Ventricular tachycardias in the absence of structural heart disease

10% of patients presenting with VT have no apparent structural heart disease
VT in structurally normal hearts can be broadly considered under
Non–life-threatening monomorphic VT
Life-threatening polymorphic VT

NON–LIFE-THREATENING
(TYPICALLY MONOMORPHIC)
Classified on basis of site of origin
Most common sites are ventricular outflow tracts and left ventricular fascicles

Idiopathic left VT
Left posterior fascicle
Left anterior fascicle
High septal fascicle
Others
Mitral annulus
Tricuspid annulus
Papillary muscle
Perivascular epicardial
Outflow tract VT
Right ventricular outflow- 80%
Pulmonary artery
Left ventricular outflow-10%
Aortic sinus of Valsalva
Aortic cusps
Area of aortomitral continuity
Superior basal septum near His bundle(Peri His bundle)
Epicardial surface of outflow tracts

OUTFLOW TRACT VT
Idiopathic VT originate most commonly in outflow tract area
Nearly 80% of which originate from RVOT
Other outflow tract sites are rare

Phenotypes are a continuum of the same focal cellular process
Premature ventricular complexes (PVCs)
Nonsustained,repetitive monomorphic VT(RMVT)
Paroxysmal, exercise-induced sustained VT
Considerable overlap observed among three phenotypes
Ablating one phenotype at a discrete site eliminates other two
Signature characteristic of sustained RVOT and LVOT is
tachycardia is termination by adenosine and verapamil
PHENOTYPES

RVOT is bounded by pulmonary valve superiorly and superior aspect of tricuspid apparatus inferiorly
RVOT is leftward and anterior to LVOT
RVOT is a muscular infundibulum circumferentially
Upper part of septal wall is the conus arteriosus, bordered below by supraventricular crest
ANATOMIC CORRELATES

LVOT is region of LV between anterior cusp of mitral valve and ventricular septum
Muscular and fibrous parts
Large of part of right and some part of left aortic sinuses of Valsalva overlie muscular LVOT
Close proximity to AV node and His bundle -early activation in VT

Non-coronary cusp and posterior aspect of left coronary cusp are continuous with fibrous aortomitral continuity
Explain lack of VT related to the non-coronary cusp

VT from aortic sinuses of Valsalva arise from muscular extensions of the LVOT to areas above the base of the aortic valve cusps
These muscle fibers often exhibit slow conduction and fractionated electrograms.

Localization of site of VT origin can be predicted using QRS morphology on surface ECG and anatomic relationships help to explain shared ECG patterns and subtle differences

LBBB and inferior axis
Right sided origin- LBBB pattern with transition from a small r-wave to a large R-wave at V3 to V4
OT site - inferior axis
RVOT VT

RVOT region can be divided into nine regions
Anterior sites demonstrate Q wave (Q or qR) in lead I and QS in lead aVL
Posterior sites demonstrate R wave in lead I and early precordial transition (R> S in V3)
Between anterior and posterior locations typically demonstrate a multiphasic QRS morphology in lead I
JADONATH AND COLLEAGUES

Differentiation of septal from free wall RVOT VT
RVOT VTs originating from septum - taller,narrower monophasic R waves in inferior leads
Free wall RVOT VT- typically broader QRS (>140ms) and R wave notching in inferior leads
Later transition in precordial leads (>V4)
DIXIT AND COLLEAGUES

Anterior position of free wall relative to septum -Accounts for deeper S wave in lead V2 than RVOT septum
Septal site associated with a Q/q wave in lead I, whereas a free-wall site inscribes an R/r wave.
Caudal (> 2 cm from PV) Versus Cranial
VT arising >2 cm of the pulmonary valve near His bundle virtually always has a negative QRS in lead aVL

