Clinical Management of Ventricular
Cara N. Pellegrini, MD, and
Melvin M. Scheinman, MD, FACC
Abstract:Ventricular tachycardia (VT) may be mono-
morphic or polymorphic. Although commonly related
to organic heart disease, a significant percentage of
VTs are idiopathic (occurring in patients with other-
wise normal hearts). Correctly identifying the sub-
strate and mechanism of the tachycardia is essential for
proper management. Although therapy for monomor-
phic VT associated with structural heart disease fo-
cuses on tachycardia suppression and reduction of
sudden cardiac death (SCD) risk, idiopathic monomor-
phic VT generally does not entail an increased risk of
SCD and treatment is aimed primarily at symptom
reduction. Polymorphic VT associated with ischemia or
an acquired precipitant that prolongs the QT interval
the congenital arrhythmia syndromes, which demand
genetic testing to define the underlying problem. This
review describes the diagnosis, mechanisms, etiology, and
management of monomorphic and polymorphic VT, with
attention to recent advances in biological understanding
and the most current therapeutic recommendations.
(Curr Probl Cardiol 2010;35:453-504.)
entricular tachycardia (VT) is an arrhythmia defined by a rate
?100 bpm that originates in the ventricles and is usually associ-
ated with wide QRS complexes (?120 ms) in adults. In its
sustained form it can produce hemodynamic compromise or cardiac
arrest. Even if nonsustained, it can be associated with bothersome
The authors have no conflicts of interest to disclose.
Curr Probl Cardiol 2010;35:453-504.
0146-2806/$ – see front matter
Curr Probl Cardiol, September 2010453
symptoms, and if persistent, can lead to degeneration of cardiac function
because of a tachycardia-induced cardiomyopathy.
VT with a single, stable QRS morphology is identified as monomorphic,
whereas polymorphic VT has a changing QRS morphology. Specifically,
if a VT has no constant morphology for more than 5 complexes, has no
clear isoelectric baseline, or has QRS complexes that are asynchronous in
multiple simultaneously recorded leads, it is said to be polymorphic.1VT
is considered sustained if it lasts ?30 seconds, although some argue that
15 seconds is sufficient, as treatment may be required in this time frame.
The electrocardiographic (ECG) diagnosis of VT can prove difficult.
Although VT accounts for up to 80% of cases of wide complex
tachycardias in unselected populations, there is a broad differential
diagnosis.2About 15%-30% of the time, a wide complex tachycardia may
be the result of a supraventricular tachycardia (SVT) with abnormal
interventricular conduction.3This can be due to bundle branch block or
aberration or preexcitation over an anomalous atrioventricular connec-
tion, such as occurs in Wolff–Parkinson–White syndrome (Fig 1).
Additionally, a ventricular paced rhythm can produce a wide complex
History and Physical Examination
A focused history can be helpful. In an emergency department based
study of wide complex tachycardia, the presence of a history of prior
myocardial infarction (MI), heart failure, or recent angina each had a
positive predictive accuracy of 95% for VT, although no clinical factors
were strongly predictive of a SVT and many cases of VT occurred in
patients without any of the above characteristics.4Of note, patients with
organic cardiac disease, especially elderly patients, also commonly present
with atrial arrhythmias, such as atrial flutter, which if the patient happens
to have a baseline bundle branch block, may mimic VT. If the tachycardia
has recurred over a period of more than 3 years, SVT is more likely5;
conversely, if the first occurrence of the tachycardia was after an MI, VT
is extremely likely.6Of note, the hemodynamic stability of a patient does
not distinguish VT from SVT, but rather has more relation to the rate of
the tachycardia and overall substrate of the patient.7Inappropriate
treatment of a hemodynamically stable patient with VT and structural
heart disease, with verapamil for presumed SVT, for example, may create
a situation of hemodynamic instability.8
454 Curr Probl Cardiol, September 2010
Physical examination may also be revealing if atrioventricular (AV)
dissociation is evident. “Cannon” A waves in the jugular venous wave-
form (due to atrial contraction against a closed tricuspid valve), a
variable-intensity S1 (due to variation in tricuspid and mitral leaflet stage
of opening at the time of dissociated ventricular systole), and variation in
systolic blood pressure unrelated to respiration (due to the dissociated
atrial contraction producing variable left ventricular filling), are all
possible manifestations of AV dissociation. Valsalva, carotid sinus
FIG 1. Examples of leads V1and V6in both left bundle branch block and right bundle branch
block types of QRS complexes in different types of wide complex tachycardia. ECG,
electrocardiogram; SVT, supraventricular tachycardia; WPW, Wolff–Parkinson–White syn-
drome. (Reproduced with permission from Miller et al.3)
Curr Probl Cardiol, September 2010455
massage, or adenosine may facilitate diagnosis of AV dissociation; if the
tachycardia terminates, SVT is strongly suggested as the etiology,9although
VT due to a triggered mechanism may be terminated as well.10-12
ECG. The ECG remains the cornerstone of VT diagnostics (Table 1).
Unfortunately, despite the plethora of criteria to help distinguish VT from
the most common alternative, SVT with aberrancy, all have limitations;
many are complicated, and in certain rare instances, even perfect
application of the criteria results in the incorrect diagnosis. Particularly
difficult situations include VT in children, VT originating from the
ventricular septum, fascicular VT, and some idiopathic VTs. The mor-
phologic criteria described below may fail as these more narrow VTs
access the heart’s specialized conduction system. In addition, SVT in the
setting of a class 1C antiarrhythmic agent and antidromic atrioventricular
reentrant tachycardia can be virtually indistinguishable from VT. None-
theless, with proper criteria application, successful diagnosis can be
performed in most patients.
Fred Morady: In antidromic atrioventricular reentrant tachycardia, ventricular
activation occurs through ventricular muscle, as in most ventricular tachy-
cardias. The ventricular insertion of left-sided accessory pathways is at the
mitral annulus. Therefore, if ventricular tachycardia arises near the mitral
annulus, the QRS morphology often is identical to that of antidromic
atrioventricular reentrant tachycardia.
At the most simple level, if a wide complex tachycardia appears to be
consistent with a typical bundle branch block (BBB) pattern, SVT is
suggested, whereas if the tachycardia is not manifest by some combina-
TABLE 1. Characteristics of wide complex tachycardia favoring diagnosis of ventricular
● QRS complexes ?0.14 s for RBBB and ?0.16 s for LBBB tachycardias (in the absence
of antiarrhythmic drugs)
● A superior frontal plan axis in RBBB and in a right inferior axis in LBBB tachycardias
● Evidence of A-V dissociation (fusion complexes, capture beats)
Morphologic criteria, focusing on ECG leads V1-2and V6
RBBB: monophasic R, qR, Rr=, and RS in V1and RS ratio ?1 in V6
LBBB: initial r wave ?0.04 s or an interval of ?0.07 s from the QRS onset to the nadir
of the S wave in V1-2,notching of the downstroke of the S wave in V1-2or an initial q
wave in V6
(Reproduced with permission from Josephson ME.1)
Abbreviations: RBBB, right bundle branch block; LBBB, left bundle branch block, A-V,
456 Curr Probl Cardiol, September 2010
tion of typical BBB or fascicular block, then it is likely VT (Fig 2).13The
Kindwall criteria formalize morphologic differences to 4 specific criteria
for VT with left bundle branch block (LBBB): an R wave in V1or V2
?30-ms duration; any Q wave in V6; a duration of ?60 ms from the onset
of the QRS to the nadir of the S wave in V1or V2; and notching on the
downstroke of the S wave in V1or V2.14Although each had low
sensitivity alone, grouped criteria had a sensitivity of 100%, specificity of
89%, and a predictive accuracy of 96% for VT. In contrast to the wide
QRS and slow deflections described above, there is relatively rapid
penetration of the ventricular His-Purkinje system in LBBB, such that the
initial vector of depolarization produces a narrow R wave and a rapid,
smooth descent to the S wave. With typical right bundle branch block
(RBBB) the initial portion of the QRS does not change, but the later
portion of the QRS reflects the delayed right ventricular depolarization
and gives rise to rR= or rsr= patterns. A monophasic R, qR, Rr=, or RS in
V1, or an RS ratio ?1, or a monophasic R in V6suggest VT.
Brugada and coworkers published a stepwise algorithm, in which 4
criteria for VT are sequentially considered.15If any are satisfied, VT is
diagnosed, while if none are fulfilled, SVT is diagnosed. First the
precordial leads are assessed for the absence of an RS complex, which
would signify VT. If an RS complex is present, but the longest RS
interval in any precordial lead is ?100 ms, VT is diagnosed. Next the
presence of AV dissociation marks VT. Finally, the QRS morphology
criteria described above are applied. The sensitivity of the 4 consecutive
steps was reported to be 0.987, and the specificity was 0.965, although
significantly lower discriminatory power has been reported in real-world
study of the criteria’s application.16
FIG 2. Diagrammatic representation of common QRS morphologies encountered in VT and SVT
with aberration, in leads V1and V6for both LBBB and RBBB QRS patterns. LBBB, left bundle
branch block; RBBB, right bundle branch block. (Reproduced with permission from Miller et al.3)
Curr Probl Cardiol, September 2010457
Fred Morady: A limitation of the study by Brugada15is that antidromic
atrioventricular reentrant tachycardias were not included in the analysis. The
criteria for ventricular tachycardia would be met by many antidromic atrio-
ventricular reentrant tachycardias.
