Focal Ventricular Tachycardias in Structural Heart Disease

JACC: CLINICAL ELECTROPHYSIOLOGY

VOL.

-, NO. -, 2019

ª 2019 PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

Focal Ventricular Tachycardias in Structural Heart Disease Prevalence, Characteristics, and Clinical Outcomes After Catheter Ablation Robert D. Anderson, MBBS,a,b,c,d Geoffrey Lee, MBCHB, PHD,a,b Ivana Trivic, BSC,c,d Timothy Campbell, BSC,c,d Timmy Pham, BMEDSCI,c,d Chrishan Nalliah, MBBS, PHD,c Eddy Kizana, MBBS, PHD,c,d Stuart P. Thomas, MBBS, PHD,c Siddharth J. Trivedi, BSC, BMEDSCI, MBBS,c,d Troy Watts, BSC,a,b Jonathan Kalman, MBBS, PHD,a,b Saurabh Kumar, BSC(MED)/MBBS, PHDc,d

ABSTRACT OBJECTIVES This study sought to summarize the procedural characteristics and outcomes of patients with structural heart disease (SHD) who have focal ventricular tachycardia (VT). BACKGROUND Scar-mediated re-entry is the predominant mechanism of VT in SHD. Some SHD patients may have a focal VT mechanism that remains poorly described. METHODS An extended induction protocol incorporating programmed electrical stimulation, right ventricular burst pacing and isoprenaline was used to elucidate both re-entrant and focal VT mechanisms. RESULTS Eighteen of 112 patients (16%) with SHD undergoing VT ablation over 2 years had a focal VT mechanism elucidated (mean age 66
13 years; ejection fraction 46
14%; nonischemic cardiomyopathy 10). Repetitive failure of termination with antitachycardia pacing (ATP) (69% of patients) or defibrillator shocks (56%) was a common feature of focal VTs. A median of 3 VTs per patient were inducible (28 focal VTs, 34 re-entrant VTs; 53% of patients had both focal and re-entrant VT mechanism). Focal VTs more commonly originated from the right ventricle (RV) than the left ventricle (LV) (67% vs. 33%, respectively). In the RV, the RV outflow tract was the most common site (33% of all focal VTs), followed by the RV moderator band (22%), apical septal RV (6%), and lateral tricuspid annulus (6%). The lateral LV (non-Purkinje) was the most common LV focal VT site (16%), followed by the papillary muscles (17%). After median follow-up of 289 days, 78% of patients remained arrhythmia-free; no patients had recurrence of focal VT at repeat procedure. In patients with recurrence, defibrillator therapies were significantly reduced from a median of 53 ATP episodes pre-ablation to 10 ATP episodes post-ablation. During follow-up, 2 patients (11%) underwent repeat VT ablation; none had recurrence of focal VT. CONCLUSIONS Focal VTs are common in patients with SHD and often coexist with re-entrant forms of VT. High failure rate of defibrillator therapies was a common feature of focal VT mechanisms. Uncovering and abolishing focal VT may further improve outcomes of catheter ablation in SHD. (J Am Coll Cardiol EP 2019;-:-–-) © 2019 Published by Elsevier on behalf of the American College of Cardiology Foundation.

T

he most common mechanism of ventricular

SHD and is rarely seen as a dominant mechanism in

tachycardia (VT) in patients with structural

patients with established or acute ischemic heart dis-

heart disease (SHD) is scar-related re-entry

ease (2), linked mechanistically to the His-Purkinje

(1). Focal VT is typically seen in patients without

system (3–6). There is a paucity of data characterizing

From the aDepartment of Cardiology, Royal Melbourne Hospital, Melbourne, Australia; bFaculty of Medicine, Dentistry, and Health Science, University of Melbourne, Melbourne, Australia; cDepartment of Cardiology, Westmead Hospital, Sydney, Australia; and the dWestmead Applied Research Centre, University of Sydney, Sydney, Australia. Dr. Anderson has been supported by postgraduate scholarships co-funded by the National Health and Medical Research Council (NHMRC), National Heart Foundation (NHF), and Royal Australasian College of Physicians NHMRC Woodcock Scholarships. Dr. Campbell was a former employee of Johnson and Johnson Medical within the last 12 months; and was a previously salaried employee of Johnson and

ISSN 2405-500X/$36.00

https://doi.org/10.1016/j.jacep.2019.09.013

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Anderson et al.

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Focal VTs in Structural Heart Disease

ABBREVIATIONS

focal VTs remote from or adjacent to regions

(GA) as previously described (8–10). An SL3 sheath

AND ACRONYMS

of dense scar in patients with SHD (2). In this

(Abbott Medical, Abbott Park, Illinois) was used to

study, we report the frequency, procedural

perform coronary sinus (CS) venography, and a

characteristics, and subsequent clinical out-

decapolar catheter was inserted into the CS. A

comes in a series of patients with SHD shown

quadripolar catheter was deployed in the RV apex.

to have a focal mechanism despite the pres-

Intracardiac echocardiography (ICE) was routinely

ence of scar and the typical electrophysiolog-

used for full 3-dimensional (3D) reconstruction of

ical milieu for re-entrant VT.

biventricular geometry (64-element, 5.5 to 10 Hz)

3D = 3-dimensional AAD = antiarrhythmic drug ARVC = arrhythmogenic right ventricular cardiomyopathy

ATP = antitachycardia pacing CL = cycle length

(SoundStar,

CS = coronary sinus EAM = electroanatomic

CARTOSOUND

module,

Biosense

Webster, La Jolla, California) or for direct visualiza-

METHODS

tion of catheter position when CARTOSOUND was not

mapping

STUDY POPULATION. Consecutive patients

available (ViewFlex Xtra, Abbott Medical). Antiar-

with SHD who had undergone a VT ablation

rhythmic drug (AAD) therapy was withheld for up to

procedure at a single center (Department of

5 days before the planned catheter ablation (except

Electrophysiology, Westmead Hospital, Syd-

for emergent procedures). Systemic anticoagulation

ney, Australia) in the previous 2-year period

was administered after sheath insertion using intra-

were included. Patients with SHD (ischemic or

venous unfractionated heparin to maintain an acti-

nonischemic) who were referred for catheter

vated

ablation for medically refractory VT also were

ventricular (LV) access, unless epicardial access was

included. During this period, 145 patients had

planned,

cardiomyopathy

undergone catheter ablation for ventricular

commenced after safe epicardial access was estab-

ECG = electrocardiogram EGM = electrogram GA = general anesthesia ICD = implantable cardioverter-defibrillator

