VENTRICULAR TACHYCARDIA IN STRUCTURALLY NORMAL HEART

Dr Dharam Prakash Saran

10% of patients presenting with VT have no apparent structural heart disease .

If structural heart disease is absent, the prognosis in patients with VT and PVCs is generally very good

Inherited VT–sudden cardiac death syndromes are an exception….

Klein LS et al Circulation 1992;85: 1666

Absence of structural heart disease is usually suggested if the ECG , echocardiogram, and CAG are normal Miles WM J Cardiovasc Electrophysiol 2001;12:536.

Structural abnormalities can be identified by MRI, even if all other test results are normal.

In addition, focal dysautonomia in the form of localized sympathetic denervation has been reported in patients with VT and no other obvious structural heart disease

CLASSIFICATIONSClassified with respect to the

• Origin of VT ( RV- VT vs LV -VT) • VT morphology (LBBB vs RBBB pattern)• Response to exercise testing• Response to pharmacological agents (Adenosine-sensitive VT vs

Verapamil sensitive VT vs propranolol-sensitive VT)• Behavior of VT (repetitive salvos Vs sustained)• Morphology (Monomorphic vs Polymorphic)

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 VTLeft posterior fascicleLeft anterior fascicleHigh septal fascicle

OthersMitral annulusTricuspid annulusPapillary musclePerivascular epicardial

Outflow tract VTRight ventricular outflow- 80% Pulmonary arteryLeft ventricular outflow-10%

NON–LIFE-THREATENING (TYPICALLY MONOMORPHIC)

OUTFLOW TRACT VT

Idiopathic VT originate most commonly in outflow tract area Nearly 80% of which originate from RVOTOther 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 istachycardia 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

ANATOMIC CORRELATES

LVOT is region of LV between anterior cusp of mitral valve and ventricular septumMuscular 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 continuityExplain 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

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 V4OT site - inferior axis

RVOT VT

RVOT VTApproximately 60% to 80% of idiopathic VTs arise from the RVOTMore common in females 3rd to 5th decade of life

Two predominant clinical forms• Nonsustained repetitive monomorphic VT (RMVT), alternating

with periods of sinus rhythm• Paroxysmal exercise-induced sustained VT

CLINICAL FEATURESMost patients present with palpitations50% develop dizzinessMinority (10%) present with syncope. Symptoms are related to frequent PVCs or NSVT. Less commonly, paroxysmal sustained VT is precipitated by exercise or emotional stress. The clinical course is benign and prognosis is excellent Sudden cardiac death is rare Spontaneous remission of the VT occurs in 5% to 20%.

ECG IN RVOT VT Sinus Rhythm- Usually normal. Up to 10% can have complete or incomplete RBBBRepetitive monomorphic VT

• frequent PVCs, couplets, and salvos of nonsustained VT,• interrupted by brief periods of NSR

Paroxysmal exercise induced VT • sustained episodes of VT precipitated by exercise or

emotional stressRate is frequently rapid but can be highly variable.

RMVT

SUSTAINED RVOT VT

RVOT LOCALIZATION:FREE WALL VS SEPTAL

• QRS duration ≥ 140 msec • QRS notching in inferior leads • Lead V3 R/S ratio ≥ 1

RVOT LOCALIZATION LEAD I: ANTERIOR(LEFT) VS POSTERIOR(RIGHT)

AMBULATORY MONITORING

Ventricular ectopy typically occurs at a critical range of heart ratesA positive correlation between the sinus rate preceding the VT and the VT durationVT occurs in clustersMost prevalent on waking and during the morning and later afternoon hours. VT is extremely sensitive to autonomic influences, resulting in poor day to day reproducibility

VT ARISING FROM THE PULMONARY ARTERY (PAVT)Thought to be from remnants of embryonic muscle sleeves that have been noted in amphibian and mammalian outflow tract

Timmermans C, Circulation 2003;108:1960

•Larger R-wave amplitude in inferior leads

•Ratio of the Q-wave amplitude in avL/avR was larger in the PA group

Atriofascicular fibers (Mahaim fibers)AVRT using Rt-sided accessory pathwayVT after repair of TOFARVD