Some of the other published criteria that we have found to be
particularly helpful include the following:
● QRS complex duration greater than 160 ms with LBBB morphology or
greater than 140 ms with RBBB morphology strongly favors VT in
patients not taking drugs that slow intraventricular conduction.2,17
● A right superior axis (?90 to ?180 degrees) favors VT, and to a lesser
extent a shift in the QRS axis of ?40 degrees from baseline also
Fred Morady: If there is a bundle branch block during sinus rhythm,
ventricular tachycardia from the ventricle that is contralateral to the bundle
branch block may have a QRS morphology that is very similar to that of the
bundle branch block.
● Concordant precordial R-wave progression pattern, with leads V1-V6
all either predominantly positive, or more suggestively, all predomi-
nantly negative, is uncommon in SVT, with the exception of the
positive concordance sometimes seen in preexcited tachycardias (Fig
3). Although the specificity of concordance for VT is high (?90%), the
sensitivity is low (?20%).17,19
● The presence of AV dissociation is perhaps the most useful electro-
cardiographic feature in distinguishing VT from SVT with aberration.
Complete AV dissociation occurs in 20%-50% of all VTs, and another
15%-20% of VTs have second-degree ventriculoatrial block, both of
which seldom occur in those with SVT, and is thus very specific for
VT.2,17Unfortunately, AV dissociation can be difficult to recognize,
particularly with rapid VT rates. Increasing the amount of ECG
analyzed, reviewing simultaneously recorded ECG leads to avoid
mistaking the terminal portion of the QRS for a P wave, and attending
to variation in QRS complex amplitude, due to scalar summation of the
P wave on the QRS complex or changes related to variable ventricular
filling in AV dissociation, can improve diagnostic accuracy.20
458 Curr Probl Cardiol, September 2010
FIG 3. (A) Negative concordance during VT in a patient with a prior anterior MI; AV
dissociation is present as well. (B) Positive concordance during VT in a patient with a prior
inferior MI. QRS amplitude alternans is seen in leads 2, 3, and aVF. (C) Positive concordance
during preexcited atrial flutter with 2:1 conduction over an anomalous AV connection in a
patient with Wolff–Parkinson–White syndrome. Note the similarity of ECG patterns between B
and C. (Reproduced with permission from Miller et al.3)
Curr Probl Cardiol, September 2010459
● Fusion beats involve blended ventricular activation from 2 different
sources, whereas capture beats represent pure ventricular activation
over the His-Purkinje system. The presence of either during a wide
complex tachycardia imply AV dissociation and are similarly diagnos-
tic of VT, with the caveat that a ventricular premature beat ipsilateral
to the “blocked” ventricle can mimic a fusion beat; thus, the presence
of a P wave shortly before the beat in question adds considerable
● A narrower QRS complex during the wide complex tachycardia than at
baseline, a contralateral BBB in tachycardia compared with baseline,
or the presence of multiple wide complex tachycardia configurations
all suggest VT.3
Mechanisms and Etiology
Sustained monomorphic tachycardia may be related to associated
organic heart disease, occurring in the setting of ischemic or nonischemic
cardiomyopathy, or idiopathic, occurring in patients with normal hearts.
VT can originate anywhere within the left or right ventricle, including the
conduction system, the outflow tract, and the perivalvular areas; it commonly
involves areas of scar.
All VTs can be attributed to 1 of 3 mechanisms: abnormal automaticity,
triggered activity, and reentry. Abnormal automaticity refers to impulse
formation by a region of ventricular cells at an accelerated rate compared
with normal (?50 bpm), due to an altered threshold for inward ventricular
myocyte sodium influx.21Accelerated idioventricular rhythms, frequently
observed in the setting of acute myocardial infarction, reperfusion,
myocarditis, or cocaine intoxication, are thought to occur based on this
mechanism.22Triggered activity results from oscillations in the mem-
brane potential that is dependent on the preceding action potential. Early
afterdepolarizations occur during phase II or III of the action potential and
have been shown to be responsible for many forms of drug- and
electrolyte-induced Torsades de pointes, and some forms of polymorphic
VT due to congenital long QT syndrome. Delayed afterdepolarizations
occur during phase IV of the action potential and are responsible for many
forms of outflow tract tachycardia and VT associated with digitalis
toxicity.23,24Finally, reentrant VT occurs commonly, but not exclusively,
in structurally abnormal myocardium and requires unidirectional conduc-
tion, fixed or functional conduction block, and a region of “slow
conduction” in which the tachycardia cycle length is longer than the
460 Curr Probl Cardiol, September 2010
longest refractory period in the circuit. Identification of the appropriate
mechanism may be important to the optimal treatment of the VT.
Although invasive electrophysiology study is often necessary, ECG clues
and the response to pharmacologic manipulation can prove suggestive or
even diagnostic (Table 2).
VT Associated with Organic Cardiac Disease. The most common
anatomic substrate for sustained monomorphic VT is chronic coronary
artery disease, with the vast majority of ventricular arrhythmias in
ischemic heart disease originating in the left ventricle or intraventricular
septum.25Each area of infarction is associated with a characteristic VT
morphology. Since in an inferior posterior infarction VT the ventricle is
activated from back to front, large R waves are usually present from V2
to V4with at least an R wave present through V6(Fig 4).25A left axis
generally denotes a septal VT exit site, or VT arising from the left
ventricular inferior wall. A right and superior axis places the exit site on
the inferolateral wall. Anterior infarctions are typically associated with a
larger area of myocardial damage, which decreases the accuracy of the
ECG in localizing the “origin” of the VT. VT from an anteroseptal site is
characterized by a LBBB or RBBB morphology with QS complexes
across the precordium (negative concordance), and a Q wave in leads I
TABLE 2. The degree to which specific ECG clues support each of the 3 VT mechanisms
Brugada ECG pattern
ECG of VT(s)
Outflow tract morphology
Paired VT morphologies
?1 VT morphology
Initiates with same VPD
Exercise testing initiates
Termination with adenosine
VT in the setting of digoxin toxicity
Zero ? does not lend support for or against this mechanism; ? ? supports this mechanism;
?? ? strongly supports this mechanism.
(Reproduced with permission from Riley MP, Marchlinski FE. J Cardiovasc Electrophysiol
Curr Probl Cardiol, September 2010461
and aVL. Apical VT generally has a RBBB pattern and a right and
superior axis. QS complexes in the anterolateral leads (V4-V6) reflect
apical origin whether septal or lateral. A predominant R wave in V5/V6
suggests a basal exit. A scheme for ECG prediction of VT exit sites,
developed and validated by Miller and colleagues, organizes these
principles (Fig 5).19,26
Ischemic VT is typically the consequence of electrical heterogeneity
developed because of an extensive healed MI. The healing process
following myocardial infarction creates an area of scar with islets of
viable cells interspersed among the fibrosis.27Conduction through this
zone is slow and discontinuous, most likely because of abnormalities in
gap junction distribution and function.28The electrophysiologic substrate
for VT is present in many within the first 2 weeks following infarction,29
although scar evolution may alter the tachycardia cycle length and even
lead to VT presentation 40 years after an inferior infarction.1Although
triggers, such as acute ischemia, surges in autonomic tone, or the onset of
FIG 4. Precordial concordance during VT. Negative concordance is seen during VT that arises
from the anterior-most regions of the ventricle, typically in anterior apical infarction (A). Positive
concordance is seen during VT that arises from the posterior-most regions, such as the basal
inferior wall (B). LV, left ventricle; RV, right ventricle; VT, ventricular tachycardia. (Reproduced
with permission from Josephson and Callans DJ.25)
462 Curr Probl Cardiol, September 2010
clinical heart failure, may induce VT, the anatomic substrate for VT both
precedes and outlasts these transient events.
Fred Morady: The fact that ventricular tachycardia may first occur decades
after a myocardial infarction is the reason that the MADIT II criteria for an
implantable cardioverter-defibrillator (ICD) for primary prevention of sudden
death apply even to patients who have had a stable course for ?10 years
after a myocardial infarction.
The severity of myocardial necrosis and left ventricular dysfunction and
the degree of septal involvement largely dictate future arrhythmic
risk.30,31A more extensive infarction, particularly coupled with a discrete
left ventricular aneurysm, predispose to stable VT more frequently than
nonsustained VT or sudden cardiac death (SCD).32Josephson has
reported that patients with VT have lower ejection fractions (27%) than
FIG 5. Scheme of regions of ventricular tachycardia exit sites in postinfarction patients. INF,
inferior axis; L, left; LBBB, left bundle branch block; R, right; RBBB, right bundle branch block;
Rev, reverse; RWP, precordial R-wave progression pattern; SUP, superior axis. (Reproduced
with permission from Miller and Scherscel.26) (Color version of figure is available online.)