ICE = intracardiac echocardiography

LV = left ventricle NICM = nonischemic

clotting in

time which

$400 case

seconds

before

anticoagulation

left was

PES = programmed electrical

arrhythmia (VA). Of these patients, 116 had

lished. Implantable cardioverter-defibrillators (ICDs)

stimulation

SHD, and 112 had a spontaneous VT evident on

were reprogrammed to disable therapies before

PVC = premature ventricular

presentation and/or had undergone a detailed

ablation. Endocardial LV was accessed either trans-

complex

induction protocol to elucidate a focal VT

septally (large curve Agilis, Abbott Medical) or

RV = right ventricle

mechanism. These 112 patients underwent a

retrogradely (SL1, Abbott Medical), or both. In cases

RVOT = right ventricular

strict

stimulation

of previously failed endocardial catheter ablation or

outflow tract

(PES) protocol (described in the section on VT

if pre-procedural imaging strongly indicated an

SHD = structural heart disease

induction protocol), followed by burst right

intramural/epicardial substrate, epicardial access (via

VA = ventricular arrhythmia

ventricular (RV) pacing down to ventricular

a percutaneous approach) was obtained as described

VF = ventricular fibrillation

refractoriness with maximum tolerable dose

previously (11). Coronary angiography was performed

of isoproterenol (2-m g bolus and up to 40 m g/

before epicardial ablation to avoid coronary injury

VT = ventricular tachycardia

min

programmed

infusion)

(7).

electrical

Pre-procedural

data,

and high-output pacing (10 mA and 10 ms) to exclude

arrhythmia history, procedural characteristics, com-

phrenic nerve capture.

plications, and follow-up information were collected.

V T i n d u c t i o n p r o t o c o l . PES was performed in all

All patients gave written informed consent for the

cases by pacing from at least 2 RV sites using a 400-

procedure. The analysis was approved by the Western

ms drive train with 4 extrastimuli beginning at

Sydney Local Health District Human Research Ethics

300 ms, decrementing by 10 ms down to ventricular

Committee.

refractoriness. LV stimulation was used if VA was noninducible after RV stimulation. This was followed

MAPPING AND RADIOFREQUENCY ABLATION. P r e -

by burst RV pacing down to ventricular refractoriness

p a r a t i o n . Procedures were performed with patients

from the RV apex. PES and burst RV pacing were then

under either conscious sedation or general anesthesia

repeated from each site using the highest tolerated

Johnson Medical. Dr. Kalman has received fellowship support from Biosense Webster, Medtronic, and Abbott. Dr. Kumar has received research grants from Biotronik, Abbott, Bayer-Cardiac Society of Australia and New Zealand, Perpetual Ramaciotti Foundation, Sylvia and Charles Viertel Foundation, Westmead Hospital Charitable Trust, and Westmead Hospital Research and Education Network; has received honoraria from Abbott Medical, Biosense Webster, Biotronik, and Sanofi Aventis; and has received fellowship support from NSW Early to Mid Career Fellowship. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Francis Marchlinski, MD, served as Guest Editor for this paper. The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page. Manuscript received June 6, 2019; revised manuscript received July 29, 2019, accepted September 4, 2019.

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Focal VTs in Structural Heart Disease

used (PentaRay 2-6-2 spacing, Biosense Webster;

T A B L E 1 Baseline Characteristics

Advisor HD Grid or Livewire Duodeca 2-2-2 spacing, 66
13 (43–90)

Age, yrs Male

15 (83)

Imaging

Abbott). In the EAM system, bipolar electrograms (EGMs) were high-pass filtered at 20 to 30 Hz and low-

Left ventricular ejection fraction at time of first procedure, %

46
14

pass filtered at 400 Hz. Bipolar EGMs were also pass

Left ventricular end-diastolic diameter at time of first procedure, mm

57
10

ing the CardioLab EP system (General Electric

RV dilation/dysfunction (>mild)

2 (11)

MRI

6 (33)

filtered from 30 to 500 Hz and digitally recorded usHealthcare, Chicago, Illinois). An endocardial and/or epicardial 3D shell of cham-

16 (89)

ber geometry was constructed for each ventricle, and

Single-chamber defibrillator

6 (38)

EGMs were recorded during sinus rhythm or paced

Dual-chamber defibrillator

10 (62)

voltage map. If atrioventricular conduction was pre-

3 (19)

served, CS pacing was performed at 600 ms. If atrio-

ICD pre-procedure*

Biventricular defibrillator Underlying heart disease

ventricular conduction was impaired, dual-chamber

Ischemic

5 (28)

Idiopathic dilated

10 (55)

Cardiac sarcoidosis

2 (11)

Arrhythmogenic right ventricular cardiomyopathy

1 (6)

pacing at 600 ms was performed. If biventricular pacing was present, dual-chamber pacing at 600 ms with LV and RV pacing was used. Activation maps of each VT were recorded if the VT was sustained and toler-

Indication for VT ablation

ated. Fill threshold (projection of color from each

Recurrent ICD shocks

9 (50)

Sustained VT

6 (33)

Nonsustained VT

3 (17)

mapping point) was set at 10 units for all maps. Conventional ventricular peak-to-peak bipolar voltage

10 (55)

parameters were used (dense scar <0.5 mV; low

Amiodarone

9 (50)

voltage was defined as EGM amplitude <8.3 mV for LV

Sotalol

5 (28)

(13) and <5.5 mV for RV (14).

