For personal use only. Not to be reproduced without permission of the editor (permissions@pharmj.org.uk) THE PHARMACEUTICAL JOURNAL (VOL 271) 20 September 2003 368 C ONTINUING P ROFESSIONAL D EVELOPMENT HEART DISEASE (8) A RRHYTHMIAS : PART 1 By Helen Williams, DipPharmPrac, MRPharmS identify gaps in your knowledge 1. What does sinus rhythm mean?
2. Name three types of arrhythmia and describe their implications.
3. What therapies are commonly employed to manage arrhythmias? Before reading on, think about how this article may help you to do your
job better. The Royal Pharmaceutical Societys areas of competence for pharmacists
are listed in Plan and record, (available at: www.rpsgb.org.uk/education) . This article relates to common disease states and their drug therapies
(see appendix 4 of Plan and record). identify plan act record evaluate PJ The diagnosis and management of cardiac arrhythmias is a complex process. This article gives a brief overview of common arrhythmias and highlights strategies, including drug therapies, that may be considered in their management A n arrhythmia is any abnormality
in heart rate (HR) or rhythm.
Some arrhythmias are benign, but
others can cause sudden death. It is estimated that 5.3 per cent of people are
managing an arrhythmia at any given time.
Many arrhythmias remain undiagnosed. Contraction of heart muscle is con- trolled by an electrical system. Specialised
cells (pacemaker cells) in the myocardium
trigger electrical activity, which travels
across the atria into the ventricles, stimulat-
ing contraction and hence controlling the
rate and rhythm of the heart. An arrhythmia is caused by a distur-
bance in the electrical conduction system. Panel 1 (p369) provides
background information on cardiac contraction. Arrhythmias can be described in terms of where they occur or their effect on heart rhythm. For example, the term supraventricular
arrhythmia encompasses disturbances of rhythm arising above the AV
node (atrial arrhythmias) and those arising at the AV junction or within
the AV node itself and the term ventricular arrhythmia refers to dis-
turbances in rhythm arising within the ventricles. Changes in HR may
be referred to as bradycardia (slow rate) or tachycardia (fast rate). Common symptoms of arrhythmia include dizziness or light- headedness, palpitations, chest pain and fatigue. Some arrhythmias
can result in loss of consciousness secondary to hypotension or
compromise blood supply to the major organs because blood no
longer circulates effectively. A small number of patients may be at
risk of cardiac arrest. The best way to diagnose an arrhythmia is to
use an electrocardiogram (ECG). The P wave indicates atrial
depolarisation, the QRS complex indicates ventricular depolarisa-
tion and the T wave ventricular repolarisation (see Figure 1). M ANAGEMENT OF ARRHYTHMIAS In many cases arrhythmias occur as a result of heart disease (eg,
cardiomyopathies) and management may focus on addressing the
underlying cause. Strategies to manage arrhythmias include drug
therapy, electrical cardioversion (see Panel 2, p370) and the insertion
of pacemaker or defibrillator devices. Anti-arrhythmic drugs work by
modifying the electrical activity of the heart. The advent of successful procedures, such as radiofre-
quency (RF) ablation (see Panel 2), has
decreased the role of drugs in managing
arrhythmias. However use of RF ablation in
the United Kingdom is limited because
there are few specialists who can perform the
procedure and there is a risk of several com-
plications (eg, stroke). Cost is also an issue. A wide variety of anti-arrhythmic drugs exists and they are commonly classified according to the Vaughan Williams system,
which divides anti-arrhythmic drugs into
groups according to their actions. Class I anti- arrhythmics (eg, quinidine, disopyramide, flecainide) block the sodium
channels. This group can be further subdivided (IA, IB, IC) according
to their effect on repolarisation. Class II anti-arrhythmics (eg, propra-
nolol, sotalol) primarily consist of the beta-blockers. These agents
reduce the arrhythmogenic effects of circulating catecholamines, delay
depolarisation and also close calcium channels by an indirect mecha-
nism. Class III agents (eg, amiodarone, bretilium) block potassium
channels and hence prolong the action potential, delaying repolarisa-
tion, while class IV (eg, verapamil, diltiazem) block calcium channels at
the AV node, delaying conduction to the ventricles. A number of
additional agents are not classified within the Vaughan Williams
system (eg, adenosine, digoxin). Alternatively, anti-arrhythmics can be
described as those used primarily for the management of supra-
ventricular arrhythmias and those targeting ventricular arrhythmias
(although there is some overlap between the two groups). B RADYCARDIA Bradycardia is defined as an HR less than 60 beats per minute (bpm).