Curr Probl Cardiol, September 2010463
patients with SCD (35%) or nonsustained VT (37%).1Despite improving
outcomes due to modern revascularization techniques, an aging popula-
tion and greater survival rates have stabilized the total number at risk for
ventricular arrhythmias and SCD.33
In nonischemic dilated cardiomyopathy, VT typically originates in a
region of scar around the mitral or tricuspid valve or from the subepicar-
dium.34Depending on particular perivalvular location, LBBB or RBBB
pattern and various axes are possible, but generally there are tall R/Rs
waves across V2-V6(Fig 6). Epicardial foci are generally identified on
ECG by slurring of the initial part of the QRS complex (pseudodelta
wave).35This was quantified by the novel measurement of the maximum
deflection index, which is defined as the time to maximum deflection in
any precordial lead divided by the QRS duration; a value of ?0.55
identified epicardial VT with a high sensitivity and specificity.36
The data regarding VT mechanism in nonischemic cardiomyopathies
are more limited, compared with ischemic VT. One study of epicardial
grid mapping in explanted hearts with a nonischemic cardiomyopathy
FIG 6. Typical ECG morphologies of clinical arrhythmias originating from the basal left
ventricular region that were localized based on site of successful ablation to the septal,
parahisian, AMC, superior MA, and superolateral MA location. QRS morphology in leads I
and V1, together with the ratio of QRS complexes in leads II/III and the precordial transition
pattern, can reliably distinguish medial from lateral locations in this region. AMC, aortomitral
continuity; MA, mitral annular. (Reproduced with permission from Dixit et al.66)
464 Curr Probl Cardiol, September 2010
demonstrated areas of slow conduction and nonuniform anisotropic
propagation in a large proportion of the hearts, indirectly suggesting
reentry as a likely VT mechanism.37Conversely, another study that
performed 3-dimensional intramural mapping found all beats of VT
induced by programmed stimulation to be initiated by a focal mechanism
arising primarily from the subendocardium.38While there were areas of
functional conduction delay and block, in the epicardium primarily, these
sites were consistently distant from sites of focal initiation. Mapping of
spontaneous nonsustained VT, couplets, and premature ventricular con-
tractions (PVCs) likewise revealed a focal mechanism to be responsible
for the initiation and maintenance of the rhythm. While none of the
human studies had sufficient mapping resolution to rule out micro-
reentry, 3-dimensional mapping in an arrhythmogenic rabbit model of
heart failure at a much higher resolution revealed similar focal activation.39
Of note, there are some data supporting a focal mechanism for a portion
of the VTs that occur in ischemic heart failure patients as well. A study
of intraoperative 3-dimensional cardiac mapping of sustained VT induced
by programmed stimulation revealed that only 50% of cases were due to
intramural reentry involving delayed conduction and fixed anatomical or
functional conduction block.40In the other 50% of cases, the sustained
monomorphic VT appeared to be initiated by a focal mechanism, based
on the lack of electrical activity between beats of VT, when multiple
intervening electrode recording sites were present.
On a cellular level, triggered activity arising from delayed and/or early
afterdepolarizations has been hypothesized to occur, in part due to action
potential prolongation and intracellular calcium overload.41,42In support
of this theory, norepinephrine has been shown to induce both delayed and
early afterdepolarizations in ventricular myocytes from failing human
hearts.43In addition, beta-adrenergic stimulation has been shown to
induce delayed afterdepolarizations in the arrhythmogenic rabbit heart
failure model.39Finally, downregulation and dephosphorylation of gap
junction proteins, such as connexin 43, may account for the conduction
delay observed in the hearts with a nonischemic cardiomyopathy,44,45as
the degree of interstitial fibrosis at the sites of focal initiation was variable
on histologic analysis.38
In addition to the usual ischemic VT and the perivalvular/subepicardial
VT seen in nonischemic cardiomyopathies, bundle branch reentrant VT
merits specific mention. It constitutes about 5%-8% of monomorphic VT
associated with structural heart disease, and up to one third of the
inducible sustained VTs at electrophysiology study in those with a
nonischemic cardiomyopathy or prior valve surgery.46,47Three categories
Curr Probl Cardiol, September 2010465
have been described.48Type A is most common and is a counterclock-
wise reentrant circuit with the right bundle branch responsible for
anterograde conduction and the left bundle branch the retrograde conduc-
tion, producing a LBBB morphology (Fig 7); type C is a clockwise circuit
producing a RBBB morphology, and type B is interfascicular reentry
within the fascicles of the left bundle. Although this arrhythmia may
present in patients with normal ventricular function, typically patients
have some structural heart disease, often with evidence of conduction
system disease on their baseline ECG, and a prolonged His-ventricular
(HV) interval at electrophysiology study.49As it uses the heart’s
conduction system, bundle branch reentrant VT is usually rapid, resulting
in hemodynamic compromise and malignant symptoms, such as syncope,
presyncope, or sudden cardiac arrest in over 70% of patients.50
Finally, 3 other cardiomyopathies that should be distinguished from an
idiopathic VT presentation are arrhythmogenic right ventricular cardio-
myopathy, cardiac sarcoidosis, and hypertrophic cardiomyopathy. Ar-
rhythmogenic right ventricular cardiomyopathy is a disease of the cardiac
desmosomes, with resulting fibrous and fatty replacement of the right
ventricular myocardium, ventricular arrhythmias, and significant risk of
sudden cardiac death that appears exacerbated by exercise.51It may be
recognized by T-wave inversions in the right-sided precordial leads, an
abnormal signal averaged ECG, multiple right-sided VT morphologies,
and observation of structural abnormalities of the right ventricle by
imaging studies. Sarcoidosis is a multisystem disorder of unknown
etiology characterized by the formation of noncaseating granulomas in
affected tissue. Cardiac involvement is likely more common than recog-
FIG 7. Schematic diagram showing the circuits in 3 types of bundle branch reentry. LAF, left
anterior fascicle; LB, left bundle branch; LPF, left posterior fascicle; RB, right bundle branch.
(Reproduced with permission from Balasundaram et al.50)
466 Curr Probl Cardiol, September 2010
nized based on autopsy studies,52,53and those with cardiac involvement
are at higher risk of death.54Ventricular tachycardia in sarcoidosis is
primarily reentrant due to slow conduction in areas of fibrosis, although
automatic foci have also been reported.55Hypertrophic cardiomyopathy
is the most common genetic cardiac disease and the most common cause
of SCD in young athletes. It is extremely heterogeneous in both its
genotype and its phenotype, with varying degrees of myocyte hypertro-
phy, disarray, and fibrosis. This substrate likely facilitates reentrant VT,
which is then triggered by other factors, such as ischemia, outflow tract
obstruction, altered autonomic tone, rapid conduction along an accessory
pathway, or paroxysmal atrial fibrillation.56,57
Fred Morady: The abnormal signal-averaged electrocardiogram in arrhyth-
mogenic right ventricular cardiomyopathy may be reflected by a deflection at
the terminal portion of the QRS complex (an epsilon wave) on a standard
Idiopathic VT. Idiopathic VT, ventricular tachycardia absent structural
heart disease or coronary artery disease, constitutes about 10% of the VT
cases evaluated by electrophysiology centers in the USA.58Right
ventricular outflow tract (RVOT) tachycardia is the most common form
of idiopathic VT and was the first recognized, but subsequently multiple
etiologies of monomorphic idiopathic VT have been described (Table 3).59
RVOT VT may either present as nonsustained repetitive monomorphic
VT wherein exercise often suppresses the tachycardia or as paroxysmal
exercise-induced sustained VT.60It is believed to be triggered by
catecholamine-mediated delayed afterdepolarizations.12Outflow tract VT
is now more broadly thought to be VT arising from an anatomic arc
connecting the anteroseptal aspect of the RVOT to the cusp region of the
aortic valve and the anterior left ventricle in front of the aortic valve, both
endocardially and epicardially, and further extending toward the aorto-
mitral continuity and superior mitral annulus.61VT arising from remnants
TABLE 3. Idiopathic monomorphic ventricular tachycardia subtypes
● Outflow tract VT: RVOT-VT, LVOT-VT, aortic cusp VT
● Fascicular VT: LAF-VT, LPF-VT, septal VT
● Adrenergic monomorphic VT
● Annular VT: mitral annular VT, tricuspid annular VT
Abbreviations: LAF, left anterior fascicular; LPF, left posterior fascicular; LVOT, left ventricular
outflow tract; RVOT, right ventricular outflow tract; VT, ventricular tachycardia.
(Reproduced with permission from Badhwar and Scheinman59).
Curr Probl Cardiol, September 2010 467
of embryonic muscle sleeves in the pulmonary artery has been described
and may be distinguished from RVOT VT by larger R-wave amplitude in
the inferior leads, larger avL/avR Q-wave amplitude ratio, and larger R/S
amplitude in V2.62,63Left ventricular outflow tract and aortic cusp VT share
many characteristics with RVOT VT, but generally may be distinguished by
ECG pattern, with RVOT VT having a later precordial transition (Table 4).64
Here tachycardia emanates from myocardial fibers in the interstices between
less commonly the right coronary cusp, and seldom the noncoronary cusp.65
VT from the aortomitral continuity may be recognized by a qR or broad R in
V1and Rs/rs complex in lead I.66
Fred Morady: The noncoronary cusp typically overlies the atrial septum and
is void of ventricular muscle fibers. This is why ventricular tachycardia rarely
arises in the noncoronary cusp.
Idiopathic left ventricular tachycardia or fascicular VT arises from the
fascicles in the left ventricle. This VT typically presents at a young age,
with a slight male predominance.67While most VT episodes occur when
the patient is at rest, VT can be triggered by exercise or emotional stress,
and incessant tachycardia of this type has been described.68,69The
verapamil-sensitive reentrant fascicular VT is the best-known, but trig-
gered adenosine sensitive VT, and automatic propranolol sensitive
idiopathic left VT have also been described.70The ECG of fascicular
VT can be difficult to distinguish from SVT with aberrancy, as the
QRS duration is typically only 140-150 ms and mimics that of a
traditional RBBB with a left anterior or posterior fascicular block.