Mexiletine

2 (11)

b-blocker

10 (55)

VT storm Antiarrhythmic therapy (pre-ablation)

Clinical VT

17 (94)

Right bundle pattern in V1

9 (53)

Left bundle pattern in V1

8 (47)

voltage 0.5 to 1.5 mV; normal >1.5 mV). Unipolar low

Electrically inexcitable scar was defined as regions with no reproducible local bipolar potential despite adequate contact force ($10 g) and failure of unipolar pacing capture with the highest possible output (10

53

mA and 9-ms pulse width) with contact force $10 g

Superior axis

23.5

(12). Image integration with pre-procedural contrast-

Horizontal axis

23.5

enhanced cardiac magnetic resonance or computer

Inferior axis

tomographic scans were used, when available, to Values are mean
SD (range), n (%), mean
SD, or %. *All had ICD postprocedure. ICD ¼ implantable cardioverter-defibrillator; MRI ¼ magnetic resonance imaging; RV ¼ right ventricle; VT ¼ ventricular tachycardia.

identify and reconstruct anatomy and were imported into the 3D mapping system. The chamber (LV or RV and space [endo/epicardial]) map was based on the characteristics of the induced or spontaneous VA(s).

dose of isoprenaline (2- mg bolus and up to 40 mg/min)

For the purpose of scar characterization, we modified

with hemodynamic support to maintain perfusion

the 17-segment American Heart Association model for

pressure with inotropic or mechanical circulatory

myocardial segmentation as previously described

support initiated at the start of the case. Isoprenaline

(15,16). We excluded LV segment 17 (apical tip)

was initially commenced at 10 m g/min, with the PES

because

and RV burst pacing protocol repeated after incre-

Furthermore, we divided septal segments (5,6,11,12)

menting the isoproterenol dose by 10 m g/min. The

into left-septal (L) and right-septal (R) and added free

maximum tolerated dose was defined as the inability

RV wall: basal (segment 17), midwall (segment 18),

it

cannot

be

mapped

endocardially.

to maintain mean arterial pressure >60 mm Hg

and apex (segment 19). The annulus was defined as a

despite the addition of inotropes or vasopressors. The

1:1 ratio between atrial and ventricular EGMs, as well

same induction protocol was repeated post-ablation.

as direct identification with ICE. Low-voltage areas

Electroanatomic

within 1 cm of the annulus were excluded from

mapping

and

catheter

a b l a t i o n . Three-dimensional electroanatomic map-

measurements.

ping (EAM) of the RV or LV (or both) was performed

Ablation was performed using irrigated catheters

using either of 2 mapping systems (EnSite Precision,

(ThermoCool SmartTouch Surround Flow SF, Bio-

Abbott; or CARTO, Biosense Webster) (12). High-

sense Webster; TactiCath SE or FlexAbility, Abbott).

resolution multielectrode mapping catheters were

The endpoint of each ablation lesion was controlled

3

4

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F I G U R E 1 Effect of ICD Therapies During Focal VT

A

B

C

Spontaneous onset/o set

D

1

2

3

4

5

6

7

E

8

Failure to revert (suppressed) with ATP

Suppressed

2

3

4

5

6

7

F

8

Cardioversion

1

Suppressed

2

3

4

5

6

7

8

Suppressed

H

G Continuous despite electrical cardioversion

1

I

Cardioversion

Cardioversion

Spontaneously initiating and terminating VT (A–C) in a 53-year-old patient with RV nonischemic cardiomyopathy after presentation with VT storm despite antiarrhythmic drug therapy with high-dose sotalol. ICD interrogation revealed multiple episodes of failed ATP (D–F) and electrical cardioversions (G–I) suggestive of an automatic mechanism. Catheter ablation demonstrated posterolateral RVOT scar extending to the tricuspid annulus and anterior RV free wall. Left bundle branch block/inferior axis VT was induced in the washout phase of 20 mg/min of isoproterenol (supported by inotropes) with a cycle length of 257 ms. Earliest site was localized to a focal region on the anteroseptal RVOT adjacent to scar with termination after ablation (30 W, 17 mL/min flow). It was noninducible despite up to 40 mg/min isoproterenol and 5 programmed electrical stimulation attempts from multiple RV sites and 10 RV burst pacing inductions from 350 ms down to 200 ms. At 2-year follow-up, no recurrence of VT had occurred. ATP ¼ antitachycardia pacing; ICD ¼ implantable cardioverter-defibrillator; RV ¼ right ventricle; RVOT ¼ right ventricular outflow tract; VF ¼ ventricular fibrillation; VP ¼ Ventricular Paced; VS ¼ Ventricular Sensed; VT ¼ ventricular tachycardia.

with $10-g contact force aiming for an impedance

during tachycardia demonstrated change in con-

drop of 20 U with a maximum power of 50 W applied

duction time and EGM morphology at the electrode

in a power-controlled mode. Ablation lesions were

recording site); 3) an exit site at a low-voltage area

repeated until the following conditions were satis-

consistent with scar was seen; 4) evidence of slow

fied: 1) the site was electrically unexcitable with

conduction with pacemaps in this region yielded a

pacing at 10 mA at 9-ms pulse width; and 2) complete

stimulus-to-QRS delay >40 ms (17); and 5) ablation

elimination of all abnormal late potentials and late

in the putative isthmus region abolished >1

abnormal ventricular activity.

morphology of VT. Re-entrant circuit sites were

D e fi n i n g t h e m e c h a n i s m o f V T . Mechanism was defined as follows:

defined by entrainment and pacemapping as reported previously (18). 2. Focal mechanism: This was defined as triggered

1. Re-entry: Scar-related re-entry was confirmed if 1)

activity or automatic only if it was spontaneous in

induction and termination were demonstrable with

initiation/termination or was induced by isopro-

PES; 2) criteria were fulfilled for entrainment

terenol and/or RV burst pacing and was not easily

(constant fusion during overdrive pacing except

terminated (suppression) with overdrive pacing

for the last paced beat, which is entrained but not

(19). Furthermore, failure to entrain the tachy-

fused; progressive fusion during overdrive pacing;

cardia and lack of fusion during rapid pacing with a

localized conduction block to a site for 1 paced beat

relatively short pre-systolic potential to QRS in-

associated with interruption of the tachycardia

terval during VT at the site of successful ablation

followed by activation of that site by the next

were shown. In addition, centrifugal activation of

paced beat from a different direction and with a

the impulse from the focal source during VT could

shorter conduction time; pacing at 2 different rates

be demonstrated. The surrounding voltage of the

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T A B L E 2 Procedural Data

T A B L E 3 Acute Procedural Outcomes

Procedural data

Procedural outcomes 1,549
1,250

Mean EAM points No. of VTs

3 (1–5) 366
107

Cycle length, ms Scar characterization Mean ventricular surface area, cm2

259.7
182.9

Success

7 (39)

Failure

0 (0)

Procedural complications

2 (11)

Abolishment of focal VT

18 (100)

