Download Ventricular Tachycardia in Structurally Normal Hearts: Recognition

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33
Supplement
Ventricular Tachycardia in Structurally Normal Hearts:
Recognition and Management
P Nathani, Sheetal Shetty, Y Lokhandwala
Abstract
Idiopathic ventricular tachycardia is a defined set of tachycardias when structural or pathological cause has been ruled out for the
same. This paper tries to define and classify these arrhythmias to organize a logical therapeutic approach to deal with them. 60-80% of
the idiopathic tachycardias originate from the right ventricular outflow tract (RVOT) and in 10% from the left ventricular outflow tract
(LVOT). Outflow tract tachycardias have either LBBB or RBBB morphology with early R wave transition in chest leads. Adenosine, beta
blockers and calcium channel blockers is the common medical treatment. Radiofrequency ablation is however the treatment of choice.
Verapamil sensitive left ventricular tachycardia (ILVT) and propranolol sensitive left ventricular tachycardia (IPVT) are the other two
forms recognized. RF ablation seems ideal for long-term management of ILVT and implantable cardioverter defibrillator (ICD) for IPVT.
Inherited channelopathies include catecholaminergic polymorphic ventricular tachycardia (CPVT), Brugada syndrome and long QT
syndrome where there is an inherited disorder in the ion-exchange channels of the cell-membrane leading to tachycardia. Prognosis
in these is variable; CPVT, in particular, has a malignant course when untreated. RF ablation and placement of an ICD are important
in the overall management of specific arrhythmia. ©
V
entricular tachycardia occurring in an otherwise
structurally normal heart is defined as idiopathic ventricular
tachycardia.1 Structural heart disease can be ruled out if the ECG (except
in Brugada syndrome and long QT syndrome), echocardiogram, and
coronary arteriogram collectively are normal.2 However, MRI can
detect theses structural abnormalities in the presence of all other
imaging diagnostic techniques being normal, especially in cases of
right ventricular outflow tract tachycardia (RVOT VT).3 Also, singlephoton emission computed tomographic scans (SPECT) detect cardiac
innervation abnormalities, which is seen in such structurally normal
hearts with ventricular arrhythmias.4 Electropharmacologic data
suggests that multiple arrhythmogenic mechanisms may account for
these arrhythmias.5,6
The classification of idiopathic ventricular tachycardia has been
with respect to ventricle of origin, response to pharmacologic agents,
evidence of catecholamine dependence and specific morphologic
features of arrhythmia (QRS morphology, axis, pattern, and whether
tachycardia is repetitive, non-sustained, or sustained) (Table 1).7
Thus following types of VT occur in the absence of structural
heart disease: a) right ventricular outflow tract (RVOT) VT, b)
idiopathic left ventricular tachycardia (ILVT), c) idiopathic propranolol
sensitive VT (IPVT), d) left ventricular outflow tract (LVOT) VT, e)
catecholaminergic polymorphic VT (CPVT), f) Brugada syndrome
and g) long QT syndrome (LQTS). RVOT VT, ILVT, IPVT generally
do not have a familial basis. RVOT VT and ILVT are monomorphic,
whereas IPVT may be monomorphic or polymorphic. CPVT, Brugada
syndrome and LQTS are inherited ion-channelopathies. CPVT may
present as bidirectional VT, polymorphic VT, or catecholaminergic
ventricular fibrillation. Syncope and sudden death in Brugada
syndrome are usually due to polymorphic VT. The characteristic
arrhythmia of LQTS is Torsades de Pointes. RVOT VT, ILVT, IPVT,
LVOT VT are referred to as idiopathic VT and have a better prognosis.
Prognosis for patients with VT secondary to ion-channelopathies is
variable. Thus as is evident there can be no watertight classification
of idiopathic ventricular tachycardias (Fig. 1) (Table 1).
QECG, Quintiles, 603 Midas Plaza, M.V Road, Andheri (East),
Mumbai-400059.
Outflow Tract Ventricular
Tachycardia
RV monomorphic extra systoles are considered benign.8 However,
they may progress to arrhythmogenic right ventricular dysplasia
and RVOT VT, with the MRI showing anatomical and functional
abnormalities of the right ventricle.8 These extra systoles have an LBBB
morphology on ECG with the QRS axis directed inferiorly. Long-term
follow up of these RV monomorphic exrasystoles showed that none
of the patients died of sudden death or developed right ventricular
dysplasia. However focal fatty replacement in the right ventricle was
seen in most.8
80-90% of the tachycardias in normal hearts originate from the
RVOT and 10% from the LVOT.6,9 RVOT VT is seen more commonly
in females in 30-50 years of age.10,11 Most patients present with
palpitations or presyncope but rarely present with frank syncope.