DIFFERENTIAL DIAGNOSIS OF RVOT VT

LVOT VTLBBB morphology with inferior axis with small R-waves in V1 and early precordial transition (R/S ≥ 1 by V2 or V3), QS or rS in L I or

RBBB morphology with inferior axis and presence of S-wave in V6

Q wave amplitude in aVL is typically more than or equal to aVR,

For LVOT VT, • Absence of an S wave in leads V5 or V6 suggests a

supravalvular location,• Presence of such waves indicates an infravalvular location

AORTIC CUSP VTOrigin from the aortic cusp is strongly suggested by

• Longer duration and greater amplitude of the R wave in leads V1 and V2

• (R/QRS duration more than 50% and R/S amplitude more than 30%) as compared with VT originating from the RVOT

because the aortic valve lies to the right and posterior to the RVOT

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.

RVOT VT Vs aortic cusp VT

R wave duration and R/S wave amplitude ratio in leads V1 and V2 were greater in tachycardias originating from cusp compared with RVOT

Precordial lead transition earlier in cusp VT occurring before lead V3

Proximity of RCC to RVOT- ECG based differentiating algorithms may not be consistently accurate Must be based on the earliest intracardiac activation or on pace mapping

ELECTROPHYSIOLOGIC MECHANISM

Outflow tract VT is due to triggered activity Secondary to cyclic AMP mediated DADExample-Exertion results in increased cyclic AMP due to beta receptor stimulationRelease of calcium from sarcoplasmic reticulum and DAD Mutations in signal transduction pathways involving cAMP may be etiology for VT in some patientsTachycardia 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 stressCircadian variation- peaks at 7 AM and between 5 and 6 PMWomen-symptoms related to changes in hormonal statusTruly idiopathic OTVT is benignSmall percentage of patients with very frequent VT –TCMRare reports of cardiac arrest and PMVT

TREATMENT

May respond acutely to carotid sinus massage, Valsalva maneuvers or intravenous adenosine or verapamilLong-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 activationPace mapping

PACE MAPPING

Useful because typically site of origin is focal and because underlying tissue is normalPerformed with a low outputResult in a small discrete area of depolarizationMapping performed at site of origin of clinical arrhythmia, ECG should mimic clinical arrhythmia perfectly (12/12, including notches)

Predictors for successful ablation

Single VT morphologyAccurate pace maps

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 rareRBBB (1%)Cardiac perforationDamage to the coronary artery (LAD) - cusp region ablationOverall 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

CHARACTERISTIC FEATURES

• Induction with atrial pacing;

• RBBB morphology with left axis deviation;

• Occurrence in patients without structural heart disease.

• Termination by verapamil.

CLINICAL FEATURES• Between the ages of 15 to 40 years• More commonly affects male.• Symptoms include palpitations, fatigue, dyspnea, dizziness, and

presyncope• Syncope and sudden death very rare• Most of the episodes occur at rest• Can be triggered by exercise and emotional stress.• Tachycardia-induced cardiomyopathy has been described• Spontaneous remission may occur with time

MECHANISM: THEORIES• Microreentry circuit in the territory of the left posterior fascicle (LPF)

• Circuit is confined to the Purkinje system, which is insulated from the underlying ventricular myocardium.

• False tendons or fibromuscular bands that extend from the posteroinferior LV to the basal septum have also been implicated in the anatomical substrate

ECG FEATURESThe resting ECG is usually normal. Symmetrical, inferolateral T wave inversion can be present after VT termination.During VT -RBBB with left anterior fascicular (LAF) block or, less commonly (5% to 10%), LPF block pattern R/S ratio >1 in V1 and V2 Upper septal fasicular VT presents as RBBB, narrow QRS complex and a normal frontal axis.