Approximately 1 cm above pulmonic valve
Associated with a precordial transition in leads V3 or V4(PA is located leftward of and anterior to RVOT)
qR configuration in lead I
Larger Q wave in lead aVL than in Avr
Location superior to RVOT results in a relatively greater R wave amplitude in inferior leads
Mapping RVOT area -low-voltage atrial or local ventricular potential of <1-mV amplitude
RF ablation performed on PA requires more attention
PULMONARY ARTERY VT

Atriofascicular fibers (Mahaim fibers)
AVRT using Rt-sided accessory pathway
VT after repair of TOF
ARVD
DIFFERENTIAL DIAGNOSIS OF RVOT VT

ECG during VT shows
S wave in lead I
R-wave transition in lead V1or V2(Earlier precordial transition zone)
More rightward axes
Taller R waves in inferior leads
LVOT VT
S wave in LI and R-wave transition in V1 suggest LVOT VT.
R:S amplitude ratio of 30% and R:QRS duration ratio of 50%
Presence of an S wave in leads V5 and V6 suggests an infravalvular origin of the tachycardia.

Shows one of the following depending on site of origin
a)Basal left interventricular or septal origin
LBBB morphology with an early precordial transition in lead V2 or V3,S wave in lead V6 (due to activation of the left bundle Purkinje system) and relatively narrow QRS complex
b)VT from region of left fibrous trigone (aortomitral valve continuity)
RBBB morphology in V1 and broad monophasic R-waves across precordium

May originate from supravalvular or infravalvular endocardial region of coronary cusp of aortic valve
Distinction is important –RF ablation
Absence of an S wave in V5 or V6 -supravalvular
S wave in leads V5 and V6-infravalvular
LVOT VT

Depending on site of origin from right or left coronary cusp-LBBB or RBBB morphology
AORTIC CUSP VT
LBBB morphology with transition by V3, tall R waves in the inferior leads, and an s wave in lead I suggest the VPC from left coronary cusp.

Most VTs arise from left cusp and specifically from junction of left and right cusps
VT originating from LCC or aortomitral continuity often demonstrate terminal S wave in lead I

RVOT VT Vs aortic cusp VT
R wave duration and R/S wave amplitude ratio in leads V1 and V2 - Greater in tachycardias originating from cusp compared with RVOT
Precordial lead transition earlier in cusp VT occurring before lead V3
Absence of an S wave in V5 or V6 -specificity of 88% for cusp VT compared with RVOT VT
OUYANG AND COLLEAGUES

OTVT originate from epicardial locations
9%–13% of idiopathic VT
Cluster along the course of the anterior interventricular vein and at its junction with great cardiac vein
Show catecholamine and adenosine sensitivity
EPICARDIAL FOCI OF VA
Q wave in lead I and terminal S wave in V2
(Paper speed 100 mm/s).

Psuedodelta wave
Interval from earliest QRS activation to earliest fast deflection in precordial leads ( > 34 ms)
Precordial maximum deflection index
Beginning of QRS to earliest maximal deflection in any precordial leads / QRS duration. (> 0.55)
(sensitivity of 100%, specificity of 98%)

Epicardial compared with endocardial VT-R wave amplitude significantly greater in inferior leads
Lead I had an S wave as part of an rS or QS pattern
Q wave amplitude greater in aVL compared with aVR (ratio >1.4)
Q wave in lead I
TADA AND COLLEAGUES

MITRAL ANNULUS,
TRICUSPID ANNULUS
PAPILLARY MUSCLE
PERIVASCULAR EPICARDIAL ECTOPY

MITRAL ANNULAR VT
Significant slurring of QRS complex onset resembling delta-wave
Regardless of where along circumference of mitral annulus VT originates ECG shows RBBB pattern across precordium
S wave in lead V6
More lateral site- more likely is presence of S wave in lead I and of notching in inferior leads
Posterior focus will have superior axis.