TABLE 4. Electrocardiographic findings suggesting VT origin from the aortic cusp
● Early transition in precordial leads (V1, V2)
● Tall R-waves in the inferior leads
● Notch in V5, lack of S in V5, V6
● Broad R-wave in V1, V2
● Larger R/S amplitude wave in V1, V2
● Notch in V1in left cusp VT (transeptal conduction)
● Lead I shows rS in left cusp VT; notched R in noncoronary cusp VT
● Phase analysis as measured from the earliest QRS onset to:
a. QRS onset in V2?7 ms
b. Initial peak/nadir in III ?120 ms
c. Initial peak/nadir in V2?78 ms
(Reproduced with permission from Badhwar and Scheinman59).
468 Curr Probl Cardiol, September 2010
Fred Morady: Nonreentrant catecholamine-mediated ventricular tachycardia
from the right ventricular outflow tract often is adenosine-responsive.
Adrenergic monomorphic VT is sometimes referred to as propranolol-
sensitive automatic VT.70This rare form of VT occurs generally in young
patients and may originate from either ventricle, giving rise to either a
RBBB and/or a LBBB morphology. Indeed, some patients may actually
present with pleomorphic VT.59It is initiated with exercise and cat-
echolamines. As the name implies, it is thought to be an automatic rhythm
arising in the Purkinje fibers that are mediated by pacemaker current If.
Patients with mitral annular VT typically present with palpitations and
repetitive monomorphic VT or frequent monomorphic PVCs.71The VT
classically has a RBBB pattern and monophasic R or Rs waves in leads
V2-V6. The arrhythmia appears to have a triggered mechanism, with some
tachycardias terminating with adenosine and intravenous verapamil. A
remnant of the atrioventricular conduction system close to the aortomitral
continuity, such as a “dead-end” tract, may play a role.72Tricuspid
annular VT, originating preferentially from the septal region of the right
ventricle, has also been described.73
Idiopathic epicardial VT generally originates from a perivascular
location, with clustering in the region adjacent to the aortic sinus of
Valsalva, the great cardiac vein, the anterior interventricular vein, the
middle cardiac vein, and other areas of the coronary venous system, or
around the coronary arteries.36,74-76These VTs are generally respon-
sive to catecholamines and terminate with adenosine, which together
with inability to entrain the tachycardia at electrophysiology study
suggest a triggered mechanism.36,77Multiple published ECG criteria
may be used to predict epicardial VT origin; as described above,
perhaps simplest and best-known among them is the maximum
deflection index, a ratio of onset-peak/total QRS duration of ?0.55.36
VT Associated with Organic Cardiac Disease. In the acute setting
intravenous antiarrhythmic medication may be helpful for patients who
do not require immediate cardioversion or for whom recurrence is an
issue (Table 5). Procainamide is recommended for initial treatment in
hemodynamically stable patients, as its onset of action is relatively fast.78
In the presence of heart failure or severe left ventricular dysfunction,
transient hypotension may result, and close monitoring is required.79Amioda-
Curr Probl Cardiol, September 2010469
rone has proven useful in hemodynamically unstable and recurrent VT,80,81and
lidocaine might be considered in patients with acute myocardial ischemia or
infarction.82Notably, beta-blockers work synergistically with membrane stabi-
lizing agents and should not be overlooked in the acute setting.83
TABLE 5. Common antiarrhythmic dosages for acute and chronic therapy of ventricular
IV: 300 mg bolus; if VF/VT recurs, supplemental dose of 150 mg
followed by infusion of 1 mg/min for 6 hours, then 0.5 mg/min
(maximum daily dose: 2.1 g)
IV: Infuse 20 mg/min until arrhythmia is controlled, hypotension occurs,
QRS complex widens by 50% of its original width, or total of 17 mg/
kg is given
IV: 1-1.5 mg/kg, if VT/VF recurs, may repeat 0.5-0.75 mg/kg boluses
every 5-10 minutes up to 3 doses. Maximum: 3 mg/kg. Follow with
continuous infusion (1-4 mg/min).
ET: (loading dose only): 2-2.5 times the I.V. dose. Decrease dose if
CHF, shock, or hepatic disease.
Abbreviations: CHF, chronic heart failure; ET, endotrachial tube; IV, intravenous; N/a, not
applicable; VF, ventricular fibrillation; VT, ventricular tachycardia.
470 Curr Probl Cardiol, September 2010
In the event that the patient becomes hemodynamically unstable or is not a
suitable candidate for pharmacologic therapy, electrical cardioversion is the
definitive short-term therapy. Occasionally, VT may be pace-terminated via
an implanted device or epicardial pacing leads in a postsurgical patient.
TABLE 5. Continued
IV therapyOral therapy
Breakthrough: 150 mg
supplemental doses over 10
Loading: 800-1600 mg/day in 1-2 doses for 1-3
weeks; once adequate arrhythmia control, decrease
to 600-800 mg/day in 1-2 doses for 1 month
Maintenance: 400 mg/day
Reduce dose if significant renal or hepatic
Loading: 15-18 mg/kg infusion over
25-30 minutes. Reduce loading
dose to 12 mg/kg in severe renal
or cardiac impairment.
Maintenance: 1-4 mg/minute
infusion. Maintenance infusions
should be reduced by 1/3 if
moderate renal or cardiac
impairment and by 2/3 if severe
Breakthrough: 0.5 mg/kg bolus and
reassessment of infusion
Loading: 200 mg every 8 hours (may load with 400
mg if necessary); adjust dose every 2-3 days.
When switching from other antiarrhythmic: 200 mg
dose 6-12 hours after stopping former agents,
3-6 hours after procainamide
Maintenance: 200-300 mg every 8 hours;
maximum: 1.2 g/day
Patients with hepatic impairment or CHF reduce
dose to 25% to 30% of usual dose
Loading: 80 mg twice daily; dose may be increased
gradually to 240-320 mg/day; adjust dose every
3 days. QTc interval must be monitored.
Maintenance: 160-320 mg/day in 2-3 divided doses.
Maximum: If life-threatening refractory VT/VF may
require doses as high as 480-640 mg/day
Reduce dose in renal failure
Loading: 75 mg infused over 5
hours twice daily. QTc interval
must be monitored. If the
frequency of relapse does not
reduce and excessive QTc
prolongation does not occur, may
increase dose every 3 days in
increments of 75 mg/day.
Maintenance: 75-150 mg twice daily.
Maximum: 300 mg twice daily.
Curr Probl Cardiol, September 2010471
Importantly, any potentially causative or aggravating conditions should be
sought out and reversed, such as hypokalemia, proarrhythmic drugs, volume
overloaded state, or ischemia. Coronary revascularization has been proven to
frequency and complexity of arrhythmias, although no controlled trials have
examined the impact of revascularization on VT/ventricular fibrillation
(VF).84,85It should be noted, however, that sustained monomorphic VT in
patients with remote MI is not likely to be affected by revascularization86nor
is myocardial revascularization expected to prevent recurrent cardiac arrest in
patients with markedly abnormal left ventricular (LV) function and obviate
the need for ICD.87Sedation may help decrease sympathetic tone, fueling the
VT. Drug-induced narcosis and left cervical sympathectomy, a treatment
most frequently adopted for patients with long QT syndrome or cat-
echolaminergic polymorphic VT, may be considered in patients who have
failed other therapies. Finally, a recent study of patients in incessant VT
(electrical storm) reported that catheter ablation acutely suppressed the VT in
all 95 patients, and 66% were free of VT recurrence at median follow-up of
almost 2 years.88
Once the patient is stable and the arrhythmia more under control,
attention often turns to minimizing recurrence, and further, prevention of
SCD. In their ubiquity of purpose, safety, and proven effectiveness,
beta-blockers rank foremost among antiarrhythmic drugs for treatment of
VT and prevention of SCD.89Purported mechanisms include competitive
adrenergic-receptor blockade of sympathetically mediated triggering
mechanisms, slowing of the sinus rate, and possibly inhibition of excess
calcium release by the ryanodine receptor, in addition to anti-ischemic
effects.90Among patients with left ventricular dysfunction and heart
failure, carvedilol, extended release metoprolol, and bisoprolol have been
proven to lower all-cause mortality and sudden cardiac death, and
observational studies suggest that this mortality benefit may extend to
other beta-blockers.91-94Beta-blockers have also been shown to reduce
mortality and SCD in postmyocardial infarction patients without heart
failure95and to reduce ventricular tachycardias and PVCs.96,97
Other antiarrhythmic drugs are generally not recommended for primary
therapy in the management of ventricular arrhythmias and prevention of
SCD, due to lack of proven efficacy and potential for adverse events,
including, but not limited to, proarrhythmia.98Of note, adenosine and
verapamil should be particularly avoided in ischemic VT given risk of
coronary steal, producing increased ischemia and higher mortality. Similarly,
1C agents are contraindicated in patients with structural cardiac disease.99
Survival benefit from amiodarone is controversial at best. Meta-analysis
472 Curr Probl Cardiol, September 2010
found amiodarone to be beneficial in terms of arrhythmic/sudden death and,
depending on statistical analysis used, overall mortality among those with
recent MI or heart failure,100although individual trials failed to find a
significant reduction in overall mortality accompanying the decrease in
arrhythmic/sudden death.101,102A European Myocardial Infarct Amiodarone
Trial Investigators substudy reported that amiodarone in combination with
beta-blockers improved survival in the post-MI population,103yet the more
recent Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) found
amiodarone to have no favorable effect on mortality in optimally mediated
patients with ischemic or nonischemic heart failure.104Sotalol also has been
shown to reduce ventricular arrhythmias, but not overall mortality.105Both
drugs have been demonstrated to reduce the frequency of ICD shocks.106,107
Thus, American College of Cardiology/American Heart Association (ACC/
AHA) guidelines generally reserve consideration of amiodarone or sotalol as
primary therapy of VT to patients who do not meet criteria for ICD or choose
against it; monitoring for adverse effects is recommended.98Finally, those
with VT storm, with or without a defibrillator, should be treated with
amiodarone and beta-blockers, or if there is no significant left ventricular or
renal dysfunction, sotalol should be considered. Of note, there is increasing
evidence that other drug classes, such as n-3 fatty acids and statins, may
reduce life-threatening ventricular arrhythmias.108,109
Fred Morady: Long-chain polyunsaturated fatty acids (fish oil) have been
shown in some randomized studies to decrease the incidence of appropriate
ICD therapies, but in other studies have been shown to have no effect.