Exercise or emotional stress usually precipitates the tachycardia.
Sudden death is rare. The characteristic morphology of RVOT VT is
a wide QRS complex tachycardia with LBBB pattern and an inferior
Fig.1: Classification of polymorphic ventricular tachycardia.
34
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© SUPPLEMENT OF JAPI • APRIL 2007 • VOL. 55
Table 1 : Types of idiopathic ventricular tachycardia
Type of VT
QRS morphology/axis
Pharmacotherapy sensitivity
Entrainment
RVOT VT and LBBB/inferior axis
Adenosine, β-blocker,
No
monomorphic
verapamil (or diltiazem) extrasystoles
LVOT VT
S wave in Lead I,
Adenosine, β-blocker,
R-wave transition in
verapamil (or diltiazem)
No
V1 or V2
RF ablation
ILVT,focal reentry RBBB/left superior axis
Verapamil
Yes
(exit, posterior fascicle);
RBBB/right inferior axis
(exit, anterior fascicle)
IPVT
RBBB or LBBB
Propranolol
No
(monomorphic or polymorphic)
axis11,12 whereas LVOT VT shows one of the following depending on
the site of origin: a) LBBB morphology with early precordial transition
in V1/V2 b) RBBB morphology in lead V1 with broad monophasic
R-waves in precordial leads c) has an R:S amplitude ratio of 30% or
more or an R:QRS duration ratio of 50% in leads V1 and V2.13
Two phenotypic forms of RVOT VT occur: nonsustained,
repetitive, monomorphic VT12 (RMVT) and paroxysmal, exerciseinduced, sustained VT. Both are terminated by the administration
of adenosine.
These have also been classified recently on the basis of site of origin
as those originating from the pulmonary artery (PA) or RV-end-OT.
R-wave amplitudes on inferior ECG leads, aVL/aVR ratio of Q-wave
amplitude, and R/S ratio on lead V2 were significantly larger in the PA
group than in the RV-end-OT group. Also, when mapping the RVOT
area, if the catheter shows a low-voltage atrial or local ventricular
potential of <1-mV amplitude, then the site of origin is the PA. Studies
have shown that RF ablation performed on the pulmonary artery
requires more attention.14
Specific ECG characteristics have been described to differentiate
RVOT VT from LVOT VT.13 R/S transition in lead V3 is a common
finding in idiopathic VT.15 In a study conducted to understand
the electrocardiographic pattern of idiopathic VT as a guide to
management, the R wave in V2 was the strongest single predictor
of whether the VT had an RVOT or an extra-RVOT origin. Analysis
of R wave duration in V2 had similar predictive values, whereas the
R/S transition zone in precordial leads had slightly lower predictive
values. LVOT VT were identified as having earlier precordial transition
zones, more rightward axes, taller R waves in inferior leads and small
R waves in lead V1.16 Seventeen of 20 arrhythmias (85%) with an R
wave amplitude < or =30% of the QRS amplitude in V2 could be
successfully located in the right ventricular outflow. 17
Treatment of Outflow Tract VT
Acute termination is by a) IV adenosine 6 mg, can be titrated upto
24 mg; b) IV verapamil 10 mg over 1 min (maximum 50% efficacy);
c) lidocaine may help; d) emergent cardioversion if hemodynamic
instability.
Long term management: Beta blockers or verapamil have 25%-50%
efficacy. RF ablation has a cure rate of 90%.10
ILVT: Idiopathic Left Ventricular
Tachycardia
The most common feature of this tachycardia is verapamil
sensitivity. Seen in second to fourth decade of life and occurs more
often in men (60%-80%).10 Symptoms during tachycardia include
palpitations, dizziness, presyncope, and syncope. Sudden death is
usually not seen. Mechanism of tachycardia is focal reentry due to
area of slow decremental conduction in Purkinje fibres. The reentry
circuit has been demonstrated to be confined to the left posterior
Purkinje network.18 This tachycardia has RBBB morphology with
left axis configuration in 90%-95% of the cases (exit site, left posterior
fascicle) and RBBB with right axis in remaining 5%-10 %( exit site, left
Treatment
β-Blocker, verapamil,
RF ablation
β-Blocker, verapamil,
Verapamil,
RF ablation
β-Blocker
anterior fascicle). Adenosine and Valsalva maneuvers usually have no
effect (unlike in RVOT VT), however adenosine sensitivity has been
seen when catecholamine stimulation with isoproterenol infusion was
done to initiate this tachycardia.19,20
Treatment of ILVT
Pharmacologic therapy with verapamil is still the treatment of
choice for ILVT because of a good long-term prognosis. RF ablation
is effective and safe with no complication recorded.21,22 After ablation
of the clinical VT, 11% of subjects showed a recurrence of both ILVT
and RVOT VT with a different morphology in a study which was
successfully reablated.23 Low energy DC shocks can be safely used
when RF ablation proves ineffective. 24
IPVT: Idiopathic Propranolol
Sensitive Ventricular Tachycardia
This is also a form of idiopathic left ventricular tachycardia.
