripples through all of medicine but particularly psychiatry o Somatisation is the presentation to a medical practitioner of a bodily symptom or set of bodily symptoms that are psychological in origin o Somatisation is common in general medical practice - Current scientific view is that the mind is generated from the material brain / grey matter rather than being a non-material concept o This overcomes the issue of a non-material structure influencing a material structure o However, there is still no overarching theory about how the mind operates and generates the unique thoughts, feelings, emotions, etc. Somatisation is the tendency to experience, to conceptualise and to communicate mental states and personal distress as bodily complaints and medical symptoms o This is a condition that can affect all people (e.g. feeling sick prior to an unpleasant occasion, and then feeling fine once the occasion is avoided) - 50 - Hence, understanding of the mind-body problem can explain somatisation this occurs as a result of the mental states created by the material brain being translated into the rest of the material body as a bodily symptom Provide a more in depth analysis of its classic manifestation - conversion disorder - ‘Conversion Disorder’ refers to a condition where: o There are symptoms / deficits that affect voluntary motor or sensory function o Clinical findings provide evidence of incompatibility between the symptoms and recognised neurological or medical / physiological conditions o Symptom deficit not better explained by another mental disorder Conversion Disorder is more likely to occur in females and people of lower socioeconomic status o Onset is most common in adolescence and young adulthood Examples of symptoms that occur in Conversion Disorder include: o Motor symptoms (e.g. seizures, impaired balance / co-ordination, paralysis) o Sensory symptoms (e.g. loss of pain sensation, blindness) Other clinical features of Conversion Disorder include: o Indifference to symptoms (though this has low specificity as a feature) o History of prior conversion disorder When diagnosing a patient with Conversion Disorder, it is important to rule out other possible illnesses (including other psychological diseases) o Remember that tests for other diseases may not exist or may provide a false negative! o As a result, Conversion Disorder should NOT be a diagnosis of exclusion, but rather an active diagnosis based on the clinical features - - - PULMONARY HYPERTENSI ON TBA – New in 2014 - Pulmonary Hypertension is defined as Mean Pulmonary Artery Pressure (mPAP) >= 25mmHg o Pulmonary Wedge Pressure (proxy for Left Atrium pressure) > 15mmHg suggests a postcapillary (i.e. left heart failure) cause of the Pulmonary Hypertension Pulmonary Circulation is a low-pressure, high-flow circulation system o Many vessels are unopened at rest as a result, the ability of unopened vessels at rest to dilate and be used during exercise ensures the mPAP remains relatively constant regardless of the flow level to the lungs o mPAP will typically be within the range of ~15-20mmHG Right Ventricle is less able to cope with increased afterload (i.e. Pulmonary Pressure) compared to the Left Ventricle o This is due to the Right Ventricle not having as much muscle in its wall, and hence cannot compensate as much when there is increased pressures o Hence, Pulmonary Hypertension will be a significant problem in the Right Ventricle, and rapidly lead to Right Ventricle Hypertrophy Pulmonary Hypertension is more likely in females and has an average age of patient of 52 years o Median survival if untreated is 2.8 years Causes of Pulmonary Hypertension include: o Genetic predisposition o Left heart failure o Drugs / toxins o Hypoxia (as this triggers vasoconstriction of the Pulmonary Vessels, resulting in Pulmonary Hypertension) o Thrombo-embolic diseases o Environmental exposures (e.g. diet) o Other diseases There are five different groups / types of Pulmonary Hypertension: - - - - 51 o - - - - - - Pulmonary Arterial Hypertension (this is the most researched type, and has the most treatments available) o Pulmonary Hypertension due to left-heart disease (this is the most common type) o Pulmonary Hypertension due to lung diseases and / or hypoxia o Chronic Thromboembolic Pulmonary Hypertension (CTEPH) o Pulmonary Hypertension with Unclear Multifactorial Mechanisms Pulmonary Hypertension is initially relatively asymptomatic, with symptoms and reduced cardiac output only occurring in severe disease o Initial symptoms of Pulmonary Hypertension include fatigue, progressive dyspnoea on exertion, palpitations, chest pain, syncope and coughing o End-stage symptoms will progress to symptoms / signs of Right Heart Failure (e.g. Oedema, Ascites) and Cyanosis Clinical presentation of Pulmonary Hypertension will include signs of Right Heart Failure (e.g. elevated JVP, Tricuspid Murmur, Peripheral Oedema, Hepatomegaly, etc.) Pulmonary Hypertension is very difficult to initially diagnose (and hence is commonly misdiagnosed) o If a patient presents with dyspnoea and no cause can be determined, persist with investigations (e.g. Chest X-Ray, ECG, Lung Function Test, Exercise Test, Echocardiogram, Right Heart Study) as these will detect the Pulmonary Hypertension o Note: Right Heart Study / Catheter is the ‘gold standard’ investigation The following investigations can be reviewed for evidence of Pulmonary Hypertension: o Review ECG for evidence of RBBB or Right Ventricular Strain / Ischaemia when assessing for Pulmonary Hypertension o Review Chest X-Ray for dilated Pulmonary Arteries (in the form of enlarged Hilum) and / or Cardiomegaly o Review Echocardiogram for size of the Right Heart, the pressure gradient / speed of flow across the Tricuspid Valve and any congenital abnormalities (e.g. VSD) that could result in Pulmonary Hypertension Increase in Tricuspid gradient and dilatation of the Right Ventricle indicates Pulmonary Hypertension Increased pressure in the Right Atrium and Pulmonary Artery confirm the existence of Pulmonary Hypertension Pericardial Effusions may also be present in severe Pulmonary Hypertension However, Echocardiograms are not that accurate in patients with respiratory disease (and so these patients often may need a Right Heart Catheter to confirm diagnosis of Pulmonary Hypertension) o Review CT Scan for the size of the different vessels as well as the size of the liver and heart; this may suggest Pulmonary Hypertension, as well as identifying different causes of Pulmonary Hypertension (e.g. thrombus) Ground-glass changes in the lung in a CT Scan are a sign of Pulmonary Hypertension CT Scan of lung may also identify a lung disease that is the cause of the Pulmonary Hypertension However, remember to always perform a V/Q Scan when assessing Pulmonary Hypertension to review for clots (especially as the CTPA may not reveal Peripheral Clots) as the condition may be caused by Chronic Thrombo-Embolism The WHO classification of Pulmonary Hypertension is commonly used to assess severity of the disease; the classes are: o Class I – no limitation of physical activity o Class II – mild limitation of physical activity o Class III – marked limitation of physical activity, but no discomfort at rest o Class IV – unable to perform physical activity at rest All patients with Pulmonary Hypertension receive a six minute walk (6MW) test every six months o This requirement is mandated by the Government (for reimbursement of prescriptions) based on evidence suggesting patients have improved prognosis with better results in a 6MW test Elevated BNP Concentration (B-Type Natriuretic Peptide) is associated with poorer outcomes / mortality these BNP levels can be measured by a blood test 52 - - - If a known genetic mutation or family history of Pulmonary Hypertension exists, there is a good rationale for annual screening Choice of Pulmonary Hypertension specific medications / treatment will depend on the severity of the Pulmonary Hypertension o Increasingly severe / progression of Pulmonary