Catheter Ablation of Ventricular Tachycardia in …lar arrhythmias (VAs), it is now possible to successfully treat many individuals with catheter ablation. In patients with structurally

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THE PRESENT AND FUTURE

STATE-OF-THE-ART REVIEW

Catheter Ablation of VentricularTachycardia in Structurally Normal HeartsIndications, Strategies, and Outcomes—Part I

Srinivas R. Dukkipati, MD, Subbarao Choudry, MD, Jacob S. Koruth, MD, Marc A. Miller, MD, William Whang, MD,Vivek Y. Reddy, MD

ABSTRACT

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Catheter ablation of ventricular tachycardia (VT) is being increasingly performed; yet, there is often confusion regarding

indications, outcomes, and how to identify those patient populations most likely to benefit. The management

strategy differs between those with structural heart disease and those without. For the former, an implantable

cardioverter-defibrillator (ICD) is typically required due to an elevated risk for sudden cardiac death, and catheter

ablation can be used as adjunctive therapy to treat or prevent repetitive ICD therapies. In contrast, VT or premature

ventricular contractions in the setting of a structurally normal heart carries a low risk for sudden cardiac death;

accordingly, there is typically no indication for an ICD. In these patients, catheter ablation is considered for symptom

management or to treat tachycardiomyopathy and is potentially curative. Here, the authors discuss the pathophysiology,

mechanism, and management of VT that occurs in the setting of a structurally normal heart and the role of catheter

ablation. (J Am Coll Cardiol 2017;70:2909–23) © 2017 by the American College of Cardiology Foundation.

W ith increased understanding of themechanisms and substrates for ventricu-lar arrhythmias (VAs), it is now possible

to successfully treat many individuals with catheterablation. In patients with structurally normal hearts,monomorphic ventricular tachycardia (VT), certaintypes of polymorphic VT, or ventricular fibrillation(VF) that are triggered by premature ventricular con-tractions (PVCs) are amenable to catheter ablation.Furthermore, symptomatic and frequent PVCs thatsometimes cause left ventricular (LV) dysfunctioncan also be ablated. Each of these arrhythmias canoccur with or without concomitant structural heartdisease. In this paper, we review the mechanismsand substrate for VAs that occur in structurallynormal hearts, and discuss the role of catheter abla-tion in their management.

m the Helmsley Electrophysiology Center, Department of Cardiology, Icah

rk. Dr. Dukkipati has received a research grant from Biosense Webster

bster and Abbott. Dr. Reddy has received research grants from and se

entific, and Abbott. All other authors have reported that they have no re

close. Roderick Tung, MD, served as Guest Editor for this paper.

nuscript received September 25, 2017; revised manuscript received Octob

MECHANISMS OF VAs

The mechanisms underlying monomorphic VT orPVCs may be triggered activity, abnormal automa-ticity, or re-entry. Triggered activity involves oscil-lations in the membrane potential that may occurduring or after cardiac depolarization. Those thatoccur during phase 2 or 3 of the action potential aretermed early afterdepolarizations (EADs) and thosethat occur following the action potential are delayedafterdepolarizations (DADs) (1,2). EAD-dependent ar-rhythmias are rate-dependent and are generally morefrequent at slow heart rates. Torsade de pointes inlong QT syndromes is thought to be secondary toEADs. DADs occur under conditions that increaseintracellular calcium. In contrast to EADs, DADstypically occur at faster heart rates and may be

n School of Medicine at Mount Sinai, New York, New

. Dr. Koruth has served as consultant for Biosense

rved as a consultant for Biosense Webster, Boston

lationships relevant to the contents of this paper to

er 13, 2017, accepted October 17, 2017.

ABBR EV I A T I ON S

AND ACRONYMS

ARVC/D = arrhythmogenic

right ventricular

cardiomyopathy/dysplasia

DAD = delayed after

depolarization

EAD = early after

depolarization

ECG = electrocardiogram

ICD = implantable

cardioverter-defibrillator

LV = left ventricle/ventricular

OTVT = outflow tract

ventricular tachycardia

PVC = premature ventricular

contraction

VA = ventricular arrhythmia

VF = ventricular fibrillation

VT = ventricular tachycardia

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induced by rapid pacing, programmed stim-ulation, or isoproterenol infusion. Idiopathicoutflow tract VT is an example of DAD-mediated triggered activity due to a cyclicadenosine monophoshate–mediated increasein intracellular calcium. VT may also resultfrom abnormal automaticity, in which case itis typically not induced or terminated byprogrammed stimulation and often requiresisoproterenol for induction. VT that is sec-ondary to triggered activity or abnormalautomaticity is primarily focal in origin,although small micro–re-entrant circuitscannot be excluded; focal VT is typicallysusceptible to discrete ablation lesions (3).

Re-entrant arrhythmias require the pres-ence of a conduction block (anatomical,functional, or both) to define part of the re-entrant circuit, unidirectional block in 1pathway, and slow conduction through the

second pathway. In order for re-entry to perpetuate,the wavelength must be shorter than the pathway,producing an excitable gap of tissue (1). The primarymechanism of VT that occurs in the setting of struc-tural heart disease is scar-related re-entry (4–6).Re-entrant VT can be induced and terminated withprogrammed stimulation.