Upper septal form of LV VT • Narrow QRS duration (100 msec)• R/S transition between V3 and V4 on the ECG during VT• Precordial QRS similar to sinus rythm

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

ANNULAR VENTRICULAR TACHYCARDIAS

VTs arising from the mitral or tricuspid annulus account for between 4% and 7% of idiopathic VTs

Most often, they are of the repetitive monomorphic type

Behave similarly to outflow tract VT, both in prognosis and in drug response

Are amenable to ablation

ANNULAR VTBased on the chamber of origin this can be classified as :

• 1. VT arising from the mitral annulus (MAVT)• 2. VT rising from the tricuspid annulus

Mechanism : appears to be triggered activity based on the response to adenosine, verapamil, and the pacing maneuvers

MITRAL ANNULAR VT RBBB pattern (transition in V1 or V2), S-wave in V6, and monophasic R or Rs in leads V2-V6. They further classified MAVT into three categories depending on the site of origin:1. Anterolateral (AL) MAVT (58%)2. Posterior (Pos) MAVT (11%)3. Posteroseptal (PS) MAVT (31%)

TRICUSPID ANNULAR VT

7% of the idiopathic VTsPreferentially seen to originate from the septal region (78%) than the free wall (22%)Septal VT

• Commonly arise from anteroseptal region (72%) • Early transition in precordial leads (V3) • Narrower QRS complexes• Qs in lead V1• Absence of “notching” in the inferior leads

IDIOPATHIC PROPRANOLOL-SENSITIVE VT (IPVT)

Usually occurs by fifth decade of life Can arise from LV or RVMorphology may be monomorphic or polymorphicNot inducible with programmed stimulationIsoproterenol infusion usually inducesBeta-blockers are effective in terminating tachycardia.

TREATMENT OF IPVT

BBs Effective in acute situations Insufficient information available regarding long-term management. Survivors of sudden cardiac death may receive ICD

REFERENCES

•Braunwald 9th edition

•Hurst 13th edition

•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

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LIFE-THREATENING(TYPICALLY POLYMORPHIC VT)

Rare Generally occurs with genetic ion channel disorders Unlike monomorphic VT associated with SCD Abnormalities exist at molecular level

Genetic syndromes

Long QTBrugada SyndromeCPVTShort QT

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 potentialResult in prolongation of QT interval Predisposition to EAD and torsade de pointes VT

Twelve different genes described LQT1, LQT2, and LQT3 account for 90%LQT1 and LQT2 -mutations of KCNQ1 and KCNH2 genes that encode subunits of IKs and Ikr potassium channels, respectively LQT3 -mutations of SCN5A gene that encode subunits of INa sodium channels Approximately 25% not have identifiable gene mutations

Mean age of symptom onset is 12 yearsPresent 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 and frequently experience events during physical activity (especially swimming).LQT2- T-wave is often notched in multiple leads.Triggers for LQT2 include startling auditory stimuli (e.g., from an alarm clock) and emotional upset.LQT3- often demonstrate long ST segmentsMost LQT3 events occur at rest or sleep.

MANAGEMENT

Avoid trigger events and medications prolong QT interval Risk stratification schemes based on degree of QT prolongation, genotype, and sex Corrected QT interval exceeding 500 ms poses a high risk for cardiac events Patients who have LQT2 and LQT3 may be at higher risk for SCD compared with patients who have LQT1

BB are indicated for all patients with syncope and for asymptomatic patients with significant QT prolongation Role of BB in asymptomatic patients with normal or mildly prolonged QT intervals remains uncertain.BB are highly effective in LQT1, but less effective in other LQTSRole of BBs in LQT3 is not established. Because LQT3 is a minority of all LQTS,symptomatic patients who have not undergone genotyping should receive BBs

ICD are indicated for secondary prevention of cardiac arrest and for patients with recurrent syncope despite BB therapy Less defined therapiesGene-specific therapy with mexiletine , flecainide , or ranolazine for some LQT3 patientsPPI for bradycardia-dependent torsade depointesSurgical left cardiac sympathetic denervation for recurrent arrhythmias resistant to BB therapy Catheter ablation of triggering PVCs-abolish recurrent VT/VF

BRUGADA SYNDROME

Characterized by coving ST-segment elevation in V1 to V3 2 mm in 2 of these 3 leads are diagnosticComplete or incomplete RBBB patternPattern can be spontaneously present or provoked by sodium-channel– blocking agents such as ajmaline,flecainide, or procainamide Typical ECG pattern can be transient and may only be detected during long-term ECG monitoring.