However, in situations where HR is lower than expected, a relative
bradycardia could be said to exist. For example, an HR of 70bpm
during an episode of acute illness, such as sepsis or acute myocardial
infarction (MI) might be considered unusually low. Sinus bradycardia occurs where the SA node fires at a slow rate, so HR falls. Sinus node disease is present when the SA node fails to
generate an electrical impulse. Bradycardias can also be caused by
failure of the AV node to conduct electrical impulses to the ventri-
cles (AV node disease, commonly referred to as heart block) or
neurocardiogenic syncope, which encompasses excess vagal nerve
activity (vasovagal syndrome) and carotid sinus hypersensitivity. If the pacemaker function of the SA node fails and HR falls significantly, secondary pacemakers take over. Initially, the AV node Ms Williams is the pharmacy team leader for cardiac services at Kings College Hospital and one of the London region CHD advisers for clinical pharmacy P T Figure 1: An ECG maps electrical activity
within the heart QRS complex THE PHARMACEUTICAL JOURNAL (VOL 271) 20 September 2003 369 C ONTINUING P ROFESSIONAL D EVELOPMENT maintains HR between 30 and 40bpm (known as a junctional
rhythm). If this fails, cells further down the conduction system (eg,
bundle of His) will maintain a ventricular escape rhythm of
between 20 and 30bpm to ensure a degree of cardiac output. In most cases, sinus node disease is idiopathic, possibly related to fibrosis of the conduction tissues, but known causes include acute
MI or cardiomyopathies. AV node disease is also frequently idio-
pathic but can occur secondary to acute MI, congenital defects and
infection, after surgery (especially following valve replacement) and
following drug therapy (eg, beta-blockers, verapamil or digoxin). Acute episodes of bradycardia can lead to sudden loss of consciousness or lightheadedness, while chronically the condition is
associated with fatigue and lethargy. Depending on the aetiology,
bradycardia can be associated with episodes of tachycardia and
palpitations (the tachy-brady syndrome) or hypotension. Following diagnosis, any reversible cause of bradycardia should be excluded. These include excess vagal tone, drug therapy and elec-
trolyte or metabolic imbalance (eg, hypothyroidism). Acute brady-
cardia associated with vasovagal episodes can be treated with
atropine, which blocks vagal nerve activity. Chronic treatment is
generally through insertion of a pacemaker unit, which is
programmed to keep HR above a specified level. Permanent pace-
maker (PPM) units are frequently used for patients with sinus node
disease or certain types of heart block. If the underlying cause of a
bradycardia is reversible or unlikely to be sustained, pacing may be
used temporarily. Indications for temporary pacing are an HR of less
than 40bpm, symptoms of low cardiac output associated with angina
or evidence of associated ventricular arrhythmias. T ACHYCARDIAS Tachycardia is defined as an HR greater than 100bpm. Supraven-
tricular arrhythmias can arise from the atria (eg, sinus tachycardia,
atrial fibrillation, atrial flutter and atrial tachycardia) or from the
atrioventricular junction (often referred to as supraventricular
tachycardias). The most common supraventricular arrhythmia,
atrial fibrillation, will be covered in the second part of this article
along with ventricular tachycardia. Sinus tachycardia Sinus tachycardia (ST) occurs when the SA node fires at a rapid rate. It is a normal response to exercise and some
drugs (particularly atropine, nicotine, thyroxine, salbutamol and
aminophylline). ST can be present in many conditions, including
hypotension, anaemia, thyrotoxicosis, hypovolaemia, pulmonary
emboli and shock, and is only considered inappropriate where there
is no obvious precipitant. In most cases, ST can be addressed by
treating the underlying cause, for example, using antibiotics to treat
infections, fluid replacement to correct hypotension and hypo-
volaemia and beta-blockers and antithyroid agents to manage thyro-
toxicosis. Management of inappropriate ST relies on the use of
rate-controlling agents such as beta-blockers or calcium channel
blockers. In some cases, RF ablation may be necessary to modify the
sinus node activity. Sinus node re-entry tachycardia Sometimes, a re-entry circuit (a localised circling of the electrical impulse) develops within the
myocardial tissue and results in rapid firing of the SA node. This is
known as sinus node re-entry tachycardia and accounts for about 5
per cent of atrial tachycardias. It is diagnosed primarily by ECG and
electrophysiological studies (see Panel 2). The tachycardia often
stops abruptly, but this can be expedited with the use of adenosine,
verapamil or beta-blockers. RF ablation can also be used. The use of
beta-blockers and rate-controlling calcium channel blockers can
prevent this type of tachycardia recurring. Atrial flutter Atrial flutter involves a re-entry circuit within the right atrium, which drives electrical activity within the left atrium.
The resultant atrial rhythm is rapid (usually 300bpm) and regular,
and flutter waves can be seen in a saw tooth pattern on ECG (see
Figure 2, p370). In atrial flutter the rapid atrial contractions
are associated with a regular ventricular response. Usually the
ventricles beat once for every two, three or four atrial flutter waves.