Hypertension will indicate usage of different / additional medications Treatment options for Pulmonary Arterial Hypertension include: o Oxygen (though there is a lack of evidence as to its effectiveness) o Diuretics (which reduces blood volume / pre-load) o Anticoagulants o Calcium-channel blockers Note: These are ineffective unless the patient is shown to be vasoreactive (which only occurs in ~7-10% of patients) o Pulmonary Hypertension specific therapies Endothelin receptor antagonists (e.g. Bosentan) Prostanoid therapy Nitric Oxide and Phosphodiesterase Inhibitors (e.g. Sildenafil) o Surgical Intervention (e.g. Atrial Septostomy, Lung Transplant, etc.) Guidelines suggest additional therapies should be provided if the goals are not being achieved o However, a challenge is that the PBS will only fund a single treatment at a time Treatment for Pulmonary Hypertension due to Lung / Heart diseases should focus on treatment of the underlying Lung / Heart diseases o There is no evidence that the treatments for Pulmonary Arterial Hypertension are effective in patients with Pulmonary Hypertension due to Lung / Heart diseases THE LINK BETWEEN DEP RESSION AND CARDIOVA SCULAR DISEASE Understand the current thinking concerning the link between depression and cardiovascular disease - Depression is a condition of pervasive, low mood for > 2 weeks that will involve loss of energy and motivation, lack of sleep, etc. o This is a chronic disease with a ~50% level of recurrence o There is a current prevalence of ~2% and lifetime incidence of ~10% o This is associated with poorer outcomes across a range of different dimensions (e.g. physical, social, psychological, etc.) Depression will impact upon the autonomic nervous system, and hence will also impact upon cardiac physiology o The impact of psychological factors on physical health are largest in younger people (compared to older people) Depression is a significant independent risk factor for the development of Cardiovascular Disease (over and above other risk factors such as smoking, hypertension, hyperlipidaemia, etc.) o The more severe and recent the depression, the larger the increase in risk of Coronary Heart Disease o People with Depression are also much more likely to have multiple risk factors for Cardiovascular Disease (e.g. smoking, obesity, etc.) Depression is also a significant independent risk factor for poorer outcomes (e.g. higher and quicker mortality) following a myocardial infarction o Depressed individuals are ~60% more likely to have another heart attack following an initial heart attack (compared to non-depressed individuals) o Furthermore, doctors commonly treat depressed patients worse upon knowing the patient is depressed (due to the bias of the doctors) Hence, depressed patients may be receiving poorer treatment (in addition to underlying physiological differences due to depression) Depression is also associated with poorer compliance with treatment - - - 53 o - Depressed people also have a different Cortisol response (and hence immune system), which can have impacts upon cardiac physiology Effective treatments for depression include exercise, anti-depressants and psychotherapy Studies have not shown Anti-depressants by themselves to significantly improve mortality outcomes for patients following a heart attack (although their quality of life does improve) o However, this is due to the failure of some of the patients receiving anti-depressants to have reduced depression o Indeed, studies have shown depressed patients who respond to anti-depressant treatment have improved cardiovascular outcomes compared to depressed patients who do NOT respond to treatment o Hence, response to treatment (rather than simply providing a treatment) is critical to ensure improved outcomes! PPD PROFESSIONAL COMMUNI CATION – HOW TO GET PUBLISHED Consider the issues involved in choosing a suitable research project - It is important to ensure your research interests are aligned with the supervisor’s research interests o Also ensure your supervisor is actively publishing; they need to know how to ‘play the game’ and get published When selecting a research project, consider whether the research question is important and will actually change practice and / or promote debate / thought o If the research question does not satisfy these criteria, then the research is unlikely to add any value to science o Furthermore, the research is unlikely to be published! - Understand why it is necessary to publish - Publication of all studies is important as otherwise there is no addition to the general body of knowledge o Failing to publish studies (especially non-significant results) creates Publication Bias that distorts the true body of evidence (and may also result in others conducting the same study without realising it has already occurred) Understand a strategy of how to successfully publish - Review articles are a simple but effective mechanism for creating a widely-cited publication o Working with a senior medical professional to develop a review article will likely create a piece of work that can be easily published (especially if discussed with an Editor beforehand) Target the appropriate journal given the quality of the paper and the content of the paper o Selecting the wrong journal will result in a waste of time (as journal may take several months to decide whether to accept or reject the paper) and / or loss of impact (as the paper may not reach the desired audience) o However, whilst there is an increase in the papers published in non-elite journals, be careful about the choice of a non-elite journal as their reputation (or potential lack thereof) will reflect upon your work If aiming to publish in a particular journal, ensure you follow the rules / style of the journal (or otherwise you will be guaranteed rejection) Use plain English rather than sophisticated / complicated terminology in the paper Submit paper together with a cover letter that places the paper in context and explains why the article in important (especially if currently newsworthy / relevant) - - Have a basic understanding of how to structure a research manuscript 54 - - - Follow the ‘IMRaD’ method for structuring a research manuscript (i.e. Introduction, Method, Results and Discussion) o Introduction should be short (~3-4 paragraphs) and engaging; this should summarise what’s known, what’s unknown and the research question Note: Assume a more sophisticated audience with Specialist Medical Journals, so there is no need for an elementary introduction to the overall area (as everyone reading will be familiar with the overall area) o Method should provide detail and clarify; an experienced reader should be able to replicate the study based on the information provided in the method o Results should present data clearly with the most important findings prioritised first State absolute numbers, relative numbers and percentages, as well as providing 95% confidence intervals Graphs / tables should be self-contained (i.e. reader of article can solely review the graph / table and completely understand the result) o Discussion should present the strengths and weaknesses of the study (vis-à-vis other studies too), and the implications for the future / policy Do NOT repeat the introduction or results in this section (though the principal findings can be re-stated) o Note: Don’t confuse the different sections (e.g. discussion should NOT be included in the Results section [as only include factual data from the study in the Results section!]) Title of article should be informative and clearly highlight the key areas of the article o Use search engine terminology / keywords in the title as this will be commonly searched upon o Avoid acronyms as people will not necessarily know to search for the acronym o This will make it easier for others to find and cite the article as well as for the results to impact upon practice Structured Abstract should include objectives, design, setting, participants, interventions, main outcome measures, results and trial