1. health and fitness
2. disease
3. heart disease

TETC32 12/2/05 14:26 Page 949
32
Ventricular Tachycardia
Lars Eckardt, Pedro Brugada, John Morgan and
Günter Breithardt
Summary
Ventricular arrhythmias are the major cause of
morbidity and mortality in patients with structural
heart disease, but can also be a mechanism of sudden
death in patients with structurally normal hearts (e.g.
channelopathies such as long or short QT syndrome,
Brugada syndrome). Infrequently, they can be generated
by mechanisms that are amenable to curative catheter
ablation. Overall, ventricular tachycardia and
ventricular fibrillation are the major cause of sudden
unexpected death. Ventricular tachycardias are
relatively organized tachyarrhythmias with discrete
QRS complexes. They can be either sustained or nonsustained, and can be monomorphic or polymorphic.
Polymorphic ventricular tachyarrhythmias tend to be
faster and less stable than monomorphic. The correct
diagnosis of a ventricular tachycardia remains a
challenge despite numerous established criteria for the
Introduction
Ventricular arrhythmias are the major cause of morbidity
and mortality in patients with structural heart disease,
but can also be a mechanism of sudden death in patients
with structurally normal hearts. Infrequently they can be
generated by mechanisms that are amenable to curative
catheter ablation. Overall, ventricular tachycardia (VT)
and ventricular fibrillation (VF) are the major cause of
sudden unexpected death. Ambulatory ECG recordings
at the time of sudden death have shown that, in approximately 60% of sudden cardiac death victims, an episode
of VT was identified as the initial event [1].. Major studies
of heart failure therapy have shown that ventricular
differentiation of ventricular from supraventricular
tachycardia with aberrant conduction. A history of
heart disease has a positive predictive accuracy of
95% for a ventricular tachyarrhythmia. A re-entry
mechanism accounts for the majority of ventricular
tachyarrhythmias in patients with structural heart
disease. The spectrum of therapies for ventricular
tachycardias includes drug therapy, device implantation
and surgical or catheter ablation techniques. In patients
with chronic coronary heart disease, the magnitude of
the survival benefit from the implantable cardioverterdefibrillator is directly related to the severity of cardiac
dysfunction. The management challenge is to deal both
with the ventricular tachycardia as the presenting
symptom, and the pervading sudden cardiac death risk
that may be the consequence of the arrhythmogenic
substrate.
arrhythmia is the commonest cause of death, whatever
the functional class of the patient.
Definitions
Ventricular tachycardia is a relatively organized tachyarrhythmia with discrete QRS complexes. It can be either
sustained (lasting longer than 30 s) or non-sustained
(defined as three or more beats but less than 30 s), and
can be monomorphic or polymorphic. If the same patient
has monomorphic ventricular tachycardias with different morphologies, it is termed pleomorphic. Polymorphic
949
TETC32 12/2/05 14:26 Page 950
950
Chapter 32
ventricular tachycardias tend to be faster and less stable
than monomorphic. The rate of ventricular tachycardia
can range from 100 beats per minute (b.p.m.) to more
than 300 b.p.m. At faster rates (usually 220 b.p.m. or
faster), ventricular tachycardia is so rapid that it may be
impossible to distinguish the QRS complex from the T
wave. This type of ventricular tachycardia is referred to as
ventricular flutter. Ventricular fibrillation is a completely
disorganized (chaotic) tachyarrhythmia without discrete
QRS complexes. When it begins, it is associated with a
coarse electrical pattern. As the heart becomes less viable,
the fibrillation becomes fine, and then, as an agonal
event, all electrical activity ceases (flat line).
Electrocardiographic diagnosis of ventricular
tachycardia
The correct diagnosis of a wide complex tachycardia (QRS
duration > 120 ms) remains a challenge despite numerous established criteria for the differentiation of ventricular from supraventricular tachycardia with aberrant
conduction. Ventricular tachycardia is the most common cause of wide complex tachycardia, accounting for
up to 80% of all cases [2]. A history of heart disease (prior
myocardial infarction or heart failure) has a positive
predictive accuracy of 95% for ventricular tachycardia
[3]. On the other hand, if a patient has had similar
episodes during previous years, a supraventricular origin
is more likely than a ventricular tachycardia. Termination of a tachycardia by physical manoeuvres, such as
the Valsalva manoeuvre or adenosine injection, strongly
suggests a supraventricular origin, although some ventricular tachycardias can also terminate by these manoeuvres (e.g. fascicular ventricular tachycardia). A wide
complex tachycardia in a patient who is alert and haemodynamically stable is not necessarily of supraventricular
origin. If it is a ventricular tachycardia in a patient with
reduced systolic function, an i.v. injection of, for example,
verapamil may result in severe hypotension and haemodynamic instability.
In general, if an electrocardiogram (ECG) showing
a wide complex tachycardia does not look like aberration, it is most likely a ventricular tachycardia. If there
is any doubt about the origin of a broad complex tachycardia, the patient should be treated as if the rhythm
is ventricular tachycardia because it is by far the more
common diagnosis. The absence of a RS complex in any
precordial lead or an interval of the R-wave onset to
the S-wave nadir of more than 100 ms strongly suggests
a ventricular tachycardia [4]. In addition, the following
ECG criteria have been suggested to distinguish between
a ventricular and a supraventricular tachycardia with
aberration.
l QRS complex duration. Ventricular tachycardia is the
probable diagnosis when the QRS duration with right
bundle branch block (RBBB) is greater than 140 ms,
and greater than 160 ms with left bundle branch
block (LBBB) morphology [2].
l QRS axis. A frontal axis of between –90 and ±180
degrees cannot be achieved by any combination of
bundle branch block and therefore suggests
ventricular tachycardia. Thus, predominantly
negative QRS complexes in leads I, II and III are useful
criteria for identifying a ventricular tachycardia.
l Concordant negative ECG patterns in the precordial leads.
If all precordial leads are predominantly negative, a
ventricular tachycardia is the likely diagnosis. If all
precordial leads are predominantly positive, the
differential diagnosis is an antidromic tachycardia
using a left-sided accessory pathway or a ventricular
tachycardia.
l QRS morphologies in V1 and V6 (Fig. 32.1). In RBBB
pattern, a monophasic R wave, a broad (> 30 ms) R or
a QR in V1 strongly suggests ventricular tachycardia.
A monophasic R wave or an S greater than an R in V6
LBBB
SVT
VT
small R
Slow descent
Broad R
V1
Fast descent
> 60 ms
V6
Q
RBBB
SVT
rSR-pattern
VT
Monophasic R
qR (or RS)
V1
R/S >1
R/S < 1 or QS pattern
V6
Figure 32.1 QRS criteria for differential diagnosis in broad
complex tachycardia: ventricular tachycardia (VT) vs.
supraventricular tachycardia (SVT) with left (LBBB) or right
(RBBB) bundle branch block.
TETC32 12/2/05 14:26 Page 951
Ventricular Tachycardia
Lead V1
LBBB pattern V1
VT from the RV or LV septum
VT from the LV
Ischaemic cardiomyopathy = likely LV with
septal origin
QRS positive V2–V6 = base of LV
QRS negative V2–V6 = apex of LV
Positive II, III, aVF, normal heart = RVOT-VT
II, III, aVF positive = anterior wall
II, III, aVF negative = inferior wall
QRS > 0.140 s = RVOT free wall
QRS < 0.140 s = RVOT septum
QS in aVR > aVL = RVOT posterolateral
QS in aVR < aVL = RVOT anterior
R wave transition before V2 = consider LVOT
Figure 32.2 Algorithm for localization of
the exit site of ventricular tachycardia.
RBBB pattern V1
I and aVL positive = septal wall
I and aVL negative = lateral wall
Multiple morphologies or negative in II, II, aVF =
consider RV-dysplasia
also suggests ventricular tachycardia. In the presence
of a LBBB pattern, a broad R wave (usually greater
than 30 ms [5]) and/or a slow descent to the S wave
nadir in V1 and a Q in V6 point towards a ventricular
tachycardia.
l Atrioventricular dissociation. This is one of the most
useful criteria for distinguishing ventricular
tachycardia from supraventricular tachycardia (SVT).
It occurs in 20–50% of ventricular tachycardia and
almost never in SVT [2,6,7]. Atrioventricular
dissociation may be diagnosed by a changeable
pulse pressure, irregular canon A waves in the
jugular veins and a variable first heart sound. It is
often very difficult to ascertain, particularly in rapid
tachycardias. It often demands long 12-lead ECG
recordings and careful ECG analysis. In addition,
about 30% of ventricular tachycardias have 1:1
retrograde conduction. In the presence of AV
dissociation, one may also observe fusion beat, which
may result from the fusion of a P wave conducted to
the ventricles.
The 12-lead ECG during ventricular tachycardia can be
helpful in providing an approximation of the site of
origin, which may be helpful for guiding ablation
(Fig. 32.2). In general, ventricular tachycardias that have
a left bundle branch block-like morphology in V1 have
an exit in the right ventricle or the interventricular
septum. A QRS axis that is directed superiorly generally
indicates an exit in the inferior wall; an axis directed
inferiorly indicates an exit in the anterior (superior) wall.
In V2–V4, dominant R waves usually indicate an exit
near the base of the ventricle. In idiopathic right ventricular outflow tract tachycardia (see RVOT ventricular
tachycardia, below), the QRS duration during ventricular
tachycardia is usually greater than 140 ms if it originates
from the free-wall of the RVOT, and less than 140 ms if
the arrhythmia originates from the septal site of the
RVOT. Furthermore, if the QS amplitude in aVR is greater
than in aVL, the initial activation occurs more posterolateral, whereas if the QS amplitude in aVL is greater than
in aVR, the origin is more anterior in the RVOT. The
precordial R-wave transition in RVOT-ventricular tachycardia usually occurs in leads V2–V4 and becomes earlier
as the site of origin advances more superiorly along the
septum. An R-wave transition in lead V2 suggests a site of
origin immediately inferior to the pulmonic valve or the
left-ventricular outflow tract [8].
Electrophysiological mechanisms of
ventricular tachycardia
Re-entrant ventricular arrhythmias
Monomorphic ventricular tachycardia is the most common form of sustained ventricular tachycardia and usually
occurs after myocardial infarction. A re-entry mechanism
accounts for the majority of these ventricular tachycardias.
In contrast with automatic arrhythmias, the conditions
for re-entry tend to be associated with chronic rather
than acute disease. Endocardial catheter mapping and
intraoperative mapping have shown that these arrhythmias originate within or at the border zone of the
diseased myocardium. The size of the re-entrant circuit
may be large, especially in patients with a left-ventricular
951
TETC32 12/2/05 14:26 Page 952
952
Chapter 32
A
500 ms
B
C
200 ms
100 m/s
I
1000 ms
25 m/s
RF
I
II
III
III
aVR
V1
*
aVL
aVF
V6
Diastolic potential
V1
V2
ABL
V3
V4
V5
V6
RVA
Figure 32.3 ECG recording in a patient with previous anterior myocardial infarction and recurrent sustained ventricular tachycardia.
(A) Catheter mapping and subsequent catheter ablation were performed. (B) Leads I, III, V1 and V6, as well as intracardiac signals
from the right ventricular apex (RVA) and the ablation catheter at the successful ablation site (ABL) anteroseptal at the leftventricular base are displayed. Note: the fragmented diastolic potential at the successful ablation site (for further details, see text),
where the ventricular tachycardia terminated a few seconds after starting radiofrequency (RF) ablation (C).
aneurysm, or may be confined to a small area. Re-entry
requires a series of conditions to be satisfied for its occurrence: (1) two potentially conducting pathways or more;
(2) unidirectional block must occur in one pathway;
(3) an activation wavefront that travels around that zone
of unidirectional block over the alternative pathway;
(4) then activation of myocardium distal to the zone of
unidirectional block with delay (i.e. with slow conduction), so allowing (5) the activation wavefront to invade
the zone of block retrogradely and re-excite the tissue
where the activation wavefront originated. For re-entry
to occur, the impulse that is conducting around the
re-entrant circuit must always find excitable tissue in the
direction in which it is propagating. This constellation
frequently occurs in the context of myocardial scarring.