OUTFLOW TRACT PVCs AND VT

MECHANISM AND SUBSTRATE. Sustained VT is un-common in patients with structurally normal hearts.Isolated PVCs are a more typical manifestation. Thereported incidence of ventricular ectopy in a healthypopulation varies widely depending on the durationof observation, with about 40% of adults having PVCson a 24-h recording (7,8). The most common site ofVAs in patients without structural heart disease is theright or left ventricular outflow tract (9). Outflow tractPVCs and outflow tract ventricular tachycardias(OTVTs) are characterized by a strongly positive QRScomplex in the inferior leads, and typically a leftbundle branch block morphology in lead V1 of theelectrocardiogram (ECG).

Although scar-related re-entrant arrhythmias canalso be seen from this region, the most common formof OTVT in structurally normal hearts occurs due toDADs from intracellular calcium overload. This ismediated by increased levels of cyclic adenosinemonophosphate (10). Adenosine is effective foracutely terminating this type of VT, presumablythrough its effects on reducing cyclic AMP in theventricular myocardium via an inhibitory G-proteincascade. Vagal maneuvers work in a similar fashion

by releasing acetylcholine, which inhibits cyclicadenosine monophosphate via another G-proteincoupled receptor. Adrenergic stimulation increasescyclic adenosine monophosphate levels via a stimu-latory G-protein, and can thereby potentiate OTVT.Beta-blockers inhibit this effect. Calcium-channelblockers inhibit the slow-inward calcium current,reducing calcium overload in the cell directly (10).

In the outflow tract, several cardiac structures lie inclose proximity (Figure 1). The right and left ventric-ular outflow tracts, aortic root, pulmonary artery, andepicardium all can give rise to outflow tract arrhyth-mias. Major coronary arterial and venous branchesalso traverse this region. Outflow tract arrhythmiastypically originate from a focal ventricular site, dis-playing a single dominant QRS morphology. Lessfrequently, multiple similar QRS morphologies canarise from a single PVC focus due to differentmyocardial exit sites. Multiple PVC morphologiesarising from multiple different ventricular sites canoccur, but are less common. Nonsustained and sus-tained VT can occur. Outflow tract PVCs are pre-dominantly seen in normal hearts, but their presencecan be an indication of underlying heart disease.Areas of scarring in the outflow tract can be seen inarrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and cardiac sarcoidosis, whichcan give rise to the re-entrant arrhythmias seen withstructural heart disease and can mimic OTVT. Malig-nant arrhythmias and sudden death have only rarelybeen reported with outflow tract arrhythmias in theabsence of structural heart disease (11,12).

For many years, isolated PVCs in patients withoutstructural heart disease were thought to be a benignfinding. More recent population cohort studies haveassociated the presence of a high PVC burden with anincreased risk of congestive heart failure and mor-tality over long-term follow-up (13–15).

PVC-induced cardiomyopathy appears to be adistinct entity from tachycardia-induced cardiomy-opathy. Patients who develop cardiomyopathy haveoverall heart rates similar to those with PVCs who donot develop LV dysfunction (16). But higher PVC bur-dens clearly portend greater risk for cardiomyopathy.One study reported a 24% PVC burden to have the bestcombination of sensitivity and specificity in identi-fying patients likely to develop cardiomyopathy,although LV function improvements occur followingcatheter ablation with PVC burdens as low as 10% (17).

A width of the PVC QRS complex >150 ms inde-pendently predicts development of PVC-inducedcardiomyopathy (18–20). The QRS duration also pre-dicts reversibility of LV dysfunction after successfulablation: a mean QRS duration of 135 ms was seen

FIGURE 1 3-Dimensional Computed Tomography Reconstruction of Cardiac Anatomy Illustrating the Complex Anatomy of

the Ventricular Outflow Tract

The left anterior oblique (left) and superior (right) views show the anatomic proximity of the RVOT, LV outflow tract, Ao, GCV, and LAA to the

summit (yellow circle). The distal RVOT and pulmonary artery are not seen in the images, but these structures are also in close proximity to

the summit. Outflow tract premature ventricular contractions and ventricular tachycardia have been reported to be successfully ablated from

each of these structures. The proximity of the coronary arteries is also shown, and their course must be appreciated to avoid collateral

damage during ablation. Computed tomography images were processed using custom software (MUSIC–Université de Bordeaux, INRIA, IHU

LIRYC ANR-10-IAHU-04, Equipex MUSIC ANR-11-EQPX-0030). Ao ¼ aorta; GCV ¼ great cardiac vein; LAA ¼ left atrial appendage; LV ¼ left

ventricular; RVOT ¼ right ventricular outflow tract.

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in patients presenting with frequent PVCs and normalLV function, and mean durations of 158 and 173 mswere seen in those with reversible LV dysfunctionand irreversible LV dysfunction after ablation,respectively (20). Other risk factors associated withdeveloping cardiomyopathy include: PVCs origi-nating from an epicardial site (19,21), interpolatedPVCs (16), longer duration of symptoms (22), andabsence of symptoms (21,22).MANAGEMENT. PVCs are commonly seen duringroutine ECG or stress testing. The optimal manage-ment strategy for patients with outflow tract PVCs orVT depends on several factors: the presence of symp-toms related to the arrhythmia, underlying heart dis-ease, and risk for developing cardiomyopathy.