of VT/VF and those at high risk for life-threatening arrhythmia due to left
ventricular dysfunction (Fig 8).104,110-115A meta-analysis of the 3 secondary
prevention trials found an absolute reduction in all-cause mortality of 7% and
a significant 25% relative reduction in mortality compared with amiodarone
therapy, due entirely to a 50% reduction in sudden cardiac death.116This
translates to 1 life saved for every 15 defibrillators implanted. Current
ACC/AHA/Heart Rhythm Society guidelines recommend ICD implantation
for most survivors of sudden cardiac arrest not due to a transient or reversible
cause.117ICD implantation is considered reasonable for those with sponta-
neous sustained VT with or without structural heart disease, although it
should be noted that ICDs have not been shown to be superior to antiar-
rhythmic drugs in those with a left ventricular ejection fraction ?35%.110
Additionally, an ICD was recommended for those with unexplained syncope
Curr Probl Cardiol, September 2010473
and clinically relevant, hemodynamically significant sustained VT or VF
the basis of ischemic or nonischemic cardiomyopathy.
While VT ablation in patients with structural heart disease has traditionally
been considered adjunctive therapy, appropriate for those who have failed
pharmacologic options and/or suffer extreme ICD shocks or VT storm, over
the last several years a more primary role for ablation in this population is
being explored. This stems in part from increasing awareness of the hazard
of sustained VT episodes. Multiple studies have shown that these episodes
are a marker for increased mortality and reduced quality of life in patients
with structural heart disease and ICDs.118-120Further, as those with both
appropriate and inappropriate shocks have increased mortality compared
with those without any shocks, the possibly that shocks may have negative
inotropic consequences, thereby increasing the risk of death as opposed to
just being a marker of increased risk, has been proposed.121A randomized
trial of prophylactic VT ablation at the time of ICD implantation in patients
with spontaneous or induced VT following an MI found the ablation group
FIG 8. Major ICD trials. Hazard ratios (vertical line) and 95% confidence intervals (horizontal
lines) for death from any cause in the ICD group compared with the non-ICD group. *Includes
only ICD and amiodarone patients from CASH. CABG, coronary artery bypass graft surgery;
EP, electrophysiological study; LVD, left ventricular dysfunction; LVEF, left ventricular ejection
fraction; MI, myocardial infarction; N, number of patients; NICM, nonischemic cardiomyopa-
thy; NSVT, nonsustained ventricular tachycardia; PVCs, premature ventricular complexes;
SAECG, signal-averaged electrocardiogram. (Reproduced with permission from Zipes et al.98)
474 Curr Probl Cardiol, September 2010
to have significantly fewer VT or VF events (12% vs 33%), which also
resulted in significantly fewer ICD shocks.122Advances in technology and
conceptual understanding now allow for the ablation of multiple and unstable
VTs with acceptable safety and efficacy, leading to a broadening in the
recommended role of ablation by the European Heart Rhythm Association/
Heart Rhythm Society Expert Consensus (Table 6).123
Fred Morady: The Ventricular Tachycardia Ablation in Addition to Implant-
able Defibrillators in Coronary Heart Disease (VTACH) trial enrolled patients
TABLE 6. Indications for catheter ablation of ventricular tachycardia
Patients with structural heart disease (including prior MI, dilated cardiomyopathy, ARVC/D)
Catheter ablation of VT is recommended
For symptomatic sustained monomorphic VT (SMVT), including VT terminated by an ICD
that recurs despite antiarrhythmic drug therapy or when antiarrhythmic drugs are not
tolerated or not desireda
For control of incessant SMVT or VT storm that is not due to a transient reversible cause
For patients with frequent PVCs, NSVTs, or VT that is presumed to cause ventricular
For bundle branch reentrant or interfascicular VTs
For recurrent sustained polymorphic VT and VF that is refractory to antiarrhythmic therapy
when there is a suspected trigger that can be targeted for ablation.
Catheter ablation should be considered
In patients who have one or more episodes of SMVT despite therapy with 1 of more Class I
or III antiarrhythmic drugsa
In patients with recurrent SMVT due to prior MI who have LV ejection fraction ?0.30 and
expectation for 1 y of survival and is an acceptable alternative to amiodarone therapya
In patients with hemodynamically tolerated SMVT due to prior MI who have reasonably
preserved LV ejection fraction (?0.35) even if they have not failed antiarrhythmic drug
Patients without structural heart disease
Catheter ablation of VT is recommended for patients with idiopathic VT
For monomorphic VT that is causing severe symptoms
For monomorphic VT when antiarrhythmic drugs are not effective, not tolerated, or not desired
For recurrent sustained polymorphic VT and VF (electrical storm) that are refractory to
antiarrhythmic therapy when there is a suspected trigger that can be targeted for ablation.
VT catheter ablation is contraindicated
In the presence of a mobile ventricular thrombus (epicardial ablation may be considered)
For asymptomatic PVCs and/or NSVT that are not suspected of causing or contributing to
For VT due to transient, reversible causes, such as acute ischemia, hyperkalemia, or drug-
induced Torsades de pointes
Abbreviations: ARVC/D, arrhythmogenic right ventricular cardiomyopathy/dysplasia; ICD, implant-
able cardioverter defibrillator; MI, myocardial infarction; VT, ventricular tachycardia; VF, ventricular
aThis recommendation for ablation stands regardless of whether VT is stable or unstable, or
multiple VTs are present. (Reproduced with permission from Aliot et al.123)
Curr Probl Cardiol, September 2010475
with prior myocardial infarction, hemodynamically stable ventricular tachy-
cardia, and an ejection fraction ?50%. The study demonstrated that catheter
ablation before ICD implantation prolonged the time to first recurrence of
ventricular tachycardia by ?1 year, with no effect on survival.
The role of ablation is worth particular mention for those suspected of
having bundle branch reentrant VT where ablation of the right bundle branch
is curative.124,125Of note, as other scar-related VTs are inducible in up to
60% of patients, ICD placement is usually recommended as well. Addition-
ally, patients with very frequent, predominantly monomorphic PVCs that are
associated with symptoms and/or cardiomyopathy may be considered for
ablation to alleviate symptoms and reverse left ventricular dysfunction.126
Generally, a PVC burden of 20,000/24 hours or ?20% of total beats have
been reported in association with LV dysfunction, although a recent study by
Bogun and colleagues found that more than 1/3 of patients with ?10 PVCs/h
had a reduced left ventricular ejection fraction, with an inverse relationship
between the burden of PVCs and the left ventricular ejection fraction.127
Successful ablation appears to result in significant improvement, and often
complete normalization, of the left ventricular function in the vast majority of
patients.126,127Although PVCs from the RVOT are the most commonly
reported in this context, patients with PVCs from other sites of origin appear
equally likely to develop a cardiomyopathy as well as to benefit from
more sophisticated, and in recent years percutaneous subxiphoid approach for
epicardial mapping and ablation has increased in practice among electrophysiol-
ogy laboratories, as well. Together with the advent and adoption of the ICD, this
has resulted in surgical ablation or resection of an arrhythmogenic focus to
generally be reserved for patients with recurrent VT refractory to drugs,
implanted defibrillators, and radiofrequency catheter ablation. That said, aneu-
rysm resection, particularly in combination with electrophysiology map-guided
resection of arrhythmogenic ventricular myocardium, may reduce or eliminate
ventricular arrhythmias in selected patients.129Cardiac transplantation remains
the final option when recurrent, symptomatic VT is refractory to medications,
ablation, ICD therapy, and surgery.
Idiopathic VT. MostpatientswithidiopathicVThaveanexcellentprognosis,
provided that they were correctly diagnosed. For example, it is important to
distinguish the LBBB VT originating from the RVOT in an otherwise healthy
ventricle from that caused by arrhythmogenic right ventricular cardiomyopathy
476 Curr Probl Cardiol, September 2010
or cardiac sarcoidosis. The sinus rhythm ECG should be carefully reviewed, as
any abnormality should increase suspicion for underlying structural disease. The
massage, verapamil, and lidocaine, all of which suppress triggered rhythms.