An understanding of these electrophysiological phenomena is critical to the diagnosis and successful ablation of re-entrant ventricular arrhythmias. Initiation and
termination of ventricular tachycardia by pacing stimuli,
the demonstration of electrical activity bridging diastole
and a variety of other clinically used techniques are
consistent with a re-entry mechanism. Entrainment by
pacing is considered the most reliable clinical method
to demonstrate the presence of a re-entry mechanism.
The areas of slow conduction have been shown to be
desirable targets of ablation. Zones of slowly conducting myocardium may be identified during endocardial
catheter mapping by fractionated and/or mid-diastolic
electrograms (Fig. 32.3), continuous electrical activity
or a long delay between a stimulus artefact and the resulting QRS complex. However, not all areas of slow conduction participate in the re-entry circuit, i.e. ‘dead end’ or
‘bystander’ pathways may exist. Therefore, for successful
ablation, localization procedures have to provide evidence that a mapping site is actually within the re-entry
circuit and is critically linked to the perpetuation of
the arrhythmia. Ischaemia seems to be less frequently
involved in the initiation of monomorphic ventricular
TETC32 12/2/05 14:26 Page 953
Ventricular Tachycardia
A
C
T
T
T
T
T
3 P 3 P 3 P 3 P 3 P
4
4
4
4
4
0
0
0
0
0
6
2
0
V
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
T
S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 S 4 D3 P 3 P3 P 3 P 3 P 3 P
0
2
0
1
0
1
0
1
0
1
1
1
3
3
3
3
3
3
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
VT
VT Rx 1/Seq 2
1500
V
S
1160
VT
VT Rx 1/Seq 2
B
I
II
III
aVR
aVL
aVF
V1
V2
V3
350
V4
V5
V6
Figure 32.4 (A) Episode of ventricular tachycardia (cycle length ∼ 400 ms) detected and terminated by an implantable cardioverterdefibrillator in a patient with a remote inferior myocardial infarction who experienced recurrent VT episodes. (B) Twelve-lead ECG
of the VT in the same patient. (C) Posterior view of an electroanatomic voltage map (Carto) of the left ventricle. Electroanatomic
mapping can be used to define isthmus boundaries and thus guide successful ablation. Colour range represents voltage amplitude.
Grey denotes dense scar tissue. A linear ablation lesion was placed from the mitral annulus to the edge of the scar tissue to prohibit
mitral ‘isthmus’ re-entrant tachycardias (around the mitral valve and/or around the posterior scar).
tachycardia. If a VT is not inducible or haemodynamically not tolerated during an ablation procedure, electroanatomical mapping systems can be used to locate critical
isthmus regions, such as the mitral isthmus (Fig. 32.4)
and to guide successful ablation. Occasionally, ischaemia
has been found to precede the onset of a monomorphic
ventricular tachycardia. More commonly, however, acute
ischaemia triggers the occurrence of polymorphic ventricular tachycardia, which may degenerate to ventricular
fibrillation rather than a sustained monomorphic ventricular tachycardia.
The underlying mechanisms of ventricular tachycardia in dilated cardiomyopathy are less well understood
than they are in coronary artery disease. As heart failure
is not a specific disease but a syndrome, there are no
specific anatomical or pathological changes in failing
hearts. The occurrence of ventricular tachycardia in
heart failure is a result of a complex interplay between a
pathological substrate and numerous environmental
triggers and facilitators evoked by left-ventricular dys-
function and medical therapy. The non-specific cardiac
changes include diffuse interstitial fibrosis, myofibrillar
degeneration and myocyte hypertrophy. All known nonspecific alterations result in disparity of electrophysiological properties within the myocardium, which provide
an appropriate abnormal substrate for arrhythmogenesis.
Also, a tachyarrhythmia itself may cause reversible heart
failure, including myocardial changes such as dilatation
and hypertrophy. Incessant or intermittent tachyarrhythmias present for months to years are known to cause
reversible cardiomyopathy in experimental heart failure
models as well as in patients (‘tachycardiomyopathy’).
Noteworthy in the presence of heart failure due to
idiopathic dilated cardiomyopathy, re-entry in the
His–Purkinje system (bundle branch re-entry, Fig. 32.5)
accounts for a substantial number of monomorphic
ventricular tachycardias. The re-entry wavefront proceeds down one bundle branch (mostly the right bundle
branch), and up the contralateral bundle. This creates
a QRS complex that has a LBBB contour and a normal
953
TETC32 12/2/05 14:26 Page 954
954
Chapter 32
500 ms
A
B
200 ms
I
I
II
II
III
V1
V6
aVR
aVL
RA
aVF
V1
RBB proximal
V2
V3
RBB distal
V4
V5
RVA
V6
Figure 32.5 ECG recording in a patient with dilated cardiomyopathy and recurrent sustained ventricular tachycardia. (A) A sustained
bundle branch re-entry tachycardia with a LBBB morphology is displayed. Intracardiac signals (B) reveal ventriculo-atrial dissociation
(RA, right atrial catheter; RVA, right ventricular apex) and activation of the right bundle branch (RBB) from proximal (RBB prox) to
distal (RBB dis). The tachycardia was successfully ablated at the distal right bundle branch using radiofrequency current.
or leftward frontal plane axis. Its significance lies in the
fact that it can be easily cured by catheter ablation of
the right bundle branch.
Automatic ventricular arrhythmias
Abnormal automaticity accounts for a minority of ventricular tachycardias. Automatic ventricular tachycardia
tends to be associated with conditions such as acute
myocardial infarction, hypoxaemia, electrolyte abnormalities and a high adrenergic tone. Automatic ventricular tachycardias that occur during the first 24–48 h
after an acute myocardial infarction are a major cause of
sudden cardiac death. They are probably related to the
residual ischaemia seen acutely in the zone of infarction. Once the infarction heals, the substrate for these
arrhythmias disappears (but the one for re-entry evolves).
Because automatic arrhythmias generally occur secondarily to metabolic abnormalities, treatment should be
aimed at identifying and reversing the underlying cause
whenever possible.
Triggered activity
Although ventricular tachycardias based on triggered
activity are uncommon, two distinct clinical syndromes
involving triggered activity have been identified: pauseand catecholamine-dependent arrhythmias. In each
syndrome, patients develop polymorphic ventricular
tachycardia. These arrhythmias tend to occur in relatively short bursts that may be accompanied by lightheadedness or syncope, but may also degenerate into
ventricular fibrillation and cause sudden death.
Pause-dependent triggered activity is caused by afterdepolarizations that occur during phase 3 of the action
potential (early afterdepolarizations). If these afterdepolarizations reach the threshold potential of the cardiac
cell, another action potential can be generated. Pausedependent triggered activity may be related to congenital ion-channel abnormalities (long QT syndrome, see
p. 961) and/or to specific conditions (hypokalaemia and
hypomagnesaemia), and/or the use of non-cardiovascular
or cardiovascular drugs (e.g. class IA or class III antiarrhythmic agents, i.e. acquired QT syndrome) that prolong repolarization. Individuals who develop ventricular
arrhythmias (i.e. torsade de pointes) [9] in the presence
of these conditions have a reduced repolarization reserve.
Torsades de pointes (Fig. 32.6) is a rapid, irregular nonsustained polymorphic ventricular tachycardia that
appears to twist around the isoelectric line and may
TETC32 12/2/05 14:26 Page 955
Ventricular Tachycardia
10 mm/mV
25 mm/s
Filter 25 Hz
I
II
III
aVR
aVL
aVF
V1
V2
V3
V4
V5
V6
Figure 32.6 Recurrent episodes of torsade de pointes in a patient with long QT syndrome.
degenerate into ventricular fibrillation. The ECG, while
in sinus rhythm, usually shows prolongation of the QT
interval (see long QT syndrome, p. 961). In addition,
distortion of the T wave and often distinct U waves
may occur. The longer the previous cycle length, the
more exaggerated the TU wave aberration of the following complex, hence the condition is ‘pause-dependent’.
The treatment of pause-dependent triggered activity is
aimed at reducing the prolonged repolarization. Drugs
that prolong the QT interval should be discontinued and
avoided. Electrolyte abnormalities should be rapidly
corrected. Intravenous magnesium sulphate ameliorates
these arrhythmias. In addition, pauses can be eliminated
by either atrial or ventricular pacing, or by beginning an
isoproterenol infusion.
Catecholamine-dependent triggered activity is caused
by afterdepolarizations that occur during phase 4 of the
cardiac action potential (delayed afterdepolarizations).
They occur in the setting of congenital ion-channel
abnormalities, digitalis toxicity or cardiac ischaemia.
Catecholamine-dependent triggered activity generally is
not dependent on pauses. Instead, these arrhythmias
may arise in conditions of high sympathetic tone. Thus,
patients experience ventricular tachycardia (manifested
by syncope or cardiac arrest) during times of exercise or
of emotional stress.
Ventricular tachycardia clinical presentation
The clinical presentation of ventricular tachycardia
depends on the haemodynamic consequences it produces. These depend partly on ventricular tachycardia
rate, the degree of myocardial dysfunction, the circumstances and suddenness of initiation, and autonomic
factors. Physical examination in a patient presenting with
ventricular tachycardia often indicates haemodynamic
distress (low blood pressure, heart failure or cardiogenic
shock). When cardiac output and blood pressure are
955
TETC32 12/2/05 14:26 Page 956
956
Chapter 32
maintained and/or when the ventricular tachycardias are
short-lived, the arrhythmia may present as palpitations,
breathlessness or chest pain. Sometimes, especially in
patients without structural heart disease, no symptoms
are reported during ventricular tachycardia.
The rate of ventricular tachycardia is a major factor
in determining clinical symptoms. Among 1130 patients
with ventricular tachycardia, the average ventricular tachycardia rate was 163 b.p.m. in asymptomatic patients, 170
b.p.m. in patients who had lightheadedness, 191 b.p.m.
in patients presenting with presyncope and 224 b.p.m. in
those with syncope [10]. Persistent, slow (< 150 b.p.m.)
ventricular tachycardia may lead to dyspnoea, pulmonary
congestion and oedema. Patients with heart failure were
more likely to present with syncope regardless of ventricular tachycardia rate. Rapid and/or persistent ventricular
tachycardia, impaired left-ventricular function and atrioventricular dissociation contribute to haemodynamic
collapse, which may result in presyncope, syncope or
sudden death.
Syncope is the single most important clinical event
for grading sudden cardiac death risk in heart failure [11].
Ventricular tachycardia was found to be the cause of
syncope in 35% of these patients [12]. Patients with heart
failure and unexplained syncope have a 1-year sudden
death rate of up to 45% [12]. The frequency and complexity of ventricular tachycardia parallel the severity of
ventricular dysfunction. In total, 15–20% of patients with
NYHA class I–II heart failure have non-sustained ventricular tachycardia compared with 50–70% of patients with
class IV heart failure. Sustained polymorphic ventricular
tachycardia is less stable than monomorphic ventricular
tachycardia. It is usually rapid and often degenerates into
ventricular fibrillation. Sustained monomorphic ventricular
tachycardia may be haemodynamically tolerated, but may
also precipitate ventricular fibrillation or may cause syncope before terminating spontaneously. Patients presenting with haemodynamically tolerated ventricular tachycardia have a lower risk of sudden cardiac death than
patients whose initial episode causes cardiac arrest, but
the risk is still substantial.
Therapy of ventricular tachycardias in
patients with structural heart disease
The spectrum of therapies for ventricular tachycardias
includes drug therapy, device implantation and surgical
or catheter ablation interventional techniques. The management challenge is to deal with both the ventricular
tachycardia that is the presenting symptom and the
pervading sudden cardiac death risk that may be the
consequence of the arrhythmogenic substrate.
Device and drug therapy of ventricular
tachyarrhythmias in patients with structural
heart disease
When ventricular tachycardia is the consequence of
structural cardiac disease, persistence or evolution of an
arrhythmogenic substrate, even after successful treatment of a presenting ventricular tachycardia, militates
against any curative therapy. For a long time, therapy of
ventricular tachycardia was dominated by drug therapy
or anti-tachycardic surgery. However, nowadays the
implantable cardioverter-defibrillator (ICD) is the best
available therapy to prevent sudden cardiac death from
ventricular tachycardia. In clinical use since 1980, the
ICD is a self-contained device that is capable of identifying ventricular tachycardia and ventricular fibrillation
and automatically terminating these arrhythmias by
anti-tachycardic pacing or delivering a shock, usually
about 35 J, directly to the heart.