Most patients are either asymptomatic or have onlymild symptoms. When reported, symptoms generallyconsist of palpitations—often described as poundingin the chest, fluttering, or a sensation of skippedbeats—and may also include light-headedness orchest discomfort. Malignant arrhythmias such asPVC-induced ventricular fibrillation should beconsidered in patients with a history of abrupt

syncope (discussed in the following text). Symptomsof heart failure raise concern for underlying heartdisease or PVC-induced cardiomyopathy.

Routine blood testing includes measurement ofelectrolytes, blood counts, and thyroid function.Patients with frequent or symptomatic PVCs shouldundergo Holter monitoring to determine the rela-tionship between symptoms and PVCs, to quantifythe PVC burden, and to assess the number of differentPVC morphologies. Longer periods of monitoring maybe warranted if symptoms are infrequent. A trans-thoracic echocardiogram is helpful to assess ventric-ular function. The presence of high-risk symptoms,multiple PVC morphologies, or other ECG abnormal-ities may indicate an underlying cardiomyopathy.Precordial T-wave inversions in leads V1 to V3 arecommonly seen in ARVC/D. Further imaging withcardiac magnetic resonance imaging or positronemission tomography is reasonable to identifyARVC/D, cardiac sarcoidosis, or other cardiomyopa-thies which may be missed by echocardiography. Acoronary evaluation can be considered in patientswith exertional symptoms or significant risk factors.

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Asymptomatic patients with <10% PVC burden donot require specific treatment. Treatment to suppressPVCs should be pursued if significant symptoms arepresent, or if they result in cardiomyopathy or ma-lignant arrhythmias. Treatment can also be consid-ered in patients with cardiac resynchronizationdevices if the frequency of premature beats impedesoptimal biventricular pacing. PVC elimination in thissetting has been shown to improve measures of heartfailure (23). For asymptomatic patients with a highPVC burden, the best management strategy is lessclear. The potential risk of cardiomyopathy andavailable management options should be discussedwith the patient. For those who opt against treat-ment, LV function by echocardiography and Holtermonitoring should be assessed periodically, initiallyyearly. Any evidence of LV dysfunction or dilationshould prompt aggressive treatment to prevent pro-gression, and hopefully reversal, of cardiomyopathy.

Pharmacological therapy with beta-blockers istypically the first-line treatment for patients withsymptomatic PVCs. The efficacy of beta-blockers islimited (24,25), but their risk is also low. Non-dihydropyridine calcium-channel blockers are also anoption (26). Although antiarrhythmic agents such asflecainide, sotalol, or amiodarone can be more effec-tive in suppressing PVCs (27–29), this is tempered bythe risks of proarrhythmia and toxicity. We typicallyreserve their use for patients who cannot undergo orhave failed catheter ablation.

Determining the site of PVC origin may be helpfulin counseling the patient (30). But, precise localizationfrom the 12-lead ECG can be difficult due to the numberof cardiac structures lying in close proximity in thisregion. A precordial R/S transition before V3 suggestsa left-sided origin. Comparison of the R/S transitionof the PVC to that during sinus rhythm can also behelpful in distinguishing a right- from left-sided origin:an R/S transition of the PVC occurring later than thesinus rhythm transition has been shown to exclude anLV outflow tract origin with 100% accuracy (31).

Catheter ablation should be offered to medication-resistant or intolerant patients. Any patient withcardiomyopathy and frequent PVCs (>10%) should bestrongly considered for catheter ablation, as LVfunction typically improves even in the presence ofother structural heart disease (17,32). Patients withmalignant arrhythmias precipitated by outflow tractPVCs should also be considered for ablation. The 2014European Heart Rhythm Association/Heart RhythmSociety/Asia Pacific Heart Rhythm Society expertconsensus document gives a Class IIa recommenda-tion for catheter ablation in patients with frequentnonsustained VAs (10,000 PVCs per 24 h) and

significant symptoms or LV dysfunction in theabsence of another detectable cause (33). The 2015European Society of Cardiology guidelines give abla-tion of right ventricular outflow tract (RVOT) tachy-cardia a Class Ib recommendation for those who failmedication or show a decline in LV function, and aClass IIa recommendation for LV outflow tract orepicardial PVCs or VT in patients who fail or refusetreatment with sodium-channel blockers (34). Theseconsensus or guideline documents differ slightly withrespect to when to consider catheter ablation. Ourapproach is summarized in the Central Illustration.OVERVIEW OF CATHETER ABLATION. Outflow tractarrhythmias may arise from the right or left ventric-ular outflow tract, aortic root, pulmonary artery, orepicardium. These sites all lie in close proximity, andthe ECG, although imperfect, can be used to differ-entiate between these locations and guide ablation.