The hallmark of IPVT is that it is not inducible with programmed
electrical stimulation, but isoproterenol infusion usually induces
this VT and beta-blockers are effective in completely terminating the
tachycardia.25
Treatment of IPVT
Beta-blockers are used to treat this form of VT because they
are effective in acute situations. This type of VT is unresponsive to
verapamil. Long-term management of IPVT has not been studied in
details, however cardioverter-defibrillator (ICD) may be implanted
in patients who survive sudden cardiac death.7
Inherited Channelopathies
CPVT: Catecholaminergic Polymorphic Ventricular
Tachycardia
CPVT is an inherited disorder characterized by a bidirectional
polymorphic VT. This type of arrhythmia is induced by exercise or
emotion or any form of increased adrenergic stimulation.26 30% of the
patients have a family history of sudden death or syncope.26 CPVT is an
important cause of sudden death and syncope in children with normal
heart.27 Since the tachycardia resembles the arrhythmia associated
with calcium overload, the abnormality was traced to the mutation
in the RyR2 gene which is important for the regulation of intracellular
calcium fluxes.28,29 The non genotyped CPVT patients were mostly
females with males at a higher risk for syncope due to RyR2CPVT.30
The RyR2CPVT patients became symptomatic at a younger age than
the non genotyped CPVT patients, thus suggesting males at a higher
risk of cardiac events. 30 Mutations of the RyR2 gene cause autosomal
dominant CPVT, while mutations of the CASQ2 gene may cause an
autosomal recessive or dominant form of CPVT. 31
Treatment of CPVT
Beta-blockers are the preferred therapy for CPVT however recent
data shows low efficacy as there is a chance of sudden death even if
a single dose is missed. 32 Therefore ICD is required in 30% of patients
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because of symptomatic recurrence of life-threatening arrhythmia in
spite of beta-blocker therapy.30 Brugada Syndrome
First reported by Brugada et al, this abnormality is characterized
by RBBB pattern (early high take-off of the ST segment but absence
of wide S wave in left lateral leads which rules out a true RBBB),
ST elevation in right precordial leads (V1-V3), normal QT interval,
absence of structural heart disease, life-threatening cardiac arrhythmia
(polymorphic VT) and a family history of sudden death. 33,34 Two
types of ST elevation have been described: coved and saddleback.
The coved type has been shown to have a greater potential to cause
arrhythmia than the saddleback type.35-37 A mutation in the cardiac
sodium channel gene (SCN5A) has been described in this syndrome.38
The electrocardiographic manifestations of the Brugada syndrome
can be unmasked using sodium channel blockers such as flecainide,
ajmaline or procainamide which further supports the sodium channel
abnormality.39 The signal averaged ECGs showing late potential has
been shown to be most useful in identifying high risk patients for
Brugada syndrome. The clinical presentation in Brugada syndrome
was studied and showed that VF was present in 76 (73%) and syncope
in 28 (27%) of the patients.40 (The Brugada-type ECG (“Brugada sign”)
may be much more common than is the clinical syndrome.41 The risk of
sudden cardiac death due to polymorphic VT or ventricular fibrillation
with Brugada syndrome is substantial.
Treatment of Brugada Syndrome
There is no effective drug treatment. Quinidine has shown to have
normalizing effect on the ECG of patients showing Brugada pattern
of ECG, thus proving some scope for Class Ia anti-arrhythmic in this
syndrome.39,42 In symptomatic patients, ICD placement is the treatment
of choice.43,44 Asymptomatic patients with Brugada-type ECG results
should undergo electrophysiologic testing. If ventricular arrhythmia
is inducible the patient should receive an ICD. Asymptomatic patients
with normal baseline ECG do not require further testing.