Mean bipolar scar area, cm2

69.9
66.9

Mean bipolar dense scar area, cm2

22.0
24.3

Duration, days

152.2
186.7

VT recurrence

Mean unipolar scar area, cm2 Mode of focal VT induction

11 (61)

Partial success

Follow-up 289 (206–357) 4 (22)

Repeat VT ablation procedure

2 (11) 6 (33)

Spontaneous only

7 (39)

Hospital readmission

Isoprenaline only

3 (17)

NYHA functional class
Burst RV pacing only

1 (5)

Reduction in AAD therapy

3 (17)

7 (39)

No change to AAD therapy

14 (78)

Isoprenaline and burst RV pacing

Increase in AAD therapy

VT mechanism Focal only

8 (44)

Re-entrant and focal

10 (56)

15 (83)

1 (5)

Values are n (%) or median (interquartile range 25%–75%). AAD ¼ antiarrhythmic drug; NYHA ¼ New York Heart Association; VT ¼ ventricular tachycardia.

Focal VT matching clinical Focal only

7 (88)

Re-entrant and focal

4 (40)

potentials, double potentials, late potentials during

Values are mean
SD, median (interquartile range 25%–75%), or n (%).

sinus and paced rhythm, and late abnormal ventric-

EAM ¼ electroanatomic mapping; other abbreviations as in Table 1.

ular activities (8). For focal VT that was not tolerated or nonsustained, both pacemapping and short periods

focal endocardial or epicardial source of the VT was

of induction to confirm activation guided the putative

sampled by averaging all the collected peak-to-

ablation site. Each induced VT was targeted with

peak EGM voltages in a 10-mm cloud around the

catheter ablation.

central ablation/local activation time (LAT) site of

Acute success was defined as noninducibility of all

the focal VT. Definitions of spontaneous and nonspontaneous VT. Spon-

inducible VTs using the same PES induction protocol

taneous (or “clinical”) VT was defined as any induc-

infusion up to 40 m g/min (8,20).

ible VT having a 12-lead electrocardiogram (ECG) morphology and rate (within 20 ms) matching a VT that was documented to have occurred spontaneously before ablation. Only the rate cutoff and intracardiac EGM data from the implanted ICD (if present) were used when the 12-lead VT morphology was not available

before

ablation.

Nonspontaneous

(or

“nonclinical”) VTs were inducible VTs that did not have a rate (>20-ms difference) or 12-lead ECG morphology identical to that of the spontaneous (“clinical”) VT documented before ablation (8). E n d p o i n t s a n d s u c c e s s o f a b l a t i o n . Ablation was

with 4 extrastimuli, repeated with isoproterenol

OUTCOMES. Acute procedural outcomes were re-

ported as complete success (noninducibility of any VT, spontaneous or nonspontaneous), partial success (elimination of at least 1 spontaneous VT), or failure (residual inducibility of spontaneous VT) (8). Followup outcomes included 1) survival free of any VA; 2) arrhythmia control defined as any reduction in the number of VA episodes or number of AADs required for arrhythmia control during follow-up; 3) overall survival; and 4) survival free of death or cardiac transplantation.

mapping

FOLLOW-UP. Programming of the ICD or cardiac

depending on the inducibility and hemodynamic

resynchronization therapy device was left to the

tolerance of each induced VT. Ablation targeted pre-

discretion of the treating cardiologist; however, in

based

on

substrate

and/or

activation

sumptive isthmus and exits, based on activation and

general 2 zones were programmed. The first zone was

entrainment mapping, if the VT was hemodynami-

set at a rate at least 20 ms below the rate of the

cally tolerated. If the VT was not tolerated, non-

slowest VT (with or without antitachycardia pacing

inducible,

substrate-based

[ATP]). The second zone was programmed at a mini-

ablation was performed for scar-related VTs. The

mum rate >188 beats/min programmed to deliver a

specific approach targeted presumptive channels and

shock (with or without ATP). All patients were

exits as determined by similarity of paced QRS

enrolled in a ICD remote monitoring program at

morphology to VT QRS morphology with a stimulus-

Westmead Hospital. All ICD activations are recorded,

to-QRS interval >40 ms, abnormal fractionated

logged, and transmitted to the clinic staff, which

or

nonsustained,

a

5

6

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C E NT R AL IL L U STR AT IO N Summary of Focal VT Sites (and Frequency) in Mapped Patients With Myocardial Scar

Anderson, R.D. et al. J Am Coll Cardiol EP. 2019;-(-):-–-. (Left) RV sites (n ¼ 12). (Right) LV sites (n ¼ 6). LV ¼ left ventricle; RV ¼ right ventricle; RVOT ¼ right ventricular outflow tract; VT ¼ ventricular tachycardia.

prompted an in-office visit for detail evaluation of

33% in sustained VT, and 17% in nonsustained VT.

clinical and device data. Hospital records and outpa-

Ten patients (55%) presented in VT storm. Before VT

tient clinic assessments were used to complete

ablation, 13 patients (68%) had VT resulting in ICD

follow-up.

therapies, with a median of 53 episodes (IQR25%–75%:

STATISTICAL ANALYSIS. The Statistical Package for

the Social Sciences for Windows (SPSS Inc., Chicago, Illinois) was used for analysis. Continuous variables are expressed at mean
SD if normally distributed, median (interquartile range 25% to 75% [IQR25-75% ]), or full ranges if the data were clearly skewed. A 2tailed p < 0.05 was considered statistically significant. Survival free of VA was estimated using the Kaplan-Meier method.

RESULTS PATIENT DEMOGRAPHICS. Eighteen of 112 patients

(16%) were demonstrated to have a focal mechanism for at least 1 of the VTs seen during the procedure. Mean age was 66
13 years (15 men; mean LV ejection fraction 46
14%) (Table 1). Procedures were pre-

4.5 to 308) treated by ATP. Nine of these 13 patients (69%) had ATP episodes that failed to revert VT successfully (median 25 episodes; IQR 25-75%: 10.5 to 54.5), and 5 of the 9 patients (56%) had failed ICD shocks (median 7; IQR 25-75%: 7 to 30), characterized by repetitive initiation. An example from an ICD interrogation is shown in Figure 1. In comparison, 36 of 98 patients (37%) without a focal VT had ATP episodes that failed to revert VT successfully (median 29 episodes; IQR 25-75%: 6 to 53.5; p ¼ 0.01), and 11 of 98 patients (11%) had failed ICD shocks (median 6; IQR 25-75%: 4.5 to 13.5; p < 0.01). Underlying

etiology

of

cardiomyopathy

was

ischemic cardiomyopathy (28%), idiopathic dilated cardiomyopathy (55%), cardiac sarcoidosis (11%), and arrhythmogenic right ventricular cardiomyopathy (ARVC) (6%).

dominantly performed with patients under GA (n ¼ 16

EAM

[89%]), with the remainder under conscious sedation.

formed in all cases. Ten patients had biventricular

Of the patients who underwent VT mapping and

EAM. Epicardial mapping was performed in 3 patients

ablation, 50% presented with recurrent ICD shocks,

(all redo cases after a previous endocardial ablation).

