Stepwise Approach for Ventricular Tachycardia Ablation in Patients With Predominantly Intramural Scar

JACC: CLINICAL ELECTROPHYSIOLOGY

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ª 2020 THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. PUBLISHED BY ELSEVIER. ALL RIGHTS RESERVED.

Stepwise Approach for Ventricular Tachycardia Ablation in Patients With Predominantly Intramural Scar Michael Ghannam, MD,a Konstantinos C. Siontis, MD,a Hyungjin Myra Kim, SCD,a Hubert Cochet, MD, PHD,b,c Pierre Jais, MD,b,c Mehdi Juhoor, ENGR,b,c Rakesh Latchamsetty, MD,a Krit Jongnarangsin, MD,a Anil Attili, MD,a Ghaith Sharaf Dabbagh, MD,a Miki Yokokawa, MD,a Fred Morady, MD,a Frank Bogun, MDa

ABSTRACT OBJECTIVE The goal of this study was to assess the value of a stepwise, image-guided ablation approach in patients with cardiomyopathy and predominantly intramural scar. BACKGROUND Few reports have focused on catheter-based ventricular tachycardia (VT) ablation strategies in patients with predominantly intramural scar. METHODS The study included patients with predominantly intramural scar undergoing VT ablation. A stepwise strategy was performed consisting of a localized ablation guided by conventional mapping criteria followed by a more extensive ablation if VT remained inducible. The extensive ablation was guided by the location and extent of intramural scarring on delayed enhanced–cardiac magnetic resonance imaging. A historical cohort who did not undergo additional extensive ablation was identified for comparison. A novel measurement, the scar depth index (SDI), indicating the percent area of the scar at a given depth, was correlated with outcomes. RESULTS Forty-two patients who underwent stepwise ablation (median age 61 [interquartile range 55-69] years, 35 male patients, median left ventricular ejection fraction 36.0% [25.0% to 55.0%], ischemic [n ¼ 4] or nonischemic cardiomyopathy [n ¼ 38]) were followed up for a median of 17 [8 to 36] months. A stepwise approach resulted in a 1-year freedom from VT, death, or cardiac transplantation of 76% (32 of 42). Patients who underwent additional extensive ablation had a lower risk of events than a clinically similar historical cohort (N ¼ 19) (hazard ratio: 0.30; 95% CI: 0.13 to 0.68; p < 0.004). SDI>5mm was associated with worse long-term outcomes (hazard ratio: 1.03; 95% CI: 1.01 to 1.06/%; p ¼ 0.03), SDI>5mm >16.5% was associated with failed ablation (area under the curve: 0.84: 95% CI: 0.71 to 0.97). CONCLUSIONS Stepwise ablation using delayed enhanced–cardiac magnetic resonance guidance is a novel approach to VT ablation in patients with predominantly intramural scarring. The SDI correlates with immediate procedural and longterm outcomes. (J Am Coll Cardiol EP 2020;-:-–-) © 2020 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.

T

he most common mechanism of ventricular

present in patients with nonischemic cardiomyopa-

tachycardia (VT) in patients with structural

thy (5,6) but can occur in patients with ischemic car-

heart disease is scar-mediated myocardial

diomyopathy. VTs in these patients often have an

re-entry (1–4). Intramural scarring is most often

intramural origin that can be difficult to target with

From the aUniversity of Michigan, Ann Arbor, Michigan; bBordeaux University Hospital and University of Bordeaux, Bordeaux, France; and cINRIA, Sophia Antipolis, France. This research was supported by funding from the French National Research Agency (ANR) under Grant Agreements Equipex MUSIC ANR-11-EQPX-0030, IHU LIRYC ANR-10-IAHU-04, and from the European Research Council under Grant Agreement ERC no. 715093. Dr. Jais reports having shares in InHeart. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. 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 August 26, 2019; revised manuscript received November 27, 2019, accepted November 27, 2019.

