Arrhythmias

22 Arrhythmias






Normal cardiac electrophysiology


The normal cardiac rhythm, sinus rhythm, is characterised by contraction of first the atria and then the ventricles (systole) followed by relaxation (diastole) during which the heart refills with blood before the next cardiac cycle begins. This orderly sequence of contraction and relaxation is regulated by the heart’s electrical activity. Heart muscle cells (myocytes) are electrically active and capable of generating action potentials, which initiate contraction of the myocyte through a process known as excitation–contraction coupling. Adjacent myocytes form electrical connections through protein channels called gap junctions. An action potential in one myocyte causes current flow between itself and adjacent myocytes which in turn generate their own action potentials and in this way an ‘activation wavefront’ spreads though the myocardium, resulting in a wave of contraction.



Cardiac action potential


An understanding of the ionic basis of the cardiac action potential is important because drugs used in the treatment of cardiac arrhythmias act by altering the function of trans-membrane ion channels. Inherited abnormalities of ion channel function (‘channelopathies’) are an important cause of sudden cardiac death due to arrhythmia and are increasingly implicated in the pathogenesis of other arrhythmias including atrial fibrillation (AF).


The phospholipid membrane of cardiac myocytes is spanned by numerous proteins known as ion channels, whose permeability to specific ions varies during the cardiac cycle resulting in a resting (diastolic) membrane potential, diastolic depolarisation in cells with pacemaker activity, and action potentials.


The resting membrane potential of -60 to -90 mV occurs because the intracellular potassium (K+) concentration is much higher than the extracellular K+ concentration as a result of a transmembrane pump known as Na+–K+–ATPase, which pumps K+ ions into the cell in exchange for sodium (Na+) ions. K+ ions diffuse out of the cell through selective K+ channels (the inward rectifier current or IK1) unaccompanied by anions, resulting in a net loss of charge and thus a negative resting, diastolic or phase 4, transmembrane potential (Fig. 22.1A).



Certain specialised myocytes form the cardiac conduction system and these cells have pacemaker activity, that is, they are capable of generating their own action potentials due to gradual depolarisation of the transmembrane potential during diastole (phase 4), referred to as the pacemaker potential (Fig. 22.1B). The pacemaker potential occurs as a result of (i) a gradual reduction in an outward K+ current called the delayed rectifier (IK) current, (ii) increasing dominance of an inward current of Na+ and some Ca2+ ions known as If (f stands for ‘funny’) and (iii) an inward calcium current ICa through voltage-gated calcium channels. As a result of the pacemaker potential, the transmembrane potential gradually becomes less negative until a threshold potential is reached at which an action potential is triggered. The rate of depolarisation of the pacemaker potential, and hence the heart rate, is influenced by the autonomic nervous system. Sympathetic nervous system activation and circulating catecholamines increase the heart rate by binding to ß1-adrenoreceptors leading to an increase in intracellular cyclic AMP, which results in changes to the permeability of the various ion channels responsible for the pacemaker current. Parasympathetic nervous system activation, mediated by muscarinic cholinergic receptors, has the opposite effect.


The rapid depolarisation of the cardiac action potential (Fig. 22.1A, phase 0) occurs because of a rapid increase in the permeability of the cell membrane to Na+ ions, which enter rapidly through ‘fast’ Na+ channels in a current known as INa. The INa current is brief as the ‘fast’ Na+ channels inactivate rapidly. The early phase of repolarisation (phase 1) is due to closure of the fast Na+ channels, an outward K+ current known as Ito (to – transient outward) and a further K+ current known as the ultra-rapid component of the delayed rectifier current or IKur. The plateau phase (phase 2) of the cardiac action potential occurs because the inward movement of Ca2+ ions (ICa) is balanced by the outward movement of K+ ions. Repolarisation (phase 3) occurs as ICa diminishes and two further components of the delayed rectifier (IK) current known as the rapid (IKr) and slow (IKs) components predominate, with an important contribution from IK1.


There is considerable variation in the expression of trans-membrane ion channels in different parts of the heart, with corresponding variation in the morphology of the action potential. The most marked example is that myocytes in the sinus and AV nodes contain few Na+ channels. The upstroke of the action potential in these cells is due, predominantly, to the influx of Ca2+ ions and, therefore, is considerably slower than the upstroke in other myocytes (Fig. 22.1B). The variation in ion channel expression throughout the heart is essential for normal cardiac function, helps to explain the pathophysiology of many inherited and acquired diseases complicated by cardiac arrhythmia and accounts for the relative selectivity of antiarrhythmic and other drugs for certain parts of the heart.