As noted in the previous text, in addition to aninferior axis, a precordial R/S transition before V3

indicates a left-sided origin, whereas a delayed tran-sition (after V3) implicates the RVOT. The aortic rootborders the septal side of the RVOT, with the post-eroseptal portion of the RVOT abutting the rightcoronary cusp (RCC) (Figures 1 and 2). PVCs from theselocations display a V3 transition. In these cases, abroad R-wave in V1 or V2 with a positive QRS in lead Iimplicates the RCC (35,36). PVCs from the left coro-nary cusp usually demonstrate a transition before V3

and have a multiphasic QRS morphology (M or Wpattern) in V1 and are flat or negative in lead I (37). AqR pattern in V1 is seen in PVCs from the aortomitralcontinuity (Figure 3). The RCC–left coronary cuspcommissure, which has been recognized as a commonsite for these arrhythmias, has a V3 transition and acharacteristic QS pattern and notching on the down-ward deflection in V1 (38). A number of distinctiveECG characteristics have been described for otheroutflow tract sites as well. Recognition of these ECGsignatures can help guide the procedure and improvesuccess of ablation.

One area that remains particularly challenging forablation is the LV summit, the most superior portionof the LV (Figure 1). Epicardial ablation in this areacan be attempted, but it is often limited due to theproximity of coronary arteries and obstruction byepicardial fat, especially in the more basal portion(39). Epicardial sites can often be accessed without adirect pericardial puncture via the great cardiac oranterior interventricular vein (40,41).

During the ablation procedure, the various outflowtract structures are carefully mapped to find theearliest ventricular activation during PVCs. Mappingthe earliest activation during PVCs is preferred

CENTRAL ILLUSTRATION Role of Catheter Ablation in the Management of Patients WithStructurally Normal Hearts

Structurally-Normal Heart

Idiopathic PMVT or VFdue to PVC TriggerIdiopathic LV VT Frequent PVCs/NSVT

ICD

AADs

Failure

Catheter Ablation

Normal LVFunction?

AADs

Failure

ReassessLVEF

YesNo

ICD if LVEF≤35%

ICD NotIndicated

No

PeriodicReassessment

Yes

CatheterAblation

MedicalTherapy

Catheter Ablation

With LV Dysfunction

High PVC Burden(>10,000 per 24 h)

ICD Not Indicated

Symptomatic without LVDysfunction

Failure

CatheterAblation

MedicalTherapy

ICD Not Indicated

Failure

Dukkipati, S.R. et al. J Am Coll Cardiol. 2017;70(23):2909–23.

In patients with sustained MMVT and PMVT/VF due to PVC triggers, catheter ablation is typically performed as adjunctive therapy to ICD implantation to reduce

arrhythmia recurrence. However, in patients with PVCs and left ventricular dysfunction, catheter ablation should be considered primary therapy, because ICD

implantation may be avoided if LVEF improves. AAD ¼ antiarrhythmic drug; BBRVT ¼ bundle branch re-entrant ventricular tachycardia; CM ¼ cardiomyopathy;

ICD ¼ implantable cardioverter-defibrillator; LV ¼ left ventricular; LVEF ¼ left ventricular ejection fraction; MMVT ¼ monomorphic ventricular tachycardia;

NSVT ¼ nonsustained ventricular tachycardia; PMVT ¼ polymorphic ventricular tachycardia; PVC ¼ premature ventricular contraction; VF ¼ ventricular fibrillation;

VT ¼ ventricular tachycardia.

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(Figure 3), but this may not be possible if PVCs areinfrequent during the ablation procedure. Inability toinduce PVCs or VT is the most common cause of un-successful ablation (42). Pharmacological inductionwith isoproterenol, epinephrine, or phenylephrine canbe attempted, but if PVCs remain rare, pace mapping isused. This method involves pacing from various sitesand comparing the paced QRS morphology with thetarget PVC to assess for similarity. Activation mappingis preferable, as pace mapping has a lower spatial res-olution (43).

Single-center ablation outcomes have reportedfavorable procedural success rates between 80% and

93% (17,44–46). An acute procedural success rate of84% was reported in a recent large multicenter study(30). Over a mean follow-up of 1.9 years, success rates(defined as an 80% decrease in PVC burden) were 71%off medication, and 85% with antiarrhythmic drugs.RVOT PVCs were ablated with the highest success.Epicardial PVC origin and multifocal PVCs had lowersuccess rates. The overall major complication rate forPVC ablation was 2.4%: more than one-half (1.3%)were related to vascular access (pseudoaneurysm,hematoma, or AV fistula), 0.8% were due to cardiactamponade, and 0.1% AV block with ablation. Majorcomplication rates were lowest for ablation in the

FIGURE 2 Catheter Ablation of Outflow Tract PVCs From the Aorta

(A) An activation map (anterior posterior view) of the Ao and RV during PVCs demonstrates the earliest site of activation (red area) to be in

the RCC. The ablation catheter (asterisk) is positioned at the site of successful ablation (red point). (B) An aortogram (anterior posterior

view) was performed before ablation to delineate the locations of the RCA and LM relative to the putative ablation site. The ablation catheter

(asterisk) can be seen in the RCC and is positioned at the site of earliest PVC activation. Ao ¼ aorta; LCC ¼ left coronary cusp; LM ¼ left main

artery; PV ¼ pulmonary valve; PVC ¼ premature ventricular contraction; RCA ¼ right coronary artery; RCC ¼ right coronary cusp; RV ¼ right

ventricle; TV ¼ tricuspid valve.

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RVOT. Care must be taken to avoid coronary arterialdamage during ablation in the aortic root, epicar-dium, or coronary veins (Figure 2). Concomitant cor-onary angiography may be helpful to excludeproximity to a coronary artery.