ISSN 2405-500X/$36.00

https://doi.org/10.1016/j.jacep.2019.11.020

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Ventricular Tachycardia and Magnetic Resonance Imaging

ABBREVIATIONS

a catheter-based ablation technique. Assess-

Excite CV/i, General Electric, Milwaukee, Wisconsin)

AND ACRONYMS

ment of scar depth and its relation to proce-

with an 8-element phased array coil placed over the

dural outcomes has not been performed

chest of patients in the supine position. Images were

systematically in patients with a predomi-

acquired

nantly intramural scar. Furthermore, the

breath-holds. Dynamic short- and long-axis images of

optimal ablation strategy in such patients

the heart were acquired by using a segmented,

has not been defined. The purpose of the cur-

k-space, steady-state, free-precession pulse sequence

rent study was to determine the value of a

(repetition time 4.2 ms, echocardiogram time 1.8 ms,

stepwise ablation approach using cardiac

1.4  1.4 mm in-plane spatial resolution, slice thick-

magnetic resonance (CMR) image integration

ness 8 mm). Ten to 20 min after administration of 0.1

to target intramural scar in patients with pre-

to 0.15 mmol/kg of intravenous gadobenate dime-

dominantly intramural scar.

glumine (MultiHance, Bracco Diagnostics, Princeton,

BMI = body mass index CI = confidence interval DE-CMR = delayed enhanced– cardiac magnetic resonance

HR = hazard ratio ICD = implantable cardioverter-defibrillator

IQR = interquartile range PVS = programmed ventricular stimulation

with

electrocardiogram

gating

during

New Jersey), two-dimensional delayed enhancement

VT = ventricular tachycardia

METHODS

imaging was performed by using an inversionrecovery sequence (8) (repetition time 6.7 ms, echo to

time 3.2 ms, in-plane spatial resolution 1.4  2.2 mm,

December 2017, consecutive adult patients with

slice thickness 8 mm) in the short-axis and 3 long-axis

structural heart disease referred for VT ablation at the

views of the left ventricle at matching cine-image

University of Michigan underwent pre-procedural

slice locations. The inversion time (250 to 350 ms)

delayed enhanced (DE)-CMR. All patients had either

was optimized to null the normal myocardium.

STUDY

POPULATION. From

January

2013

sustained VT lasting >30 s or had VT terminated by an

At the time of the CMR, 34 of 42 patients had an

implantable cardioverter-defibrillator (ICD). Of 254

ICD implanted; in these patients, the CMR was

patients with VT and structural heart disease who

limited to the sequence of delayed enhancement and

were screened, 42 exhibited predominantly intra-

limited to a specific absorption rate of 2.0 (W/kg).

mural scarring on CMR and were enrolled in a pre-

A modified broad-band CMR sequence (9) was used to

determined protocol. Intramural scar was defined as

avoid artifacts from the ICD generator in patients with

midwall striae or patches of enhancement with rela-

implanted devices. DE-CMR data were analyzed in an

tive

sub-

automated manner, and the amount of intramural

epicardium (7). Two independent reviewers assessed

scar was determined after endocardial and epicardial

the scars and visually determined whether they had a

contours were manually traced.

sparing

of

the

subendocardium

and

predominant intramural location. Discrepancies were resolved by consensus. The reviewers agreed in all cases (kappa value of 1.0). These patients underwent a stepwise CMR-guided ablation protocol consisting of a localized ablation guided by conventional mapping criteria, followed by an extensive ablation covering the entire CMR-defined scar area if VT remained inducible. In addition to this enrolled cohort, a historical control group was included to assess the benefit of the extensive ablation step that was used in the stepwise approach after the localized ablation failed. This control group comprised 19 consecutive patients with nonischemic cardiomyopathy who underwent catheter-based VT ablation with an irrigated tip catheter before 2013 using only a localized ablation approach with no preprocedural CMR. All patients who had a localized ablation approach failed to eliminate VTs were included (N ¼ 19). The study protocol was approved by the Institutional Review Board of the University of Michigan.

ELECTROPHYSIOLOGICAL STUDY AND MAPPING.

After patients’ informed consent was obtained, multielectrode catheters were positioned in the high right atrium, the His position, and the right ventricular apex. Electrograms were filtered at 50 to 500 Hz. The intracardiac electrograms and leads V1, I, II, and III were displayed on an oscilloscope and recorded at a speed of 100 mm/s. The recordings were stored on optical disk (St. Jude Medical, St. Paul, Minnesota). Electroanatomical

mapping

(CARTO,

Biosense

Webster, Inc., Diamond Bar, California) was performed with a 3.5-mm tip, open-irrigation ablation catheter (THERMOCOOL, Biosense Webster). Intracardiac ultrasound was used to create anatomical contours of the ventricles and aortic root on the mapping system. Low voltage was defined as a bipolar voltage amplitude #1.5 mV (10) and unipolar amplitude #6.8 mV (11). For left ventricular mapping, a bolus of 3000 U of heparin and continuous infusion was used to achieve an activated clotting time of 250 to 300 s. In the event of an epicardial procedure,

CMR IMAGING. The DE-CMR studies were performed

heparin was administered after the pericardial punc-

on a 1.5-T cardiac magnetic resonance scanner (Signa

ture was performed.