Beta-blockers and calcium channel blockers are considered first-line therapy for
long-term suppression, with synergistic action when combined, and efficacy in
25%-50% of patients.131,132Antiarrhythmic drugs have also been demonstrated
to suppress VT episodes, with sotalol trending toward superiority in 1 study.133
Catheter ablation has a reported success for outflow tract tachycardias of greater
than 90% with a recurrence rate of 5%.134,135When ablating in the aortic cusp,
care must be taken to avoid the ostia of the coronary arteries as well as damage
to the aortic valve. Based on the speed of VT termination with appropriately
placed lesions in their series, Ouyang and colleagues recommend that ablation
applications not extend beyond 10 seconds if the tachycardia has shown no
response up to that point.64
Fred Morady: The guidelines of the Heart Rhythm Society indicate that
catheter ablation also is appropriate first-line therapy for outflow tract
Acute termination of fascicular VT can be achieved with intravenous
verapamil, and oral verapamil, 120-480 mg d?1may be used.59Those
with more severe symptoms, or for whom antiarrhythmic therapy is
intolerable or ineffective, may benefit from ablation. There are multiple
different ablation strategies reported, among them targeting the earliest
high-frequency Purkinje potential during VT136,137or sites with retro-
grade Purkinje potentials during sinus rhythm,138and successful ablation
sites have stretched from the basal septum139to the apical inferior septal
region.136Of note, pace-mapping is not very effective, as pacing of the
Purkinje network that is not critical to the reentrant circuit can yield a
perfect pace map. Long-term success rates of about 90%, with rare
complications have been reported.68,136,137,140
Adrenergic monomorphic VT is responsive to beta-blockers, but not
verapamil.141Adenosine transiently suppresses but does not terminate the
tachycardia. The role of ablation is not well-defined, although 1 study
found that varying ECG morphologies led to a poor response to catheter
Curr Probl Cardiol, September 2010477
Mitral annular VT has been reported to acutely terminate with adeno-
sine, 10-40 mg, and intravenous verapamil.143Activation and pace
mapping have been reported to be successful ablation strategies with
acute success obtained in all patients in 2 series.71,143Ablation from
within the coronary sinus was required for some patients, and a recurrence
rate of 8% was reported in 1 of the series.143
Epicardial VT is increasingly being treated with percutaneous ablation
following dissemination of the subxiphoid pericardial puncture technique
developed by Sosa and colleagues.144Ablation through the coronary
veins may also be successful.36With either technique care must be taken
to avoid ablation near an epicardial coronary artery, and coronary
angiography is routinely recommended. Additionally, pacing to identify
phrenic nerve capture can help avoid ablation-induced diaphragmatic
paralysis. Hemopericardium, reported to occur in 30% of pericardial
ablation cases by 1 investigator, is usually not significant,145and resulting
symptomatic pericarditis generally responds well to anti-inflammatory
Polymorphic VT may be associated with normal or abnormal ventric-
ular repolarization, manifesting as a long QT interval. Polymorphic VT in
the setting of a normal QT interval is most frequently seen in the context
of acute ischemia or MI.147In the immediate post-MI period polymorphic
VT is generally thought to indicate ongoing or recurrent ischemia and has
been shown not to be consistently related to an abnormally long QT
interval, sinus bradycardia, preceding sinus pauses, or electrolyte abnor-
mality. The excessive dispersion of repolarization in ischemic polymor-
phic VT is due to uneven shortening of the action potential in different
myocardial layers, enabling reentrant arrhythmias triggered by extrasys-
toles with very short coupling intervals.148,149
Torsades de pointes or “twisting of the points” denotes polymorphic VT
generally occurring in the setting of a long QT interval and characterized
by QRS complexes of changing amplitude that appear to “twist” around
the isoelectric line.150Torsades may present with short self-terminating
bursts and cause palpitations and syncope, or be sustained and deteriorate
into VF causing cardiac arrest. Outside of the context of congenital
syndromes, such as long QT syndrome, Torsades occurs most frequently
following exposure to a QT-prolonging drug; additionally, metabolic
abnormalities, heart block, nervous system injury, and heart failure may
serve as acquired precipitants.151
478 Curr Probl Cardiol, September 2010
Acquired Precipitants and Torsades de Pointes
Significant QT prolongation, possibly associated with Torsades, occurs
in 1%-10% of patients receiving QT-prolonging antiarrhythmic drugs and
in even more who receive “noncardiovascular” QT-prolonging agents.98
Multiple drugs with QT-prolonging potential have been identified; for an
up-to-date list, the reader is referred to http://www.torsades.org or
http://www.qtdrugs.org. Classically, drug-induced Torsades is bradycar-
dia dependent and initiated by a “short-long-short” sequence that is a
PVC followed by a pause, then a normally conducted beat, then another
PVC, occurring in the context of a QT interval of ?500 ms. There are
often prominent U waves on the ECG as well. Frequently those who
develop drug-induced Torsades have 1 or more additional risk factors
(Table 7).152Of note, 5%-10% of persons who develop Torsades de
pointes on exposure to QT-prolonging drugs harbor mutations associated
with the long QT syndrome and thus are considered to have a subclinical
form of the congenital syndrome.153-155Additionally, common polymor-
phisms (with frequencies up to 15% in certain populations) that cause
subtle variations in the functions of channels that contribute to the
generation of the cardiac action potentials might become unmasked and
contribute to the development of Torsades de pointes only on exposure to
an IKr-blocking drug, hypokalemia, or heart failure.156-158
Typical pause-dependent Torsades following an MI has been reported to
occur without any evidence of recurrent ischemia.149This is postulated
to be facilitated by action potential prolongation of Purkinje fibers leading
to early afterdepolarizations and triggered arrhythmias, in the setting of
enhanced heterogeneity of repolarization across infarcted and healthy
tissue, which is maximal within a few days of an infarct, allowing for
TABLE 7. Risk factors for drug-induced Torsades de pointes
● Female gender
● Recent conversion from atrial fibrillation, especially with a QT-prolonging drug
● Congestive heart failure
● Digitalis therapy
● High drug concentrations (with the exception of quinidine)
● Rapid rate of intravenous infusion with a QT-prolonging drug
● Baseline QT prolongation
● Subclinical long QT syndrome
● Ion channels polymorphisms
● Severe hypomagnesemia
(Reproduced with permission from Roden DM.151)
Curr Probl Cardiol, September 2010479
multiple waves of reentry and Torsades.159,160Alternative theories have
also been proposed, such as downregulation of potassium channel gene
expression and potassium currents, with consequent action potential
prolongation and early afterdepolarizations, in the noninfarcted remod-
eled regions of the left ventricle.149,161Pause-dependent Torsades without
QT prolongation has also been reported in patients at varying stages
post-MI and without evidence of ongoing ischemia.162It is thought to be
triggered and possibly maintained by activity originating from the distal
Purkinje arborization in the border-zone of the MI.
Left ventricular dysfunction or structural heart disease can facilitate
Torsades. Areas of slow conduction, modified tissue, or cellular propen-
sity to increased dispersion of refractoriness, and general myocardial
damage are thought to enhance the production of early afterdepolariza-
tions and favor reentrant mechanisms.163Further, left ventricular ejection
fraction and presence of structural heart disease, together with relative
QTc dispersion, have been shown to be independent predictors of VF in
patients who experienced a documented pause-dependent Torsades de
pointes related to acquired long QT syndrome.164
Congenital Syndromes Associated with Polymorphic VT
The genetic arrhythmia syndromes are rare inherited diseases, with
estimated prevalence below 5/10,000 people.98They are characterized by
a genetically determined susceptibility to VT/VF and SCD without
recognizable structural abnormalities of the heart. Given their rarity, these
diseases generally lack randomized trials of any therapies, and instead
risk stratification schemes are largely derived from registries, with an
attendant bias toward inclusion of sicker and more symptomatic patients.
QT Syndromes. One of the oldest and richest registries was developed
to study the long QT syndrome. The long QT syndrome is a disorder
characterized by prolonged ventricular repolarization, manifest as a long
QT interval, leading to a significantly increased propensity for arrhythmic
syncope, Tosades, and sudden cardiac death. Multiple genetic deficits
have been identified, most involving ion channels, causing a reduction in
repolarizing potassium currents (loss of function) or an augmentation of
late inward sodium or calcium current (gain of function).165Inheritance is
typically autosomal dominant with variable penetrance, although about
15% of cases are due to a de novo mutation.
LQT1, LQT2, and LQT3 genotypes account for 97% of the mutations
identified in long QT syndrome patients.166Each of the genotypes has a
distinctive T-wave pattern (Fig 9), risk mechanism, and long-term clinical
480 Curr Probl Cardiol, September 2010
course. Specifically, individuals with LQT1 are most susceptible to
cardiac events occurring during exercise, while LQT2 patients are at
higher risk with auditory stimuli or emotion, and LQT3 patients have
most events during rest or sleep. Although LQT3 patients have the lowest
cardiac event rates, they have the highest probability of dying with an
event (20%).167The groups also differ in terms of responsiveness to
beta-blockade, with LQT1 patients showing the greatest benefit.
The short QT syndrome, first described in 2000, is the mirror image
disorder of the long QT syndrome.168It is defined by an abnormally
short QT interval on ECG, ?360 ms, with a range of 220-360 ms, with
an unusually flat QT/RR relationship and tall peaked T waves in the
precordial leads.168-170Affected patients have structurally normal
hearts, yet manifest a high incidence of SCD due to VF, in addition to
palpitations, syncope, and atrial fibrillation; indeed, atrial and ventric-
ular refractory periods are very short at electrophysiologic study.
