Arrhythmia - C. Golding-Wiles 2024 Students.pptx

Mrs Channtal Golding-Wiles [email protected] Outline Review of the cardiac conduction system Review of cardiac action potential through electrocardiogram Pathophysiology of arrhythmias Vaughan-Williams classification of antiarrhythmic drugs  Cardiac Conduction System Conduction sy...

Mrs Channtal Golding-Wiles [email protected] Outline Review of the cardiac conduction system Review of cardiac action potential through electrocardiogram Pathophysiology of arrhythmias Vaughan-Williams classification of antiarrhythmic drugs  Cardiac Conduction System Conduction system generates and transmits impulses to stimulate rhythmic contraction of the myocardium The conduction system first stimulate contraction of the atria followed by the ventricles Pacemaker cells (autorhythmic cells) – Primarily located in the Sinoatrial (SA) Node are responsible for maintaining the rhythmic contraction of the heart Action Potential of Cardiac Cells An electrical stimulation created by a sequence of ion fluxes through specialized channels in the membrane of cells leading to contraction. Occurs in all cells ○ Muscle cells ○ Nerve cells ○ Cardiac cells Action Potential of Cardiac Cells In healthy cells Cell membrane channels open → positively charged ions to rush in → Depolarization After depolarization, positively charged ions (usually K+) are extruded from the cell → Repolarization – cell returns to its original polarized state Types of Action Potential of Cardiac Cells 1. The Pacemaker Cells (Conducting Cells) Generate spontaneous action potentials. Also termed "slow response" action potentials – slower rate of depolarization. Normally found in the sinoatrial (SA) and atrioventricular (AV) nodes of the heart, purkinje fibres. Types of Action Potential of Cardiac Cells 2. Non-pacemaker Action Potentials (Contractile cells): Also called "fast response" action potentials –rapid depolarization Found predominantly in atrial and ventricular myocardium. Action Potential of Pacemaker Cells Unstable (No true rest phase); but it usually starts out near -60mv then they spontaneously depolarize and repolarize in a cycle of three phases: 1.Phase-4: Initial phase of slow spontaneous depolarization – (determines HR) Slow Ca2+ currents are likely responsible for the gradual rise towards threshold potential (-40mV) 2. Phase-0: Slow depolarization up to +10mv Rapid Ca2+ influx due to L-type Ca2+ currents; no fast Na+ currents operate in the SA nodes 3. Phase-3: repolarization Voltage controlled K+ channels open – Efflux of K+ - help repolarize the cell as Ca2+ channels inactivate Cycle repeated Action Potential of Pacemaker Cells  Refractory Period Once an action potential is initiated at phase-0, a new action potential cannot be initiated until membrane is back at rest (phase-4). This is termed the effective refractory period (ERP) or the absolute refractory period (ARP) of the cell The ERP is the time during which a cell is unable to respond to excitation and initiate a new action potential Rest The Electrocardiogram (ECG/EKG) The Electrocardiogram (ECG/EKG) The ECG is a record of the electrical activity (depolarization & repolarization) of the heart. Measures: 1. Time intervals on the ECG – determine how long the electrical wave takes to pass through the heart. 2. Amount of electrical activity passing through the heart muscle – determine if heart is enlarged or overworked. An Electrocardiogram (ECG) Normal ECG (Sinus Rhythm) ECG Waves 1. P wave: Sequential depolarization of right and left atrial myocardium Signals onset of atrial contraction (systole) Normal duration: 0.08 – 0.10 seconds (80-100 ms) ECG Waves 2. QRS Complex: Simultaneous depolarization of right and left ventricular myocardium Signals onset of ventricular contraction (systole) Q= depolarization of septum R= depolarization of ventricles S= last phase of ventricular  ECG Waves 2. QRS Complex: Normal duration: 0.06 – 0.10 secs (60- 100 msec) > 0.10 sec = conduction is impaired within the ventricles. ○ Bundle branch blocks ○ An ventricular foci (abnormal pacemaker site).  ECG Waves 3. T wave: Ventricular repolarization Signals onset of ventricular relaxation (diastole) Inverted T waves = conditions affecting repolarization.  