FEATURES. Endocardial

mapping was per-

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F I G U R E 2 Example of Focal VT Induced by RV Burst Pacing With Isoproterenol in Scar Border Zone (Normal Bipolar Voltage)

A 47-year-old female athlete with newly diagnosed gene-elusive arrhythmogenic right ventricular cardiomyopathy presented with LBIA, frequent premature ventricular complexes refractory to medical therapy. Surface echocardiography demonstrated normal LVEF (58%) and mildly dilated RV with mildly impaired systolic function. Cardiac MRI revealed 1 major MRI criterion for ARVD with normal left ventricular dimensions and LVEF with mildly dilated RV (end-diastolic volume ¼ 129 mL/m2) and moderate RV dysfunction (RV ejection fraction 30%). There was regional dyskinesia in the RV free wall. There was RV late gadolinium enhancement inferiorly. At electrophysiological study, endocardial mapping of the RV revealed extensive RV free-wall scar, basal RVOT, and inferior RV extending to the apex with septal sparing. A single VT morphology was induced that matched the clinical VT (LBIA), with late precordial transition at a cycle length of 300 ms (not hemodynamically tolerated, requiring termination). Activation and pacemap localized this focal VT to the septal RVOT in a region of surrounding normal voltage on the border of free-wall RVOT scar. Ablation at this site (loss of ventricular capture with high-output pacing at 20 mA @ 9 ms) made this VT noninducible (programmed electrical stimulation to 4 Extrastimulii and repeat boluses of isoproterenol). LBIA ¼ left bundle, inferior axis; LVEF ¼ left ventricular ejection fraction; MRI ¼ magnetic resonance imaging; other abbreviations as in Figure 1.

Mapping features (mapping point density, scar sur-

[32%]). Twelve-lead ECGs of the clinical VT were

face area, distribution) are summarized in Tables 2

available for 17 patients. A total of 61 VTs were

and 3, Online Table 1, and Online Figure 1.

inducible or occurred spontaneously (with or without

CHARACTERISTICS OF INDUCIBLE VTs AND SITES OF FOCAL VTs. M o d e o f i n d u c t i o n o f V T . Mode of

focal VT onset was spontaneous in 7 patients (39%). Induction required isoproterenol alone in 3 patients (17%), burst RV pacing alone in 1 (5%), and both isoproterenol and burst RV pacing in 7 (39%) (Table 2). Focal VT was present spontaneously at the start of the case in 7 patients (39%). In the other patients it was seen either 1) when isoproterenol/burst RV pacing was performed after programmed ventricular stimulation when the baseline state failed to induce any VT; or 2) after abolishment of re-entrant VTs when isoproterenol/burst RV pacing was performed to elucidate residual VTs.

catheter manipulation) for the 18 procedures (median 3 VTs per procedure; IQR25-75% : 1 to 5). In 5 of the 10 patients (50%) who presented with VT storm, the focal VT matched the spontaneous or clinical VT. Mean cycle length (CL) of induced VT was 366
107 ms (median 335 ms; IQR25-75%: 280 to 455 ms) (Table 2). CL of re-entrant VT was 353
104 ms and of focal VT was 391
113 ms. The mechanism was scar re-entry in 34 VTs and focal in 28 VTs (including 1 case

of

premature

ventricular

complex

[PVC]-

triggered ventricular fibrillation [VF] with coexistent nonsustained VT with the same morphology). Four of the 18 patients had >1 focal VT that was inducible (median 3.5; IQR25-75%: 2.75 to 4.25). Sixteen focal VTs (57%) in 10 patients were hemodynamically stable

V T c h a r a c t e r i s t i c s . The site of earliest activation

and able to perform activation mapping and entrain-

and termination was at a remote site with normal

ment maneuvers. In the remainder, focal VTs were

voltage (n ¼ 12 [67%]) or at the scar border zone (n ¼ 6

mapped

using

pacemap

matching.

Focal

VTs

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F I G U R E 3 Example of Focal VT Originating From the Lateral LV

A 43-year-old man with cardiac sarcoidosis (LVEF 50% with akinetic inferior wall) and a secondary prevention ICD underwent a failed endocardial VT ablation in 2015 that targeted scar in the basal inferior septum. He was unable to undergo cardiac MRI due to the ICD implant. He re-presented with recurrent ICD activations and a right bundle (positive precordial leads), inferior axis VT. Epicardial VT ablation induced 4 VT morphologies (VT1 to VT4). Epicardial mapping demonstrated basal inferior and septal scar. VT1 to VT3 were all induced with programmed electrical stimulation and were all successfully ablated in the basal septal and inferior regions of scar. None of these VTs matched the clinical VT. VT4 was induced by RV pacing on isoproterenol, which is suggestive of a focal origin located in a region of normal voltage on the basal lateral left ventricle and successfully targeted with ablation. LV ¼ left ventricle; other abbreviations as in Figures 1 and 2.

comprised 54% from the idiopathic dilated cardio-

12 cases (67%) and 6 (33%) of cases, respectively. The

myopathy group, 29% from the ischemic cardiomy-

right ventricular outflow tract (RVOT) was the most

opathy group, 14% from cardiac sarcoid group, and

common site of focal VTs in 6 of 18 patients (33%; 4

3% from the ARVC group. In 10 of the 18 cases (56%),

from anteroseptal RVOT, 2 from RVOT free wall),

both focal and scar re-entrant VTs were inducible

followed by the moderator band in 4 patients (22%),

(including 1 case of PVC-triggered VF/nonsustained

apical septal RV in 1 (6%), and lateral tricuspid

VT). In 4 of these cases (40%), the focal VT corre-

annulus in 1 (6%). An example of a septal RVOT focal

sponded to the clinical VT (Online Figure 2). In the

site on scar border zone is shown in Figure 2.