Ischaemic heart disease and idiopathic dilated
cardiomyopathy
Implantable cardioverter-defibrillator trials for
secondary prevention of sudden cardiac death
The antiarrhythmics vs. implantable defibrillator (AVID)
trial [13] was the first large-scale randomized study that
compared ICD therapy with antiarrhythmic drug treatment in patients with documented symptomatic ventricular tachycardia (55%) or ventricular fibrillation (45%).
Patients with ventricular tachycardia also had either
syncope or other serious cardiac symptoms, along with
a left-ventricular ejection fraction of < 40%; 81% of
these patients had coronary artery disease. In total, 1016
patients with documented ventricular tachycardia were
randomized to ICD or antiarrhythmic drug therapy,
almost exclusively with amiodarone. Mortality in the
group treated with antiarrhythmic drugs was 17.7%,
25.3% and 35.9% after 1, 2 and 3 years respectively. The
total death rate was significantly reduced by 39% in the
TETC32 12/2/05 14:26 Page 957
Reduction with ICD therapy (%)
Ventricular Tachycardia
All cases mortality
Arrhythmic death
80
70
60
50
40
30
20
10
0
AVID
CASH
CIDS
Figure 32.7 Relative risk reduction of total death rate by ICD
implantation in secondary prevention trials (for details, see text).
ICD group after 1 year and by 27% and 31% after 2 and
3 years respectively. The results of AVID were consistent
among all prespecified subgroups: coronary artery disease
vs. other diseases, ventricular fibrillation vs. ventricular
tachycardia, all age groups, and all ejection fractions.
There was a small trend towards less benefit in patients
with an ejection fraction above 35%.
The Canadian Implantable Defibrillator Study (CIDS)
[14] and the Cardiac Arrest Study Hamburg (CASH) [15]
recruited similar patient cohorts as AVID (Fig. 32.7).
CIDS [14] randomized 659 patients with symptomatic
ventricular tachycardia, aborted sudden death or syncope in the presence of inducible ventricular tachycardia
to ICD treatment or empirical amiodarone. Two-year
mortality in the drug arm was about 22%. There was a
reduction of total death rate by ICD implantation (risk
reduction 19.6% at 3 years) but this did not reach statistical significance.
In CASH [15] a total of 346 patients with a history of
cardiac arrest were randomized to ICD or treatment with
metoprolol, amiodarone or propafenone. After inclusion
of 230 patients that were randomly assigned to propafenone, amiodarone, metoprolol or the implantable
defibrillator, the propafenone arm was stopped because
of excess mortality compared with the ICD group [15].
This study demonstrated a 37% survival benefit of
patients receiving ICDs in comparison with metoprolol
or amiodarone at 2 years. Two-year mortality in these
arms was 19.6%. Noteworthy, the ejection fraction of the
patients in CASH (0.46) was much higher than in AVID
(0.32) or CIDS (0.34). In CASH primary ventricular fibrillation patients were also included.
Data from AVID, CIDS and CASH (only amiodarone
and ICD arms) were merged into a meta-analysis [16].
This analysis showed a significant reduction in death
from any cause, with the ICD having a mean hazard ratio
of 0.72. This 28% reduction in the relative risk of death
with the ICD was largely the result of the reduction in
arrhythmic death. Survival was extended by a mean of
4.4 months by the ICD over a follow-up period of 6 years.
Patients with left-ventricular ejection fraction of ≤ 35%
had a significantly higher benefit from ICD therapy than
those with a better-preserved left-ventricular function.
This was also found in a post hoc analysis of CIDS [17].
This analysis showed that three clinical risk factors were
predictors of death and benefited from the ICD: age ≥ 70
years, left-ventricular ejection fraction ≤ 35% and New
York Heart Association class III or IV.
In contrast with patients with coronary artery disease,
risk stratification in patients with idiopathic dilated cardiomyopathy is much more difficult. These patients are
under-represented in all ICD studies. In AVID, CASH and
CIDS only 15%, 11% and 10%, respectively, of all patients
had idiopathic dilated cardiomyopathy. All of these
studies showed a reduction of total mortality in patients
with non-ischaemic dilated cardiomyopathy of 20–40%
compared with conventional therapy [13–15]. However,
the confidence intervals for patients with non-ischaemic
dilated cardiomyopathy was much wider than for patients with coronary artery disease. In the meta-analysis of
these three studies, only 225 out of 1832 patients had
non-ischaemic cardiomyopathy [16]. These patients had
a hazard ratio for reduction of total mortality of 0.78,
which was very similar to the total cohort (0.72). However, the 95% confidence intervals for these patients
ranged from 0.45 to 1.37. The significance of syncope in
dilated cardiomyopathy without documented ventricular tachycardia is still unclear. A non-randomized study
showed similar event rates of appropriate ICD discharges
in patients who received an ICD because of syncope,
and patients who received a defibrillator after aborted
sudden death or episodes of ventricular tachycardia or
ventricular fibrillation [18]. Another study showed significantly lower event rates in a series of consecutive
patients treated with an ICD than in conventionally
treated patients [19]. Hence, it seems reasonable to treat
patients with non-ischaemic dilated cardiomyopathy and
syncope similar to those after aborted sudden cardiac
death if other causes of syncope are excluded.
Implantable cardioverter-defibrillator trials for
primary prevention of sudden cardiac death
(Fig. 32.8)
The Multicenter Automatic Defibrillator Implantation
Trial (MADIT) [20] was the first study that showed a
benefit of implanting an ICD in patients with coronary
heart disease and left-ventricular dysfunction, whereas
the CABG-Patch trial [21] (ICD therapy vs. no specific
antiarrhythmic therapy—the other studies compared
957
TETC32 12/2/05 14:26 Page 958
Chapter 32
Reduction with ICD therapy (%)
958
All cases mortality
Arrhythmic death
80
70
60
50
40
30
20
10
0
MADIT 1
MUSTT
MADIT 2
SCD-HEFT
Figure 32.8 Relative risk reduction of total death rate by I
CD implantation in primary prevention trials (for details,
see text).
the ICD with antiarrhythmic drugs—for the primary
prophylaxis of sudden cardiac death) in patients with
impaired left-ventricular function scheduled for elective
bypass surgery demonstrated no benefit. MADIT [22]
enrolled patients after myocardial infarction (in 75% of
the patients, the interval between infarction and enrolment was more than 6 months) with an ejection fraction
below 0.36, non-sustained ventricular tachycardia and
inducible ventricular tachycardia (not suppressible by a
class I drug). During an average follow-up of 27 months,
the risk of death was reduced by 54% in the ICD arm.
MADIT II [23] was designed to investigate whether
the ICD would be effective in the prevention of all-cause
death in patients after myocardial infarction, with a low
ejection fraction (≤ 30%) as the only inclusion criterion.
A randomization ratio of 3:2 to receive an ICD or conventional therapy was selected. After inclusion of 1232
patients, the trial was terminated because of a significant
(31%) reduction in all-cause death in patients assigned to
ICD therapy.
In a post hoc analysis, Moss and colleagues [22] found
that patients with an ejection fraction of less than 26%
had a far greater benefit from ICD implantation than
patients with an ejection fraction of between 26% and
35% [24]. Later they identified three independent risk
factors: ejection fraction < 26%, QRS duration ≥ 120 ms
and a history of heart failure treatment [25]. The benefit from ICD treatment increased with the number of
risk predictors. Thus, in patients with chronic coronary
heart disease, the magnitude of the survival benefit
from the ICD is directly related to the severity of cardiac
dysfunction and its associated mortality risk. The same
was found in a post hoc analysis of the Multicenter Unsustained Tachycardia Trial (MUSTT) [26]. The combination of an ejection fraction of ≤ 30% and an abnormal
signal-averaged ECG identified a subgroup of particularly
high risk, constituting 21% of the total study population.
In contrast with MADIT and MADIT II, where 85% of
the patients were included > 6 months post myocardial
infarction, the yet unpublished DINAMIT study, which
included patients within the first 40 days after a myocardial infarction, failed to demonstrate a benefit from
prophylactic ICD implantation, despite the fact that
most patients had a large anterior infarction and leftventricular ejection fraction was low (average 28%) (for
comment, see ref. no. 27).
Very recently, the first results of SCD-Heft trial have
been presented. This trial determined if amiodarone or an
ICD reduces all-cause mortality compared with placebo
in patients with either ischaemic or non-ischaemic NYHA
class II and III heart failure and an ejection fraction of
< 35%. The ICD decreased mortality by 23%, whereas
amiodarone, when used as a primary preventative agent,
did not improve survival. Two other prospective studies
in patients with non-ischaemic cardiomyopathy without
prior arrhythmias and one in patients with asymptomatic non-sustained ventricular tachycardia have been
reported.
The Cardiomyopathy Trial (CAT) [28] was a pilot
study in patients with a recently diagnosed (< 9 months)
non-ischaemic dilated cardiomyopathy (EF < 30%) that
included 102 patients. Patients were randomized to ICD
therapy or no antiarrhythmic drug therapy. The primary
end-point was total mortality after 2 years. In contrast
with the investigators’ expectations, the total mortality
after 2 years was only 8–9% in both groups. The study
was terminated, as more than 1300 patients would
have been needed to demonstrate a significant difference
between the two groups. In the first 2 years after inclusion into the study, there was not a single case of sudden
death in the control group. In the ICD group, there were
11 patients with a ventricular tachycardia faster than
200 b.p.m. All ventricular tachycardias were terminated
by the ICD. Nevertheless, after 5 years only 50% of those
patients with appropriate ICD discharges survived, in
contrast with 85% of the patients without appropriate
ICD discharges. This finding is in analogy to the finding
of an association between appropriate ICD discharges
and death from progressive heart failure [29].
The findings of the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) [30,31]
trial are in contrast with the results of the CAT trial. DEFINITE was the first large-scale trial investigating the use
of ICD for the primary prevention of sudden cardiac death
in patients with non-ischaemic dilated cardiomyopathy.
It enrolled a total of 458 patients with non-ischaemic
dilated cardiomyopathy, left-ventricular dysfunction (ejection fraction < 35%), NYHA class I–III heart failure and
spontaneous ventricular tachycardia (premature ventricular complexes or non-sustained ventricular tachycardia).
TETC32 12/2/05 14:26 Page 959
Ventricular Tachycardia
Patients with unexplained syncope within 6 months,
prior cardiac arrest or ventricular tachycardia of > 15
beats at a rate of > 120 b.p.m. or those on amiodarone
treatment for ventricular tachycardia were excluded from
the study. Patients were randomized to drug therapy
with beta-blockers and ACE inhibitors (if tolerated)
or drug therapy plus an ICD. The study’s primary endpoint was total mortality; the secondary end-point was
arrhythmic death. During a mean follow-up of 26 months,
total mortality observed in the ICD group was 8.1%, a
result that did not reach statistical significance when
compared with control subjects (although there was a
clear trend toward a benefit). The absolute mortality
benefit in the ICD group was 5.7% at 2 years and the
relative risk reduction was 34%. ICDs were associated
with a significantly lower rate of arrhythmic death, the
study’s secondary end-point. Use of an ICD was associated with a 74% relative reduction in arrhythmic death
(P = 0.01). Subgroup analyses uncovered that patients
with class III heart failure who received an ICD had a 67%
relative risk reduction in all-cause mortality compared
with those who received drug therapy alone (P = 0.009).
As ICD therapy has been shown to be beneficial in
patients with impaired left-ventricular function and nonsustained ventricular tachycardia in the MADIT and the
MUSTT trials [22,26], the hypothesis that ICD therapy
would be superior to antiarrhythmic drug therapy also
in patients with non-ischaemic dilated cardiomyopathy
and non-sustained ventricular tachycardia was tested in
the AMIOVIRT study [32]. Patients (n = 103) with nonischaemic dilated cardiomyopathy, left-ventricular ejection fraction of < 35% and asymptomatic non-sustained
ventricular tachycardia were randomized to receive
either amiodarone or an ICD. The primary end-point was
total mortality. The study was stopped because of the
unexpectedly low total mortality in both arms. The percent of patients surviving at 1 year (90% vs. 96%) and
three years (88% vs. 87%) in the amiodarone and ICD
groups, respectively, was not different. As there was no
true placebo group in this study, it cannot be clarified
whether non-sustained ventricular tachycardia is useful
as a risk predictor in non-ischaemic dilated cardiomyopathy or whether amiodarone is highly efficient in this
patient cohort. The latter had already been suggested
retrospectively by the CHF-STAT trial, when amiodarone
proved more effective in non-ischaemic vs. ischaemic
patients [33]. However, in a prospective registry including 343 patients with idiopathic dilated cardiomyopathy,
only reduced left-ventricular EF and lack of beta-blocker
therapy were predictors of an increased arrhythmic risk
[34]. Signal-averaged ECG, QTc dispersion, heart rate
variability, baroreflex sensitivity and microvolt T-wave
alternans did not predict arrhythmia risk, and non-
sustained ventricular tachycardia on Holter was associated only with a trend towards higher arrhythmia
risk. In contrast with these findings, patients with nonsustained ventricular tachycardia in the CAT trial had
a markedly increased total mortality rate with only
63% surviving after 6 years compared with 77% of the
patients without non-sustained ventricular tachycardia.