PVCs or VT also originate from RVOT along region of tricuspid annulus
Most common site is para-Hisian
Characteristic ECG findings are
Left bundle branch block pattern (Qs in lead V1)
Early transition in precordial leads (V3)
Narrower QRS complexes
Inscription of an R wave in lead I and Avl
Relatively small R wave in inferior leads
Sites of successful ablation record an atrial and a ventricular potential
PARA-HISIAN

ELECTROPHYSIOLOGIC MECHANISM
Outflow tract VT is due to triggered activity
Secondary to cyclic AMP mediated DAD
Example-Exertion results in increased cyclic AMP due to beta receptor stimulation
Release of calcium from sarcoplasmic reticulum and DAD
Mutations in signal transduction pathways involving cAMP may be etiology for VT in some patients
Tachycardia may terminate with Valsalva maneuvers, adenosine, BB or CCB

CLINICAL FEATURES
20 and 40 years,Slight female preponderance
May be asymptomatic but often present with palpitations, chest pain, dyspnea, presyncope and even syncope
Occur more frequently with exertion or emotional stress
Circadian variation- peaks at 7 AM and between 5 and 6 PM
Women-symptoms related to changes in hormonal status
Truly idiopathic OTVT is benign
Small percentage of patients with very frequent VT –TCM
Rare reports of cardiac arrest and PMVT

TREATMENT
May respond acutely to carotid sinus massage, Valsalva maneuvers or intravenous adenosine or verapamil
Long-term oral therapy with either BB or CCB
Nonresponders (33%)- class I or III antiarrhythmic agents

RFA
When medical therapy is ineffective or not tolerated
High success rate (>80%)
Ablation of epicardial or aortic sinuses of Valsalva sites is highly effective
Technically challenging and carries higher risks -proximity to coronary arteries

Tachycardia localization
12-lead ECG
Intracardiac activation
Pace mapping

BIPOLAR ACTIVATION MAPPING

PACE MAPPING
Useful because typically site of origin is focal and because underlying tissue is normal
Performed with a low output
Result in a small discrete area of depolarization
Mapping performed at site of origin of clinical arrhythmia,
ECG should mimic clinical arrhythmia perfectly (12/12, including notches)

ELECTROANATOMIC RE-CREATION OF 3D ANATOMY
Helpful for catheter mapping and localization of site of origin
Incessant VT- 3D anatomy should ideally be created during tachycardia which should be able to localize earliest site to a small region (<5 mm) with centrifugal activation
Typically pace mapping from this region should achieve a perfect match

Predictors for successful ablation
Single VT morphology
Accurate pace maps
Absence of a deltalike wave at beginning of QRS during tachycardia
Ability to use pace mapping and activation mapping

Some tachycardias arise from epicardium, necessitate ablation from great cardiac vein or epicardium itself using pericardial puncture technique
Coronary angiography is performed before ablation on epicardium or in aortic sinus

Complications during outflow tract VT ablation are rare
RBBB (1%)
Cardiac perforation
Damage to the coronary artery (LAD) - cusp region ablation
Overall recurrence rate is approximately 10%

IDIOPATHIC LEFT VT
Three varieties
left posterior fascicular VT -RBBB and LAD (90%)
left anterior fascicular VT -RBBB and RAD
high septal fascicular VT -relatively narrow QRS and normal axis

15 to 40 years
More in men (60%)
Most occur at rest
Usually paroxysmal
Incessant forms leading to TCM are described

Re-entrant mechanism
Orthodromic limb -zone of slow, decremental conduction in intraventricular left septum proceeding from base to apex
Lower turnaround point is toward the apex
Retrograde limb is formed by Purkinje network
ELECTROPHYSIOLOGIC MECHANISM

During VT two distinct potentials can be observed before ventricular electrogram
Purkinje potential (PP or P2)-activation of LPF or Purkinje fiber near LPF
Relative activation time of PP to onset of QRS complex 5-25 ms
Brief, sharp, high-frequency potential preceding onset of QRS during tachycardia
Nakagawa and colleagues

Pre Purkinje potential (Pre-PP or P1) Represents excitation at entrance to specialized zone in ventricular septum which has decremental properties and is sensitive to verapamil
Relative activation times of pre-PP to onset of QRS complex is 30-70 ms
Pre-PP is a dull, lower frequency potential preceding the PP during tachycardia