remaining 6 cases, the 12-lead ECG morphology of the

Lv sites. The lateral LV was the most common site of

clinical VT correlated to a scar re-entrant VT in 5 cases

left-sided focal VTs, seen in 3 of 18 patients (16%).

and was not available in 1 case. In 8 of the 18 cases

Mitral periannular and basal inferior scar was seen

(44%), only a focal VT was inducible (despite the

in these cases. An example of a lateral LV focal site

presence of scar substrate, including 1 case of PVC-

is shown in Figure 3. The clinical VT in all 3 of these

triggered VF/nonsustained VT). In 7 of these cases

patients

(88%), the induced focal VT corresponded to the

posteromedial papillary muscle was the site of focal

clinical VT on 12-lead ECG. In the remaining 1 case,

VT in 2 of the 18 patients (11%) and the anterolateral

nonclinical VT was induced.

papillary muscle in 1 patient (6%). Examples of

S i t e o f f o c a l V T s . Rv sites. The sites of focal VTs are

these focal sites are shown in Figures 4 and 5.

summarized in the Central Illustration and Online

CATHETER ABLATION AND ACUTE PROCEDURAL

Table 1. Focal VTs were induced in the RV and LV in

OUTCOMES. Ablation was performed in all patients.

matched

the

focal

VT

induced.

The

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F I G U R E 4 Example of PMP Focal VT Ablation in a 66-Year-Old Man With VT Storm

VT was inducible on the washout phase of isoproterenol at 10 mg/min: spontaneous onset and offset and was entirely isoproterenol dependent. Morphology was RBBB/ LSA with precordial transition in V5/V6, and cycle length was 340 ms (hemodynamically stable). ICE was used to reconstruct the RV and LV. Epicardial access and mapping demonstrated large bipolar scar over the LV inferior wall extending to the apex and large septal and lateral extensions and the RV anterior wall. Activation mapping showed earliest activation 20 ms in the inferior LV epicardium with radiofrequency energy delivered at 40 W (half-normal saline) after coronary angiography. Endocardial LV mapping showed earliest activation 36 ms originating from the PMP (seen using ICE) (Online Videos 1, 2, and 3). Ablation at the earliest site (20–30 W; half-normal saline) terminated VT in the midportion of the muscle. Despite reinduction up to 40 mg/min and >10 attempts of burst RV pacing down to 250 ms, no VT was inducible. Substrate modification of the inferior scar was performed (40–50 W; normal saline). ICE ¼ intracardiac echocardiography; LSA ¼ left superior axis; PMP ¼ posteromedial papillary muscle; RBBB ¼ right bundle branch block; other abbreviations as in Figures 1 to 3.

Procedural outcomes are summarized in Table 3.

OUTCOMES AND FOLLOW-UP. Follow-up ICD data

Of the 18 patients, complete success was achieved in

were available for all 18 patients (Table 3). At median

11 (61%), partial success in 7 (39%), and failure in

follow-up of 289 days (IQR 25-75% : 206 to 357 days), 4

none of the patients. Focal VT was abolished in all

patients (22%) had VT recurrence (Figure 6). In the

cases.

group with recurrence, patients had a median of 53

Acute procedural complications occurred in 2 of 18

ATP episodes (IQR 25-75% : 4.5 to 308) before ablation,

patients (11%). Specifically, 1 patient developed

which was reduced to a median of 10 ATP episodes

pericardial tamponade with post-procedural hemo-

(IQR 25-75%: 8.5 to 11.5) post-ablation. Nine patients

dynamic

peri-

experienced ICD shocks pre-ablation (median 11;

cardiocentesis and pericardial drain but no need for

IQR 25-75%: 3 to 16) compared to only 1 patient

cardiac surgery (attributed to intraprocedural perfo-

post-ablation. Repeat catheter ablation was per-

ration of the CS catheter). Another patient developed

formed in 2 patients with no recurrence of the pre-

anticipated complete heart block after extensive

viously targeted focal VT. In the remaining 2 patients

ablation to the substrate for VT involving the left

who did not undergo repeat ablation, ICD interroga-

basal septum with subsequent cardiac resynchroni-

tion showed ATP terminated VT with ICD EGM

zation therapy upgrade. One patient died within

morphology and/or CL different from the focal VT

30 days after readmission with multiorgan dysfunc-

(Online Figure 3). Mean LV ejection fraction 6 months

tion without recurrent VAs. No cases of periproce-

post-catheter ablation was 46
12% (unchanged from

dural death or stroke occurred.

pre-ablation measurement). Three patients (17%) had

collapse

that

required

urgent

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F I G U R E 5 Example of Focal VT Localized to Top of Anterolateral Papillary Muscle in a 78-Year-Old Man

(A) The patient had a history of ischemic cardiomyopathy (percutaneous coronary intervention to left anterior descending coronary artery/left circumflex coronary artery), LVEF of 45%, and an episode of PVC-triggered VT/VF. VT demonstrated an RBBB/inferior axis morphology. Electroanatomic mapping demonstrated a large basal-midseptal, periaortic, and inferior wall scar (more extensive unipolar scar). The PVC trigger was localized to a region adjacent to anterolateral scar in a border zone region corresponding to the anterolateral papillary muscle, which was successfully eliminated by catheter ablation. (B) The patient had VT recurrence 2 months after the procedure. ICD therapies reverted all episodes successfully, with a combined endocardial and epicardial procedure that induced 5 different and nonfocal morphologies consistent with scar re-entry (induced only with programmed electrical stimulation despite high-dose isoproterenol). PVC ¼ premature ventricular complex.

a reduction of AAD therapy; 14 patients (78%)

(16% of consecutive patients), originating remote

remained on the same regimen as before ablation;

from or adjacent to the scar border when a strict

and only 1 patient (5%) required an increase in AAD

protocol of RV burst pacing and catecholamine stim-

therapy post-ablation (recommenced amiodarone

ulation protocol (when tolerated) was used. These

tablets 200 mg daily post-recurrence). At the end of

sites predominantly show normal bipolar and unipo-

follow-up, 1 patient had died and 1 patient was

lar voltage, often originating from sites classic for

referred for cardiac transplantation (severe ischemic

otherwise “idiopathic” forms of VT. 2) Focal VTs were

cardiomyopathy). No ventricular assist devices were

common in patients with nonischemic cardiomyopa-

placed.