registration o Abstract should be ~250 words and should summarise the key results of the article Gain insights into the perils of publishing - Perils of publishing include: o Conflicts of Interest Explicitly state your conflict of interest (as failing to specify any conflicts that exist may potentially damage your reputation) o Duplicate Publication Do NOT submit the same paper to two journals concurrently (only submit to second journal if it is already rejected by the first journal) o Fraud o Plagiarism o Ghost Writing o Authorship Ensure you fully understand and can vouch for a publication if you are named as an Author Your reputation is invested within any publication where you are an author and so it is CRITICAL to verify and validate the findings and insights from the paper o ‘Salami Slicing’ This refers to attempting to generate multiple publications from the same study This might be possible in a large study However, if it’s a smaller study, it’s better to have one quality publication with several interesting findings than several dull publications with only a single relevant finding o Disclosure of Findings prior to Publication 55 SEMINARS SEMINAR – EXERCISE AND THE HEART Describe and explain the changes in cardiovascular variables (e.g. blood pressure, heart rate, cardiac output and vascular resistance) during dynamic exercise in humans o The goal will be to produce a flow diagram that will explain the underlying mechanisms - Exercise is important clinically as most patients with heart disease / heart failure will first present due to exercise intolerance Exercise will increase the demand for oxygen (due to higher metabolic requirements) by peripheral tissue; this can be achieved by: o Increased cardiac output o Increased ventilation o Increased blood pressure Maximum heart rate, blood pressure and tidal volume can be achieved within ~20-30 seconds of intensive exercise The autonomic nervous system (via reduced parasympathetic and increased sympathetic activity) can trigger an increased heart rate and increased stroke volume (and hence increased cardiac output) during exercise o Increased heart rate occurs from sympathetic stimulation of the SA Node o Increased stroke volume occurs from sympathetic stimulation of myocytes resulting in increased contractility Increased heart rate during exercise reduces the time for the heart to fill as well as increasing blood pressure o This will increase the pressure / contractility needed by the Left Ventricle in order to pump enough blood (as there is higher arterial pressure to pump against and there is less time available for systole) o This increased contractility is illustrated by the increase in Pulse Pressure (i.e. difference between Systolic and Diastolic Pressure) Reduction in Total Peripheral Resistance (TPR) during exercise will increase the ease of perfusion of the capillaries of the peripheries o Blood Pressure only increases moderately during exercise due to this decline in TPR - - - - Understand the effects of changes in cardiac function (e.g. an improvement as would occur during training, or a deterioration as a result of cardiac failure) - Chronic Endurance training will increase cardiac function; this will reduce resting heart rate (whilst maintaining cardiac output by increasing stroke volume) o This creates a larger potential increase in heart rate (and hence cardiac output) during maximum exercise Conversely, deterioration of cardiac function will increase resting heart rate (to maintain cardiac output as stroke volume decreases) o This reduces the potential increase in heart rate (and hence cardiac output) available during maximal exercise - SEMINAR – CARDIOVASCULAR DISEA SE – A POPULATION MEDICIN E PERSPECTIVE – THE INDIVIDUAL WITHIN THE COMMUNI TY Be able to access and interpret data showing the contribution of cardiovascular disease to morbidity and mortality in developed and developing countries - Cardiovascular Disease is the leading cause of death globally (~22% of deaths in 2008) 56 - - Cardiovascular disease is NOT only a problem facing developed countries, but instead affects people across the entire world o However, it should be noted the nature / precise types of Cardiovascular disease are different throughout the different parts of the world (e.g. Rheumatic Heart Disease in developing countries vs. Coronary Heart Disease in developed countries) o The increase in the number of deaths from Cardiovascular Disease in the next decade is predicted to be driven from developing countries rather than developed countries In 2020, it is predicted Cardiovascular Disease will cause ~25 million deaths worldwide (~37% of total deaths) o 19 million of these deaths (~76%) will be in developing countries, with the remaining 6 million deaths (~24%) in developed countries Discuss the reasons for current increasing prevalence of CVD including specific risk factors for cardiovascular disease and links with other chronic co-morbidities - There a range of different risk factors for Cardiovascular Disease (and hence there are numerous different mechanisms / options for reducing the level of risk of Cardiovascular Disease) Key risk factors include: o Age o Gender o Smoking o Hypertension o Cholesterol o Diabetes o Alcohol o Obesity The increased prevalence of these risk factors is resulting in the increased prevalence of Cardiovascular Disease - - Describe appropriate risk reduction measures to prevent cardiovascular disease with particular emphasis on primary and secondary prevention - Primary Prevention refers to steps taken to reduce the risk of Cardiovascular Disease when there is no clinical disease (though there is the existence of risk factors) o In contrast, Secondary Prevention involves steps taken to reduce risk of / treat Cardiovascular Disease when there is clinical disease ‘Population Approach to Prevention’ focuses on strategies that impact the whole population and aim to reduce the risk of the whole population o Whilst there may be a small benefit per person, the large number of people assisted may result in a large / material overall benefit (although it may be difficult to motivate individuals and doctors given the low risk for most patients) o Furthermore, focusing on the overall population will avoid any stigma being attached to a ‘high-risk’ group In contrast, the ‘High-Risk Approach to Prevention’ focuses specifically on the small proportion of people with the highest risk of cardiovascular disease o Focusing on this high-risk population will result in greater efficiency, improved costeffectiveness and lower NNT in the delivery of improved outcomes The optimal approach will include elements of both a population strategy (reduce overall risk of the entire population) and an individualised strategy (reduce the risk of the ‘high-risk’ component of the population) Numerous studies have demonstrated Aspirin is effective in reducing vascular events in patients with Cardiovascular Disease o Similarly, numerous studies have demonstrated Beta-Blockers, ACE Inhibitors and Statins are effective in reducing vascular events in patients with Cardiovascular Disease - - - - 57 - - Patients with known Cardiovascular Disease should ideally be prescribed with cholesterol lowering medication (e.g. Statins) regardless of whether their current cholesterol levels are normal o Lower cholesterol levels (regardless of the absolute level) will reduce the risk of a Cardiovascular Event Lifestyle factors (e.g. diet, exercise and smoking cessation) may also reduce the likelihood of a Cardiovascular Event Explain the contributions of the following to the successful management of cardiovascular disease in the community: o Primary and specialist care o Multi-disciplinary teams - Complex pathophysiology of Heart Failure is such that an individualised approach to management / treatment is needed o This requires utilisation of multi-disciplinary teams that can develop and implement individualised management plans o For example, multi-disciplinary teams will include allied health