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F I G U R E 1 DE-CMR–Guided Stepwise Ablation

(A) Short-axis view of a cardiac magnetic resonance (CMR) image with predominantly intramural scar in the lateral left ventricular free wall (white arrows). (B) The scar from the CMR (red) has been registered to the electroanatomical map of the left ventricle (green). The mitral valve annulus is shown in blue. (C) Same view as in panel B; a bipolar voltage map shows mostly preserved left ventricular endocardium. The bipolar voltage cutoff is set to 1.5 mV. A localized ablation targeting the epicardium that was closer to the intramural scar failed in this patient, and ventricular tachycardia (VT) remained inducible. An extensive ablation was performed. (D) Bipolar voltage map of the left ventricular endocardium after an extensive ablation approach was performed. The bipolar voltage cutoff is set to 1.5 mV. The scar has been endocardialized, and the bipolar voltage was reduced in the area overlying the scar that was ablated. Thereafter, no additional ventricular tachycardia was inducible in this patient. MA ¼ mitral annulus.

Before mapping and ablation, programmed ven-

RADIOFREQUENCY ABLATION. Radiofrequency en-

tricular stimulation (PVS) was performed in all pa-

ergy was delivered at an initial power setting of 30 W

tients with 1 to 4 extrastimuli at twice the ventricular

at the endocardium. Applications of radiofrequency

capture threshold from 2 right ventricular sites to

energy were titrated up to 50 W to achieve an

induce VT. Inducible VT was defined as monomorphic

impedance drop of 10 U or noncapture with high

VT lasting >30 s or requiring termination because of

output pacing (20 mV at 2.0 ms). At sites adjacent to

hemodynamic instability (12).

intramural scar, radiofrequency energy was applied

The access and mapping approach was determined

for up to 120 s at a particular location. In the peri-

before the ablation procedure based on the location of

cardial space, only irrigated tip catheters were used

scar on CMR imaging. If the scar was predominantly

with a targeted impedance drop of 10 U or noncapture

intramural in the left ventricular septum, the right

with high output pacing (20 mV at 2.0 ms), starting at

and left ventricular endocardium were mapped. If the

a power of 20 W and titrated up to 50 W.

scar involved the free wall, the left ventricular

Coronary angiography was performed before abla-

endocardium and epicardium were mapped. In the

tion in the epicardial space or before ablation in the

presence of multifocal scar, the predominant scar

coronary venous system, and ablation was not per-

determined the mapping strategy. The surface closest

formed within 5 mm of coronary arteries (14). High-

to the intramural scar was targeted first, followed by

output pacing (pulse amplitude 20 mV with pulse

mapping and ablation on the opposing surface over-

duration of 2.0 to 10 ms) was used to delineate the

laying the scar if VTs remained inducible.

course of the phrenic nerve; in case of phrenic nerve

The scar was registered as previously reported

capture, ablation was only performed if measures

(3,13). In brief, after fiducial points were obtained in

(including placing a balloon catheter [15] in the

the aortic cusps, the mitral annulus, and the left

epicardial space or infusion of a saline/air mixture

ventricular apex, the CMR-derived three-dimensional

into the pericardial space [16]) resulted in noncapture

endocardial surface was registered with the electro-

of the phrenic nerve.

anatomical map.

A stepwise ablation approach was used. During the

In the presence of hemodynamically tolerated VT,

mapping procedure, the ablation catheter was guided

the catheter was positioned in the area facing the

to areas adjacent to the registered intramural scar

intramural scar, and entrainment and activation

(Figures 1A to 1C). Radiofrequency energy was guided

mapping was performed during VT. For nontolerated

first by using conventional mapping criteria (localized

VTs, pace mapping was performed in the area of the

approach). Pace mapping was performed during sinus

scar.

rhythm for nontolerated VTs, and activation or

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F I G U R E 2 Schema Demonstrating the Measurement of the SDI

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Ventricular Tachycardia and Magnetic Resonance Imaging

voltage to <1.0 mV. In the absence of voltage reduction after up to 120 s of radiofrequency delivery, an alternate site for radiofrequency delivery was identified and targeted. Radiofrequency energy was delivered for a total of 60 to 120 s and was repeated if the ablation resulted in VT termination. Radiofrequency energy was delivered in a unipolar manner. After extensive ablation was complete, PVS was repeated with up to 4 extrastimuli from 2 right ventricular

sites.