thy (NICM) (72% of the 18 patients with SHD in this series), suggesting that standard induction protocols

DISCUSSION

without the use of burst pacing and isoproterenol could miss this VT mechanism and may help explain

MAJOR FINDINGS. 1) In patients with SHD and

the high rate of recurrent VT during follow-up in such

myocardial scar, focal VTs are commonly revealed

patients (21). 3) Focal VTs are more commonly located

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F I G U R E 6 Kaplan-Meier Curve for Freedom From VA

His-Purkinje system/fascicles, and these VTs may exhibit

catecholamine-sensitive

behavior

in

the

chronic post-infarct setting (3). Spontaneous depolarization due to heightened automaticity and triggered activity also can be seen in the actively ischemic Purkinje network, particularly at the scar border zone (4,30). However, none of the patients in our cohort were acutely ischemic, offering a potential explanation for the lack of Purkinje potentials at any of the successful ablation sites (either in sinus rhythm or VT). Scar not only promotes re-entry but can be directly arrhythmogenic by promoting spontaneous depolarization and automaticity (31). Altered gap junction coupling and amplification of the ratio of myofibroblasts to myocytes (typically seen in the scar VA ¼ ventricular arrhythmia; VT ¼ ventricular tachycardia.

border zone regions) increase the myocyte resting membrane threshold and reduce the source-sink

in the RV, particularly in the RVOT and intracavity

mismatch, thus increasing the propensity for spon-

structures, namely, the RV moderator band. The lo-

taneous ectopy (32). The mechanism of focal VTs at

cations of LV focal VTs were in the basolateral LV and

scar border zone may be related to direct arrhyth-

papillary muscles, sites typically seen in patients with

mogenesis or potentially may be due to a promoting

otherwise no SHD or “idiopathic” VTs. 4) When focal

trigger such that the close proximity of arrhythmo-

VT sources were identified, catheter ablation termi-

genic substrate to scar facilitates re-entrant circuits

nated the VT in all cases with no recurrence of focal

when an appropriately timed PVC encounters slow

VT during follow-up.

conduction tissue. However, in many cases the focal

MECHANISMS OF VT IN SHD. We present a hetero-

geneous group of patients with myocardial scar

VT origin was remote from scar sites, so it is plausible that the focal VT was unrelated to scar.

shown to exhibit focal, automatic VT in sites either

PREVIOUS STUDIES. Focal VTs have been demon-

adjacent to or distant from scar. The predominant

strated in 9% of patients with previous evidence of

mechanism of VT induced in the presence of

ischemic heart disease. Das et al. (2) studied 46 pa-

myocardial scar is re-entry (1,22). Slow conduction

tients with recurrent shocks or drug-refractory sus-

through surviving myocardial bundles interspersed

tained VT. Unlike the current study, patients with

between fibrosis creates nonuniform anisotropy and a

NICM were not evaluated. In 9 patients, focal VTs

predisposition to unidirectional block and re-entrant

were induced, predominantly from the anterior or

excitation (23,24). The incidence and characteristics

septal basal LV in 75% of cases. These were all shown

of VT attributed to non-re-entrant, focal mechanisms

mechanistically to be automatic or triggered activity.

in patients with SHD have received little attention in

The investigators provided specific characteristics

the literature (2,3,25–28).

that were able to differentiate focal from re-entrant

Focal VTs are due to enhanced automaticity

VTs. Nonsustained and spontaneous episodes, in-

or triggered activity mediated by cyclic adenosine

duction and sustainment with isoproterenol, origin

monophosphate

afterdepolarizations.

from normal voltage or border zone sites, and basal/

Differentiating focal VTs from re-entrant VT is

periannular LV location all favor a focal mechanism

important because ablation site characteristics differ

in a cohort of patients with previous myocardial

significantly depending on the mechanism. Focal VTs

infarction. However, adenosine sensitivity was not

typically are induced by catecholamine exposure

routinely assessed during VT to further support an

and/or burst pacing and are adenosine sensitive (29).

idiopathic focal VT mechanism. As in the current

Focal VTs most commonly originate from endocardial

study, micro–re-entry could not conclusively be dis-

and epicardial sites in the outflow tracts, ventricles,

missed as a possible mechanism. It has been shown

and valvular annuli in the absence of scar or SHD

that micro–re-entry can occur in a region as small as

(idiopathic VT). Less commonly, nonscar-mediated

0.05 cm, which would be difficult to detect even with

re-entrant VT is seen in patients with acute myocar-

the spatial resolution of current mapping catheters

dial ischemia and in patients with late post infarction

(28). Despite this, the lack of entrainment and the

VT. The mechanism of such VTs may involve the

majority of sites being located within normal voltage

delayed

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Focal VTs in Structural Heart Disease

areas do support a focal mechanism. We also

automatic focal VT will only be temporarily sup-

demonstrated normal voltage in the majority of sites

pressed by rapid ventricular pacing (such as ATP), this

surrounding successful focal ablation sites that typi-

finding may explain the majority of patients who had

cally were remote from myocardial scar.

ATP failed to revert a proportion of VT episodes as

Other investigators have shown that focal VTs are

demonstrated by ICD interrogation before catheter

present almost exclusively within regions of scar

ablation. Post-ablation, none of the patients who had

(2,27,28). Using a PES induction protocol only, Nüh-

a recurrence had ICD therapies with ATP that were

rich et al. (27) showed that 36% of induced VTs were

unsuccessful, potentially indicating elimination of

focal in origin in a group of 22 patients with ischemic

the focal mechanism. Furthermore, the original focal

or NICM, and was located only in dense scar or border

VT was noninducible in the 2 patients who had un-

zone regions. Others have also shown that focal VTs

dergone a redo procedure during follow-up.

originate in nonischemic scar and may be more common than in ischemic scar, with an incidence of

STUDY LIMITATIONS. The experience reported in

27% (5,6).

this retrospective study is drawn from a single center

Catecholamine-facilitated focal VTs have been

with a small sample size, which limits statistical

reported in patients with ARVC originating from the

interpretation; therefore, predominantly descriptive

scar border zone region (25). Discerning the VT

statistics were used in this study. Despite this limi-

mechanism in this group is difficult because both

tation, this study highlights the novel finding of focal

focal and re-entrant (macro- or micro–re-entry)