Irregularity in the atrial or ventricular rate usually indicates atrial
fibrillation rather than atrial flutter. The unusual conduction pathways operating in atrial flutter generally disturbs atrial contraction and results in stasis of blood
within the atria. Anticoagulation is therefore recommended to The conduction system Four structures conduct electrical impulses through the cardiac muscle: the sinoatrial (SA) node, the
atrioventricular (AV) node, the bundle of His (or AV bundle) and
the Purkinje fibres. In the healthy heart, the SA node (located in the
right atrium) acts as the cardiac pacemaker by generating electrical
impulses, hence the term sinus rhythm for a normal rhythm. Electrical activity The movement of electrolytes, in particular potassium, sodium and calcium ions, is key to myocardial contrac-
tion. In the resting state an uneven distribution of these ions exists,
with a greater concentration of potassium ions inside cells and
more sodium and calcium ions outside cells. In specialised pace-
maker tissues, this imbalance creates a negative electrical charge of
approximately 60mV (the membrane potential) across the cell
membrane. Changes in membrane permeability gradually allow
sodium and potassium ions to flow into cells, leading to a change
in the membrane potential. When there is a large enough voltage
change across the cell membrane (ie, when a threshold potential
of about 40mV is reached) voltage-sensitive calcium channels
open to allow an influx of calcium ions. This leads to the develop-
ment of a positive membrane potential, a process known as depo-
larisation. As these events occur in the pacemaker cells, adjacent
non-pacemaker cells are triggered to depolarise and a wave of
electrical activity is conducted throughout the myocardium. Impulses arising in the SA node travel across both atria, and into the AV node, which is sited between the right atrium and ven-
tricles. From the AV node the current then passes down the bun-
dle of His and via the Purkinje fibres throughout the ventricles.
After depolarisation, redistribution of the intra and extracellular
ions restores the resting membrane potential (repolarisation).
Contraction of the myocardial cells occurs at the point of depolar- isation. The atria contract significantly earlier than the ventricles
because conduction though the AV node is slower than through
atrial or ventricular pathways. Control of heart rate Resting heart rate (HR), controlled by the SA node, is around 70bpm. HR is adjusted by the autonomic nervous
system. For example, during exercise sympathetic stimulation of the
SA node increases the influx of calcium ions. This allows cells to
reach threshold potential quicker, and the rate of contraction there-
fore increases. Conversely, parasympathetic stimulation via the vagal
nerve increases the outflow of potassium ions. Cells therefore take
longer to reach the threshold potential and heart rate decreases. Secondary pacemakers Cells in the AV node, the bundle of His and the Purkinje fibres can also generate action potentials, but
these impulses are usually overridden by the SA nodal rate because
the SA node generates action potentials more quickly. P ANEL 1: C ARDIAC CONTRACTION Sinoatrial node Bundle of His Purkinje fibres Atrioventricular
node THE PHARMACEUTICAL JOURNAL (VOL 271) 20 September 2003 370 C ONTINUING P ROFESSIONAL D EVELOPMENT prevent the formation of localised thrombi and reduce the risk of
secondary thromboembolic events. Drugs that slow AV node conduction can be used to control the ventricular response to the rapid flutter waves. Conversely, drugs
that reduce atrial rate should be avoided because if atrial rates slow
sufficiently, 1:1 conduction of the flutter waves to the ventricle
may be possible. This can result in rapid ventricular rates and signif-
icantly compromise cardiac output. For example, if flutter waves
(300bpm) conduct to the ventricles at a ratio of 2:1, the ventricular
rate is 150bpm. Slowing the atrial rate to 220 bpm could allow
conduction of flutter waves to the ventricles at a ratio of 1:1,
resulting in a ventricular rate of 220bpm. Direct current (DC) cardioversion can be used to convert atrial flutter to sinus rhythm. Because a return to normal rhythm could
dislodge any clots that have formed, patients undergoing elective
DC cardioversion, must be adequately anticoagulated for one
month before and after the procedure to reduce the risk of MI or
stroke. DC cardioversion is generally only successful in treating
flutter of short duration. Persistent atrial flutter can often be
successfully treated by RF ablation of the focus (the source of
electrical impulses) or conduction pathway. Atrial tachycardia Tachycardias can arise anywhere in the atria. Atrial tachycardias, other than atrial flutter and atrial fibrillation are
rare and most often caused by the presence of a single ectopic atrial
focus (a focus in the atria that depolarises faster than the SA node) or
the creation of a re-entry circuit. During a true atrial tachycardia, the atrial contraction rate is regular and usually between 150 and 200bpm. Atrial tachycardia can
occur with structural heart disease, cardiomyopathies or cor
pulmonale (ie, as a result of chronic obstructive lung disease) or
following acute MI or digoxin toxicity. This type of arrhythmia
often responds poorly to drug therapy, although agents that control