Reentrant circuit of fascicular tachycardia is completed by a zone of slow conduction between Pre PP and PP areas in basal interventricular septum
Upper turn around point of circuit
Located close to the main trunk of LBB
Nakagawa and colleagues

Area is captured antidromically during tachycardia and at higher pacing rates-pre-PP precedes PP during tachycardia.
Captured orthodromically in sinus rhythm and at relatively lower pacing rates- pre PP follows ventricular complex
Nakagawa and colleagues

DD
Supraventricular tachycardia with aberrancy
VA dissociation,
EP-Rapid atrial pacing during tachycardia can demonstrate AV dissociation
Interfascicular VT(typical RBBB morphology and left or right axis deviation )
Common in patients with AWMI and either LAHB or LPHB
EP -ventricular depolarization is preceded by His bundle depolarization in interfascicular VT which is not seen in fascicular VT
Idiopathic mitral annulus VT (RBBB morphology with right axis deviation )

VT originates from a false tendon extends from posteroinferior left ventricle to basal septum
Resection of tendon or ablation at septal insertion site eliminate tachycardia
Exact role tendon is unclear
Specificity is low
Gallagher JJet al. AJCardiol 1988;61(2):27A–44A
Merliss AD, Seifert MJ, Collins RF, etal Electrophysiol 1996;19(12 Pt 1):2144–6.
Thakur RK, Klein GJ, Sivaram CA, et al.Circulation 1996;93(3):497–501.

ECG
Baseline 12-lead ECG is normal in most patients
Exit near the area of the left posterior fascicle
RBBB + left superior frontal plane axis
Relatively narrow QRS duration (<140 msec)
RS interval <80 msec
Exit near the area of the left anterior fascicle
RBBB+ right frontal plane axis

Long-term prognosis is very good
Patients who have incessant tachycardia may develop tachycardia related cardiomyopathy
Intravenous verapamil is effective in acutely terminating VT
Mild to moderate symptoms oral –verapamil
BB and class I and III antiarrhythmic agents useful in some
Medical therapy is often ineffective in patients who have severe symptoms

RADIOFREQUENCY ABLATION
Associated with significant symptoms or who are intolerant or resistant to medical therapy
Strategies employed to identify the ideal site for ablation
Pace mapping
Endocardial activation mapping
Identifying diastolic Purkinje potentials (MC approach)
Identifying late diastolic potentials
When VT is noninducible-ablation during sinus rhythm using electroanatomic mapping may be considered

LIFE-THREATENING
(TYPICALLY POLYMORPHIC VT)
Rare
Generally occurs with genetic ion channel disorders
Associated with SCD
Abnormalities exist at molecular level

Long QT Syndrome
Brugada Syndrome
CPVT
Short QT Syndrome
LIFE-THREATENING
(TYPICALLY POLYMORPHIC VT)

LONG QT SYNDROME
Corrected QT interval 440 ms in men and 460 ms in women with or without morphological abnormalities of the T waves
Decrease in outward potassium currents or increase in inward sodium currents
Prolongs repolarization phase of cardiac action potential
Result in prolongation of QT interval
Predisposition to EAD and torsade de pointes VT
Twelve different genes described
LQT1, LQT2, and LQT3 account for 90%

BASIS FOR THE LONG QT SYNDROME

Approximately 25% not have identifiable gene mutations

Mean age of symptom onset is 12 years
Present with syncope, seizures, or cardiac arrest.
Clinical presentation and ECG repolarization (ST-T) patterns have been correlated to genotype

LQT1 -often have broad-based T waves
LQT2- T-wave is often notched in multiple leads.
LQT3- Demonstrate long ST segments

MANAGEMENT
Avoid trigger events and medications prolong QT interval
Risk stratification -degree of QT prolongation, genotype and sex
Corrected QT interval >500 ms -high risk
LQT1 and LQT2 -higher risk of events than LQT3
Risk of events-higher during adulthood in females and during adolescence in males
Number of mutations increase the risk
Once a clinical event occurs (syncope or survival after sudden cardiac death), recurrence is frequent