VT remote from myocardial scar using a standard in-

types can exist from the same area of scar. How-

duction protocol that incorporates burst pacing and

ever, induction with RV burst pacing and isopro-

isoproterenol to expose an alternative VT mechanism

terenol (without PES) and the inability to be

other than re-entry.

entrained favor cyclic adenosine monophosphate–

Our definition of focal VTs included those that

induced triggered activity. Poorly coupled myocar-

were induced by PES or occurred spontaneously. In

dium due to fibrofatty infiltration may increase the

only 1 patient was a focal VT induced by PES (after

propensity of electrically loaded cells to exhibit

commencing isoproterenol), as shown in Figure 2.

focal activity. Furthermore, the 2 patients with

This patient was removed from the series to make our

sarcoidosis in our study had Purkinje-independent

definition of focal VT more specific and to exclude the

focal VTs localized to the basal lateral LV and RV

potential of this case being a re-entrant VT.

moderator band, both matching spontaneous VT.

It cannot be conclusively proven that micro–

One of these patients had both focal and re-entrant

re-entry is not a potential mechanism of these focal

VT (related to a basal LV aneurysm); in the other

VTs. Although constant and progressive fusion is a

patient, only focal VT was induced with isoproter-

requirement in the diagnostic pathway for micro–

enol. The absence of Purkinje potentials in either

re-entry, it can be difficult to clearly demonstrate in a

case

of

small circuit. However, we believe micro–re-entry is

Purkinje-mediated focal VT has been described as a

unlikely because these VTs could not be entrained.

relatively common mechanism (16% of cases) in

Future studies of adenosine sensitivity may help

patients with cardiac sarcoidosis (26).

confirm the mechanism in the majority of focal VTs, as

is

intriguing

given

that

the

presence

In this study, we demonstrated that an extended induction protocol incorporating RV burst pacing and

adenosine has no effect on micro–re-entrant VT (33). It is important to consider the impact of the anes-

catecholamine stimulation reveals a group of patients

thetic

with a focal mechanism. Targeting and eliminating a

catecholamine-sensitive VAs. GA was used in the

focal mechanism of VT in patients with SHD, partic-

majority of cases, with the regimen determined by the

ularly if it matches the clinical morphology, may

attending anesthetist. Most commonly, this involved

improve outcomes by reducing VT recurrences and

a combination of propofol, remifentanil, and rocuro-

prolonging arrhythmia-free periods in this group. The

nium (total intravenous anesthesia). The antiar-

fact the patients with NICM were common in this

rhythmic effects of propofol and remifentanil in

series suggests that standard PES induction protocols

suppressing VAs likely influenced VT inducibility in

without burst RV pacing or isoproterenol may miss

this study (34,35), although focal VT was reliably

focal

potentially

induced in all cases. Inhaled anesthetics with poten-

explaining, to some degree, the high rate of recur-

tial effects on prolonging action potential duration

rence during follow-up in this group (21). An inter-

were not used at the cost of using cardiodepressive

esting observation is that the clinical VT matched the

agents

focal VT morphology in the majority of patients. As

inotropic support (36).

VT

sources

in

such

patients,

strategy

(propofol),

on

arrhythmia

increasing

the

induction

threshold

of

for

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Because only a minority of patients had undergone

explain the high rate of recurrence during follow-up

endocardial and epicardial mapping, it is possible that

in such patients. Whether uncovering focal and re-

focal VTs represented endocardial breakthrough of an

entrant VT mechanisms routinely during ablation

epicardial exit, especially given the high proportion

procedures will improve outcomes of VT ablation is

of NICM in our cohort in which unipolar low voltage

worthy of future study.

was more extensive than bipolar scar area and/or segments (Online Table 1) (37). Future prospective

ADDRESS FOR CORRESPONDENCE: Associate Prof.

studies

and

Saurabh Kumar, Department of Cardiology, West-

epicardial mapping to provide further details of the

mead Hospital, Westmead Applied Research Centre,

complete VT circuit. Finally, routine transthoracic

University of Sydney, Darcy Road, Westmead, New

echocardiography

South Wales-2145, Australia 2145. E-mail: saurabh.

will

require

combined

performed

6

endocardial

months

post-VT

ablation demonstrated no improvement in LV ejec-

[email protected].

tion fraction, suggesting that in patients with NICM, the high burden of PVCs/VT was not due to

PERSPECTIVES

arrhythmia-induced cardiomyopathy. COMPETENCY IN MEDICAL KNOWLEDGE 1: In patients

CONCLUSIONS

with VT and SHD, an extended VT induction protocol incorporating catecholamine stimulation and RV burst pacing reveals a

Focal VT is a common, potentially underrecognized

group of patients with a focal mechanism, typically localized on

mechanism of VT in patients with SHD (16% in this

the scar border zone region or remote from scar. When identified,

series), often coexisting with re-entrant VTs. The high

catheter ablation is a highly effective treatment for successfully

rate of failure of device therapies in terminating VT

eliminating focal VT sites.

(ATP and/or shock) and repetitive initiation is a unique feature of focal VTs, with VT storm being a

COMPETENCY IN MEDICAL KNOWLEDGE 2: A hallmark of

common feature. Focal VT sources were seen more

focal VTs is repetitive initiation with failure of device therapies to

commonly in NICM substrates. The origin of focal VTs

terminate VT (ATP or defibrillator shocks).

is commonly from regions of normal voltage or scar border zones. The sites of origin of focal VTs are commonly from areas otherwise classic for “idiopathic” VT, such as the moderator band, outflow tracts, valve annuli, and papillary muscles. When identified, focal VTs were eliminated in all patients, with no recurrence of focal VT during follow-up. Lack of burst RV pacing and/or isoproterenol use in most induction protocols may miss focal VT mechanisms in

TRANSLATIONAL OUTLOOK 1: Additional strategies to reduce the high VT recurrence rates post-catheter ablation are needed, especially in patients with NICM. TRANSLATIONAL OUTLOOK 2: Future studies are needed to assess whether uncovering both focal and re-entrant VT mechanisms routinely during catheter ablation will improve long-term outcomes.

patients with SHD, especially NICM, which may help

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