Ion channel defects

Mutations affecting genes that code for cardiac ion channels can lead to unusual forms of
ventricular tachycardia. The most common and best recognised condition is the long QT
syndrome. This condition can be caused by mutations of at least six genes coding for either
cardiac potassium or sodium channels. The defective channels result in prolongation of the
cardiac action potential, adn tendency to develop polymorphic VT. The term polymorphic
indicates that the morphology of the QRS complex is highly variable during tachycardia. The
most common variant is torsades de pointes VT. A rarerbat increasingly recognised condition
is the B=bruguda syndrome, characterused by right bundle branch block and ST segment
elevation in the right precordial leads and familial sudden death. It is associated with a
sodium channel mutation.
Diagnosis of VT
Clinical features
The clinical presentation of VT is highly variable. It may be discovered coincidentally with
ambulatory monitoring, without symptoms. Palpitation adn dizziness commonly accompany
episodes of VT. In patients with very rapid VT, or with accompanying ventricular
impairment, VT can causes syncope,haemodynamic collapse or cardiac arrest. In considering
whether VT or SVT is the most likely diagnosis in a patients with a broad complex
tachycardia, consider the previous medical history. VT is favoured by a history of ischaemic
heart disease or cardiomyopathy, while SVT is more likely in young individuals without a
cardiac history. A drug history is important, as many drugs can cause VT or umask a
propensity to it. Examination should focus on two areas. First, determinate whether the
patient is haemodynamically compromised by VT, as this directs immediate management.
Secondly, examination is directed at identifying clinical signs of cardiac enlargement, hart
failure and valvular disease as potential triggers for VT.
ECG diagnosis of VT
VT nearly always produces a broad complex tachycardia , because of eccentric, sequential
activation of the ventricles. (a rare exception is his bundle tachycardia during which the
ventricles are activated in a normal sequence). The QRS duration usually exceeds 120 ms.
The presence of atrioventricular dissociation, capture or fusion beats confirm the diagnosis of
VT. Diagnosis is inade difficult by the fact that many patients with VT, atrioventricular

dissociation does not occur. ECG features that help distinguish VT from SVT are given in
table 4. In heamodynamically stable patients, an i.v. adenosine challenge is particularly
helpful as VT is rarely terminated by adenosine whereas SVT are either slowed or terminated
by it.
VT management
Management of an acyte episodes of VT
VT in the stable patient
Initial management of acute VT depends on how the patients is affected by the arrhythmia
assessment comprises assessment of airways, breathing, and circulation. If stable, a brief,
focused history should be taken to determine possible causes of the arrhythmia (e.g.
ischaemic symptoms, new medicatin history of structural or valvular disease). A 12 leads ecg
recorded during tachycardia is helpful is distinguishing VT from SVT. An ecg recorded after
termination of tachycardia may provide clues as to underlying cause (e.g. acute MI, long QT
interval). Identification and treatment of underlying cause include electrolyte disturbance,
acute coronary syndrome and drug-induced arrhytmia. Serum electrolyte should be checked,
including potassium,magnesium, and corerected calcium concentrations. Electrolyte
disturbance is espicially common in patients taking diuretics (hypokalemia and
hypomagnesaemia), alcohol abusers (hypomagnesaemia) and patients with isnulin dependent
diabetes mellitus (hyperkalemia in association with ketoacidosis). VT is also especially
common within the first twenty four hours of acute myocardia infarctin and can complicate
other acute coronary syndromes.
Drug treatment of acute VT
For many patients with VT, antiarrhythmic drug treatmentn is required to terminate the
arrhythmia. The optimal choice of agent is dictated by whether the patients has significant
underlying left ventricular impairment or cardiac failure. In the absence of these factors, iv
lidocaine is often effective at terminate VT. Lidocaine reduces myocardial contractility and
should be avoided in patients with hearth failures. Here iv amiodarone is very effective, but
has to given via central venous line as it can cause severe phlebitis. In peri-arrest situation it
is acceptable to use a peripheral venous cannula. Much less commonly, young patients
without known hearth disease may present with VT. Here a catecholamine resposive
tachycardia may be the mechanism and b blokers are useful. some patients fail to respond to