MEDICATIONS PROLONG QT INTERVAL
Antiarrhythmic: procainamide, quinidine, amiodarone, sotalol
Antihistamine: astemizole, terfenadine
Antimicrobial/antifungal: trimethoprim sulfa, erythromycin, ketoconazole
Psychotropics: haloperidol, risperidone, thioridazine, tricyclics
Other: epinephrine, diuretics, cisapride, bepridil, ketanserin

MANAGEMENT
BB -patients with syncope and asymptomatic patients with significant QT prolongation
Role of BB in asymptomatic with normal or mildly prolonged QT -uncertain
BB are highly effective in LQT1, less effective in others
Role of BBs in LQT3 is not established
Preferable is non selective BB

MANAGEMENT
ICD are indicated for secondary prevention of cardiac arrest and for patients with recurrent syncope despite BB therapy
Less defined therapies
Gene specific therapy -mexiletine , flecainide or ranolazine (LQT3)
PPI for bradycardia-dependent torsade depointes
Surgical left cardiac sympathetic denervation for recurrent arrhythmias resistant to BB therapy
Catheter ablation of triggering PVCs-abolish recurrent VT/VF

Characterized by ST-segment elevation in V1 to V3
Inverted T wave
2 mm in 2 of these 3 leads are diagnostic
Complete or incomplete RBBB pattern
Abnormally prolonged and biphasic P
BRUGADA SYNDROME

ST-SEGMENT ABNORMALITIES IN LEADS V1 TO V3

Typical ECG pattern can be transient and may only be detected during long-term ECG monitoring
Methods to document type-1 ECG
Move V1 lead from fourth intercostal space to second
Take an ECG after a large meal -positive in approximately 50% of patients
Provoked by sodium-channel blocking agents-
ajmaline, flecainide or procainamide

CLINICAL PRESENTATION
0.12% to 0.14% in general population
Syncope or cardiac arrest
Predominantly in men in third and fourth decade
SCD in young men,typically occurs at night
Prone to atrial fibrillation and sinus node dysfunction
Precipitated by a febrile state, vagotonic agents, a-adrenergic agonists,BBs, TCAs, hypokalaemia,alcohol and cocaine toxicity

Risk of SCD with Brugada syndrome is substantial
Risk of recurrent events during 4 years of follow-up
62% for those with cardiac arrest
19% for those with syncope.
Asymptomatic group -8% event rate during 2 years
Brugada P, Brugada R, Brugada J. Sudden death in patients and relatives with the syndrome of right bundle branch block, ST segment elevation in the precordial leads V(1) to V(3) and sudden death. Eur Heart J 2000;21:321-6.

TREATMENT
Drugs inhibit Ito (such as quinidine) and increase calcium current (such as isoproterenol) are effective
Lowdose quinidine may be used to treat frequent VAs in patients who already have an ICD
Quinidine and isoproterenol may be useful in VT storms
Catheter ablation of triggering PVCs and ablation of RVOT epicardial musculature successful in abolishing recurrent VT/VF in a small number of patients
Dimethyl lithospermate B (Danshen’s extract)
cilostazol

ICD are effective in preventing SCD
Indicated for cardiac arrest survivors
Patients with spontaneous ECG pattern and syncope are at high risk - ICD insertion is generally recommended for primary prophylaxis
ICD

Different genes involved
SCN5A gene mutations (BrS1) - loss of function of cardiac sodium channel (NaV 1.5) account for majority
BrS1 and LQT3 share SCN5A mutations
Mutation of the ankyrin-binding motif of Nav1.5
Mutation of glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) gene
Mutations cardiac L-type calcium channel genes

Codes for cardiac sodium channel that opens during phase 2 of the action potential
In Brugada, it opens poorly in RV epicardial cells
Autosomal dominant inheritance
20-30% of cases have abnormal SCN5A gene
SCN5A GENE
Priori, S. G. et al. Circulation 1999;99:674-681
1
2
3
4
0
4