professionals and cardiac nurses who can assist patients to minimise their risk factors and manage their condition more effectively Primary care medical professionals can assist with the education of individuals to prevent the incidence of Cardiovascular Disease as well as the stable management of existing Cardiovascular Disease o This will include education on risk factors, prescription of medications to reduce risk (e.g. ACE Inhibitors, Statins, Aspirin) and monitoring for progression / exacerbations of cardiac failure (which may enable more prompt treatment / management and the avoidance of hospital admission / further morbidity) Specialist care medical professionals are responsible for ensuring the appropriate medical treatment to patients in acute situations o They are also responsible for ensuring patients have the appropriate dosage titration schedule on discharge to ensure their dosage of ACE Inhibitors and Beta-Blockers is increased to the full, effective amount o Specialists also may need to communicate / engage with GPs and educate them on the best treatment options available - - Discuss the strengths and limitations of the current evidence about the distribution and cause of cardiac disease, its prevention and its management, especially with regard to cardiac failure and hypertension - There is a lack of definitive data on the number of Australians with cardiac failure, though estimates have been extrapolated based on overseas information o This suggests ~300,000 Australians are currently affected by Heart Failure with another ~30,000 new cases annually There have been several studies as to the causes, preventative approaches / treatments (e.g. ACE Inhibitors, Statins, Aspirin) and the appropriate management for Cardiac Disease - Demonstrate an understanding of the future role of health care professionals in reducing the prevalence of cardiovascular disease globally - Health care professionals have a responsibility to communicate to the population the risk factors for cardiovascular disease, and to attempt to influence the general population to change behaviours to reduce their risk exposure o This role will also include providing medical treatment for co-morbidities associated with cardiovascular disease (e.g. hypertension, diabetes, etc.) SEMINAR – COMPLEMENTARY ALTERN ATIVE MEDICINE 58 Introduction to encountering complementary and alternative medicines in practice - The definition of Complementary Alternative Medicines (CAMs) will vary depending on the country involved (e.g. Acupuncture and Ayurvedic Medicine are routine in China and India respectively) o CAMs is heterogeneous in nature and encompasses diverse forms of therapy and belief systems o The breadth of what is defined as CAMs can be ambiguous / uncertain (e.g. is spiritual healing / prayer included as part of CAMs or is this viewed as a health / wellbeing practice?) We should consider accepting / tolerating CAMs due to: o Effectiveness (even if it is placebo effect) o Minimal side effects (though not always the situation) o Respect for patient autonomy o Lower cost compared to orthodox Western-based medicines (though not always the situation) o Providing the patient with alternative means of engaging with their illness / condition (i.e. different paradigm) o CAMs being associated with other support services that are valuable / useful for the patient o Respect for other cultural traditions o Avoiding confrontation with the patient that could destroy trust in the relationship o Humility (as western-trained doctors don’t know everything) Whilst there may be a tendency to preference western medicine, remember there are significant limitations in the evidence of orthodox Western-based medicine such as: o Bias towards publishing positive results (and hence bias against disproving / publishing negative results regarding efficacy of medications) o Empirical evidence suggesting ‘significant’ benefit of medications (based on initial clinical trials) are non-significant following years of empirical use (especially in mental health) o Bias in sample selected for clinical trials (e.g. exclusion of patients with co-morbidities) o Assumption that population-based results will apply to the unique individual The rationale for the usage of CAMs generally cannot be assessed using Randomised Control Trials (RCTs) o Patients are looking for a CAM rather than a dose-response drug o Prescription of CAMs are tailored to the specific individual circumstances of the patient rather than being a standard medicine applying to an overall population However, it should be noted that some CAM practitioners have a view of what ‘normal’ should be and indeed will apply a population-based approach rather than tailoring it to the individual o Note: Medical interventions can still be viewed as effective without confirmation via a RCT (e.g. surgical techniques, nursing techniques) It can be difficult to evaluate CAMs especially given the importance typically placed on the skills and experience of the CAM practitioner o This introduces significant variability that may make CAMs difficult to assess in a populationbased study o Instead, it may be that CAM techniques can be effective depending on the specific patient and the specific practitioner Potential benefits from CAMs may result from provide beneficial ‘Context Effects’, which have been demonstrated to lead to physiological changes and better outcomes o Beneficial ‘Context Effects’ may be achieved by a close, empathetic bond between the CAM practitioner and patient (i.e. high quality engagement with the patient) The patient’s view and interpretation of their health condition will be shaped by their interaction with their health practitioner o The questions / approach of the health practitioner towards the patient will provide a frame through which the patient interprets their condition o Patients may prefer and benefit from the frame that CAM practitioners provide A key differentiator of orthodox Western-based medicine is that it is structured in a manner that will enable continual discovery / innovation / progress o In contrast, CAMs are more static in nature and do not offer the same level of innovation - - - - - - - 59 o - - Furthermore, CAMs usually provide explanatory mechanisms of action that appear extremely implausible and simplistic (in contrast to complicated mechanisms of action in orthodox Western-based medicine) The harms of CAMs need to be considered in the context of the harms of orthodox Western-based medicine (as many of the same issues apply) o However, one key differential is the number of extravagant, outrageous claims being made by some CAM practitioners (without any capacity for patients to navigate amongst these claims) There is significant levels of exploitation associated with CAMs as different cultures are appropriated / misrepresented to sell a particular product / approach SEMINAR – SENSING BLOOD FLOW Understand the echocardiographic appearance of the heart, and the methods used for sensing blood flow in the heart and arteries using Doppler techniques - The structures within the body can be imaged (i.e. Ultrasound) based on an understanding of the speed and frequency of sound; for instance, this includes understanding: o Sound will reflect when it passes from one medium to another medium o The denser the material, the faster sound will transmit through that material ‘M-Mode’ of an Ultrasound involves a single dimension view (with only one signal being sent and received) o If this signal is directed towards the valve, then the opening and closing of the valve can be viewed in this ‘M-Mode’ ‘B-Mode’ of an Ultrasound involves hundreds / thousands of adjacent single dimension views displayed radially to provide a 2-Dimensional view Right Ventricle can be distinguished on an Ultrasound (from the Left Ventricle) as the chamber where the inlet valve and outlet valve are separated by muscle Murmur is the detection of blood flowing greater than 1 metre / second o Blood flow in a normal heart will be less than 1 metre / second, so the presence of a murmur indicates an abnormal heart o The greater the constriction / stenosis of a valve, the faster blood will flow through the valve Hence, the specific speed of blood flow can provide an indication of the level of stenosis The pressures / pressure gradient within the heart can be calculated based on the speed of blood flow across two chambers o Pressure Gradient = 4 x (Velocity of Blood Flow^2) - - - SEMINAR – CARDIOVASCULAR DISEA SE – A POPULATION MEDICIN E PERSPECTIVE – SOCIAL AND SYSTEMIC RESPONSES Understand how social and environmental changes have contributed to the increased prevalence of cardiovascular disease globally - Social and Environmental changes have resulted in the increase in risk factors for cardiovascular disease, such as the increase in air pollution and reduction in physical activity o Increased industrial production and usage of motor vehicles has resulted in increased levels of air pollution Air pollution can include Particulate Matter (PM), Ozone, Nitrogen Dioxide, CO, Lead, etc. Evidence suggests a strong relationship between PM and Adverse Cardiovascular Effects (even stronger than the relationship to Chronic Respiratory Disease) The smaller the size of the PM particles, the deeper into the lungs they are able to penetrate 60 o - Rise in electronics and other technological advances has reduced the level of physical activity in current society Social changes have also resulted in the development of Built Environments that encourage / require behaviours that will increase the risk factors of cardiovascular disease Describe the mechanism by which air pollution causes cardiovascular disease - Mechanisms though which air pollution can cause cardiovascular disease include: o Systemic Oxidative Stress and Inflammation o Triggering Vasoconstriction and Platelet Aggregation in the blood o Autonomic Nervous System Imbalance (i.e. increased sympathetic and decreased parasympathetic stimulation) Understand the advantages of population strategies compared to individual (high risk strategies) - A Societal Approach to Cardiovascular Disease (rather than an Individualised Approach) has the benefit of treating a much larger number of people o Hence, there is an opportunity to deliver a larger absolute benefit (i.e. reduction in burden of disease) compared to a approach focusing only on high-risk individuals o Furthermore, focusing on the overall population will avoid any stigma being attached to a ‘high-risk’ group Note: The optimal approach will include elements of both a population strategy (reduce overall risk of the entire population) and an individualised strategy (reduce the risk of the ‘high-risk’ component of the population) - Describe the contribution of lifestyle factors to the risk and prevention of cardiovascular disease - The four key risk factors for non-communicable disease are tobacco, unhealthy diets, physical inactivity and harmful alcohol intake o The four key non-communicable diseases are cardiovascular disease, diabetes, cancer and chronic lung disease A study illustrated that physical inactivity (i.e. being a bus driver) was associated with cardiovascular disease o Physical activity goes beyond exercise / sport, and instead includes other activities too (as many of the benefits from physical activity arise from activities below the training threshold in an exercise program) Studies have shown Physical Activity has major health benefits across a range of different areas (e.g. cardiovascular, mental health, cancer prevention, functional status, etc.) o The biggest incremental benefits from physical activity occur from changing a person from low levels of physical activity to medium levels of physical activity This incremental benefit is greater than compared to changing a person from medium levels of physical activity to high levels of physical activity A study illustrated that whilst a group of patients given stents had a wider lumen than a group of patients prescribed exercise, the patients undertaking exercise had much better physical fitness and oxygen uptake o Exercise resulted in a significantly lower incidence of Cardiovascular Events, as well as being significantly cheaper than stents - - - Discuss the role of non-health sectors in improving population health - Urban Environments / Built Environments have a major impact on population health o There are aspects of the Built Environment harming health o As such, changes to the Built Environment can improve health 61 - - For example, Urban Sprawl and Land Zoning have resulted in a dependency on motor vehicles (in order to move from home to work, home to entertainment, etc.); this has resulted in: o Reduced levels of physical activity, which inhibits the health of the population o Increased commuting and less time for engagement with the local community, which inhibits mental health / happiness o Less local production of food and home cooking, resulting in unhealthier diets o Increased fossil fuel consumption this increases air pollution, which inhibits the health of the population Designing healthier Built Environments (e.g. functional grid street pattern to encourage walking, public transport, well-maintained public space, etc.) will improve population health Discuss actions that can be taken at community and policy levels to reduce the prevalence of cardiovascular disease locally and globally - Developing policies that promote healthier built environments will reduce risk factors (e.g. physical inactivity, exposure to pollution, etc.) and hence the prevalence of cardiovascular disease o Similarly, community lobbying to shape the local built environment in a manner that encourages healthy living can play an important role Policies to reduce air pollution / emissions will reduce the prevalence of cardiovascular disease; this can include policies such as: o Reducing motor vehicle emissions (e.g. cleaner fuels, vehicles and fleet, reducing vehicle use, improving and influencing transport choice) o Making businesses even cleaner (e.g. major industry, small businesses) o Making homes and local environments cleaner, healthier and more liveable o Targeting particle pollution in regional areas (e.g. wood smoke heaters) o Better public transport - Understand the role of the individual clinician as an advocate for improving population health - Health Professionals can improve population health by: o Educating patients about the risks of air pollution and steps to minimise exposure (e.g. follow Air Health alerts, avoid unnecessary exposures, reduce indoor exposures, etc.) o Regularly asking patients about physical activity and encouraging increased physical activity o Promoting healthy eating and socialising o Advocating for healthy developments / built environment o Getting involved in the local community in shaping the local built environment for the better SEMINAR – TEAM CONFERENCE – CHEST PAIN Outline the differential diagnosis of chest pain, including life-threatening and non-life-threatening causes of chest pain - There is a vast range of potential differential diagnoses for chest pain; this makes it difficult to deal with given the breadth of potential problems from this non-specific symptom o Physical examination of chest pain will assist in ruling out some of the non-cardiac causes of chest pain and / or identifying the possible complications of ACS The differential diagnoses for chest pain include: o Cardiac – AMI, Unstable Angina, Stable Angina o Pericardial – Pericarditis, Pneumomediastinum o Vascular – Aortic Dissection o Pleuritic – Pulmonary Embolism, Pneumothorax, Pneumonia, Pleurisy o Gastro-oesophageal – Gastro-oesophageal Reflux, Oesophageal Spasm o Musculoskeletal – Myalgia, Muscle Strain, Costochondritis o Neurological – Herpes Zoster, Nerve Root Compression o Abdominal – Pancreatitis, Peptic Ulcer - 62 - The key life-threatening conditions include Pulmonary Embolism, Pneumothorax, Aortic Dissection and AMI Describe a systematic approach to the evaluation of patients presenting with chest pain, including: o History o Examination o Diagnostic testing - ECG, chest x-ray, biochemical cardiac markers - History will include: o Description of pain and associated features Patient history for Chest Pain commonly will not fit signs / symptoms for ACS when there is an underlying ACS therefore, NEVER rule out ACS based on history alone o Risk factors for Cardiovascular Disease (although very limited diagnostic value in an acute setting) o Risk factors for Thromboembolic Disease Physical Examination will be aimed at identifying non-cardiac causes of Chest Pain or complications of ACS; this will encompass: o Evidence of Arrhythmia, Cardiogenic Shock and / or Congestive Heart Failure o Abdominal Examination (look for signs of tenderness, guarding, Murphy’s sign) o Chest Wall Palpation for Pain Pain on Chest Wall Palpation does NOT necessarily mean the Chest Pain is muscular This should only be considered if Chest Wall Palpation reproduces the specific type of pain that the patient is presenting for (though even then it is not definitive) o Signs of DVT o Bilateral BP discrepancy Diagnostic Testing will include: o ECG (EVERY patient presenting to the ED with Chest Pain must have an ECG performed!) o Chest X-Ray (aimed at identifying non-cardiac causes of Chest Pain or complications of ACS) o Biochemical Markers (e.g. Troponin) o Others (e.g. D-Dimer for PE, CT Aortogram for Aortic Dissection, etc.) - - Explain the importance of a systematic approach to chest pain, with regard to: o The limitations of 'textbook' descriptions of chest pain in real-world diagnosis o The limitations of risk factors in acute diagnosis of chest pain o The potential for cognitive error in diagnosis - especially diagnostic anchoring and early closure - Diagnostic aids / systematic approach to chest pain will assist with accurate diagnosis and early management o Applying a systematic approach is critical given the wider diversity in presentations for ACS making a heuristic based ‘clinical judgment’ is likely to result in missed diagnoses (which can be fatal in ACS!) Focusing on risk factors may result in missed diagnoses if the patient does not fit with the ‘typical’ risk factor profile (e.g. 22-year old with ACS) Real-life evidence also shows differences in the type of chest pain in ACS vs. the ‘textbook’ descriptions of chest pain in ACS o Following a systematic approach will assist in maximising diagnostic accuracy and avoiding common diagnostic pitfalls such as: Diagnostic Anchoring – over/under value critical pieces of information Early Closure – stop looking when an abnormal result is identified o Note: The systematic patient evaluation has a primary focus on ACS (given the high prevalence and significant adverse consequences of failure to diagnose ACS) Systematic approach will also enable risk stratification based on clinical and diagnostic test findings this will assist in determining the strategy for management - 63 SEMINAR – CRITICAL APPRAISAL O F SYSTEMATIC REVIEWS TBA - Systematic Review is a thorough, defined literature search o This will have clear, objective inclusion criteria (and a clearly defined search strategy) o This will often focus on a specific clinical question rather than being broad in scope o Not all systematic reviews include a meta-analysis (as individual studies may be too heterogeneous for statistical comparison) Meta-Analysis is a statistical technique for combining data from multiple similar studies into a quantitative summary statistic (i.e. a weighted average of the individual study effects) The two tests for heterogeneity (Chi squared and I squared) have low power, so there may still be heterogeneity even if these metrics do not identify any heterogeneity o If heterogeneity is detected, then the researcher will need to understand and explain why this exists (e.g. different research designs, different sample demographics, different dosage levels of treatment, etc.) o Note: I squared measures the percentage of the result that CANNOT be explained by chance Funnel Plot will identify Publication Bias (i.e. not publishing negative results), as this will result in a asymmetrical Funnel Plot o Other biases that can be detected in a Funnel Plot include Location Bias, English Language Bias, Database Bias, Citation Bias, Multiple Publication Bias, Poor Methodological Quality of Small Studies and Bias in Provision of Data Systematic Review of Individual Patient or Participant Data will enable increased accuracy as the researcher will be able to better control for heterogeneous factors across studies o This will also enable sub-group analyses that can show different effects of a treatment / therapy depending on the circumstances of the patient (which will enable more targeted prescription of a treatment to those benefiting the most from that treatment) Increased power of Systematic Reviews will not only enable easier detection of intervention effects, but also easier detection of harmful side-effects Critical Appraisal of a Systematic Review will involve consideration of: o Is there a well formulated question? (i.e. PICO) o Are there appropriate inclusion criteria? o Was there a comprehensive literature search? o Was there validity appraisal of studies? o Is there heterogeneity of results? If so, are the reasons explored? Important considerations when interpreting results of a systematic review include: o Are the people in the studies generalisable to my patients? o Is the treatment feasible? o Are all important outcomes reported? o Do benefits outweigh harm? o Do my patients have particular values / preferences that influence the choice of treatment? - - - - - SEMINAR – INVESTIGATION OF CAR DIAC ABNORMALITIES I N KIDS Understand the clinical assessment and investigations indicated in common cardiac abnormalities - Echocardiography is the gold standard investigation to observe and assess the heart o Other investigations include Chest X-Ray, ECG, Angiography, CT and MRI When interpreting an ECG, take into consideration the age of the patient (as the ‘normal’ ECG is different in children vs. adults) o There is Right Axis Deviation in newborn babies as they have a thicker, dominant Right Ventricle (as the Left Ventricle has not had to pump blood to the systemic circulation inutero) o The Axis transitions towards 90 degrees (i.e. normal Axis) in a normal one-year old o Normal 8 year-old will have an ECG heading towards an adult ECG o Normal 17 year-old will have an adult ECG with Left Ventricle dominance - 64 - - - - - - - - - Changes that can affect the Paediatric ECG include: o Age o Size o Position of heart relative to the body o Body physique o Physiological changes (e.g. autonomic nervous system) Tall P wave (i.e. >2.5mm) is suggestive of Right Atrial Hypertrophy o Conversely, elongated P wave (i.e. >0.10 seconds) is suggestive of Left Atrial Hypertrophy QRS Complex duration in children should typically be <0.08 seconds o The normal QRS Complex duration will increase with age (as there will be increasing muscle mass in the heart) Threshold in children for ST Elevation is >1mm whilst ST Depression is >0.5mm Early repolarisation in adolescents may appear like an upward sloping ST interval leading into a T wave (similar to upward slope of a Delta Wave) o However, this is normal and NOT ST Elevation! Continuation of Upright T-wave in Lead V1 (rather than changing to an Inverted T-wave) beyond the first few days post-birth can be indicative of Right Ventricular Hypertrophy Presence of Delta Wave (slow upstroke in QRS complex) and Tachycardia is labelled Wolff-ParkinsonWhite (WPW) Syndrome Prolonged QT Interval (i.e. >0.45 seconds after adjusting for heart rate) is associated with Sudden Death o If the T wave does not smoothly return to the isoelectric line, then an imaginary line is drawn to the isoelectric line as if the T wave did return smoothly o This intersection of the imaginary line with the isoelectric line is taken as the end of the T wave for the purposes of calculating the duration / length of the QT Interval The threshold for Left