However, in CAT, even in this subgroup, there was no
benefit from ICD implantation. In patients with nonischaemic dilated cardiomyopathy, non-sustained ventricular tachycardia seems to be more a marker for
increased total mortality than for a high arrhythmic risk.
Catheter ablation or surgical treatment of
ventricular tachyarrhythmias
Catheter ablation might be an adjunctive but rarely
curative option for a highly select group of patients with
refractory or incessant ventricular tachycardia (i.e. patients
with multiple ICD discharges due to ventricular tachycardia—Fig. 32.3). Catheter ablation has been successfully applied in ventricular tachycardia that is caused
by ischaemic heart disease. Results with computerized
mapping systems and mapping techniques using noncontact mapping systems that do not require sustained
ventricular tachycardia during the ablation procedure
have demonstrated promising results in ventricular tachycardia ablation. Surgical techniques for treatment of
ventricular tachycardia may be effective in ICD carriers
with sustained monomorphic ventricular tachycardia
resulting from coronary artery disease, especially when a
discrete left-ventricular aneurysm and inducible monomorphic ventricular tachycardia are present [35]. In
selected patients, anti-tachycardia operations can be carried out with an acceptable mortality and a relatively
high long-term survival rate. However, these procedures
cannot be expected to alter the natural history of the
underlying heart disease. Bundle branch re-entry ventricular tachycardia, which may be relatively commoner in
idiopathic dilated cardiomyopathy, is particularly amenable to catheter ablation (see above).
Other cardiomyopathic conditions
Arrhythmogenic right ventricular
cardiomyopathy
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) was first described in 1982 [36] and since
959
TETC32 12/2/05 14:26 Page 960
960
Chapter 32
then has been diagnosed with increased frequency. ARVC
is a primary myocardial disorder with a genetic background. In recent years, the disease has been recognized
as a major cause of ventricular arrhythmias and sudden death, particular in young patients and athletes
with apparently normal hearts. ARVC is characterized
by localized or diffuse atrophy of predominantly rightventricular myocardium, with subsequent replacement
with fatty and fibrous tissue, and usually manifests with
ventricular tachycardia and/or sudden death, frequently
before structural abnormalities become apparent [36–
38]. Diagnostic criteria of ARVC were proposed by an
international study group [39] and include major and
minor criteria in different categories. Eight chromosomal
loci for autosomal dominant forms of ARVC and two loci
for autosomal recessive inheritance (one of which is
Naxos disease) have been reported. In Naxos disease, a
syndromic variant of ARVC with palmoplantar keratosis
and woolly hair, a mutation in the gene encoding the
cytoskeletal protein plakoglobin was identified. Several
years later, a mutation in the desmoplakin gene, another
protein involved in cell-to-cell junctions (adherens junctions and desmosomes), was identified in a classical form
of ARVC (ARVC-8), with frequent left-ventricular involvement. In a rare and rather atypical subgroup of ARVC
(ARVC-2) with minor right ventricular abnormalities
and polymorphic ventricular arrhythmias, a mutation in
the gene encoding the cardiac ryanodine receptor (RyR2)
was identified.
In ARVC, episodes of ventricular tachycardia are
frequently well tolerated, mainly due to the preserved
left-ventricular function. Antiarrhythmic treatment of
ARVC includes drug therapy, catheter ablation and ICD
implantation. The available but limited data on risk stratification indicate that patients with severe right ventricular dysfunction, left-ventricular involvement, a history
of syncope or cardiac arrest, family history of sudden
cardiac death, inducible ventricular tachycardia/ventricular fibrillation and ECG abnormalities (epsilon potential,
late potential) are more prone to life-threatening ventricular tachycardia and sudden death. In patients with
ARVC and low risk of sudden death, antiarrhythmic
drug therapy is an alternative option. Low-risk cohorts
include patients with localized right-ventricular disease
and monomorphic ventricular tachycardia suppressed
by antiarrhythmic drugs.
Despite high efficacy rates of radiofrequency catheter
ablation in abolishing regional sites of ventricular
tachycardia, there is a high recurrence rate due to new
ventricular tachycardia morphologies and origins.
Main indications for catheter ablation in ARVC include
monomorphic ventricular tachycardia in localized rightventricular abnormalities and incessant or frequent ven-
tricular tachycardia not suppressed by antiarrhythmic
treatment. Recent studies [40,41] in high-risk patients
with ARVC after resuscitated cardiac arrest, life-threatening ventricular tachycardia or drug-refractory ventricular tachycardia demonstrated the high efficacy of ICD
implantation in the prevention of sudden death. The
estimated survival benefit of ICD therapy was 21%, 32%
and 36% after 1, 3 and 5 years, respectively, of follow-up.
The role of ICD therapy for primary prevention of sudden
death in ARVC remains unclear to date because only
very preliminary data are available. Patients with welltolerated and non-life-threatening ventricular tachycardia are usually treated empirically with antiarrhythmic
drugs, including amiodarone, sotalol, beta-blockers,
flecainide and propafenone, alone or in combination.
ICDs are usually reserved for patients with life-threatening ventricular tachycardia, in whom drug therapy is
either ineffective or undesirable. Wichter and colleagues
[41] found that, in a series of 60 patients in a single
centre during a mean follow-up of 80 ± 43 months,
event-free rate after 5 years was only 26% for ventricular
tachycardias and 59% for potentially fatal ventricular
tachycardias with a rate > 240 b.p.m. Extensive rightventricular dysfunction was identified as a predictor for
appropriate ICD discharges.
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is an inherited
myocardial disorder with an autosomal dominant trait
and is caused by mutations in one of 10 genes known so
far, each encoding for protein components of the cardiac
sarcomer. There is broad heterogeneity not only concerning disease-causing genetic mutations, but also in
terms of phenotypic expression, treatment and prognosis.
Patients with hypertrophic cardiomyopathy often present
with ventricular ectopy or non-sustained ventricular tachycardias that are associated with a high risk of sudden
cardiac death. Symptoms of HCM range from dyspnoea
and angina pectoris to palpitations, dizziness and syncope
[42]. Treatment of symptomatic HCM patients includes
drugs (verapamil, beta-blockers or disopyramide) or nonpharmacological options (septal myectomy, DDD pacing,
alcohol septal ablation) in those with obstructive HCM
[43]. These treatment options are targeted to reduce
symptoms and improve quality of life, but have not been
shown to have an impact on survival.
Sudden cardiac death may occur without warning
signs or symptoms, as the initial disease manifestation,
and may be triggered by vigorous exercise or competitive
sports activity. The highest risk for sudden cardiac death
has been associated with prior cardiac arrest or spontaneous sustained ventricular tachycardia/ventricular
TETC32 12/2/05 14:26 Page 961
Ventricular Tachycardia
fibrillation. In such patients, the implantation of an
ICD is strongly recommended for secondary prevention
of sudden death. In a multicentre retrospective study in
high-risk HCM patients, appropriate ICD interventions
occurred in 25% of patients after a follow-up period of
only 3 years. Potentially life-saving ICD therapies were
reported at a rate of 11% per year in patients receiving
the ICD for secondary prevention (aborted sudden death
or sustained ventricular tachycardia/ventricular fibrillation), compared with a rate of 5% per year in the primary
prevention cohort (based solely on non-invasive risk
factors) [44].
In the setting of primary prevention, major risk factors
for sudden death in HCM include a high-risk mutant
gene, a family history of premature sudden death, unexplained syncope, abnormal exercise blood pressure,
non-sustained ventricular tachycardia (Holter), and severe
left-ventricular hypertrophy (≥ 30 mm). In individual
patients, atrial fibrillation, myocardial ischaemia, leftventricular outflow-tract obstruction and vigorous physical exertion or competitive sports may be additional
risk factors [45,46]. ICD implantation is considered the
most effective and reliable treatment option and has
been recommended in HCM patients at high risk of sudden death [44–46]. HCM patients without risk factors are
at low risk of sudden death and should be reassured and
followed clinically. Little or no restriction is necessary
with regard to employment and recreational activities
but patients should be excluded from strenuous exercise
and competitive sports.
Table 32.1 Ventricular tachycardias in patients with
primary electrical disease and inherited myocardial diseases
‘Primary electrical disorders’, in which an organic heart disease is
not detectable
Long QT syndrome (LQTS)
Short QT syndrome (SQTS)
Catecholaminergic polymorphic ventricular tachycardia
(CPVT)
Idiopathic right-ventricular outflow tract tachycardia
(RVOT-VT)
Idiopathic left-ventricular tachycardias (ILVT)
Idiopathic ventricular fibrillation (IVF)
Brugada syndrome
‘Arrhythmogenic cardiomyopathies’, in which an inherited
myocardial disease may primarily manifest with ventricular
tachyarrhythmias
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Hypertrophic cardiomyopathy (HCM)
Dilated cardiomyopathy (DCM)
precipitating factors (e.g. exercise), site of origin (i.e. left
or right ventricle), by response to antiarrhythmic drugs
(e.g. adenosine or verapamil) or on the basis of an underlying organic heart disease (primary electrical disorder
vs. inherited myocardial disease—Table 32.1).
Ventricular tachycardia in patients without
structural heart disease but not currently
amenable to curative therapies
Ventricular tachycardia in patients without
structural heart disease: ‘idiopathic’
ventricular tachycardia
‘Idiopathic ventricular tachycardia’ is a non-specific term
that represents a heterogeneous group of arrhythmias.
Awareness of this entity has existed since it was first
described by Gallavardin [47] in 1922. Patients can be
completely asymptomatic or have transient symptoms
including palpitations, dizziness or presyncope, but these
arrhythmias, with the exception of rapid polymorphic
ventricular tachycardia or idiopathic ventricular fibrillation occurring in the setting of inherited arrhythmic
syndromes, are rarely life threatening. The underlying
mechanisms include re-entry, triggered activity and
catecholamine-mediated automaticity. Idiopathic ventricular tachycardia can be categorized according to
the clinical presentation (non-sustained vs. sustained),
Long QT syndrome (LQTS) is characterized by a prolonged QT interval in the surface ECG, recurrent syncope
or sudden death resulting from torsade de pointes
(Fig. 32.6) [48–51]. The incidence of LQTS has been estimated as 1 in 7000 to 1 in 10 000 live births. More than
250 mutations in seven genes (LQTS 1–7) have been
described. Mutations involve genes encoding potassium
channels [LQT1, 2, 5 and 6, Jervell Lange–Nielsen ( JLN) 1
and 2], sodium channels (LQT3) and ankyrin B (LQT4),
which acts as a targeting and anchoring molecule for the
sodium channel. In 30–40% of all patients with LQTS, no
gene defect can be found, pointing towards a large heterogeneity of gene loci. The term acquired LQTS [52,53]
is reserved for a syndrome similar to the congenital
form but caused by exposure to drugs that prolong the
duration of the ventricular action potential or to QT
prolongation secondary to bradycardia or an electrolyte
961
TETC32 12/2/05 14:26 Page 962
962
Chapter 32
imbalance. Drugs that prolong the QT interval, and
thereby predispose to torsade de pointes, are listed on
websites such as www.qtdrugs.org.