Nattel and Carlsson Nature Reviews Drug Discovery 5, 1034–1049 (December 2006) | doi:10.1038/nrd2112
Defective sodium channels: shorter AP (phase 0), deeper notch (phase I), and shorter phase 2.
Creates juxtaposition of depolarized and repolarized cells, setting up possibility of PHASE 2 RENTRY, closely grouped PVCs, and VT or V Fib.
On EKG, ST segment not at baseline because no longer have uniform depolarization of the entire ventricle.

Disorder of myocardial calcium homeostasis
Clinically manifested as exertional syncope and SCD due to exercise induced VT
Often polymorphic or bidirectional
CATECHOLAMINERGIC PMVT

Autosomal dominant (50% )-mutation of cardiac ryanodine receptor (RyR2 gene)
Autosomal recessive (3% to 5% )-mutations of calsequestrin 2 gene (CASQ2)

Ryanodine receptor spans membrane of sarcoplasmic reticulum
Releases calcium triggered by calcium entry into cell through L-type calcium channels
Calsequestrin-protein sequestrates calcium ions within sarcoplasmic reticulum
RyR2 and CASQ2 mutations cause intracellular calcium overload and DAD -basis of arrhythmogenesis

Resting ECG is unremarkable, prominent U waves may be seen
Typical VT patterns are reproducible with exercise or catecholamine infusion
VAs typically appear during sinus tachycardia rates of 120 beats/min to 130 beats/min, with progressive frequency of PVCs followed by bursts of polymorphic or bidirectional VT
Mean age for presentation with syncope is 4 years
EP study is not helpful in risk stratification

Medical management-BB
46% may have recurrent events while receiving therapy
CCB -limited effectiveness
Flecainide (blocks RyR2 receptor) also used

ICD
Cardiac arrest
Life-threatening VA despite maximal medical therapy
Initial ICD shock with its accompanying pain and anxiety may trigger further VAs
Surgical left cardiac sympathetic denervation -resistant cases

SHORT QT SYNDROME
Rare disorder
Characterized by short QT intervals of 300 to 320 ms
Shortening or absence of the ST segment, with T wave initiating immediately from S wave
Diagnostic criteria involving corrected QT interval, clinical history, and genotyping
Syndrome is associated with SCD and atrial fibrillation
Patients may present early in childhood

ICD implantation for secondary and primary prevention
Preliminary observations suggest quinidine might be useful

IDIOPATHIC PROPRANOLOL-SENSITIVE VT (IPVT)
Usually occurs by fifth decade of life
Can arise from LV or RV
Morphology may be monomorphic or polymorphic
Not inducible with programmed stimulation
Isoproterenol infusion usually induces

TREATMENT OF IPVT
BBs effective in acute situations
Insufficient information available regarding long-term management
Survivors of sudden cardiac death may receive ICD

REFERENCES
ZIPES 5th EDITION
BRAUNWALD 9TH EDITION
HURST 13TH EDITION
VENTRICULAR ARRHYTHMIAS IN NORMAL HEARTS,SHUAIB LATIF, MD Cardiol Clin 26 (2008) 367–380
VENTRICULAR TACHYCARDIA IN STRUCTURALLY NORMAL HEARTS:
RECOGNITION AND MANAGEMENT,P NATHANI Supplement of JAPI • April 2007 • vol. 55
VENTRICULAR TACHYCARDIA IN THE ABSENCE OF STRUCTURAL HEART DISEASE KOMANDOOR SRIVATHSAN, MD,
IPEJ (ISSN 0972-6292), 5(2): 106-121 (2005)
VENTRICULAR ARRHYTHMIAS IN THE ABSENCE OF STRUCTURAL HEART DISEASE ERIC N. PRYSTOWSKY, MD,
Vol. 59, No. 20, 2012 ISSN 0735-1097 JACC