Normal cardiac conduction


During normal sinus rhythm (Fig. 22.2), an activation wavefront begins in the sinus node, a group of cells with pacemaker activity on the upper free wall of the right atrium. The rate of diastolic depolarisation and hence the rate of discharge of the sinus node is increased by sympathetic nerve stimulation, circulating catecholamines or sympathomimetic drugs mediated by ß1-adrenoreceptors on the cell membranes of the sinus node myocytes. Parasympathetic (vagus) nerve stimulation exerts the opposite effect, mediated by muscarinic cholinergic receptors.



An activation wavefront spreads across the atrial myocardium, leading to atrial contraction and generating the P wave on the surface electrocardiogram (ECG; Fig. 22.3). The last part of the atria to be activated is the atrioventricular (AV) node, the electrical and structural properties of which result in a slow conduction velocity, allowing atrial emptying to be completed before ventricular contraction begins and represented by the PR interval on the ECG. Conduction velocity in the AV node is increased by sympathetic nerve stimulation, circulating catecholamines or sympathomimetic drugs, mediated by ß1-adrenoreceptors while parasympathetic (vagus) nerve stimulation exerts the opposite effect via muscarinic cholinergic receptors.



The atria and ventricles are electrically isolated from each other by the annulus fibrosus, the electrically non-conductive fibrous tissue forming the valve rings. In the normal heart, there is just one electrical connection between the atria and ventricles, the bundle of His, which conveys the activation wavefront from the AV node and penetrates the annulus fibrosus before dividing into the right and left bundle branches. The bundle branches ramify into a sub-endocardial network of Purkinje fibres, which convey the activation wavefront rapidly across the ventricles ensuring near-simultaneous contraction of the ventricular myocardium, and are represented by the narrow QRS complex of the ECG. Finally, the activation wavefront spreads from endocardium to epicardium. A wave of repolarisation then spreads across the ventricles resulting in the T wave. The QT interval on the ECG, therefore, represents the duration of ventricular depolarisation and repolarisation. There is an inverse relationship between the time to activation of different areas of the ventricular myocardium and APD such that the latest areas to be activated have the shortest APD. The purpose of this relationship is that repolarisation is rapid and uniform throughout the ventricular myocardium, which serves to maintain electrical stability.



Arrhythmia mechanisms


Cardiac arrhythmias occur because of abnormalities of impulse formation or propagation.



Abnormal impulse formation



Abnormal automaticity


Automaticity is another term for pacemaker activity, a characteristic possessed by all cells of the specialised cardiac conduction system during health and, potentially, by other cardiac myocytes during certain disease states. The rate of firing of a pacemaker cell is largely determined by the duration of the phase 4 diastolic interval (Fig. 22.4). This in turn is determined by (i) the maximum diastolic potential following repolarisation of the preceding action potential, (ii) the slope of diastolic depolarisation due to pacemaker currents and (iii) the threshold potential for generation of a new action potential. In the healthy state, there is a hierarchy of firing rates within the specialised conduction system with the highest rate in the sinus node followed by the AV node and then the His–Purkinje system. The sinus node is, therefore, the dominant pacemaker and determines the heart rate, while the pacemaker activity in the distal conduction system is ‘overdriven’ by the sinus node. Abnormal automaticity describes either accelerated pacemaker activity in cells of the distal cardiac conduction system such that they escape from overdrive suppression by the sinus node, or the development of pacemaker activity in cells that do not form part of the cardiac conduction system.




Triggered activity


Triggered activity describes impulse formation dependent upon afterdepolarisations. Early afterdepolarisations (EADs) occur during phase 2 or 3 of the cardiac action potential whereas delayed afterdepolarisations (DADs) occur during phase 4 (Fig. 22.5). In both cases, afterdepolarisation may reach the threshold potential required for generation of a new action potential.



EADs are characteristic of the congenital and acquired long QT syndromes. The prolonged APD promotes reactivation of the inward calcium current ICa which may directly cause EADs during phase 2. Furthermore, action potential prolongation and ß-adrenoreceptor stimulation promote calcium overload in the sarcoplasmic reticulum. This in turn leads to the spontaneous release of calcium in bursts by the sarcoplasmic reticulum. The resultant increase in intracellular calcium concentration activates the transmembrane Na+/Ca2+ exchanger which moves one calcium ion out of the myocyte in exchange for three sodium ions and, therefore, results in an EAD during phase 3. In the long QT syndromes, an EAD may initiate a form of polymorphic ventricular tachycardia (VT) known as Torsade de Pointes. EADs are more prominent at slow heart rates.