Associations between genotype and phenotype have
been investigated based on the International LQTS
Registry, which was started in 1979. Moss and colleagues
[54] identified a gene-specific phenotype in the repolarization pattern of the surface ECG. Patients with LQT1
show a broad and prolonged T wave, whereas LQT2
patients have a notched, low-amplitude T wave. Patients
of the LQT3 demonstrate a long isoelectric ST segment
with a delayed, peaked narrow T wave. In LQT3, cardiac
events occur more frequently at rest or during sleep,
whereas they are typically related to emotion or exercise
(in particular, swimming) in LQT1 and auditory stimuli
in LQT2 [55,56]. Of 533 genotyped index patients (243
LQT1, 209 LQT2, 81 LQT3) and 1842 family members
mortality was highest in patients with LQT3 followed
by male patients with LQT1 and 2 and female patients
with LQT1 and 2, but arrhythmic events occurred more
frequently in LQT1 and LQT2 [57]. Priori and colleagues
[55] presented a scheme for risk stratification, based on
analysis of 647 patients. High risk was considered in
patients with LQT1 and QTc > 500 ms1/2 and in male
patients with LQT2 or LQT3 and QTc > 500 ms1/2.
High-risk patients should be treated prophylactically
using beta-blockers [58], although the effect is less beneficial in patients with LQT3 [59]. Beta-blocker therapy
is associated with a significant reduction in the rate of
cardiac events. Event rates within 5 years while on betablocker were higher in those patients who were symptomatic before starting this therapy (32%) than in those
who had been asymptomatic (14%) [60]. Subgroup analysis in genotyped patients with LQT1, LQT2 and LQT3
showed that beta-blocker therapy had only minimal
effects on QTc in all three genotypes. Treatment was associated with a significant reduction of events in LQT1
and LQT2 patients, whereas there was no evident effect
in LQT3 [60]. In selected patients with LQT1, LQT2
and LQT5, potassium channel openers (i.e. pinacidil,
nicorandil) may become a therapeutic option [61,62].
In LQT3, mexiletine may selectively suppress the mutant channel phenotype by inhibition of late openings
[63,64] and lidocaine showed similar effects [65]. Priori
and colleagues [66] were able to show a significant reduction of QTc prolongation in LQT3 patients carrying mutant sodium channels that were known to be influenced
by mexiletine in vitro. Similar effects were reported with
flecainide [67].
There is only limited information available on the role
of ICD therapy in patients with LQTS. The ACC/AHA
2002 guidelines have designated the ICD for primary
prevention of SCD as a class IIb indication. In clinical
practice, the decision for prophylactic ICD implantation
is not based on gene analysis. Usually, prophylactic
ICD implantation is considered in patients with syncope
despite beta-blocker therapy or in patients with syncope
and with a family history of sudden death. A benefit from
ICD has been suggested by retrospective analyses. Zareba
and colleagues [68] compared 73 LQTS patients who
were treated with ICD because of prior cardiac arrest (n =
54) or recurrent syncope despite beta-blocker therapy
(n = 19) with 161 LQTS patients who had similar indications (89 cardiac arrest and 72 recurrent syncope despite
beta-blocker therapy) but did not receive ICD. There was
one (1.3%) death in 73 ICD patients following an average of 3 years, whereas there were 26 deaths (16%) in
non-ICD patients during a mean 8-year follow-up. However, it was noted by Viskin [69] that, after exclusion of
the patients who died within 1 month after inclusion
and therefore likely from residuals of their first aborted
sudden death, the difference between both groups was
only marginal. Hence, a long-term prospective study
is needed to determine the benefit of ICD therapy in
LQTS.
Short QT syndrome
Very recently, a new syndrome associated with sudden
cardiac death in otherwise healthy patients with structurally normal hearts has been described, the short QT
syndrome [70,71]. The prevalence of this syndrome is
unknown. Patients with the short QT syndrome (SQTS)
present with a short QT interval on the 12-lead ECG,
familial sudden death and palpitations, syncope or sudden cardiac arrest. Six patients from two European families were extensively tested by non-invasive and invasive
methods. Mean QT intervals were 252 ± 13 ms (QTc = 287
± 13 ms). In four patients, electrophysiological studies
were performed, revealing short atrial and ventricular
refractory periods in all and an increased propensity to
ventricular vulnerability to fibrillation in three out of
four patients [70,71]. The genetic basis has only recently
been uncovered. In two families, two different missense
mutations of the cardiac potassium channel HERG
(KCNH2) were identified, resulting in the same amino
acid change. These mutations dramatically increase the
potassium current IKr, leading to heterogeneous abbreviation of action potential duration and refractoriness.
The affinity of the affected channels to IKr blockers is
markedly reduced [72]. Currently, ICD implantation is
the only therapeutic option. First experience with ICD
therapy in SQTS indicates an increased risk of inappropriate device discharge owing to atrial fibrillation and
T-wave oversensing, which constitutes a significant and
specific risk in patients with SQTS [73].
TETC32 12/2/05 14:26 Page 963
Ventricular Tachycardia
Catecholaminergic polymorphic ventricular
tachycardia
Catecholaminergic polymorphic ventricular tachycardia
(CPVT) is a clinically and genetically heterogeneous
disease. It is characterized by episodes of syncope or sudden death in response to physiological or emotional
stress occurring in structurally normal hearts [74–79].
Documented arrhythmias include bidirectional ventricular tachycardia, polymorphic ventricular tachycardia
and, in rare patients, catecholaminergic idiopathic ventricular fibrillation. CPVT was first described in a Bedouin
tribe from Israel [80] but has also been identified in
other populations [77,81,82]. A family history of juvenile
sudden death and stress-induced syncope is present in
approximately one-third of cases. Mortality is high and
reaches up to 30–50% by the age of 30 years [83]. Around
40–60% of the patients with CPVT carry mutations in the
cardiac ryanodine receptor gene (RyR2) [82] or in the
calsequestrin 2 gene (CASQ2) [84]. Genotype–phenotype
analysis showed that men are at higher risk of cardiac
events (i.e. syncope) and that mutation carriers became
symptomatic at a younger age [76]. Current treatment of
CPVT consists of β-adrenergic blockers [76,80], antiarrhythmic drugs and/or ICD implantation, mainly based
on empirical grounds or the results of serial exercise/
pharmacological testing [83].
Idiopathic ventricular fibrillation
In 5–10% of survivors of cardiac arrest due to ventricular
arrhythmias, no structural abnormality of the heart as
the underlying cause is found. In the absence of demonstrable structural heart disease, myocardial ischaemia,
drug effects, electrolyte or metabolic abnormalities and
toxicity, and ventricular fibrillation and unexplained
cardiac arrest is rare [85 – 88]. However, it appears to be
more frequent than previously thought and accounts
for approximately 6–12% of all sudden deaths (lifetime
prevalence < 0.5 in 10 000), with a higher percentage in
the young population below the age of 40 years. Ventricular fibrillation in patients with apparently normal hearts
may represent a true ‘primary electrical disease’, but it
may also be the first manifestation of a cardiomyopathy.
The diagnosis of idiopathic ventricular fibrillation must
therefore be made by exclusion, implying that adequate
and extensive diagnostic evaluation is necessary in order
to rule out subclinical structural heart disease. Idiopathic
ventricular fibrillation is associated with a high mortality
rate. Available data suggest an 11% rate of sudden death
within 1 year of diagnosis or recurrence rates of up to
30% 5 years after an initial episode of survived cardiac
arrest [85]. Therefore, effective treatment is mandatory
to improve the long-term prognosis. In one report, quinidine (class IA antiarrhythmic agent) was highly effective
in preventing arrhythmia re-induction during electrophysiological study [88]. ICD implantation is currently
the treatment of choice in patients with idiopathic
ventricular fibrillation in order to prevent sudden death
from recurrent episodes of ventricular fibrillation. In
selected patients, catheter ablation may be a potential
new option in the treatment of idiopathic ventricular
fibrillation by targeting premature ventricular beats arising from the Purkinje conducting system, which have
been observed to trigger polymorphic ventricular tachycardia [89].
Brugada syndrome
In 1992, Brugada and Brugada [90] reported a new clinical entity with a RBBB pattern and ST segment elevation
in right precordial ECG leads (Fig. 32.11) and a high incidence of sudden cardiac death in patients with structurally
normal hearts. The disease is considered as a subgroup of
idiopathic ventricular fibrillation and has been referred
to as Brugada syndrome. It manifests with episodes of
polymorphic ventricular tachycardia, syncope, and cardiac arrest during adulthood at a mean age of 40 years
but within a large age range. Because symptoms occur
mostly at night, this syndrome is also assigned as ‘sudden
unexpected nocturnal death syndrome’. It accounts for
approximately 4–12% of sudden deaths and for 20–40%
of sudden cardiac arrest in patients without structural
heart disease. It dominantly occurs in males and appears
to be most prevalent in South-East Asia and Japan, where
the disorder is a leading cause of natural death among
young men with an estimated annual mortality rate of
26–38 per 100 000 [91].
Diagnostic criteria were recently proposed and reported
in a consensus document [92] and mainly rely on electrocardiographic abnormalities after exclusion of structural heart disease by detailed cardiac investigation.
Before making the diagnosis of Brugada syndrome, it is
mandatory to exclude myocardial ischaemia and organic
heart disease, particularly affecting the right ventricle
(i.e. arrhythmogenic right-ventricular cardiomyopathy)
as well as extracardiac and electrolyte abnormalities.
Brugada syndrome is considered a ‘channelopathy’
that belongs to the group of ‘primary electrical diseases’
of the heart. In familial Brugada syndrome (20–30%),
genetic mutations identified so far refer to the alphasubunit of the cardiac sodium channel (SCN5A) [93].
Assessment of these mutations in expression systems
demonstrated loss of function of the sodium channel.
963
TETC32 12/2/05 14:26 Page 964
964
Chapter 32
B
A
I
Pulmonic valve
II
III
aVR
aVL
Site of
RF ablation
aVF
V1
C
V2
V3
V4
V5
V6
Figure 32.9 Non-contact mapping of a ventricular bigeminus with LBBB inferior axis morphology originating from the right
ventricular outflow tract in a highly symptomatic patient (A). The multielectrode array catheter (MEA) is part of the non-contact
mapping system (EnSite 3000; Endocardial Solutions). The system permits mapping of a single complex. The MEA, which is filled
with a contrast saline medium, is positioned in the right-ventricular outflow tract (RAO/LAO, right/left anterior oblique views). The
system calculates electrograms from 3000 endocardial points simultaneously by reconstructing far-field signals. Non-depolarized
myocardium is shown in purple in this three-dimensional isopotential map (B). The map also shows the site of earliest depolarization
(white circle). At this site the extrasystoles were successfully ablated using radiofrequency ablation. The ablation catheter is located at
the successful ablation site. RA, diagnostic catheter in the right atrium (C).
However, mutations in the SCN5A gene have been
detected in only a minority of patients, thus indicating
genetic heterogeneity. In the more common sporadic
disease (70–80%), mutations in the SCN5A gene are very
infrequent [94]. Although, at present, genetic testing is
not helpful in risk stratification and clinical decisionmaking, it is important for the expansion of pathophysiological knowledge and understanding of genotype–
phenotype correlations [95].
Three types of repolarization patterns can be described
in Brugada syndrome [92]. Type 1 demonstrates a coved
ST segment elevation of ≥ 2 mm (0.2 mV) and negative
T waves in the right precordial leads (Fig. 32.11). Type 2
is characterized by a saddleback appearance with a high
take-off ST segment elevation (≥ 2 mm) followed by a
gradually descending ST segment (remaining ≥ 1 mm
above baseline) and positive or biphasic T waves. Type 3
has either coved or saddleback morphology, with an ST
segment elevation of < 1 mm. These electrocardiographic
manifestations of Brugada syndrome may be transient
or concealed but can be unmasked or challenged with
sodium channel blockers (i.e. ajmaline, flecainide and
others) [96,97], vagotonic stimulation [98] or fever [99].
Only type 1 should be considered diagnostic. Types 2
and 3 must be considered suspicious and an ajmaline test
has to be performed to uncover type 1 for the diagnosis.
The diagnostic and prognostic impact of an incidental
finding of Brugada-type ECG signs in asymptomatic
individuals without a family history represents a controversial and currently unresolved yet growing problem in
clinical decision-making. Because ventricular fibrillation
is the most important and frequently first manifestation
of Brugada syndrome, appropriate diagnosing and early
risk stratification are vital for patient management and
prevention of sudden cardiac death.