Mutations in 5 different genes have been described, affecting potas-
sium and calcium channels.171-174Inheritance is believed to be
Catecholaminergic Polymorphic VT. Catecholaminergic polymorphic
VT is a relatively rare and highly lethal inherited arrhythmogenic disease.
Mutations in the ryanodine release channel lead to calcium “leak” from
the sarcoplasmic reticulum in the autosomal-dominant form,175while
mutations in calsequestrin, a sarcoplasmic reticulum buffering protein,
lead to the less common autosomal-recessive disease.176Patients may
initially present with VT, syncope, or SCD, following a physical or
emotional stress trigger, with first presentation often occurring during
FIG 9. Distinctive T-wave patterns in the 3 major LQTS genotypes: LQT1—typical broad-based
T-wave pattern; LQT2—typical bifid T-wave; LQT3—typical late-onset peaked/biphasic T-wave.
(Reproduced with permission from Moss AJ, Zareb W, Benhorin J, et al. Circulation 1995;92:
Curr Probl Cardiol, September 2010481
childhood or adolescence.177Baseline ECG is usually unremarkable, with
the possible exception of prominent U waves.178While the most typical
observed arrhythmia is bidirectional VT, SVTs also occur, and in fact
may act as a trigger for development of delayed afterdepolarizations in
the ventricle (Fig 10).
Short-Coupled Torsades. Another cause of Torsades occurs in patients
with a normal QT interval and is initiated by a short-coupled PVC falling
on the ascending limb of the T wave; the PVC follows the conducted beat
with a coupling interval of ?300 ms, compared with the 600-800 ms
classically seen in Torsades (Fig 11).179Like typical Torsades, the
short-coupled variant is manifest by polymorphic VT, with progressive
changes in morphology, amplitude, and polarity of the QRS complexes.150
In the original report of 14 young adult patients, 30% of subjects had a
family history of sudden death. They presented with syncope due to
ventricular arrhythmias, and isolated short-coupled PVCs; 10 of the 14
FIG 10. Exercise stress test in a patient with polymorphic VT and carrier of an RyR2mutation.
Ventricular arrhythmias are observed with a progressive worsening during exercise. Typical
bidirectional VT develops after 6 minutes of exercise at a sinus heart rate of approximately
120-130 beats/min. Arrhythmias rapidly recede during recovery. (Reproduced with permission
from Napolitano C, Priori SG. Catecholaminergic polymorphic ventricular tachycardia. In:
Zipes DP, Jalife, J, editors. Cardiac Electrophysiology from Cell to Bedside. 4th edition.
Philadelphia, PA: Saunders, 2004. p. 633-9.)
482 Curr Probl Cardiol, September 2010
were observed to have malignant Torsades that degenerated to VF. As
only 1 of the 14 patients in the series was inducible at electrophysiology
study, and given the short ventricular refractory periods observed, the
mechanism was initially believed unlikely to involve reentry. Subsequent
work by Shiga and coworkers found that nifekalant, a pure potassium
channel blocker, significantly prolonged the ventricular refractory period
and inhibited the Torsades without affecting the frequency of the
short-coupled PVCs, which were only abolished with intravenous vera-
pamil. They concluded that triggered early afterdepolarizations were
responsible for the initial short-coupled PVCs, while the shortness of
local ventricular refractory periods and heterogeneity of ventricular
refractoriness were responsible for the development and maintenance of
a reentrant tachycardia.180
Brugada Syndrome. The Brugada syndrome is characterized by syn-
cope and SCD typically in young otherwise healthy males, with a higher
incidence among southeast Asians.181,182SCD is due to VF and most
commonly occurs at night. Fever may serve as a provocateur. Mutations
in the SCN5A gene that encodes for the ? subunit of the cardiac sodium
FIG 11. Salvo of short-coupled variant of torsades de pointes (initiating PVCs all have coupling
intervals of ? 300 ms), with degeneration into ventricular fibrillation. S, second. (Reproduced
with permission from Leenhardt et al.179)
Curr Probl Cardiol, September 2010 483
channel gene account for about 18%-30% of Brugada syndrome cases.182,183
Diagnosis is made by ECG, with type I having J-point elevation in
V1-V3, often with an associated RBBB pattern, and type II described as
a “saddleback” deformity of the ST segments in the same leads, although
this finding is less specific. As sodium channel blockers and beta-blockers
provoke the ECG pattern, they are sometimes helpful in diagnosis and
conversely should be avoided in patients who are known to have this
disease. Patients with syncope and spontaneous Brugada ECG pattern are
considered at higher risk for SCD, while those who are asymptomatic and
with the ECG pattern intermittently or only with drug provocation are felt
to be at lower risk.
Early Repolarization Variants. Early repolarization is a common ECG
finding reported to occur in 1%-5% of the population.184,185While it has
generally been regarded as a benign normal variant, a specifically defined
subset wherein there is at least 1-mm elevation of the QRS-ST junction (J
point) in at least 2 inferior and/or lateral leads has been reported to be
more frequent in case subjects with idiopathic VF than in control
subjects.186The increased incidence of recurrent ventricular arrhythmias
in those with early repolarization, the accentuation of repolarization
before the onset of arrhythmia, and the concordance between the origin of
triggering beats and the region of early repolarization further support the
linkage between this ECG finding and arrhythmogenicity. It is thought
that heterogeneity of action potentials across the ventricular wall at the
end of phase 1 plays a role in the trigger and substrate of VF in these
patients.187An augmenting role of increased vagal tone has been
postulated on the basis of the high occurrence of death during rest or
sleep. An underlying genetic abnormality has not yet been proven,
although a case report describes an IK(ATP)gene mutation.188
Patients with polymorphic VT in the context of acute ischemia may
benefit from intravenous beta-blockade, which has been shown to
improve mortality in the setting of recurrent polymorphic VT following
MI.189Amiodarone also may be useful.98,190Coronary angiography
should be considered whenever ischemia is suspected as an etiology for
the VT, and treatment of heart failure or other associated and correctable
conditions should be undertaken. Offending drugs should be discontinued
whenever possible; metabolic abnormalities should be corrected, and
potassium and magnesium should be repleted. A subset of patients with
polymorphic VT in the setting of nonischemic or fully revascularized
ischemic cardiomyopathy, who have a high density of PVCs with VF
484 Curr Probl Cardiol, September 2010
triggered by an isolated PVC, has been treated with ablation of the local
Purkinje network along the scar border-zone with excellent results; about
90% of patients remained free from recurrent arrhythmias during follow-
up, although the number of patients treated thus far is small.162,191-193
Torsades de Pointes. Torsades may be effectively suppressed by
intravenous magnesium via a decrease in the amplitude of early afterde-
polarizations to subthreshold values.194,195Temporary pacing can be
life-saving in recurrent Torsades via a shortening of the QT interval and
suppression of ventricular ectopy. When Torsades is definitely caused by
acquired long QT syndrome, with pause-dependence and bradycardia,
and cardiac pacing cannot be started immediately, isoproterenol infusion
may be used.151Of note, experimental models suggest that isoproterenol
may prolong repolarization and promote early afterdepolarizations via
increased calcium release in congenital long QT syndrome and even some
cases of drug-induced Torsades.196,197Conversely, beta-blockers may be
used in recurrent Torsades not responsive to magnesium if the underlying
rhythm is sinus tachycardia and the patient is protected from excessive
pauses by cardiac pacing.151Sedation and anesthesia may also be helpful
in polymorphic arrhythmic storms.198
Congenital Arrhythmic Syndromes. Genetic testing is helpful in many
of the congenital arrhythmic syndromes. In the long QT syndrome it may
be used to provide more accurate risk stratification and to guide
therapeutic strategies. Beta-blockers are the first-choice therapy for
patients regardless of genotype,199although their benefit in LQT3 is
debated. They should be used with some caution in these patients, as
extremely low heart rates will increase dispersion of repolarization in
LQT3 and may facilitate Torsades.200A reduction in risk of cardiac
events in excess of 60% has been reported with beta-blockers,201with
LQT1 patients drawing the largest benefit.202Despite this, 10%-32% of
patients, depending on genotype, develop cardiac events while taking
adequate beta-blocker therapy.203Experimental data supporting the
adjunctive use of sodium channel blockers in patients with LQT3,
potassium channel agonists in long QT syndrome, and calcium channel
blockers in long QT syndrome, particularly LQT8/Timothy syndrome, are
promising, but clinical data are so far limited.200Pacemaker therapy may
be helpful in congenital long QT syndrome patients as well, particularly
patients with LQT3204,205; “rate-smoothing” algorithms that prevent
postextrasystolic pauses should be used when possible.206ICDs are
indicated for patients at high risk of SCD, such as those with a history of
aborted SCD or syncope despite adequate beta-blockade.207Left cervi-
cothoracic sympathetic ganglionectomy may be considered for high-risk
Curr Probl Cardiol, September 2010485
patients with recurrent syncope and/or aborted cardiac arrest despite
combined ICD and beta-blocker therapy or in patients intolerant of
beta-blockers.208Finally, ablation of the ventricular premature beats that
trigger tachycardia/fibrillation may be a valuable tool.209
Although optimal risk stratification schemes and treatment options have
not yet been defined for short QT syndrome, implantation of ICD for
primary prevention of SCD is recommended unless contraindicated or
refused by the patient.210Inappropriate shocks due to detection of short
coupled and tall peaked T waves are an issue in this disease, and device
algorithms that permit reduced sensitivity and linear or programmable
decay after the R wave may be helpful.211Data regarding pharmacologic
therapy are limited and primarily pertains to patients with SQT1.