treatment, in which case spesialist help should be shought. Other include flecainide and
procainamide. If VT fails to respond to the above measures, cardioversion should ben
considered. In patients with recurrent or resistant VT, a temporary pacing wire may be placed
in the right ventricle. Rapid pacing at a rare faster than the tachycardia, may cause conduction
block during re-entrant VT and terminate it. This is knowns as overdrive pacing, and is the
principle by which implantable cardiovertet defibrillators can terminate VT episodes.
Overdrive pacing risks accelerating VT and can trigger ventricular fibrillation, and should
only be performed in a coronary care unit or intensive care unit.
VT with haemodinamic compromises
VT sometimes cause profund haemodynamic compromise or complete loss cardiac output. If
the latter occurss. European Resuscitation Council (ERC) guidelines for management of
cardiac arrest should be followed. In conscious compromised patients, prompt cardioversion
should be considered, either using benzodiazepine sedation, or general anaesthesia if
immediately avaible. ERC have also produced gidelines for management of peri-arrest
arrhythmia, which apply to patients in this situation.
Torsa de pointes VT
This special case VT demands a difeerent approach. Torsades de pointes VT may present
with cardiac

arrest, in which case ERC protocols should be followed. More often it

presentsnwith reccurent, repetitive tachycardia associated with presyncope pr syncope. It

affects individuals with the long QT syndrome, but more pften as a result of drug toxicity.
Class III antiarrhythmic drugs such as sotalol caise torsades in susceptible individuals,
especially in the presence of hypokalaemia or if co-prescribrd with other drugs that prolomg
the QT interval (e.g. antipsychotics,antihistamines,erythromycin), iv magnesium is first line
treatment for drug induced torsades. Iv isoprenaline helps prevent torsades by increasing the
sinus rate and shortening the QT interval. Temporary atrial pacing can also be used to achieve
the same effect.
Long term management of VT
Patiens with VT associated with a transient or reversible cause do not generally require any
long term preventive treatment. This includes patients with myocardial infarction where VT
occurs during the acute event. Patients who have late VT (more than 48 hours aftterwards)
are at rissk further arrhythmia and require investigatin for ongoing treatment or an

impalntable defibrillator. For patients with other aetiologies, a decision has to be taken
whether any treatment is required. Taht decision mainly rests with the patients risk of
arrhtyhmic death. In general, patients with the VT and structural hearth disease (especially
left ventricular impairment) are at greatest risk. The choice of treatment lies mainly between
drug therapy and the implantable defibrillator. For some patients, VT is not associated with a
significantly increased risk of syncope or sudden death(e.g. normal hearth VT) and treatment
is given to control symptoms only.
Antiarrhythmic drugs
The best choice of drug for VT prophylaxis depends on the underlying cause. Some patients
experience VT during exercise or sympathetic arousal. Examples are normal heart VT and
ischaemic VT. In these instances B- blokers are likely to be effective. For patients with VT
associated with ischaemic heart disease and prior myocardial infarction. Amiodarone is
moderately effective at preventing VT, but has significant incidence of side effects. The
implantable defibrillator is more affective at preventing sudden death patients with prior
myocardial infarction and significant left ventricular impairment. For other aetiologies of VT
the class Ic sodium channel blockers flecainide and propafenone are effective agents but
should be avoided in patients with ischaemic heart disease due to risk of proarrhythmia.
Sotalol is also occasionally used for VT prophylaxis because of its combined b-blocking and
class III (potassium channel blocking) action, but is contraindicated for torsades/VT
associated with a long QT interval.
Implantable cardioverter defibrillator (ICD)
ICD therapy for VT is reserved for patients with significant left ventricular impairment
(principally patients with significant prior myocardial infarction or with dilated
cardiomyopathy). The ICD is normally programmed to use overdrive pacing as first line
treatment and shock therapy is only used if pacing fails or if the heart rate rapid enough to
cause haemodynamic compromise.
Catheter ablation
Ablation is very effective in patients with VT arising from a discrete focus within the heart.
The most common indication a normal heart VT. More recently ablation has been used to
treat re-entrant VT after myocardial infarction by blocking part of the re-entry circuit. Here