Brugada and colleagues [100] identified male gender,
TETC32 12/2/05 14:26 Page 965
Ventricular Tachycardia
spontaneous ST segment elevation and inducible ventricular tachycardia/ventricular fibrillation as indicators
of high risk. In their study population, patients with a
family history of Brugada syndrome appeared not to be
at increased risk when compared with those with sporadic
disease. Patients with an episode of aborted sudden death
were at highest risk for recurrent arrhythmic events,
whereas symptomatic (i.e. syncope) and asymptomatic
patients with spontaneous ST segment elevation were
at moderate risk. In these patients, the result of programmed electrical stimulation appeared to be helpful
in clinical decision-making. Asymptomatic patients with
ST segment elevation only after challenge with sodium
channel blockers were at low risk for life-threatening
arrhythmias [100]. The role of programmed electrical
stimulation for risk stratification has been a matter
of controversial discussion. Some studies [96,101,102]
failed to find a correlation between ventricular tachycardia/ventricular fibrillation recurrence and inducibility of
ventricular tachyarrhythmias. Priori and colleagues [102]
collected clinical data from 200 patients with Brugada
syndrome and identified patients with the combined
presence of a spontaneous right precordial ST segment
elevation and the history of syncope at highest risk of
sudden death (hazard ratio 6.4; P < 0.002). Spontaneous
ST segment elevation of ≥ 2 mm without history of syncope indicated intermediate risk (hazard ratio 2.1, not
significant). A history of syncope per se and the results
of programmed electrical stimulation were not helpful in
identifying individuals at higher risk of major arrhythmic
events [102]. Very recently, Eckardt and colleagues [103]
reported data on a large population of individuals with a
type 1 Brugada ECG pattern. During a mean follow-up of
40 ± 50 months, 4 out of the 24 patients (17%) with
aborted sudden cardiac death and 4 out of 65 (6%) with a
prior syncope had a recurrent arrhythmic event, whereas
only 1 out of 123 asymptomatic individuals (0.8%) had
a first arrhythmic event. A previous history of aborted
sudden death or syncope and the presence of a spontaneous type 1 ECG were the only significant predictors of
adverse outcome. The results of programmed electrical
stimulation correlated only poorly to outcome. Hence,
available data on risk stratification for symptomatic
and asymptomatic patients in Brugada syndrome are
inconclusive, and patient management and therapeutic
strategies are controversial and under constant debate
and refinement. β-Adrenergic (i.e. isoproterenol) or anticholinergic agents may be helpful in restoring the balance of currents during phase 1, whereas beta-blockers
and amiodarone have demo strated no clinical efficacy
[104]. Reports from Belhassen and colleagues [105,106]
indicate a potential efficacy of quinidine in the treat-
ment of ventricular tachycardia and prevention of
sudden death in Brugada syndrome [107]. However, systematic or randomized studies on the clinical efficacy
of quinidine in Brugada syndrome are not available.
Currently, ICD implantation is the treatment of choice
in secondary and primary prevention of sudden death in
high-risk patients with Brugada syndrome [105,108].
Ventricular tachycardia in patients without
structural heart disease, who are amenable
to curative therapies
Idiopathic right-ventricular outflow-tract
ventricular tachycardia
This arrhythmia, which has also been termed repetitive
monomorphic ventricular tachycardia, usually originates
in the right ventricular outflow tract. It is usually seen in
younger patients (female > male) without structural
heart disease and accounts for up to 70% of idiopathic
ventricular tachycardia. Although the majority of cases
appear to occur sporadically rather than on a familial
basis, the condition is generally considered as a ‘primary
electrical disease’. It is important in the differential diagnosis of various entities, in particular mild or subclinical
forms of arrhythmogenic right ventricular cardiomyopathy [109]. Most data suggest that the mechanism of
RVOT-ventricular tachycardia is triggered activity due
to adenylcyclase-mediated delayed afterdepolarizations
[110]. They are usually exertion- or stress-related arrhythmias. They can also present as recurrent extrasystolies
(Fig. 32.9) or non-sustained arrhythmias tending to
occur at rest (‘repetitive monomorphic ventricular tachycardia’), or provoked only with exercise (Gallavardin’s
tachycardias [47]). However, these forms may just represent different spectra of the same arrhythmia. Idiopathic
RVOT-ventricular tachycardia is usually well tolerated,
probably owing to the preserved ventricular function.
Hence, RVOT-ventricular tachycardia has a favourable
long-term prognosis compared with ventricular tachycardia in structural heart disease. It manifests as a left
bundle branch block ventricular tachycardia with an
inferior axis (Fig. 32.9). Pacing the heart at a rapid rate
or isoproterenol infusion can often induce the arrhythmia. The arrhythmia is responsive to therapy with
beta-blockers [111], sotalol [111,112] or calcium channel
blockers [110,113] and can also be amenable to transcatheter ablation (Fig. 32.9) [109,114].
965
TETC32 12/2/05 14:26 Page 966
966
Chapter 32
1s
A
2s
B
Aortic valve
I
II
III
aVR
aVL
aVF
V1
C
V2
I
V3
II
V1
V4
V5
Site of
RF ablation
Abl
V6
3s
Figure 32.10 Non-contact mapping of an idiopathic left-ventricular tachycardia with RBBB left axis deviation (A). The multiple
electrode array (Ensite 3000, Endocardial Solutions) was placed in the left ventricle (for details, see legend to Fig. 32.9). At the distal
part of the left posterior fascicle, radiofrequency ablation almost immediately terminated the ventricular tachycardia (C), which,
thereafter, was no longer inducible.
Idiopathic left-ventricular tachycardias (fascicular
ventricular tachycardia)
This arrhythmia tends to occur in younger, predominantly male patients, without structural heart disease
[115,116]. An association with exertion or stress is uncommon. The arrhythmia has a relatively narrow (0.10–
0.14 s) RBBB morphology with a rapid downstroke of
S waves in the precordial leads and a left superior axis
(Fig. 32.10). It is inducible with programmed stimulation. ILVT is thought to have a re-entrant basis or derives
from triggered activity secondary to delayed afterdepo-
larizations [117]. It arises on or near to the septum near
the left posterior fascicle [118–121]. Rarely, ventricular
tachycardia can arise from the left anterior fascicle [115]
and thus produce an RBBB pattern with right-axis deviation. Catheter ablation (Fig. 32.10) [122] offers curative
therapy and should be considered early in the management of symptomatic patients. It can be performed using
pace mapping [118,123], presystolic Purkinje potential
[123,124] or diastolic potential during ventricular tachycardia [120,120]. Alternatively, ILVT tends to respond to
therapy with beta-blockers and calcium channel blockers
[112,115].
TETC32 12/2/05 14:26 Page 967
Ventricular Tachycardia
A
B
I
aVR
II
aVL
III
aVF
V1
V4
V2
V5
V3
V6
O
V
V
Figure 32.11 Twelve-lead ECG of a resuscitated patient with Brugada syndrome. The ECG is characterized by a prominent coved ST
segment elevation displaying a J wave amplitude or ST segment amplitude elevation of ≥ 0.2 mV at its peak, followed by a negative T
wave, with little or no isoelectric separation (A). Patients with such an ECG may develop syncope or sudden cardiac death due to fast
polymorphic ventricular tachycardia (B: for details, see text).
Personal perspective
During the recent decades, our understanding of the
clinical problem of ventricular tachycardia has
markedly changed. At the beginning of my training in
the early 1970s, ventricular tachycardia was a problem
that seemed to represent a common entity. It took some
time to understand that the mechanisms and the
prognostic implications of sustained ventricular
tachycardia often were markedly different, despite
similar electrocardiographic appearances. Our
understanding was greatly improved by experimental
and clinical–electrophysiological studies for which the
introduction of programmed electrical stimulation by
the late Philippe Coumel and by Hein J.J. Wellens was of
paramount importance. Experimental and clinical work,
often done by the same persons or at least the same
groups, have fertilized each other and have contributed
to the rapid expansion of electrophysiological studies,
drug assessment, techniques for localization of
the underlying electrophysiological substrate, antitachycardia surgery, catheter ablation and, finally, as the
now established therapy of first choice in most cases,
the implantable cardioverter-defibrillator pioneered by
Michel Mirowski. We had to learn that not everything
is re-entry but that abnormal automaticity, especially
after depolarization, plays an important role, too.
Seminal observations, such as the one by Dessertenne,
describing torsades de pointes as a specific type of
ventricular tachycardia, were followed by decades
of clinical observations and experimental and
pharmacological studies, which finally led to the
identification of the underlying molecular genetic
background of long QT syndromes.
Nowadays, ventricular tachycardia, appearing
under different aetiologies, can frequently be viewed
as separate entities with different electrophysiological
substrates, different arrhythmia mechanisms and often
markedly different prognosis. The spectrum of therapy
has changed with almost complete disappearance of
anti-tachycardia surgery and, instead, dominance of the
implantable cardioverter-defibrillator in patients at risk
of sudden cardiac death. For me, the field of experimental
and clinical research on ventricular tachycardia is one
of the almost ideal examples of translational research
‘from bench to bedside’ and vice versa.
967
TETC32 12/2/05 14:26 Page 968
968
Chapter 32
References
1 Bayes-de-Luna A, Coumel P, Leclercq JF. Ambulatory
sudden cardiac death: mechanisms of production of fatal
arrhythmia on the basis of data from 157 cases. Am Heart J
1989; 117: 151–159.
2 Akhtar M, Shenasa M, Jazayeri M, Caceres J, Tchou PJ.
Wide QRS complex tachycardia. Reappraisal of a common
clinical problem. Ann Intern Med 1988; 109: 905 –912.
3 Baerman JM, Morady F, DiCarlo LA, Jr, De Buitleir M.
Differentiation of ventricular tachycardia from supraventricular tachycardia with aberration: value of the
clinical history. Ann Emerg Med 1987; 16: 40 –43.
4 Brugada P, Brugada J, Mont L, Smeets J, Andries EW. A
new approach to the differential diagnosis of a regular
tachycardia with a wide QRS complex. Circulation 1991;
83: 1649 –1659.
5 Kindwall KE, Brown J, Josephson ME.
Electrocardiographic criteria for ventricular tachycardia
in wide complex left bundle branch block morphology
tachycardias. Am J Cardiol 1988; 61: 1279 –1283.
6 Wellens HJ, Bar FW, Lie KI. The value of the
electrocardiogram in the differential diagnosis of a
tachycardia with a widened QRS complex. Am J Med 1978;
64: 27–33.
7 Kremers MS, Black WH, Wells PJ, Solodyna M. Effect of
preexisting bundle branch block on the
electrocardiographic diagnosis of ventricular tachycardia.
Am J Cardiol 1988; 62: 1208 –1212.
8 Kamakura S, Shimizu W, Matsuo K et al. Localization of
optimal ablation site of idiopathic ventricular tachycardia
from right and left-ventricular outflow tract by body
surface ECG. Circulation 1998; 98: 1525 –1533.
9 Dessertenne F. La tachycardie ventriculaire à deux foyers
opposés variables. Arch Mal Coeur 1966; 59: 263 –272.
10 Morady F, Shen EN, Bhandari A, Schwartz AB, Scheinman
MM. Clinical symptoms in patients with sustained
ventricular tachycardia. West J Med 1985; 142: 341–344.
11 Packer M. Sudden unexpected death in patients with
congestive heart failure: a second frontier. Circulation
1985; 72: 681– 685.
12 Stevenson WG, Middlekauff HR, Stevenson LW, Saxon LA,
Woo MA, Moser D. Significance of aborted cardiac arrest
and sustained ventricular tachycardia in patients referred
for treatment therapy of advanced heart failure. Am Heart J
1992; 124: 123 –130.
13 A comparison of antiarrhythmic-drug therapy with
implantable defibrillators in patients resuscitated from
near-fatal ventricular arrhythmias. The Antiarrhythmics
versus Implantable Defibrillators (AVID) Investigators.
N Engl J Med 1997; 337: 1576 –1583.
14 Connolly SJ, Gent M, Roberts RS et al. Canadian
implantable defibrillator study (CIDS): a randomized
trial of the implantable cardioverter defibrillator against
amiodarone. Circulation 2000; 101: 1297–1302.
15 Kuck KH, Cappato R, Siebels J, Ruppel R. Randomized
comparison of antiarrhythmic drug therapy with
implantable defibrillators in patients resuscitated from
cardiac arrest: The Cardiac Arrest Study Hamburg (CASH).
Circulation 2000; 102: 748 –754.