DADs are seen during reperfusion following ischaemia, heart failure, digitalis toxicity and in catecholaminergic polymorphic VT. They occur because of spontaneous release of calcium in bursts by the sarcoplasmic reticulum, activating the Na+/Ca2+ exchanger as described for EADs and resulting in a DAD during phase 4. A DAD may result in a single extrastimulus (‘ectopic beat’) or in repetitive firing, that is, tachycardia. DADs are more prominent at rapid heart rates and during sympathetic nervous stimulation of ß-adrenoreceptors.



Abnormal impulse propagation



Re-entry


Many clinically important arrhythmias are due to re-entry, in which an activation wavefront rotates continuously around a circuit. Re-entry depends upon a trigger in the form of a premature beat, and a substrate, that is, the re-entry circuit itself. A precise set of electrophysiological conditions must be met in order for re-entry to occur (Fig. 22.6): (i) there must be a central non-conducting obstacle around which the re-entry circuit develops, (ii) a premature beat must encounter unidirectional conduction block in one limb (a) of the re-entry circuit, (iii) conduction must proceed slowly enough down the other limb (b) of the re-entry circuit that electrical excitability has returned in the original limb (a), allowing the activation wavefront to propagate in a retrograde direction along that limb, and (iv) the circulating activation wavefront must continue to encounter electrically excitable tissue. This is a function of the length of the re-entry circuit, the conduction velocity of the activation wavefront and the effective refractory period of the myocardium throughout the circuit. Class I antiarrhythmic drugs block sodium channels and, therefore, reduce the amplitude and rate of rise of the cardiac action potential and in so doing, reduce the conduction velocity of an activation wavefront. Class I antiarrhythmic drugs may exert their major antiarrhythmic effect by abolishing conduction altogether in areas of diseased myocardium forming part of a re-entry circuit in which conduction is already critically depressed. Class III antiarrhythmic drugs prolong cardiac APD and hence the refractory period. If previously activated cells in a re-entry circuit (the ‘tail’) remain refractory when the re-entrant wavefront (the ‘head’) returns to that area, conduction will fail and re-entry will be abolished. Drug-induced prolongation of the refractory period may, therefore, terminate and/or prevent re-entrant arrhythmias.




Clinical problems


Patients with a cardiac arrhythmia may present with a number of symptoms:







Arrhythmias may aggravate heart failure in two ways: (i) the haemodynamic effect of the arrhythmia may precipitate heart failure or aggravate existing heart failure and (ii) prolonged tachycardia of any type may lead to tachycardia-induced cardiomyopathy.



Diagnosis


A detailed history should be obtained, covering all of the symptoms listed above. A characteristic of cardiac arrhythmias is their random onset. Symptoms occurring under specific circumstances are less likely to be due to arrhythmia, but there are exceptions including certain uncommon types of VT, some cases of supraventricular tachycardia (SVT) due to an accessory pathway and vasovagal syncope (faints). Other key features of the history include:






Physical examination is essential but often normal between episodes of arrhythmia. Mandatory investigation includes a 12-lead ECG and an echocardiogram to detect structural heart disease. Other investigations for structural and ischaemic heart disease may be indicated at this stage with the aim of detecting any underlying structural heart disease. If the history does not include sinister features such as syncope or a family history of sudden unexpected death at a young age, and the resting 12-lead ECG and echocardiogram are normal, then the patient can be reassured that they are extremely unlikely to have a serious heart rhythm disturbance. The extent of further investigation will be dictated by how troublesome the symptoms are.


The most certain way of reaching a firm diagnosis is a 12-lead ECG recorded during the patient’s symptoms demonstrating arrhythmia. As many arrhythmias occur intermittently, some form of ECG monitoring is often necessary. This may include a continuous ambulatory ECG (Holter) recording for up to 7 days at a time if the symptoms occur frequently or, for less frequent symptoms an event recorder, which may store ECG strips automatically if it detects an arrhythmia or if activated by the patient during their symptoms. An insertable loop recorder may be implanted subcutaneously and is an ECG event recorder with a battery life of about 3 years, making it a useful tool for the diagnosis of infrequent arrhythmias.



Management


Pathological tachycardia is conventionally defined as a resting heart rate over 100 beats/min and can be classified according to whether it arises in or involves the atria (supraventricular tachycardias) or the ventricle (ventricular tachyarrhythmias).



Supraventricular tachycardias


These are tachycardias arising from or involving the atria.




Atrial flutter


Atrial flutter is a right atrial tachycardia with a re-entry circuit around the tricuspid valve annulus. The atrial rate is typically 300 min–1. The long refractory period of the AV node protects the ventricles from 1:1 conduction: In the presence of a healthy AV node and the absence of AV node-modifying drugs, there is usually 2:1 AV conduction resulting in a regular narrow-complex tachycardia with a ventricular rate of 150 min–1.