results are variable and many patients continue to require antiarrhythmic drugs despite
ablation therapy.
Electrophysiological testing and radiofrequency ablation
Certain patients with known orn suspects arrhythmia require in depth evualuation by means
of an invasive electrophysiological. The EP study is undertaken for three main reasone
evaluation of risk of malignant ventricular arrhythmia or sudden death evaluation of patients
with known or suspucted bradycardias and determinatin of the mechanism of arrhythmia
prior to radiofrequency ablation treatment. EP studies are performed in the cardiac
cathererisation laboratory, and involve placement of catheter electrodes into the heart via the
femoral veinss, under local anaesthesia. These catheter are used to stimulate the heart using a
pulse generator and monitor the electical activity of the heart in response to these stimuli.
EP study for evaluating risk of sudden death and ventricular arrhythmia
In this setting the EP study is perfomed using a single catheter electrode placed in the right
ventricle. The heart is stimulated using a series of six to ten paced extrastimuli. Extrastimuli
stimulates the ectopic beats that often trigger ventricular arrhythmia. The drive train is
repeated with extrastimuli timed progressiverly carlier in the cardiac cycle. Afull EP study
consist of provoking the heart using a series of drive trains with up to three consecutive
extrastimuli, at two different drive rates and from two deifferent sites in the heart (e.g. the
apex and outlow tract of the right ventricle). The EP study is deemed positive if sustained
ventricular tachycardia is induced and this correlates with an increased clinivcal risk of
malignant arrhythmia. EP studies have in the past been used to the efficacy of antiarrhythmic
drug therapy, but this practice has largely fallen out of favour since the widespread adoption
of ICD for managing malignant arrhythmia. Indicatios for EPS in this setting include
evaluation of patients for ICD therapy after myocardial infarction and evaluatiom of patients
with cardiac disease and unexplained presynocope or syncope.
EP study for evaluating known or suspected bradycardia
This is not common indication for EP study, since most patients can be assessed using noninvasive methods such as ambulatory monitoring. Here EPS is used to assess sinus node and
his-purkinje function. Catheters are placed in the right atrium over His bundle on the
anteroseptal aspect of the tricuspid valve, and in the right ventricle. Sinus node function is
usually assessed by measuring the sinus node recovery time (SNRT). The right atrium is

placed faster than sinus rate for thirty seconds, then pacing is abruptly stopped. The SNRT is
the interval between the last paced beat and the first sinus beat. The normal range is less than
1500 msec. Patients with sinus node disease tend to have a prolonged SNRT. AV node
function is assessed by pacing the right atrium and measuring the Wenckebach rate (the heart
rate at which AV block occurs). The Wenckebach rate is highly variable and dependent on
autonomic factors. It may be very slow in fit individuals with high vagal tone, but this does
not reflect a clinical risk of bradycarida due to AV block. A more useful index risk of AV
block is derived from the His Catheter recording. Three deflrctions are seen an atrial (A). His
bundle (H), and ventricular (V) deflection. The HV interval is an index of the integrity of the
His-Purkinje system. A normal interval is between 30-55 miliseconds and a prolonged HV
interval predicts clinical risk of developing infaranodal AV block
EPS and radiofrequency ablation of arrhytmias
By far the most common indication for EP study is in the evaluation of patients with SVT
with a view to catheter ablation therapy. Other arrhythmia can also be treated with ablation
but this section will focus on SVT, as it is the most common indication. The EP study
involves placement of catheters in strategic position in the heart in order to deliver paced
stimuli, and to monitor electrical traffic in response to thes stimuli. A stimulator a recording
console and an ablator are required as well as fluoroscopy facilities to allow placement of
catheters is usually placed in the coronary sinus , which is conveniently positioned adjacent
to the mitral valve sinus annulus. The coronary sinus cathter typically has eight or ten
electrode poles that can be used to located left-sided accessory pathways or foci.
The SVT study
A major objective of the SVT study is to induce the patients clinical tachycardia so that its
mechanism can be examined. Different strategies can be used to induce SVT. In the same as
described earlier for VT induction, a drive traun and extrastimuli (from either the right atrium
or right ventricle) can be used to provoke SVT. Sometimes it is not possible to induced SVT
during the EP study, but valuable clues can still be obtained as to the tachycardia mechanism
by examining thr response to pacing manoeuvres. The dua AV nodal physiology associated
with AV nodal re-entrant tachycardia can be identified during atrial pacing and accessory
pathways may be located by examining the size of earliest atrial activation during right
ventricular pacing.

Radiofrequency ablation
Radiofrequency ablation (RF) consists of targeted cauterisation of tissue by local application
of radiofrequency energy. Targets are identified during the EP study by recording the cardiac
activation sequence during tachycardia. During ablation heating occurs at the interface
between catheter and endocardium. Cell death occurs at temperatures exceeding 47 oC.
Ablation has become the treatment of choice for most patients with SVT due to accessory
pathways or to AV nodal re-entrant tachycardia and more recently, atrial flutter. Techniques
are under development for ablation of trigeer foci in patient with paroxysmal atrial fibrilation
and ventricular tachycardias. Ablation is associated with rare but important risks. Cardiac
tamponade, strokr or myocardial infarction can occur, and the risk of life- theretening
complicatio is approximately one in two thousand. Other complications include
pneumothorax, pericarditis, tricuspid regurgitation and femoral artery pseudoaneurysm. AV
block requiring permanent pacemaker implantation affects between 1 in 100 and 1 in 650
patients depending on proximity of the target to the AV node.