In patients with cardiomyopathy who underwentablation for frequent PVCs, 67% had improvements inLV ejection fraction of $10%, and another 18% hadimprovements of <10%. This is concordant with otherstudies that showed significant improvements incardiomyopathy after successful ablation (>80%reduction) of frequent PVCs (17,32,47). Most of theimprovement in LV function occurs in the first6 months, with successful reduction in PVC burdenbeing the most important predictor of response (32).

PAPILLARY MUSCLE PVCs AND VT

MECHANISM AND SUBSTRATE. Papillary muscle VAsin the structurally normal heart make up 5% to 12% ofall idiopathic VAs. This arrhythmia commonly pre-sents as PVCs, but can also present as nonsustained orsustained VT. The diagnosis is conclusively madeonce localized to a papillary muscle, and was

recognized as a distinct clinical entity only in the lastdecade. They are considered to be non–re-entrant,focal arrhythmias related to either abnormal auto-maticity or triggered activity. However, re-entry–based papillary muscle arrhythmias have beendescribed in post-infarction patients; this is distin-guished by the presence of structural heart diseaseand abnormal cardiac magnetic resonance imaging.Papillary muscle VAs can originate from either theanterolateral or posteromedial LV papillary musclesor, less commonly, the right ventricular papillarymuscles (48–51). In patients with bileaflet mitral valveprolapse, PVCs originating from the papillary musclesor fascicular region, sometimes alternating withoutflow tract PVCs, have been associated with anincreased risk of sudden cardiac death (52).

MANAGEMENT. These arrhythmias can occur spon-taneously or be exercise-induced. They affect adultsfrom either sex and across a wide age range (oftenolder adults, mean age w50 to 60 years) (48–51).Additional symptoms such as pre-syncope or syncopeare infrequent, given that sustained VT is relativelyuncommon. Sudden death from PVC-triggered VF,

FIGURE 3 Catheter Ablation of Outflow Tract PVCs

III

IIIaVRaVLaVF

A B

V1

V2

V3

V4

V5

V6

MAP

(A) Activation maps of the RV, Ao, GCV, and LV (not shown) were performed during PVCs. The area of earliest activation (red) was identified in

the distal GCV, and ablation in this location (red points) only temporarily suppressed PVCs. Although activation was slightly later at the LV

aortomitral continuity, prolonged ablation at this location (blue points) abolished the PVCs. Coronary angiography was performed before

ablation in the distal GCV to exclude proximity to the coronary arteries. (B) The PVC morphology is of right bundle branch block morphology

with an inferior axis (positive in leads II, III, and aVF) and is consistent with an outflow tract morphology. The qR pattern in lead V1 is

consistent with an aortomitral continuity location for the PVC. The MAP at the site of earliest activation in the distal GCV identified a local

activation time that preceded the onset of the PVC (orange line) by 28 ms. MAP ¼mapping catheter; other abbreviations as in Figures 1 and 2.

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although rare, has been described in some patientswith structurally normal hearts (discussed in thefollowing text). Therefore, when unheralded syncopeoccurs in the setting of these PVCs, one should besuspicious of this more malignant presentation.Similar to other idiopathic PVCs from the outflowregion, PVC-induced cardiomyopathy can occur andis related to the PVC burden.Medica l therapy . Antiadrenergic agents such asbeta-blockers are typically used as first-line therapyfor symptomatic arrhythmia. Class I or III antiar-rhythmic drugs are typically restricted to situationswhere catheter ablation is either not feasible or suc-cessful. In general, these arrhythmias are thought tobe less responsive to beta-blockers and calcium-channel blockers (in contrast to fascicular VT’sresponsiveness to verapamil; see the following text),thus leading to earlier adoption of catheter ablation.

OVERVIEW OF CATHETER ABLATION. For patientsthat fail or refuse medical therapy, catheter ablationcan be offered. As with other idiopathic VAs, catheterablation without a trial of medical therapy can bepursued for papillary muscle PVC cardiomyopathy or

syncope (Central Illustration). During the mappingphase of the procedure, activation mapping canlocalize PVCs to a papillary muscle, followed byconfirmation by intracardiac echocardiography(Figure 4). Targeted ablation at the earliest site ofactivation results in termination of arrhythmia. Insituations where the VAs are infrequent, ablation canagain be directed by pace-mapping, but this approachis often less effective (53).

The overall success rate of catheter ablation variesbetween published reports, but a recent multicenterstudy reported a somewhat lower success rate (60%)compared with ablation of other idiopathic VT (30).Recurrences are related to the difficulty of eitherreaching deep intramural locations within (the oftenthick) papillary muscles, or maintaining stable cath-eter contact with the contracting intracavitary papil-larymuscle. Their intramural localization often resultsin changes to the exit site after ablation along 1 aspectof the muscle, leading tomorphological changes eitherintraprocedurally or at the time of recurrence. As aresult, these arrhythmias often require prolongedirrigated RF ablation or cryoablation (54).