ECG Waves 3. U wave: (occasionally seen) Last phase of ventricular repolarization Prominent U waves = underlying pathology or conditions affecting repolarization. ECG Intervals 1. PR interval: Extends from start of atrial depolarization to start of ventricular depolarization Represents time taken for signal to travel for SA node to AV node ECG Intervals 1. PR interval: Normal duration: 0.12 to 0.20 secs (120-200 msec) > 0.20 sec = damage to conducting pathway or AV node AV node conduction block/ first degree heart block This type of block can be caused by enhanced vagal tone, digitalis, beta-blockers, calcium channel blockers, or ischemic damage to the nodal tissue ECG Intervals 2. Q-T interval: Ventricular cycle – time required for ventricles to undergo a single cycle of depolarization and repolarization Normal duration: 0.20 – 0.40 sec (200-400 msec), depending upon heart rate ECG Intervals 2. Q-T interval: Can be lengthened by ○ electrolyte disturbances ○ conduction problems ○ coronary ischemia ○ myocardial damage ECG Intervals 3. R-R interval: 4. P-P interval: Interval between ventricular Between 2 successive P waves depolarizations Indicates the duration of atrial Indicates the duration of cycle (atrial rate of contraction) ventricular cardiac cycle (ventricular rate of contraction) ECG Segments 1. P-R Segment: A brief isoelectric (zero voltage) period following the P-wave and ending at the beginning of the QRS. Represents the time taken for the impulse to travel within the AV node and the bundle of His. Serves as baseline for the ECG curve, normal duration: approx. 0.08 secs ECG Segments 2. S-T Segment: Isoelectric period following the QRS and ending at the beginning of the T-wave The time at which both ventricles are completely depolarized. Normal duration: approx. 0.08 secs ECG Segments 2. S-T Segment: This segment roughly corresponds to the plateau phase of the ventricular action potentials (Phase-2). ECG Segments 2. S-T Segment: Very important in the diagnosis of ventricular ischemia or hypoxia ST segment depression - coronary artery disease ST segment elevation - heart attack due to clot Normal ECG (Sinus Rhythm) https://www.youtube.com/watch?v=RYZ4daFwMa8 Cardiac Arrythmias A Normal ECG Cardiac Arrhythmia Cardiac arrhythmias/ dysrhythmia is any irregularity in electrical activity of heart (i.e., heart rate or rhythm) Cardiac Arrhythmia Cardiac arrhythmias may develop in 2 main ways: 1. Defects in electrical impulse formation/ automaticity (Pace-maker cells) ○ In the SA node – also in AV node, bundle of His, Purkinje fibres ○ Ectopic pacemaker activity – non-pacemaker cells (atrial and ventricular muscles) develop spontaneous phase 4 depolarization Cardiac Arrhythmia Cardiac arrhythmias may develop in 2 main ways: 2. Defects in electrical impulse conduction in the heart ○ Due to ischemic or damaged areas of the heart: → AV Block → Re-entry After depolarization Disturbances of Automaticity Observed on ECG as variations of the normal electrical conduction or rhythm of the heart Sinus bradycardia: ○ HR is 100 beats/minute ○ Excessive discharge of sympathetic neurons innervating SA Node e.g. exercise Classification of Cardiac Arrhythmia 1. Disturbances of Automaticity  1. Disturbances of Automaticity Atrial fibrillation  1. Disturbances of Automaticity Ventricular flutter Ventricular Fibrillation  2. Disturbances of Conduction AV Nodal Block Impaired conduction through the AV node→ ↓ conduction from the atria to the ventricles. ○ First degree ○ Second degree ○ Third degree  2. Disturbances of Conduction First degree AV Nodal Block  2. Disturbances of Conduction Second degree AV Nodal Block 1 2  2. Disturbances of Conduction Third degree AV Nodal Block  2. Disturbances of Conduction Reentry (Recirculating Activation) Reentry establishes a localized, self-sustaining circuit capable of repetitive cardiac stimulation ○ Local reentry – a small local region within the heart (atria or ventricles) ○ Global reentry – between the atria and ventricles 2. Disturbances of Conduction  2. Disturbances of Conduction Reentry (Recirculating Activation)  2. Disturbances of Conduction After Depolarization (Triggered activity) Occurs when abnormal action potentials are triggered by a preceding action potential. Occurs in early phase 3 or late phase 4 when the action potential is nearly or fully repolarized. Lead to a series of rapid depolarizations (i.e., atrial or ventricular tachyarrhythmia). 