atrial rate (including those from class IA, class IC or class III) can be
tried. The choice of drug is based primarily on the presence or
absence of left ventricular dysfunction. If the left ventricle is
impaired, class IA and IC are contraindicated (proarrhythmic effects are possible). Sotalol can be used in mild left ventricular dysfunc-
tion, while amiodarone is more appropriate in moderate to severe
dysfunction. In addition, drug therapies to control the resulting
ventricular rate can be used, including beta-blockers or rate-
controlling calcium channel blockers. RF ablation may be required
to control recurrent atrial tachycardia. AV junction tachycardias Most junctional tachycardias are caused by the presence of a re-entry circuit either within the AV node or via
a remote accessory pathway (rather than conducting down the AV
node and bundle of His, the impulses take an abnormal route). They
usually present with atrial rates of between 120 and 260bpm. The
degree of symptoms experienced primarily depends on the resultant
ventricular rate patients with more rapid rates generally present
with palpitations, hypotension and breathlessness, while those with
less rapid rates may not report any significant symptoms. Acute treatment may initially involve vagal manoeuvres, such as carotid sinus massage to reduce vagal nerve activity, or the valsalva manoeuvre, in which the supine patient is asked to breath out hard
with a closed glottis for 15 seconds, and then asked to relax. These
relatively simple techniques can result in a return to sinus rhythm in
up to 70 per cent of patients. In more resistant cases the drug of
choice is adenosine, which blocks conduction across the AV node.
This will terminate arrhythmias caused by re-entry via the AV node,
and will help to identify the presence of accessory pathways or
underlying atrial flutter waves. However, adenosine can precipitate
bronchospasm and must therefore be avoided in asthmatics.
Verapamil may be a suitable alternative where adenosine is
contraindicated, but ventricular tachycardia must be excluded first.
Following restoration of sinus rhythm, some patients can return to
normal activities without the need for chronic therapy. Suppression
of recurrent supraventricular tachycardias can be achieved using a
wide range of drugs, but beta-blockers or rate-controlling calcium
channel blockers may be safer than options such as propafenone or
amiodarone. RF ablation to break re-entry circuits or accessory
conduction pathways is increasingly performed. Wolff-Parkinson White syndrome Wolff-Parkinson White syn- drome is a specific supraventricular tachycardia, where an accessory
pathway conducts electrical activity directly from the atria to the
ventricles and allows a circuit to form around this pathway and the
AV node. This is a serious condition, particularly if it occurs in
conjunction with atrial fibrillation, which can lead to rapid,
potentially fatal, ventricular rates. Every effort should be made to
prevent the development of atrial fibrillation in these patients. RF
techniques may be used to ablate the accessory pathway. action: practice points Reading is only one way to do CPD and the Society will expect
to see various approaches to CPD in a pharmacists portfolio. 1. Do you know the difference between pacemaker and non pacemaker cardiac cells? Refer to a standard textbook. 2. Speak to a patient being treated for an arrhythmia. What symptoms did he or she experience? Does the patient know
what type of arrhythmias he or she has? 3. Make sure you understand all the terms in this article explain them to a colleague. evaluate For your work to be presented as CPD, you need to evaluate
your reading and any other activities. Answer the following
three questions: What have you learnt?
How has it added value to your practice? For example, have you
applied this learning or had any feedback?
What will you do now and how will this be achieved? P ANEL 2: G LOSSARY Electrical cardioversion In electrical cardioversion the aim is to disrupt the abnormal electrical conduction pathways in order to
convert an arrhythmia to sinus rhythm. This involves the
delivery of a low voltage shock to the heart through the chest
wall (eg, using paddles). More than one shock is needed in some
cases. The procedure can be painful so the patient is given a
short-acting anaesthetic. Radiofrequency ablation Radiofrequency (RF) ablation is a procedure whereby a catheter with an electrode at its tip is
guided to the site on the myocardium that is responsible for the
generation or conduction of abnormal impulses. RF energy is
then transmitted locally to destroy the affected tissue and
remove the conduction pathway. The procedure is done under
mild sedation and local anaesthetic. It has a high success rate and
patients can return to normal activities in a few days. Electrophysiological studies An electrophysiological study is used to investigate the exact location and characteristics of an
arrhythmia in detail (eg, the focus responsible for generating an
atrial tachycardia can be pinpointed in order to carry out RF
ablation). This is achieved by placing several electrodes on the
heart surface (via a catheter) and mapping electrical activity. Figure 2: In atrial flutter, atrial activity is seen as rapid flutter waves
between each complex