FIGURE 4 Catheter Ablation of PVCs Originating From the Anterolateral Papillary Muscle

I

II

III

aVR

aVL

aVF

V1

V2

V3

V4

V5

V6

MAP

A B

C

(A) The 12-lead electrocardiographic morphology of the PVCs is right bundle branch block with an inferior axis and rS complexes in leads V5/V6

is consistent with an anterolateral papillary muscle origin. The MAP positioned on the anterolateral papillary muscle at the earliest

activation site showed local activation to precede the QRS complex (orange line) by 30 ms. (B) An activation map of the left ventricle (LV)

(left anterior oblique projection) identified the earliest activation sites (red) to be within the cavity of the LV and is consistent with the

location of the anterolateral papillary muscles. Ablation at these early locations (red points) rendered the PVC noninducible. (C) Intracardiac

echocardiography was used during the procedure and confirmed that the earliest activation sites identified by the MAP (arrow) were on the

anterolateral papillary muscle (dashed white line). Abbreviations as in Figures 1 to 3.

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Posteromedia l pap i l la ry musc le VAs. These canbe recognized by a distinctive ECG morphology—rightbundle branch block (RBBB) with mid-precordialtransition and either right or left superior axis. Thesite of earliest activation is typically located at thebase of the papillary muscle, and signals at this sitefrequently have characteristic pre-potentials. How-ever, their ECG similarity to left posterior fascicularVTs and anatomical proximity of the posteromedialpapillary to the left posterior fascicle can complicatethe diagnosis (55).Anterolatera l pap i l la ry musc le VAs. These are farless common than those originating from the poste-rior papillary muscles and are recognized by theirRBBB morphology, but with a right inferior axis

pattern consistent with their more anterolaterallocation (Figure 4).Right ventr i cu lar pap i l la ry musc le VAs. Thesecan originate from any of the 3 papillary muscles inthe right ventricle—anterior, posterior, and septalpapillary muscles. Their diagnosis and ablation arefacilitated by intracardiac echocardiography both tolocalize the earliest activation to a papillary muscleand to differentiate them from other intracavitarystructures, such as the moderator band (Figure 5).Similar to their left-sided counterparts, these ar-rhythmias are thought to be related to triggered ac-tivity or enhanced automaticity, and successfulablation sites can demonstrate Purkinje-like pre-potentials. They present with LBBB morphology and

FIGURE 5 PVCs Originating From the RV Papillary Muscle

(A) An activation map of the RV (right anterior oblique view) during PVC demonstrated an intracavitary location for the earliest site of

activation (red area). The ablation catheter (asterisk) is positioned at the sites of successful ablation (red points). (B) The same activation

map is shown in a left anterior oblique view. (C) Intracardiac echocardiography demonstrated that the successful ablation site was situated on

an RV papillary muscle (dashed lines). Abbreviations as in Figure 2.

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superior axis, with the anterior and posterior papil-lary PVCs presenting with a precordial transitionbeyond V4 given their relative apical location withinthe right ventricle. PVCs originating from the septalpapillary muscle tend to be more common and havean earlier precordial transition as well as an inferiorlydirected axis (56). Others have reported a late pre-cordial transition and superior axis, indicating thatvariable exits from this papillary may producedifferent ECG morphologies (57).

IDIOPATHIC LV VT OR FASCICULAR VT

MECHANISM AND SUBSTRATE. Idiopathic LV VT inthe structurally normal heart, also termed fascicularVT, constitutes between 10% and 20% of all idiopathicVTs. Based on their sensitivity to verapamil, they arealso referred to as verapamil-sensitive VTs (58,59).This monomorphic VT involves the Purkinje networkalong the endocardial aspect of the septal LV. Fascic-ular VT typically occurs in otherwise healthy young

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adults (between the ages of 15 and 40 years), present-ing as an RBBB morphology tachycardia with left-axisdeviation with a relatively narrow QRS duration(usually <140 ms) (60,61). It is often exercise-induced,with a male predilection (60% to 80%).

This VT has several morphological variants arisingfrom differential involvement of the 3 LV fascicles:posterior, anterior, and septal (62). The complexanatomy of the conduction system with its variablearborization and cross-linking between fascicles allowfor these variations. In order of prevalence, the 3common variants are: 1) left posterior fascicular VT(RBBB and superior axis); 2) left anterior fascicular VT(RBBB and right axis); and 3) upper septal VT with anarrow QRS (usually RBBB and<110 ms with normal orrightward axis). More recently, less common variantswith multiform morphologies have also beendescribed (63). The majority of idiopathic LV VTs havea re-entrantmechanism, butmore recently, focal, non–re-entrant variants have been reported (64).Lef t poster ior fasc i cular VT. This constitutes 90%of all fascicular VTs, and its subendocardial substrateis located along the posterior aspect of the mid LVseptum in proximity to the left posterior fascicularnetwork. Catheter mapping during VT demonstratescharacteristic potentials thought to represent activa-tion of abnormal Purkinje fibers. These potentials,referred to as “P1” potentials, represent the antegradelimb of the macro–re-entrant circuit (65). They arelocated proximally in the inferior septum (Figure 6).Sharper, pre-systolic Purkinje potentials (“P2” po-tentials) are often seen further distally and representthe retrograde limb of the circuit (66). This limb isthought to be the left posterior fascicle itself,although the left posterior fascicle is not critical to themaintenance of the arrhythmia (67). Finally, theprecise location of the region of slow conduction(critical for any re-entrant circuit) for this VT isthought to exist within the myocardium and not ineither limb. This explanation is likely an over-simplification of the actual circuits responsible for thespectrum of fascicular VTs, but provides a conceptualbasis for mechanistic understanding and guidingablation strategies.Left anter ior fasc icu lar VT . This morphologymakes up 9% to 10% of fascicular VTs. Clinical char-acteristics, prognosis, and strategies for ablation aresimilar to that for left posterior fascicular VTs (68).Upper septa l VT. This is the least common (<1%)variant of fascicular VT. The circuit is located furtherbasally along the septum. The circuit involves a septalfascicle, which is responsible for slow retrogradeconduction, followed by simultaneous antegradeconduction down the left anterior and posterior

fascicles as well as the right bundle branch. This ac-counts for the relatively narrow and characteristicQRS (<110 ms) during tachycardia (69).