2. Disturbances of Conduction Anti-Arrythmia Drugs Anti-arrhythmia Drugs  Class I Drugs – Sodium Channel Blockers Bind to fast potential Na+ channels (responsible for the rapid depolarization – phase 0) in atrial and ventricular myocytes  Class I Drugs – Sodium Channel Blockers – Actions Na + 1. ↓ Phase 0 depolarization → slope 2. ↑ threshold → ↓ automaticity phase 0 → ↓ conduction velocity → ↓ AP amplitude  Class IA Drugs Examples: quinidine, procainamide, disopyramide These drugs bind to the Na+ channels in rapid open state (during phase-0) 1. Slows conduction velocity in the myocardium; exploited for ventricular arrhythmias 2. Prolong refractory period of the heart; exploited for suppression of re-entry arrhythmias 3. Used for conversion of atrial flutter & fibrillation to normal rhythm (50% of patients remain in sinus rhythm)  Class IA Drugs – Actions Refractory Period Na + 1. ↓ Phase 0 depolarization → slope 2. Prolong repolarization of the phase 0 → ↓ conduction velocity myocardium → ↑ refractory period→ → ↓ AP amplitude slower recovery from inactivation → ↑ AP duration 3. ↑ threshold → ↓ automaticity Class IA Drugs – Actions  Class IA Drugs Quinidine ○ GI upset – nausea, vomiting, diarrhea (30% frequency; quinidine must be stopped, due to the risk of developing arrhythmia as a result of the electrolyte imbalance) ○ Anticholinergic (atropine like action) → ↑ AV conduction (used with digoxin, β blocker or Ca2+ channel blocker) ○ Torsades de pointes (a ventricular arrhythmias associated with marked QT prolongation). ○ Heart block – with 50% increase in QRS complex duration (reduce dosage) ○ Cinchonism – blurred vision, hearing disturbance, tinnitus, headaches ○ Hypotension – Quinidine blocks α-adrenergic receptors causing vasodilation and reflex tachycardia (IV use uncommon)  Class IA Drugs Procainamide Uses: ○ Second choice management of sustained ventricular arrhythmias (in the acute myocardial infarction setting) ○ Effective in suppression of premature ventricular contractions and paroxysmal ventricular tachycardia rapidly following IV administration Adverse effects: ○ Lupus-related syndrome – in 25-50% of patients (long-term use avoided) ○ May cause peripheral vasodilation/hypotension (due to ganglion blockade)  Class IA Drugs Disopyramide Uses: ○ Management of atrial flutter and fibrillation ○ Approved use (USA): ventricular arrhythmias – ventricular fibrillation or tachycardia Adverse effects: ○ Anticholinergic effects – may cause urinary retention, dry mouth ○ Depression of cardiac contractility – undesirable with preexisting left ventricular dysfunction (may promote congestive heart failure)  Class IB Drugs Examples: lidocaine, mexiletine These drugs bind to the Na+ channels in open or closed state in ventricles (during phases 4 and 0) 1. Reduce conduction velocity (minor effect in comparison to class IA) 2. Reduce the duration of ventricular action potential by shortening the phase 3 repolarization; useful for suppression of arrhythmias in depolarized or in rapidly firing cardiac tissues (ischemic myocardial sites).  Class IB Drugs – Actions Na + 1. Slope phase 0 = conduction 2. Shorter RP due to shortened velocity in fast beating or ischemic Phase 3 (repolarization) tissues (no change in normal tissues) These drugs exhibit “Use-dependent or state-dependent blockade of sodium channels” Class IB Drugs – Actions  Class IB Drugs Lidocaine ○ Used (intravenously) to treat ventricular arrhythmias in emergency situations. Not effective for supraventricular arrhythmias. ○ It is also used to treat patients with premature ventricular contractions (PVCs). ○ May reduce incidence of ventricular fibrillation following acute myocardial infarction ○ It has a short plasma half-life. It is also used as a local anaesthetic ○ Adverse effects include confusion, seizure (large doses, rapidly administered), dizziness  Class IB Drugs Mexiletine ○ Only used in life-threatening ventricular arrhythmias ○ Possibly effective in decreasing neuropathic pain (diabetic neuropathy, nerve injury) when alternative medications have proven ineffective ○ Adverse effects include tremor, nausea & vomiting  Class IB Drugs Phenytoin ○ Used to treat ventricular tachycardia in young children. ○ It is also used to treat arrhythmia induced by digoxin. ○ Phenytoin is primarily an anti-epileptic drug.  Class IC Drugs Examples: Flecainide, encainide, moricizine, propafenone The most potent Na+ channel blockers (mostly in resting or inactivated state (Phase 0 & 4) & they dissociate slowly. 