Atrial flutter confers a risk of thromboembolism similar to that of AF and this risk should be managed in the same way. Emergency management of atrial flutter is dictated by the clinical presentation but may include d.c. cardioversion or ventricular rate control with drugs which increase the refractory period of the AV node such as ß-blockers, verapamil, diltiazem or digoxin. ß-Blockers, verapamil and digoxin may be given intravenously. As the re-entry circuit is confined to the right atrium and does not involve the AV node, adenosine will not terminate atrial flutter but will produce transient AV block, allowing the characteristic flutter waves to be seen on the ECG (Fig. 22.7).



There is a limited role for antiarrhythmic drugs, whether used acutely to achieve chemical cardioversion or in the longer term to maintain sinus rhythm. Class Ic antiarrhythmic drugs such as flecainide should be used only in conjunction with AV node-modifying drugs such as ß-blockers, verapamil, diltiazem or digoxin because they may otherwise cause slowing of the atrial flutter circuit and 1:1 conduction though the AV node which may be life-threatening. Sotalol and amiodarone have been used to restore and maintain sinus rhythm and have the advantage of controlling the ventricular rate where rhythm control is incomplete. Catheter ablation of atrial flutter is highly effective and safe and is increasingly used in preference to long-term drug treatment.




Junctional re-entry tachycardia


The term ‘supraventricular tachycardia’ (SVT) is widely used to describe junctional re-entry tachycardias but is a misnomer because it implies any tachycardia arising from the atria. Junctional re-entry tachycardia is a more specific term and may be preferable.


Two mechanisms account for most junctional re-entry tachycardias: both involve a macroreentry circuit (Fig. 22.8). AV nodal re-entry tachycardia (AVNRT) rotates around a circuit including the AV node itself and the so-called AV nodal fast and slow pathways, which feed into the AV node. Atrioventricular re-entry tachycardia (AVRT) comprises a re-entry circuit involving the atrial myocardium, the AV node, the ventricular myocardium and an accessory pathway, a congenital abnormality providing a second electrical connection between the atria and ventricles in addition to the His bundle, thus forming a potential re-entry circuit.



Many accessory pathways conduct only retrogradedly from the ventricles to the atrium. In these cases, the ECG during sinus rhythm appears normal and the accessory pathway is described as ‘concealed’. Other accessory pathways conduct anterogradely and retrogradely. In these cases, the ECG during sinus rhythm is abnormal and is described as having a Wolff–Parkinson–White pattern (Fig. 22.9). This abnormality is characterised by a short PR interval as the conduction velocity of an accessory pathway is usually faster than that of the AV node, and a delta wave, a slurred onset to the QRS complex which occurs because an accessory pathway inserts into ventricular myocardium which conducts more slowly than the His–Purkinje system.



Junctional re-entry tachycardias are characterised by a history of discrete episodes of rapid regular palpitation that start and stop suddenly and occur without warning and apparently at random. The peak age range at which symptoms begin is from the mid-teens to the mid-thirties and the condition is more common in women. There are no symptoms between episodes, and cardiac examination and investigation at these times are usually normal. The diagnosis is usually made on the basis of the history, ideally confirmed by an ECG recorded during an episode showing a regular narrow-complex tachycardia with no discernible P waves or P waves occurring in a 1:1 relationship with the QRS complexes.


Acute treatment of junctional re-entry tachycardia aims to terminate the tachycardia by causing transient conduction block in the AV node, an obligatory part of the re-entry circuit. Vagotonic manoeuvres such as carotid sinus massage, a Valsalva manoeuvre or eliciting the diving reflex by immersion of the face in ice-cold water may all result in a brief vagal discharge sufficient to block conduction in the AV node, terminating tachycardia. The same effect may be achieved with intravenous adenosine given as a rapid bolus injection in doses up to 12 mg. Intravenous verapamil 5 mg also as a rapid bolus injection is a good alternative where adenosine is contraindicated.


Junctional re-entry tachycardia is often recurrent. There is a limited role for prophylactic drug treatment as this is generally not a dangerous condition affecting young and otherwise healthy people. Among other factors, the efficacy, toxicity and acceptability of what may be long-term drug treatment require careful consideration. Options for prophylactic drug treatment include ß-blockers, verapamil, flecainide and sotalol. Particular importance should be given to discussion about the management of junctional re-entry tachycardia during pregnancy. Catheter ablation is curative in one sitting in a majority of cases.


Jun 18, 2016 | Posted by in PHARMACY | Comments Off on Arrhythmias

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