MANAGEMENT. The vast majority of patients presentwith symptoms of rapid heart action. Additionalsymptoms of hypoperfusion, such as dizziness andpresyncope, can occur at high ventricular rates. Syn-cope and sudden death are extremely rare, andappropriate reassurance should be given to theseyoung patients. Medical therapy can be offered topatients with infrequent symptoms or for those whoprefer noninvasive options. Given their relative youthat the time of presentation, the prospect of long-termsuppressive medical therapy is often unattractive(Central Illustration). Not surprisingly, the high suc-cess and safety of catheter ablation has led to its earlyadoption. This option is especially useful for severesymptomatology such as pre-syncope, or the rareoccurrence of tachycardia-induced cardiomyopathy.

Medica l therapy . The use of calcium-channelblockers, particularly verapamil, is effective, andintravenous administration will frequently acutelyterminate tachycardia. It can also be used orally,although recurrence rates of up to 20% occur overtime (70). Beta-blockers have limited efficacy. Class Ior III antiarrhythmic drugs can be used if catheterablation is unsuccessful or infeasible.

OVERVIEW OF CATHETER ABLATION. Reports sug-gest long-term success rates of w70% with catheterablation, with a risk of recurrence reported to be up to20% in some reports (71,72). Additionally, when re-currences occur, subtle changes in the ECGmorphologyare frequently observed and are a result of ablation ofnoncritical portions of the conduction system leadingto changes in VT exit. Recent reports have also notedthat the more common variants can convert to lesscommon upper septal VT at the time of recurrence.

There are multiple approaches to catheter ablationof fascicular VT. A common ablation strategy targetsthe earliest Purkinje potentials (P2) in the retrogradelimb of the circuit during VT (Figure 6). IdentifyingPurkinje potentials along the LV septum that have theearliest timing relative to the local myocardial acti-vation allows for the best success. For left posteriorfascicular VT, the earliest potentials are typicallyfound at the junction of the mid and distal third of theLV septum, although their location can be furtherdistal or proximal in some patients. Reports have alsoshown successful ablation at the confluence of P1 andP2 potentials and local ventricular activation, whichis thought to be the lower turnaround point of the VTcircuit. Other operators have pursued a differentstrategy where only the antegrade limb of the circuit

FIGURE 6 Catheter Ablation of ILVT

III

IIIaVRaVLaVF

III

IIIaVRaVLaVF

V1

V2

V3

V4

V5

V6

V1V2V3V4V5V6

MAP

Left Anterior Fascicle

Left Septal FascicleLeft Posterior Fascicle

Left Bundle

Antegrade Limbof Circuit (P1) Retrograde Limb

of Circuit (P2)

p

MAP d

A B

C

(A) A 12-lead electrocardiogram of a patient with ILVT (rate 176 beats/min) shows a right bundle branch block with a superior axis and QRS

width of 115 ms. The morphology is consistent with ILVT involving the left posterior fascicle. (B) Mapping the LV inferior septum during

tachycardia revealed a pre-potential (P2) preceding the QRS by 24 ms (arrow) on the MAP distal (MAP d) and proximal (MAP p) electrodes.

Ablation at this site terminated the tachycardia. (C) A schematic representation of the ILVT circuit is shown (bottom). Conduction through

the antegrade limb may be identified by discrete early diastolic potentials (P1) and conduction through the retrograde limb (left posterior

fascicle) by pre-systolic potentials (P2). ILVT ¼ idiopathic left ventricular tachycardia; other abbreviations as in Figures 1 and 3.

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is targeted by identifying P1 Purkinje potentials. Thisrequires more basal ablation and can be more chal-lenging, as the P1 potential is not consistently iden-tified in all patients.

These arrhythmias are often difficult to induceand are sensitive to mechanical suppression by thecatheter during mapping. When VT is either non-sustained or noninducible, an empiric anatomically-directed approach can be used for ablation, wherebylinear lesions are placed so as to interrupt the likelylocation of the distal turnaround of the circuit (73).

Other approaches when VT cannot be sustainedinclude targeting high-frequency retrograde Purkinjepotentials in the vicinity of the offending fascicleduring sinus rhythm. For left anterior fascicularVT, the ablation target is located in the anteriorseptum.