Ventricular Hypertrophy in adults (i.e. height of S wave in V1 plus height of R wave in V5 or V6 > 35mm) is not the same for children with Left Ventricular Hypertrophy o Instead, Left Ventricular Hypertrophy can be identified in children by asymmetric T-wave inversion in Leads V5 or V6 RBBB is more common in children compared to LBBB o This can occur after cardiac surgery, myocarditis, etc. o This will be diagnosed by an ‘RSR’ wave and a broad QRS complex Incomplete RBBB (IRBBB) will have a ‘RSR’ wave but will not have a prolonged QRS complex However, the presence of a ‘RSR’ wave alone is a non-specific finding and can be found in normal children Thymus is very large in a newborn and will be part of the mediastinum structures o In a Chest X-Ray, it is common to mistakenly view the thymus as part of an enlarged heart rather than a different structure Cardiomegaly is assessed in a Chest X-Ray if the ratio of the diameter of the heart to the diameter of the Thorax is > 50% in Adults o However, this threshold in >60% in children and >70% in infants As Pulmonary Vascular Resistance falls at ~4-6 weeks after birth, many of the Congenital Heart Defects will only present at this stage (as Pulmonary Vascularity increases to a level at which the Congenital Heart Defects cause problems) SEMINAR – NORMAL ECG DEMONSTRATION Demonstrate the process of recording and the interpretation of the ECG - ECG measures the net electrical difference between two electrodes QRS Complex is larger than the P wave, as there is more cells that depolarise in the Ventricle compared to the Atrium Positive T wave (rather than a negative T wave) in Lead I is due to the length / duration of the action potentials being different in the Endocardium vs. Epicardium - 65 o - - - - The Endocardium has a longer action potential compared to the Epicardium, which means the Epicardium repolarises before the Endocardium this results in a positive T wave (rather than a negative T wave) Repolarisation of the P wave does exist in the ECG, but the size of the electrical potential from this repolarisation is relatively small (as the action potential in the P wave does NOT plateau; hence the electrical difference is small) o As a result, this repolarisation of the P wave is difficult to identify amongst the rest of the ECG The Q wave results as the action potential travels down the Left Bundle Branch quicker than the Right Bundle Branch o This results in an initial wave of depolarisation in the direction from the Left Bundle Branch towards the Right Bundle Branch, which is more than 90 degrees from the average vector for Ventricular depolarisation (i.e. R wave) o As a result, the direction of this impulse is negative relative to the R wave (i.e. negative electrical signal pre-R wave [which is the Q wave]) The S wave results as the last part of the heart the action potential travels towards is the superior lateral border of the Left Ventricle o The direction of this electrical impulse is more than 90 degrees from the average vector for Ventricular depolarisation (i.e. R wave) o As a result, the direction of this final impulse is negative relative to the R wave (i.e. negative electrical signal post-R wave [which is the S wave]) Change in heart rate with the breathing cycle (i.e. higher heart rate with inspiration, lower heart rate with expiration) occurs due to the impact of breathing on the autonomic nervous system (via Vagal Tone) o Inspiration triggers the mechanoreceptors in the lung, which send a signal to the area of the brain that controls the Vagus Nerve this results in a decrease in Vagal Tone (which results in higher heart rate) o This sinus pattern of increasing and decreasing heart rate is described as ‘Sinus Arrhythmia’ SEMINAR – DRUGS IN THE COMMUNI TY Discuss the use and role of medications in the community - The objectives of the National Medicines Policy are: o Timely access to Medicines that Australians need (include consideration of affordability) o Medicines of appropriate standards (i.e. quality, safety, efficacy) o Maintaining an appropriate and viable Medicines Industry ‘Quality Use of Medicine’ refers to the judicious selection of treatment options (i.e. drug vs. non-drug therapy), appropriate choice of drug when it is required and safe / effective use of the selected drug ‘NO TEARS’ is a very useful pneumonic to enable the quality use of medicines; this involves applying the following pneumonic when determining the choice of medications: o Need and indication for drugs o Open questions to patient about other drugs used (including Complementary and Alternative Medications) o Tests and monitoring needed for each single medication o Evidence and guidelines o Adverse events o Risk reduction or prevention (i.e. consider strategies that will reduce risk) o Simplification and switches of medications prescribed Australian Therapeutic Guidelines and / or Australian Medicines Handbook are excellent sources of information regarding the appropriate choice of medications for treating particular conditions o These resources will specify the first-line, second-line, third-line, etc. medications for each of the different conditions o These resources will also identify the key adverse events from these medications too The pharmaceutical usage of Indigenous Australians is 1/3 of the usage of Non-Indigenous Australians (despite having a higher burden of disease!) - - - 66 o - - - Given the significant rate of non-compliance in adherence to medications in disadvantaged populations, there is likely a significant rate of non-compliance in Indigenous communities o This non-compliance may be due to lack of affordability for medications Medications listed on the PBS are subsidised and will cost $34.50 for one month’s supply o However, medications prescribed for ‘off-label’ usage are not funded by the PBS (i.e. patient covers the full cost!) o Similarly, medications not listed on the PBS will require the patient to cover the full cost Medications are classified differently according to the Poisons Schedule this classification determines who can sell the medication (e.g. pharmacist only, pharmacy assistant, supermarkets, etc.) and what is needed for sale (e.g. prescription) Every medication has a range of Prescribing Information (PI) for medical professionals (which can be accessed on MIMS) as well as Consumer Medical Information for patients (which can be accessed on the manufacturer’s website); the PI includes: o Composition o Description o Actions (i.e. Pharmacology, Pharmacokinetics, Clinical Trials) o Indications o Contraindications o Precautions o Interactions o Adverse Reactions o Dose / Administration o Overdose o Presentation o Storage o Poisons Schedule o TGA Approval Date SEMINAR – CRITICAL APPRAISAL O F INTERVENTION STUDI ES TBA - There are three explanations for any result of a study: o Truth o Chance (i.e. random error) o Bias (i.e. systematic error) CONSORT is not a tool for assessing bias or quality, but rather is a tool for reporting Cochrane ‘Risk of Bias’ Assessment will assess 7 different evidence-based domains of quality as high, low or unclear risk (with justification / support for each rating); these domains are: o Random sequence generation o Allocation concealment o Blinding of participants and personnel o Blinding of outcome assessment o Incomplete outcome data o Selective reporting o Other bias Do NOT combine the different domains / elements of quality into a single weighted average score o This will result in a distorted view of the quality as there is no justification for the different weightings to apply to the different elements o Instead, report on each element of quality separately The treatment effect is typically relatively modest, so the introduction of bias due to inadequate allocation concealment is likely to have a larger impact than the true treatment effect ‘Double blinding’ is an ambiguous term as this does not specify who is blinded o Blinding of specific groups will mitigate / avoid specific biases, so it’s important to know which groups were