35
genotypes. However, there was greater risk for LQT2 in females and
LQT3 in males. Asymptomatic (“silent carriers”) were also highest in
LQT1 than in LQT2 and LQT3.48
Typical ECG patterns have been defined for various genotypes of
long-QT. LQT1 showing a broad based, peaked or late onset-T wave;
LQT2 showing bifid T wave; LQT3 showing a late-onset, peaked or
biphasic T wave; making a diagnosis of LQTS likely.46 Family history
may be helpful for diagnosis of LQTS. Recurrence of a clinical event
is quite frequent in LQTS.
Treatment of LQTS
Adrenergic modulation with beta-blockers is the most useful
therapy since 1970 in both symptomatic and asymptomatic patients.
The number of patients with cardiac events was significantly reduced
after the initiation of beta-blocker therapy (preferably non-selective
beta-blockers). 49 However the study showed that it does not absolutely
prevent death. Also patient compliance was an issue. Pacemekers
can be used when sinus bradycardia and sinus pauses become
exacerbated. Surgical sympathectomy is an adjuvant treatment but is
now done rarely. Oral potassium may be useful in certain genotypes.50
ICD placement, along with beta-blocker therapy, offers the best
protection in high-risk patients (survivors of sudden death and those
with recurrent syncope).51
Medications that prolong QT interval must be carefully excluded
from the patient’s medication list.
Drug induced QT prolongation and Torsades de
Pointes
LQTS –Long QT syndrome
LQTS is an uncommon disorder due to mutations in 7 genes
(Table 2).
Some investigators have classified Andersen syndrome (AS) a
rare, inherited disorder characterized by periodic paralysis, long
QT (LQT) with ventricular arrhythmias and skeletal developmental
abnormalities as a form of LQTS (LQTS7).47
ECG 1: Long QT syndrome (LQTS), best seen in V2, V3, maybe missed
in other leads.
Individual with LQTS and deafness (Jervell Lange-Neilsen
syndrome) have the highest risk for experiencing life threatening
arrhythmias. The most common clinical presentation is syncope or
sudden cardiac death, triggered by exercise (LQT1) and acute arousal
such as sudden loud noise (LQT2). Sudden death can occur at rest
or during sleep (LQT3). Priori et al conducted a study on 647 LQTS
patients and found that the risk of cardiac events is higher in LQT2
and LQT3 as compared to LQT1. Gender had no influence across most
ECG 2: Torsades de pointes (TdP) starting with a VPB on the descending
limb of the previous T wave.
Table 2 : Classification of the genes responsible for LQTS45,46
LQTS subtype
Mutated gene
Ionic current affected
Clinical frequency, %
Trigger of clinical event
LQT1
KvLQT1
Slow activating 44-54
Conditions of increased
potassium current
sympathetic activity,
exercise, swimming
LQT2
HERG
Rapid activating 53-35
Sudden arousal, emotions,
potassium current
auditory stimuli-loud noises
LQT3
SCN5A
Activating sodium current
6-11
Sleep, night-time
LQT4
Ankyrin B
Sodium pump, sodium/
calcium exchanger and
inositol receptors
Rare LQT5
KCNE1 (minK)
Slow activating
potassium current
Rare LQT6
KCNE2 (MiRP1)
Rapid activating
potassium current
Rare
36
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ECG 5: Pseudo VT with artifacts. Arrows indicate normal QRS.
ECG 6: Atrial Fibrillation with WPW syndrome.
ECG 3: RVOT VT; LBBB morphology with RAD (axis=120º).
ECG 7: Polymorphic VT; WPW with atrial fibrillation.
recently non-cardiac drugs like terfenadine and cisapride and certain
antipsychotic drugs have also shown positive QT prolongation
in drug trials on healthy volunteers. Immediate action for drug
induced QT prolongation is to suppress the tachyarrhythmia.
Intravenous magnesium sulphate has been shown to be useful. 52
In a study conducted among US adults, the results showed that
female sex, hypocalcemia (men), hypokalemia (women), a history
of thyroid disease and myocardial infarction (men) were associated
with a prolonged QTc interval. In addition, taking QT-prolonging
medications in the past month was associated with more than a
twofold increase in the odds of prolonged QTc interval in both men
and women53 (Fig. 2).
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can lead to TdP. Acquired QT prolongation is most due to medication.
Anti arrhythmic drugs have known QT prolonging effects, however
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