PVC-TRIGGERED POLYMORPHIC VT AND VF

MECHANISM AND SUBSTRATE. In certain patientswithout structural heart disease, polymorphic VT or VF

FIGURE 7 Polymorphic VT Triggered by Unifocal PVCs in a Patient With Prior Myocardial Infarction

III

IIIaVRaVLaVF

V1V2V3V4V5V6

MAP

A B

(A) An activation map of the LV septum is shown in a right anterior oblique view. The area of earliest activity during PVC (red area, arrow) is

noted on the midbasal LV septum. Radiofrequency ablation (red points) at this site abolished PVCs and polymorphic VT. (B) The MAP

positioned at the earliest activation site shows characteristic Purkinje-like potentials during sinus rhythm (first arrow on the left) which also

precedes the PVCs (subsequent arrows) that trigger polymorphic VT. During sinus rhythm, the Purkinje potential just precedes the local

electrogram. With each successive PVC, the Purkinje potential becomes increasingly early, suggesting that these potentials are the source of

the ventricular ectopy. Surviving Purkinje fibers along the scar border are often sources of PVCs that trigger polymorphic VT and ventricular

fibrillation in post–myocardial infarction patients. VT ¼ ventricular tachycardia; other abbreviations as in Figures 1 to 3.

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can be initiated by isolated spontaneous PVCs (74).These triggersweremapped to the right or left Purkinjesystem in 83% and the ventricular myocardium in theright ventricular outflow tract in 17% (11). Certain pa-tients with structural heart diseasemay also have PVCsthat trigger polymorphic VT/VF. In post-myocardialinfarction patients, focal PVC triggers from survivingPurkinje fibers situated along the scar border maycause polymorphic VT/VF (75–78). Additionally, PVCtriggers for polymorphic VT/VF from the Purkinjesystem or ventricular myocardium have also been re-ported in long QT syndrome, Brugada syndrome,catecholaminergic polymorphic VT, and early repo-larization (79–81). In Brugada syndrome, the PVC trig-gers are from the RVOT. Focal PVC triggers from thepapillary muscles of the right and left ventricle and theright ventricular moderator band have also beenimplicated in polymorphic VT and VF (82–84). PVCsfrom the right ventricular moderator band can berecognized by their characteristic ECG pattern with aleft bundle branch block, left superior axis, rapid QRSdownstroke in the precordial leads, and late precordialtransition (>V4) (84).

In addition to PVC triggers of VF, recent studieshave demonstrated that Brugada syndrome repre-sents a special situation where the VF substrate itself

can be mapped. In 2011, Nademanee et al. (85) re-ported that a region of the RVOT epicardium charac-terized by abnormal, low-voltage, fractionatedelectrograms was critical to the type 1 Brugada ECGphenotype and pathogenesis of Brugada-related VF.In a histological examination of RVOT myocardiumfrom Brugada patients obtained either post-mortemor during intraoperative surgical ablation, theepicardial substrate was characterized by interstitialfibrosis and reduced gap junction expression,indicating that abnormal myocardial structure andconduction are responsible for the syndrome (86).OVERVIEW OF CATHETER ABLATION. The tech-nique for catheter ablation of PVC triggers of poly-morphic VT/VF involves identifying the earliest siteof endocardial or epicardial ventricular activation ofthe PVC, often similar to outflow tract or papillarymuscle PVCs. For Purkinje fiber PVCs, the triggeringsite is characterized by the presence of a Purkinjepotential preceding the QRS by 10 to 150 ms duringthe PVC and 11 � 5 ms during sinus rhythm (11).Radiofrequency ablation at these sites eliminatesthese triggering PVCs and subsequent VF in mostpatients (Figure 7). A subsequent multicenter studyreporting outcomes of catheter ablation for idiopathicVF in 38 patients, reported an 82% rate of freedom

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from recurrent VF during a median follow-up of5 years (87). The majority of patients with recurrenceunderwent successful repeat ablation. The sameablation strategy is employed for Purkinje fiber-related PVC triggers of polymorphic VT/VF followingmyocardial infarction (75–78). In these post-infarctionpatients, when PVCs are not inducible, successfulablation is achievable by targeting Purkinje potentialsalong the scar border in sinus rhythm.

Beyond PVC triggers, the VF substrate itself can beablated in Brugada syndrome. After pericardial ac-cess, targeting the substrate (low voltage, fraction-ated electrograms) along the RVOT epicardial surfacecan normalize the ECG and prevent VF (85).

CONCLUSIONS

In the absence of structural heart disease, catheterablation can be performed for symptomatic andfrequent PVCs or idiopathic LV VT either as first-line

treatment or for arrhythmias refractory to medicaltherapy. When PVCs are frequent, they may result inreversible LV dysfunction, which may normalizefollowing successful catheter ablation. As the risk ofsubsequent sudden cardiac death is low, ICDs are notindicated in these individuals except in the rare caseswhere concomitant polymorphic VT or VF occurs dueto reproducible PVC triggers or when LV dysfunctionfails to normalize following catheter ablation. In pa-tients with structurally normal hearts, the outcomesof catheter ablation are excellent, and these patientsshould be referred earlier for potential curativetreatment.

ADDRESS FOR CORRESPONDENCE: Dr. Vivek Y.Reddy, Icahn School of Medicine at Mount SinaiMedical Center, One Gustave L. Levy Place, Box 1030,New York, New York 10029. E-mail: [email protected].

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KEY WORDS catheter ablation, normalheart, premature ventricular contractions,ventricular fibrillation, ventriculartachycardia