CLINICAL PRESENTATION

Syncope or cardiac arrestPredominantly in men in third and fourth decadeAlso been linked to SCD in young men in Southeast Asia and has several local names,including Lai Tai (“died during sleep”) in Thailand Prone to atrial fibrillation and sinus node dysfunction

ELECTROPHYSIOLOGY STUDY Induction of VAs has inconsistent predictive value Fragmented QRS interval -predict poor prognosis

TREATMENTNo well-validated preventive medical therapy Patients who don’t have cardiac arrest risk stratified on the basis of spontaneous ECG pattern and syncopeLowdose quinidine may be used to treat frequent VAs in patients who already have an ICDQuinidine and isoproterenol may be useful in patients having VT storms Catheter ablation of triggering PVCs and ablation of RV outflow epicardial musculature successful in abolishing recurrent VT/VF in a small number of patients

ICD

ICD are effective in preventing SCD and are indicated for cardiac arrest survivors Major management dilemma arises in decision to place prophylactically an ICD based on patient’s perceived risk of SCD

Patients with spontaneous ECG pattern and syncope are at high risk and ICD insertion is generally recommended for primary prophylaxisAsymptomatic patients with spontaneous ECG pattern are at intermediate risk, and their best therapeutic options may need to be individualizedAsymptomatic patients without spontaneous ECG pattern are at low risk and may be followed up clinically Family history of SCD and specific genotypes do not predict events

7 different genes involved SCN5A gene mutations (BrS1) - loss of function of cardiac sodium channel (NaV 1.5) account for majority of genotyped cases Typical Brugada syndrome ECG pattern- a positive genotype is obtained only in 13% BrS1 and LQT3 share SCN5A mutations Overlapping phenotypes of Brugada syndrome and LQT3 have been reported

Disorder of myocardial calcium homeostasisClinically manifested as exertional syncope and SCD due to exercise induced VT Often polymorphic or bidirectional

CATECHOLAMINERGIC PMVT.

Autosomal dominant form involves mutation of cardiac ryanodine receptor (RyR2 gene) in approximately 50% of patients Autosomal recessive form, accounting for only 3% to 5% of genotyped cases-mutations of calsequestrin 2 gene (CASQ2)

Ryanodine receptor spans membrane of sarcoplasmic reticulum and releases calcium triggered by calcium entry into cell through L-type calcium channelsCalsequestrin is a protein that sequestrates calcium ions within the sarcoplasmic reticulumRyR2 and CASQ2 mutations cause intracellular calcium overload and DAD -basis of arrhythmogenesis

Resting ECG is unremarkable 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 7.8 4 yearsElectrophysiology study is not helpful in risk stratification

Mainstay of medical management is BB therapy46% may have recurrent events while receiving therapyCCB may have limited effectiveness as adjunctive therapyFlecainide blocks RyR2 receptor and shows promise as a medical therapy

ICD insertion is appropriate for patients who had cardiac arrest and with life-threatening VA despite maximal medical therapy Recurrent ICD shocks may occur and an initial shock with its accompanying pain and anxiety may trigger further VAsSurgical left cardiac sympathetic denervation -resistant cases

SHORT QT SYNDROME

Rare disorder characterized by short QT intervals of 300 to 320 ms. Diagnostic criteria involving corrected QT interval, clinical history, and genotypingSyndrome is associated with SCD and atrial fibrillationPatients may present early in childhood

Mutations leading to gain of function of 3 genes encodingfor repolarizing potassium currents (IKr, IKs, and IK1)

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

REFERENCES

•Braunwald 9th edition

•Hurst 13th edition

•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

THANK YOU

THANK YOU

MITRAL ANNULAR VT

ECG of ventricular complexes originating from mitral annulus may show significant slurring of QRS complex onset resembling a delta-waveRegardless of where along circumference of mitral annulus VT originates ECG shows RBBB pattern across precordium and an S wave in lead V6.More lateral site- more likely is the presence of S wave in lead I and of notching in inferior leadsIn contrast with other mitral annular sites, posterior focus will have superior axis.

PVCs or VT also originate from RVOT along region of tricuspid annulus Most common site is para-HisianCharacteristic ECG findings are Inscription of an R wave in lead I and Avl Relatively small R wave in inferior leads QS wave in V1 Precordial transition in V2 to V4Sites of successful ablation record an atrial and a ventricular potential

TRICUSPID ANNULAR VT