1. Substantial reduction in conduction velocity by depressing Phase-0 of action potential 2. No significant effect on the action potential duration (no shift) Class IC Drugs – Actions Class IC Drugs Examples: Flecainide, encainide, moricizine, propafenone They are used for life-threatening arrhythmias that are unresponsive to other drugs Very effective in suppressing PVCs and preventing paroxysmal supraventricular tachycardia. May produce significant depression of cardiac functions – also have the potential to produce arrhythmias and sudden death (due to slow conduction in healthy areas of the heart). Class I Drugs  Class II Drugs – β-Blockers Examples: atenolol, metoprolol, esmolol (cardio- selective β1 blockers), propranolol (non-selective β-blocker). ○ These drugs inhibit sympathetic stimulation of β1 receptors (via norepinephrine) at the SA and AV nodes →↓ the rate of phase-4 depolarization (due to Ca 2+) →↓ automaticity →↓ HR and contractility ○ → prolongs AV conduction →↓ conduction velocity ○ → prolongs repolarization of these nodal cells →↑ increase refractory period →↑ AP duration Class II Drugs – β-Blockers  Class II Drugs – β-Blockers The effects are exploited for: prevention of re-entry arrhythmias. treatment supraventricular & ventricular arrhythmias due to sympathetic nerve stimulation. They are the most useful anti-arrhythmic drugs available  Class II Drugs – β-Blockers Note: should be avoided in significant conduction blockade at the AV node. Adverse effects include bronchospasm, cold extremities, impotence (mostly with non-selective agents), cardiac depression, bradycardia, insomnia, depression Class III Drugs – Potassium Channel Blockers Examples: amiodarone, ibutilide, dofetilide, sotalol, bretylium. These drugs block potassium channels → prolong repolarization →↑ refractory period →↑ AP duration; this is exploited for suppression of re-entry tacharrythmias. Can cause early-after depolarization and Torsades de pointes (prolongs QT interval). Class III Drugs – Actions  Class III Drugs Amiodarone: Multiple effects – Wide Spectrum ○ Blockade of ion channels – K+; Na+ & Ca2 channels ○ Blockade of adrenergic receptors – α and β receptors ○ →↑ refractory period & AP duration ○ → ↓ automaticity at pacemaker cells  Class III Drugs Amiodarone: Multiple effects – Wide Spectrum ○ → ↓ conduction velocity Disruption of lipid membranes where the ion channels & receptors are located  Class III Drugs Amiodarone: Multiple effects – Wide Spectrum ○ Uses: ventricular arrhythmias, recurrent paroxysmal atrial fibrillation and flutter. ○ Adverse effects: depression of cardiac, pulmonary, thyroid & hepatic functions, Corneal microdeposits ○ There is low incidence of torsades de pointes  Class III Drugs Ibutilide & dofetilide are used for termination of atrial flutter & fibrillation. ○ The major adverse effect is the potential to precipitate torsades de pointes. ○ Dofetilide, ibutilide are the most selective in this class – lead to arrhythmia and so only used for in-patient settings. ○ Use of dofetilide is restricted  Class III Drugs Sotalol blocks K+ & β receptors →↑ AP duration. ○ Uses – treatment of severe ventricular arrhythmia & prevention of atrial flutter & fibrillation. ○ Adverse effects include fatigue, bradycardia, potential to precipitate torsades de pointes.  Class III Drugs Bretylium has both anti-arrhythmic & antihypertensive properties: ○ Depleting sympathetic nerve terminals of norepinephrine →↑ AP duration in normal & ischemic cardiac myocytes. ○ It acts mainly on Purkinje fibres to suppress recurrent ventricular tachycardia and fibrillation. Class III Drugs  Class IV Drugs – Calcium Channel Blockers Examples: verapamil, diltiazem. They act preferentially at the SA & AV nodal cells →↓ Ca2+ dependent depolarization (Phase 0) →↓ automaticity and conduction. They are useful for suppression of re-entry supraventricular tachyarrhythmia involving the AV node. Adverse effect: GI disturbances, cardiac depression; should not be combined with β-blockers because severe heart failure may occur. Class IV Drugs – Action Anti-arrhythmia Drugs – Summary  Other Anti-arrhythmia Drugs Digoxin – Heart Failure Treatment  Other Anti-arrhythmia Drugs Digoxin – Arrhythmia Treatment ○ Stimulates Parasympathetic System →↑ Vagal activity on M2 receptors on Heart ○ → ↓ SA node discharge rate →↓ automaticity →↓ conduction through AV node →↓ HR; exploited for atrial tachycardia. Other Anti-arrhythmia Drugs - Digoxin  Other Anti-arrhythmia Drugs Adenosine ○ This is a natural purine nucleoside produced from ATP. ○ On A1 receptors → ↓ cAMP induced Ca2+permeability in the nodes →↓ automaticity →↓ HR; exploited for first- line treatment of paroxysmal supraventricular tachycardia.  Other Anti-arrhythmia Drugs Adenosine ○ It has a half-life of 10 seconds. ○ Main adverse effects include chest pain, hypotension, flushing, headache  Other Anti-arrhythmia Drugs Magnesium Sulphate Anti-arrhythmia Drugs – Summary