Quinidine has shown promise in prolonging the QT to the normal range,
increasing ventricular refractory periods, and suppressing ventricular
arrhythmia induction.212Disopyramide has also been shown to increase
the QT interval and ventricular refractory period.213Patients with atrial
fibrillation only may benefit from propafenone, which has been shown to
be effective in preventing atrial fibrillation paroxysms without any effect
on QT interval or ventricular arrhythmia occurrence.214
Catecholaminergic polymorphic VT is considered one of the most
severe of the inherited arrhythmogenic disorders, with 80% of patients
experiencing cardiac events before age 40 years.154As patients tend to
have arrhythmias triggered by increased adrenergic tone, exercise, and
emotional stress, beta-adrenergic blockers are the primary pharmacologic
therapy177and may also be of benefit for acute termination of arrhyth-
mias.215Unfortunately, beta-blockers do not provide full protection from
all related arrhythmias and SCD; incidences of polymorphic VT during
therapy of 35%-45% have been reported, and SCD was reported in 4 of
21 patients treated with beta-blockers.216-218ICDs are recommended for
those who continue to have severe ventricular arrhythmias despite
beta-blocker therapy, although it should be noted that implantation of an
ICD does not obviate the need for continued pharmacologic arrhythmia
suppression.216Verapamil may be an alternative for patients unable to
tolerate beta-blockers, although data are more limited and less compel-
ling.178,218,219Flecainide has been reported to inhibit cardiac ryanodine
receptor-mediated Ca2?release in an animal model and suppress arrhyth-
mias in early human testing.220Benefit of adjunctive therapy with left
cervicothoracic sympathetic ganglionectomy has been demonstrated in
the cathecholaminergic polymorphic VT population as well.221Approx-
imately 55%-70% of patients with clinical catecholaminergic polymor-
phic VT are genotyped successfully; given the incomplete penetrance of
486 Curr Probl Cardiol, September 2010
the disease and the fact that SCD can be the first manifestation, genetic
testing of those with the disease and family members of probands is
recommended.154,178,222Beta-blockers are recommended for all silent
carriers of an RyR2 mutation.98
Patients believed to have the short-coupled variant of Torsades should
generally be offered ablation and backup ICD therapy.179Ablation of the
triggering PVC, most commonly originating in the distal Purkinje fibers,
has been reported to result in a low 18% recurrence rate at median
follow-up of over 5 years, with repeat ablation achieving at least acute
success in most of these “failures.”223,224While beta-blockers, amioda-
rone, and quinidine have been used, their long-term benefit is not clear.
Intravenous verapamil has been shown to suppress the inciting short-
coupled ventricular extrasystoles, although it should not be considered a
replacement for an ICD in terms of SCD prevention.180In one study,
ventricular overdrive pacing actually promoted Torsades and exposed a
pause-related Torsades initiation pattern induced by premature atrial
beats.225As of yet, there is no role for genetic testing in this syndrome.
In Brugada syndrome genetic testing is recommended to support the
clinical diagnosis, for early detection of relatives at potential risk, and to
advance our understanding of the genotype-phenotype relationship.182At
present, however, most patients with clinical evidence of the Brugada
syndrome will not test positive for a known genetic mutation, and the
presence of specific mutations has yet to be linked to prognosis. Drugs
that induce Brugada-like ECG patterns are probably best avoided (Table 8).
Defibrillators are the only proven effective treatment for the disease.226
SCD risk stratification by electrophysiology study is controversial, with
Brugada and colleagues finding an association between VT/VF inducibil-
ity and future risk that several others have failed to corroborate.227-230
Nonetheless, and perhaps for lack of better options, current recommen-
dations by some do use the electrophysiology study to risk stratify
patients for ICD implantation (Fig 12).182Quinidine, an Ito-blocker, has
shown some promise as a treatment option, although long-term efficacy
studies are limited; cilostazol, a phosphodiesterase III inhibitor, with
effects on ICaand Itomay also prove beneficial.231,232Ablation of focal
triggers has shown early promising results.209
While the clinical precipitating factors for VF associated with early
repolarization are unknown, experimentally, sodium and calcium-channel
blockers, activation of IK-ATP, hypercalcemia, and hypothermia increase
the electrical gradient, are arrhythmogenic, and thus should be avoided in
patients with this syndrome (Fig 13).233Conversely, continuous infusion
of isoproterenol has been shown to successfully treat electrical storm in
Curr Probl Cardiol, September 2010 487
these patients and restore a normal ECG.187It is thought that by
increasing the ICa-Lcurrent, isoproterenol decreases the electrical
gradient between the epicardium and endocardium during early
repolarization, aided by an increase in heart rate and reduced inacti-
vation of Ito.233Quinidine has been shown to effectively prevent
recurrence of VF in 1 multicenter cohort study and several case
reports, presumably by blocking Ito.187,234,235The defibrillator re-
mains the cornerstone of treatment. Genetic testing does not yet have
a role in management of this syndrome.
Ventricular tachycardia is a heterogeneous arrhythmia. An understand-
ing of its mechanism—automatic, triggered, or reentrant—and the context
in which it is occurring, greatly aids appropriate management. Beta-
blockers are a mainstay across multiple different forms of VT. In recent
TABLE 8. Drug-induced Brugada-like ECG patterns
I. Antiarrhythmic drugs
1. Na?channel blockers
Class IC drugs (Flecainide, Pilsicainide, Propafenone)
Class IA drugs (Ajmaline, Procainamide, Disopyramide, Cibenzoline)
2. Ca2?channel blockers
II. Antianginal drugs
1. Ca2?channel blockers
Isosorbide dinitrate, nitroglycerin
3. K?channel openers
III. Psychotropic drugs
1. Tricyclic antidepressants
Amitriptyline, nortriptyline, desipramine, clomipramine
2. Tetracyclic antidepressants
4. Selective serotonin reuptake inhibitors
IV. Other drugs
2. Cocaine intoxication
3. Alcohol intoxication
(Reproduced with permission from Antzelevitch et al.182)
488 Curr Probl Cardiol, September 2010
FIG 12. Indications for ICD implantation in patients with Brugada syndrome. Class I designation
indicates clear evidence that the procedure or treatment is useful or effective; Class II, conflicting
evidence about usefulness or efficacy; Class IIa, weight of evidence is in favor of usefulness or
efficacy; Class IIb, usefulness or efficacy is less well established. BS, Brugada syndrome; NAR,
nocturnal agonal respiration; SCD, sudden cardiac death. (Reproduced with permission from
Antzelevitch C et al.182)
Curr Probl Cardiol, September 2010489
years, ablation has emerged as a potential therapy for a growing number
of patients, including even those with hemodynamically unstable VT,
epicardial VT, and triggered forms of ventricular fibrillation. ICDs remain
the gold standard for sudden cardiac death prevention, while the role of
genetic testing has expanded as new arrhythmia syndromes and associ-
ated mutations are identified, and risk stratification has grown more
Fred Morady: This excellent review provides a thorough update on the
diagnosis and management of ventricular tachycardia. One of the few
aspects of ventricular tachycardia that was not addressed is the management
of nonsustained ventricular tachycardia. In patients without structural heart
disease, treatment of nonsustained ventricular tachycardia is appropriate for
relief of bothersome symptoms or for prevention of left ventricular dysfunc-
tion when the PVC burden is ?15%-20%. Drug therapy and catheter ablation
both are reasonable first-line therapies, but catheter ablation generally is
more effective and better tolerated than long-term antiarrhythmic drug
therapy. In patients with a prior myocardial infarction, management of
nonsustained ventricular tachycardia depends on the ejection fraction. If the
ejection fraction is ?40%, therapy is not required except for relief of
FIG 13. The Brugada syndrome and the early repolarization syndrome both entail development
of a transmural voltage gradient and share similar provocations and treatment. Transmembrane
action potentials from the epicardium and endocardium and an ECG were simultaneously
recorded from 2 different canine arterially perfused right ventricular wedge preparations. Left,
Brugada syndrome, combined K?channel opener and calcium channel blocker cause loss of
the action potential, leading to the development of a large transmural voltage gradient, which
is responsible for the marked ST-segment elevation. Right, early repolarization syndrome.
Acetylcholine (3 ?mol/L) depresses the epicardial action potential plateau, leading to the
development of a transmural voltage gradient, responsible for a relatively smaller ST-segment
elevation. ACh, Acetylcholine; ECG, electrocardiogram; Endo, endocardium; Epi, epicardium.
(Reproduced with permission from Gussak I and Antzelevitch C. J Electrocardiol 2000;33:299-
490 Curr Probl Cardiol, September 2010
symptoms. If the ejection fraction is 30%-40%, electrophysiological testing is
indicated and an ICD is appropriate if there is inducible ventricular tachycar-
dia. If the ejection fraction is ?30%, the nonsustained ventricular tachycardia
is irrelevant, because an ICD is indicated whether the patient has ventricular
arrhythmias. In patients with structural heart diseases other than coronary
artery disease, the need for an ICD is dictated by an ejection fraction ?35%,
not nonsustained ventricular tachycardia.
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