16 Connolly SJ, Hallstrom AP, Cappato R et al. Meta-analysis
of the implantable cardioverter defibrillator secondary
prevention trials. AVID, CASH and CIDS studies.
Antiarrhythmics vs Implantable Defibrillator study.
Cardiac Arrest Study Hamburg. Canadian Implantable
Defibrillator Study. Eur Heart J 2000; 21: 2071–2078.
17 Sheldon R, Connolly S, Krahn A, Roberts R, Gent M,
Gardner M. Identification of patients most likely to
benefit from implantable cardioverter-defibrillator
therapy: the Canadian Implantable Defibrillator Study.
Circulation 2000; 101: 1660 –1664.
18 Knight BP, Goyal R, Pelosi F et al. Outcome of patients
with nonischemic dilated cardiomyopathy and
unexplained syncope treated with an implantable
defibrillator. J Am Coll Cardiol 1999; 33: 1964–1970.
19 Fonarow GC, Feliciano Z, Boyle NG et al. Improved
survival in patients with nonischemic advanced heart
failure and syncope treated with an implantable
cardioverter-defibrillator. Am J Cardiol 2000; 85: 981–985.
20 Moss AJ, Hall WJ, Cannom DS et al. Improved survival
with an implanted defibrillator in patients with coronary
disease at high risk for ventricular arrhythmia. N Engl J
Med 1996; 335: 1933 –1940.
21 Bigger JT. Prophylactic use of implanted cardiac
defibrillators in patients at high risk for ventricular
arrhythmias after coronary-artery bypass graft surgery.
N Engl J Med 1997; 337: 1569 –1575.
22 Moss AJ, Hall WJ, Cannom DS, Daubert JP et al. Improved
survival with an implanted defibrillator in patients with
coronary disease at high risk for ventricular arrhythmia.
N Engl J Med 1996; 335: 1933 –1940.
23 Moss A, Zareba W, Hall WJ et al. Prophylactic
implantation of a defibrillator in patients with myocardial
infarction and reduced ejection fraction. N Engl J Med
2002; 346: 877–883.
24 Moss AJ. Implantable cardioverter defibrillator therapy:
the sickest patients benefit the most. Circulation 2000;
101: 1638 –1640.
25 Moss AJ, Fadl Y, Zareba W, Cannom DS, Hall WJ. Survival
benefit with an implanted defibrillator in relation to
mortality risk in chronic coronary heart disease. Am J
Cardiol 2001; 88: 516 –520.
26 Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky
EU, Hafley G. A randomized study of the prevention of
sudden death in patients with coronary artery disease.
N Engl J Med 1999; 341: 1882 –1890.
27 Nisam S, Breithardt G. Lessons learned from neutral ICD
trials. Circulation in press.
28 Bänsch D, Antz M, Boczor S, Volkmer M et al. Primary
prevention of sudden cardiac death in idiopathic dilated
cardiomyopathy: the Cardiomyopathy Trial (CAT).
Circulation 2002; 105: 1453 –1458.
TETC32 12/2/05 14:26 Page 969
Ventricular Tachycardia
29 Bänsch D, Böcker D, Brunn J, Weber M, Breithardt G,
Block M. Clusters of ventricular tachycardias signify
impaired survival in patients with idiopathic dilated
cardiomyopathy and implantable cardioverter
defibrillators. J Am Coll Cardiol 2000; 36: 566 –573.
30 Kadish A, Quigg R, Schaechter A, Anderson KP, Estes M,
Levine J. Defibrillators in nonischemic cardiomyopathy
treatment evaluation. Pacing Clin Electrophysiol 2000; 23:
338–343.
31 Kadish A, Dyer A, Daubert JP, Quigg R, Estes M.
Prophylactic defibrillator implantation in patients with
nonischemic dilated cardiomyopathy. N Engl J Med 2004;
350: 2151–2158.
32 Strickberger SA, Hummel JD, Bartlett TG et al. Amiodarone
versus implantable cardioverter-defibrillator: randomized
trial in patients with nonischemic dilated cardiomyopathy and asymptomatic nonsustained ventricular
tachycardia—AMIOVIRT. J Am Coll Cardiol 2003; 41:
1707–1712.
33 Massie BM, Fisher SG, Deedwania PC, Singh BN, Fletcher
RD, Singh SN. Effect of amiodarone on clinical status and
left ventricular function in patients with congestive heart
failure. Circulation 1996; 93: 2128 –2134.
34 Grimm W, Christ M, Bach J, Muller HH, Maisch B.
Non-invasive arrhythmia risk stratification in idiopathic
dilated cardiomyopathy: results of the Marburg
Cardiomyopathy Study. Circulation 2003; 108:
2883–2891.
35 Borggrefe M, Podczeck A, Ostermeyer J, Breihardt G.
Long-term results of electrophysiologically guided
antitachycardia surgery in ventricular tachyarrhythmias:
a collaborative report on 665 patients. In: Breihardt G,
Borggrefe M, Zipes D, eds. Nonpharmacological Therapy of
Tachyarrhythmias. Mount Kisco, New York: Futura
Publishing; 1987: 109 –132.
36 Marcus FI, Fontaine GH, Guiraudon G et al. Right
ventricular dysplasia: a report of 24 adult cases. Circulation
1982; 65: 384 –398.
37 Corrado D, Fontaine G, Marcus FI et al. Arrhythmogenic
right ventricular dysplasia/cardiomyopathy: need for an
international registry. Study Group on Arrhythmogenic
Right Ventricular Dysplasia/Cardiomyopathy of the
Working Groups on Myocardial and Pericardial Disease
and Arrhythmias of the European Society of Cardiology
and of the Scientific Council on Cardiomyopathies of
the World Heart Federation. Circulation 2000; 101:
E101–E106.
38 Thiene G, Nava A, Corrado D, Rossi L, Pennelli N. Right
ventricular cardiomyopathy and sudden death in young
people. N Engl J Med 1988; 318: 129 –133.
39 McKenna WJ, Thiene G, Nava A et al. Diagnosis of
arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and
Pericardial Disease of the European Society of Cardiology
and of the Scientific Council on Cardiomyopathies of
the International Society and Federation of Cardiology.
Br Heart J 1994; 71: 215 –218.
40 Corrado D, Leoni L, Link MS et al. Implantable
cardioverter-defibrillator therapy for prevention of sudden
death in patients with arrhythmogenic right ventricular
cardiomyopathy/dysplasia. Circulation 2003; 108:
3084 –3091.
41 Wichter T, Paul M, Wollmann C et al. Implantable
cardioverter/defibrillator therapy in arrhythmogenic right
ventricular cardiomyopathy: single-center experience of
long-term follow-up and complications in 60 patients.
Circulation 2004; 109: 1503 –1508.
42 Wigle ED, Rakowski H, Kimball BP, Williams WG.
Hypertrophic cardiomyopathy. Clinical spectrum and
treatment. Circulation 1995; 92: 1680 –1692.
43 Maron BJ, McKenna WJ, Danielson GK et al. American
College of Cardiology/European Society of Cardiology
clinical expert consensus document on hypertrophic
cardiomyopathy. A report of the American College of
Cardiology Foundation Task Force on Clinical Expert
Consensus Documents and the European Society of
Cardiology Committee for Practice Guidelines. J Am Coll
Cardiol 2003; 42: 1687–1713.
44 Maron BJ, Shen WK, Link MS et al. Efficacy of implantable
cardioverter-defibrillators for the prevention of sudden
death in patients with hypertrophic cardiomyopathy.
N Engl J Med 2000; 342: 365 –373.
45 McKenna WJ, Behr ER. Hypertrophic cardiomyopathy:
management, risk stratification, and prevention of sudden
death. Heart 2002; 87: 169 –176.
46 Maron BJ, Estes NA, III, Maron MS, Almquist AK, Link MS,
Udelson JE. Primary prevention of sudden death as a
novel treatment strategy in hypertrophic cardiomyopathy. Circulation 2003; 107: 2872 –2875.
47 Gallavardin L. Extrasystolie ventriculaire a paroxysmes
tachycardiques prolonges. Arch Mal Coeur Vaiss 1922; 15:
298–306.
48 Moss AJ, Schwartz PJ, Crampton RS, Locati E, Carleen E.
The long QT syndrome: a prospective international study.
Circulation 1985; 71: 17–21.
49 Moss AJ, Schwartz PJ, Crampton RS et al. The long QT
syndrome. Prospective longitudinal study of 328 families.
Circulation 1991; 84: 1136 –1144.
50 Schwartz PJ, Locati E. The idiopathic long QT syndrome:
pathogenetic mechanisms and therapy. Eur Heart J 1985;
6: 103 –114.
51 Camm AJ, Janse MJ, Roden DM, Rosen MR, Cinca J, Cobbe
SM. Congenital and acquired long QT syndrome. Eur Heart
J 2000; 21: 1232 –1237.
52 Haverkamp W, Breithardt G, Camm AJ et al. The
potential for QT prolongation and proarrhythmia b
y non-antiarrhythmic drugs: clinical and regulatory
implications. Report on a policy conference of the
European Society of Cardiology. Eur Heart J 2000; 21:
1216 –1231.
53 Eckardt L, Haverkamp W, Borggrefe M, Breithardt G.
Experimental models of torsade de pointes. Cardiovasc Res
1998; 39: 178 –193.
54 Moss AJ, Zareba W, Benhorin J et al. ECG T-wave patterns
969
TETC32 12/2/05 14:26 Page 970
970
Chapter 32
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
in genetically distinct forms of the hereditary long QT
syndrome. Circulation 1995; 92: 2929–2934.
Priori SG, Schwartz PJ, Napolitano C et al. Risk stratification in the long-QT syndrome. N Engl J Med 2003; 348:
1866 –1874.
Schwartz PJ, Priori SG, Spazzolini C et al. Genotypephenotype correlation in the long-QT syndrome:
gene-specific triggers for life-threatening arrhythmias.
Circulation 2001; 103: 89 –95.
Zareba W, Moss AJ, Locati EH et al. Modulating effects of
age and gender on the clinical course of long QT syndrome
by genotype. J Am Coll Cardiol 2003; 42: 103–109.
Priori SG, Aliot E, Blomstrom-Lundqvist C et al. Task
Force on Sudden Cardiac Death, European Society of
Cardiology. Europace 2002; 4: 3–18.
Chiang CE, Roden DM. The long QT syndromes: genetic
basis and clinical implications. J Am Coll Cardiol 2000; 36:
1–12.
Moss AJ, Zareba W, Hall WJ et al. Effectiveness and
limitations of beta-blocker therapy in congenital long-QT
syndrome. Circulation 2000; 101: 616 – 623.
Sato T, Hata Y, Yamamoto M et al. Early
afterdepolarization abolished by potassium channel
opener in a patient with idiopathic long QT syndrome.
J Cardiovasc Electrophysiol 1995; 6: 279 –282.
Shimizu W, Kurita T, Matsuo K et al. Improvement of
repolarization abnormalities by a K+ channel opener in
the LQT1 form of congenital long-QT syndrome.
Circulation 1998; 97: 1581–1588.
Wang DW, Yazawa K, Makita N, George-AL J, Bennett PB.
Pharmacological targeting of long QT mutant sodium
channels. J Clin Invest 1997; 99: 1714 –1720.
Kehl HG, Haverkamp W, Rellensmann G et al.
Images in cardiovascular medicine. Life-threatening
neonatal arrhythmia: successful treatment and
confirmation of clinically suspected extreme long
QT-syndrome-3. Circulation 2004; 109: e205 –e206.
An RH, Bangalore R, Rosero SZ, Kass RS. Lidocaine block
of LQT-3 mutant human Na+ channels. Circ Res 1996; 79:
103–108.
Priori SG, Napolitano C, Cantu F, Brown AM, Schwartz
PJ. Differential response to Na+ channel blockade, betaadrenergic stimulation, and rapid pacing in a cellular
model mimicking the SCN5A and HERG defects present
in the long-QT syndrome. Circ Res 1996; 78: 1009 –1015.
Benhorin J, Taub R, Goldmit M et al. Effects of flecainide
in patients with new SCN5A mutation: mutation-specific
therapy for long-QT syndrome? Circulation 2000; 101:
1698 –1706.
Zareba W, Moss AJ, Daubert JP, Hall WJ, Robinson JL,
Andrews M. Implantable cardioverter defibrillator in
high-risk long QT syndrome patients. J Cardiovasc
Electrophysiol 2003; 14: 337–341.