blinded and which were not - - - 67 o - - - - - For example, patients receiving the intervention who are not blinded may introduce a placebo effect Intention-to-treat analysis is a useful technique to account for incomplete outcome data o This introduces bias towards the null hypothesis (as patients who may not have actually received the intervention [and hence will have had no improvement] are analysed on the assumption they were treated) The impact of incomplete outcome data will be influenced by the number of events occurring in the rest of the sample o If the number of missing participants / data is large relative to the number of events, this is likely to introduce significant bias Advantage of survival curve is that data from a participant can be used up till the point they are lost to follow-up Reporting bias can include the failure to report all the outcomes measured in favour of only those outcomes that are statistically significant o Changing the primary outcome from one measure to a different measure is another means of reporting bias o Instead, the study design and protocol should be agreed and finalised prior to commencement of the study, and reporting should be based on this initially agreed protocol Early stopping of a study is associated with bias towards the intervention o If a study is reported based on data only from an initial period of the study (rather than the whole period), this may suggest reporting bias (as the study may not be significant over the whole period, but does show a significant difference in the initial period) Other bias includes asking the wrong question / using the wrong methodology (e.g. comparing intervention against placebo rather than against current best available care, using an inappropriate dosage for comparator drug, etc.) SEMINAR – ECG AND ARRHYTHMIAS Understand the disturbances of rhythm arising from the ventricles of the heart, how they are classified, their mechanisms and effects and how they may be diagnosed and treated - Atrial Fibrillation will involve occasional P waves in the ECG, but these are NOT regularly prior to the QRS Complexes o QRS Complexes are also occurring, albeit at a different rate, as not all the Atrial electrical signals are transmitted to the Ventricles (as the AV Node has a refractory period that prevents it from continually being stimulated) o This arrhythmia involves the Atrium contracting inappropriately (resulting in the irregular pattern of an excessive number of P waves) The electrical activity in the Atrium normally arises from the SA Node, but electrical activity will arise from other parts of the Atrium or near the Pulmonary Veins in Atrial Fibrillation As a result, electrical activity in Atrial Fibrillation is in a state of chaos with numerous electrical impulses firing in a random pattern This results in the Atrium no longer contracting in a coordinated manner Slowing the ventricular rate can occur by increasing the refractory period of the AV Node o Digoxin is an effective treatment for increasing the refractory period of the AV Node o Similarly, Beta-Blockers are an effective treatment for increasing the refractory period of the AV Node There is less toxicity compared to Digoxin and hence Beta-Blockers are preferred Cardiac Output will be reduced in Atrial Fibrillation as there is insufficient diastolic filling time this means that stroke volume is significantly reduced o The reduction in stroke volume has a greater impact on cardiac output than the increase in heart rate, which results in an overall reduction in cardiac output Atrial Fibrillation increases the risk of thrombosis (due to turbulent blood flow resulting in blood pooling in the Left Atrial Appendage) - - - 68 o - - - - - - - Overall though, patients with congenital Atrial Fibrillation can live long, normal lives without much impact on cardiac output (assuming the heart rate isn’t excessive) ‘Coupled Ventricular Ectopic Beat’ will have the following three defining characteristics on an ECG: o No P wave preceding the Ventricular Ectopic beat (i.e. QRS complex) o Prolonged QRS Complex with atypical shape (i.e. heightened amplitude) in the Ectopic Beat o Premature (i.e. Ectopic Beat prior to the normal expected location of the next Ventricular contraction) The prolonged QRS Complex in the Ectopic Beat occurs due to the triggering electrical signal arising from one particular side of the heart rather than from the Atrium and down the normal conduction pathways o As a result, there is a longer distance to travel to reach all of the heart (compared to an electrical signal commencing centrally down the Bundle of His) resulting in a prolonged QRS Complex o Furthermore, the different site of origin of the Ectopic Beat will result in the axis being different, which results in the atypical shape (e.g. higher amplitude QRS complex, inversion of T wave, etc.) o Note: The precise site of origin of the Ectopic Beat can be inferred based on understanding the precise shape and nature of the QRS complex and associated T wave In a patient with a Coupled Ventricular Ectopic Beat, the pulse of the normal beat will be stronger, as there is a longer filling time preceding this beat o The longer filling time occurs due to the occurrence of the refractory period after the Ectopic Beat, which delays the timing of the normal Ventricular Contraction o In contrast, the pulse of the Ectopic Beat will be weak as there is a short filling time preceding this beat Ventricular Ectopic Beats are usually benign and will not require treatment o However, when treatment is needed, this will involve the use of Beta-Blockers for symptom control and potentially Cardiac Ablation for curative treatment Second Degree Type 2 Heart Block will involve regular P waves, but with the P waves sometimes having an associated QRS Complex and other times not having an associated QRS Complex o This usually occurs due to a failure of conduction at the level of the Bundle of His-Purkinje Fibre system (i.e. below AV Node) In contrast, Second Degree Type 1 Heart Block is generally due to a block at the level of the AV Node o Cardiac Output is typically reduced as the heart rate is low (although the stroke volume is normal) In patients with chronic heart block, the ventricle may dilate / hypertrophy allowing an increase in stroke volume that will compensate for the reduced heart rate (which would enable maintenance of cardiac output) o The Atrial rate is relatively high (>100bpm) as the body attempts to increase the heart rate by increasing Atrial contractions Note: Some of the P waves may be ‘hidden’ within some of the QRS Complexes and T waves Second Degree Heart Block has the biggest adverse impact on life, as it may take a short period of time for the tertiary pacemaker (i.e. Bundle of His) to activate when there is a heart block o As a result, there may be a short period where there is insufficient contraction of the heart, resulting in a loss of perfusion and loss of consciousness! Ventricular Fibrillation may result due to either a rapid Ventricular Ectopic Beat triggering VF, or alternatively a re-entry circuit o A re-entry circuit will require a unidimensional block and slow conduction in addition to the existence of a circuit o A unidimensional Block can result due to the shape of the damaged cardiac tissue preventing electrical impulses from conducting in one direction, but allowing electrical impulses to be conducted in the other direction There may be insufficient cells being excited from one direction to overcome the block (as less cells result in less current) 69 - In contrast, more cells may be excited from the other direction, resulting in sufficiently high levels of current to progress through / overcome the block Cardiac output during Ventricular Fibrillation is zero this is a medical emergency! o Defibrillation will be the appropriate treatment as shocking the heart will cease all the existing electrical circuits and ideally allow the SA Node to spontaneously fire once again and return the heart to a sinus rhythm 70