Viskin S. Implantable cardioverter defibrillator in highrisk long QT syndrome patients. J Cardiovasc Electrophysiol
2003; 14: 1130 –1131.
Gussak I, Brugada P, Brugada J et al. Idiopathic short QT
interval: a new clinical syndrome? Cardiology 2000; 94:
99–102.
71 Gaita F, Giustetto C, Bianchi F et al. Short QT Syndrome:
a familial cause of sudden death. Circulation 2003; 108:
965–970.
72 Brugada R, Hong K, Dumaine R et al. Sudden death
associated with short-QT syndrome linked to mutations
in HERG. Circulation 2004; 109: 30 –35.
73 Schimpf R, Wolpert C, Bianchi F et al. Congenital short
QT syndrome and implantable cardioverter defibrillator
treatment: inherent risk for inappropriate shock delivery.
J Cardiovasc Electrophysiol 2003; 14: 1273–1277.
74 Viskin S, Belhassen B. Polymorphic ventricular
tachyarrhythmias in the absence of organic heart disease:
classification, differential diagnosis, and implications for
therapy. Prog Cardiovasc Dis 1998; 41: 17–34.
75 Swan H, Laitinen PJ. Familial polymorphic ventricular
tachycardia: intracellular calcium channel disorder. Card
Electrophysiol Rev 2002; 6: 81–87.
76 Priori SG, Napolitano C, Memmi M et al. Clinical and
molecular characterization of patients with
catecholaminergic polymorphic ventricular tachycardia.
Circulation 2002; 106: 69 –74.
77 Marks AR, Priori S, Memmi M, Kontula K, Laitinen PJ.
Involvement of the cardiac ryanodine receptor/calcium
release channel in catecholaminergic polymorphic
ventricular tachycardia. J Cell Physiol 2002; 190: 1–6.
78 Laitinen PJ, Brown KM, Piippo K et al. Mutations of the
cardiac ryanodine receptor (RyR2) gene in familial
polymorphic ventricular tachycardia. Circulation 2001;
103: 485 –490.
79 Bauce B, Rampazzo A, Basso C et al. Screening for
ryanodine receptor type 2 mutations in families with
effort-induced polymorphic ventricular arrhythmias and
sudden death: early diagnosis of asymptomatic carriers.
J Am Coll Cardiol 2002; 40: 341–349.
80 Lahat H, Eldar M, Levy-Nissenbaum E et al. Autosomal
recessive catecholamine- or exercise-induced polymorphic
ventricular tachycardia: clinical features and assignment
of the disease gene to chromosome 1p13–21. Circulation
2001; 103: 2822 –2827.
81 Postma AV, Denjoy I, Hoorntje TM et al. Absence of
calsequestrin 2 causes severe forms of catecholaminergic
polymorphic ventricular tachycardia. Circ Res 2002; 91:
e21–e26.
82 Priori SG, Napolitano C, Tiso N et al. Mutations in the
cardiac ryanodine receptor gene (hRyR2) underlie
catecholaminergic polymorphic ventricular tachycardia.
Circulation 2001; 103: 196 –200.
83 Fisher JD, Krikler D, Hallidie-Smith KA. Familial
polymorphic ventricular arrhythmias: a quarter century
of successful medical treatment based on serial exercisepharmacologic testing. J Am Coll Cardiol 1999; 34:
2015 –2022.
84 Lahat H, Pras E, Olender T et al. A missense mutation in a
highly conserved region of CASQ2 is associated with
autosomal recessive catecholamine-induced polymorphic
ventricular tachycardia in Bedouin families from Israel.
Am J Hum Genet 2001; 69: 1378 –1384.
85 Survivors of out-of-hospital cardiac arrest with apparently
normal heart. Need for definition and standardized
TETC32 12/2/05 14:26 Page 971
Ventricular Tachycardia
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
clinical evaluation. Consensus Statement of the Joint
Steering Committees of the Unexplained Cardiac Arrest
Registry of Europe and of the Idiopathic Ventricular
Fibrillation Registry of the United States. Circulation 1997;
95: 265–272.
Belhassen B, Viskin S. Idiopathic ventricular tachycardia
and fibrillation. J Cardiovasc Electrophysiol 1993; 4:
356–368.
Priori SG, Napolitano C, Grillo M. Concealed
arrhythmogenic syndromes: the hidden substrate of
idiopathic ventricular fibrillation? Cardiovasc Res 2001;
50: 218–223.
Viskin S, Belhassen B. Idiopathic ventricular fibrillation.
Am Heart J 1990; 120: 661– 671.
Haissaguerre M, Shoda M, Jais P et al. Mapping and
ablation of idiopathic ventricular fibrillation. Circulation
2002; 106: 962 – 967.
Brugada P, Brugada J. Right bundle branch block,
persistent ST segment elevation and sudden cardiac death:
a distinct clinical and electrocardiographic syndrome. A
multicenter report. J Am Coll Cardiol 1992; 20: 1391–1396.
Nademanee K, Veerakul G, Nimmannit S et al.
Arrhythmogenic marker for the sudden unexplained
death syndrome in Thai men. Circulation 1997; 96:
2595–2600.
Wilde AA, Antzelevitch C, Borggrefe M et al. Proposed
diagnostic criteria for the Brugada syndrome: consensus
report. Circulation 2002; 106: 2514 –2519.
Chen Q, Kirsch GE, Zhang D et al. Genetic basis and
molecular mechanism for idiopathic ventricular
fibrillation. Nature 1998; 392: 293 –296.
Schulze-Bahr E, Eckardt L, Breithardt G et al. Sodium
channel gene (SCN5A) mutations in 44 index patients
with Brugada syndrome: different incidences in familial
and sporadic disease. Hum Mutat 2003; 21: 651–652.
Smits JP, Eckardt L, Probst V et al. Genotype-phenotype
relationship in Brugada syndrome: electrocardiographic
features differentiate SCN5A-related patients from nonSCN5A-related patients. J Am Coll Cardiol 2002; 40:
350–356.
Brugada R, Brugada J, Antzelevitch C et al. Sodium
channel blockers identify risk for sudden death in patients
with ST-segment elevation and right bundle branch block
but structurally normal hearts. Circulation 2000; 101:
510–515.
Rolf S, Bruns HJ, Wichter T et al. The ajmaline challenge
in Brugada syndrome: diagnostic impact, safety, and
recommended protocol. Eur Heart J 2003; 24: 1104 –1112.
Miyazaki T, Mitamura H, Miyoshi S et al. Autonomic and
antiarrhythmic drug modulation of ST segment elevation
in patients with Brugada syndrome. J Am Coll Cardiol
1996; 27: 1061–1070.
Antzelevitch C, Brugada R. Fever and Brugada syndrome.
Pacing Clin Electrophysiol 2002; 25: 1537–1539.
Brugada J, Brugada R, Brugada P. Determinants of sudden
cardiac death in individuals with the electrocardiographic
pattern of Brugada syndrome and no previous cardiac
arrest. Circulation 2003; 108: 3092 –3096.
Eckardt L, Kirchhof P, Schulze-Bahr E et al.
102
103
104
105
106
107
108
109
110
111
112
113
114
115
Electrophysiologic investigation in Brugada syndrome:
yield of programmed ventricular stimulation at two
ventricular sites with up to three premature beats. Eur
Heart J 2002; 23: 1394 –1401.
Priori SG, Napolitano C, Gasparini M et al. Natural history
of Brugada syndrome: insights for risk stratification and
management. Circulation 2002; 105: 1342–1347.
Eckardt L, Probst V, Smits JP, Schulze-Bahr E et al. Longterm prognosis of individuals with right precordial STelevation—Brugada syndrome. Circulation; in press.
Brugada J, Brugada R, Brugada P. Right bundle-branch
block and ST-segment elevation in leads V1 through V3: a
marker for sudden death in patients without demonstrable structural heart disease. Circulation 1998; 97:
457–460.
Belhassen B, Viskin S, Antzelevitch C. The Brugada
syndrome: is an implantable cardioverter defibrillator the
only therapeutic option? Pacing Clin Electrophysiol 2002;
25: 1634 –1640.
Belhassen B, Glick A, Viskin S. Efficacy of quinidine in
high-risk patients with Brugada syndrome. Circulation
2004; 110: 1731–1737.
Belhassen B, Viskin S, Fish R et al. Effects of
electrophysiologic-guided therapy with Class IA
antiarrhythmic drugs on the long-term outcome of
patients with idiopathic ventricular fibrillation with or
without the Brugada syndrome. J Cardiovasc Electrophysiol
1999; 10: 1301–1312.
Brugada J, Brugada R, Antzelevitch C et al. Long-term
follow-up of individuals with the electrocardiographic
pattern of right bundle-branch block and ST-segment
elevation in precordial leads V1 to V3. Circulation 2002;
105: 73–78.
O’Donnell D, Cox D, Bourke J et al. Clinical and
electrophysiological differences between patients with
arrhythmogenic right ventricular dysplasia and right
ventricular outflow tract tachycardia. Eur Heart J 2003;
24: 801–810.
Lerman BB, Stein K, Engelstein ED et al. Mechanism of
repetitive monomorphic ventricular tachycardia.
Circulation 1995; 92: 421–429.
Mont L, Seixas T, Brugada P et al. Clinical and
electrophysiologic characteristics of exercise-related
idiopathic ventricular tachycardia. Am J Cardiol 1991;
68: 897–900.
Mont L, Seixas T, Brugada P et al. The
electrocardiographic, clinical, and electrophysiologic
spectrum of idiopathic monomorphic ventricular
tachycardia. Am Heart J 1992; 124: 746 –753.
Gill JS, Blaszyk K, Ward DE, Camm AJ. Verapamil for the
suppression of idiopathic ventricular tachycardia of left
bundle branch block-like morphology. Am Heart J 1993;
126: 1126 –1133.
Ribbing M, Wasmer K, Monnig G et al. Endocardial
mapping of right ventricular outflow tract tachycardia
using noncontact activation mapping. J Cardiovasc
Electrophysiol 2003; 14: 602 –608.
Ohe T, Shimomura K, Aihara N et al. Idiopathic
sustained left ventricular tachycardia: clinical and
971
TETC32 12/2/05 14:26 Page 972
972
Chapter 32
116
117
118
119
120
electrophysiologic characteristics. Circulation 1988; 77:
560–568.
Lin FC, Finley CD, Rahimtoola SH, Wu D. Idiopathic
paroxysmal ventricular tachycardia with a QRS pattern
of right bundle branch block and left axis deviation:
a unique clinical entity with specific properties. Am J
Cardiol 1983; 52: 95 –100.
Nakagawa H, Beckman KJ, McClelland JH et al.
Radiofrequency catheter ablation of idiopathic left
ventricular tachycardia guided by a Purkinje potential.
Circulation 1993; 88: 2607–2617.
Rosenbaum MB, Blanco HH, Elizari MV et al. Electrotonic
modulation of the T wave and cardiac memory. Am J
Cardiol 1982; 50: 213 –222.
Blanchot P, Warin JF. [A further case of ventricular
tachycardia by re-entry]. Arch Mal Coeur Vaiss 1973; 66:
915–923.
Touboul P, Claveyrolas R, Huerta F, Porte J, Delahaye JP.
[Ventricular tachycardia due to premature supra-
121
122
123
124
ventricular beats with a normal QRS complex.
Analysis of a case]. Arch Mal Coeur Vaiss 1975; 68:
969 –976.
Ward DE, Nathan AW, Camm AJ. Fascicular tachycardia
sensitive to calcium antagonists. Eur Heart J 1984; 5:
896–905.
Kottkamp H, Chen X, Hindricks G et al. Idiopathic
left ventricular tachycardia: new insights into
electrophysiological characteristics and radiofrequency
catheter ablation. Pacing Clin Electrophysiol 1995; 18:
1285 –1297.
German LD, Packer DL, Bardy GH, Gallagher JJ.
Ventricular tachycardia induced by atrial stimulation in
patients without symptomatic cardiac disease. Am J
Cardiol 1983; 52: 1202 –1207.
Eckardt L, Breithardt G, Haverkamp W. Idiopathic left
ventricular tachycardia localized at the distal end of the
posterior fascicle by non-contact activation mapping.
Heart 2002; 87: 374.