Successful

catheter

ablation

was

defined as non-inducibility of any monomorphic, sustained VT. Unsuccessful ablation was defined as the inducibility of any monomorphic sustained VT or an inability to undergo repeat programmed stimulation after the initial induction due to hemodynamic instability. IMAGE ANALYSIS. The scar was delineated with

proprietary software (MUSIC) from the University of Bordeaux. First, a region of interest containing the entire scar was identified and traced (Figure 1A). Within this region, the area encompassing pixels with values $M/2, using the traditional method of full width half maximum (17), was identified and defined as the core scar. Thresholds for scar core and total scar were 50% and >35% of the maximal signal intensity, respectively. Both volumes were quantified and expressed in cubic centimeters. In a post hoc analysis, the scar depth of the intramural scar was projected onto the nearest surface, and the proportions of the scar area within a depth of 0 to 3 mm (i.e., 0 to #3 mm), 3 to 5 mm (i.e., >3 to #5 mm), and (A) Total scar surface as it projects on the closest reachable surface that is the endocar-

>5 mm were determined. We used the notation

dium. (B) Distance of the scar surface to the endocardium at a depth of 0 to 3 mm. This is

SDI depth to reflect the proportion of the scar surface

55% of the total scar surface. (C) Distance of the scar surface to the endocardium at a

located

depth of 3 to 5 mm. This is 31% of the total scar surface. (D) Distance of the scar surface to the endocardium at a depth of >5 mm. This is 14% of the total scar surface. SDI ¼ scar depth index.

at

the

indicated

depth.

For

example,

SDI 0–3mm ¼ 60% means that 60% of the scar surface area is located within the #3 mm depth. The method to compute SDI 0–3mm, SDI 3–5mm, and SDI >5mm is illustrated in Figures 2 and 3. The different depths bins

entrainment mapping was performed during VT for tolerated VTs. Sites with isolated potentials and fragmented electrograms were also targeted in areas of preserved voltage and low-voltage scar. After these initial ablation steps, PVS was repeated. If VT remained inducible thereafter, the next step con-

were arbitrarily chosen with the notion that an ablation lesion will likely be complete at a scar depth of 0 to 3 mm but may not be complete at a depth of 3 to 5 mm, and will likely be incomplete at a depth >5 mm. These measurements were correlated with outcomes of the stepwise approach.

sisted of radiofrequency energy delivery over the

FOLLOW-UP. Patient clinical outcomes were recor-

entire registered intramural scar (extensive ablation

ded until death or last clinical follow-up. The

approach) (Figure 1D). This was performed from both

endpoint of interest was occurrence of VT, cardiac

aspects of the scar. The ablation endpoint was voltage

transplantation, or death after the ablation proced-

reduction over the intramural scar with the objective

ure. All patients were seen in follow-up 3 to

to endocardialize or epicardialize the intramural scar.

6 months after the ablation procedure and subse-

The latter was defined as achieving a decline of bi-

quently

polar voltage from >1.5 mV to <1.5 mV or, if the bi-

implanted devices were followed up with regular

polar voltage was 1.0 to 1.5 mV, to decrease bipolar

home monitoring reports.

every

6

to

12

months.

Patients

with

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F I G U R E 3 Intramural Scar Depth and Location on DE-CMR

(A) Short-axis delayed enhanced–cardiac magnetic resonance (DE-CMR) slice in a patient with an intramural scar located close to the right ventricular endocardium. Localized ablation from the right ventricular endocardium eliminated all ventricular tachycardias (VTs). Picture A shows the intramural septal scar that is colored in red in panel B. The surface of the scar is projected onto the closest endocardial surface (here the right ventricular outflow tract [picture C]). Picture D shows the proportion of the scar surface located at a depth of 0 to 3 mm displayed in green. Picture E shows the proportion of the scar surface located at a depth of 3 to 5 mm, and picture F shows the proportion of the scar surface at a depth >5 mm. (B) Short-axis DE-CMR slice in a patient with an intramural scar located close to the left ventricular endocardium. Localized ablation failed to eliminate VT but an extensive approach did. Picture A shows the intramural septal scar that is colored in red in picture B. The surface of the scar is projected onto the closest endocardial surface (here the left ventricular outflow tract) in picture C. Picture D shows the proportion of the scar surface located at a depth of 0 to 3 mm displayed in green. Picture E shows the proportion of the scar surface located at a depth of 3 to 5 mm, and picture F shows the proportion of the scar surface at a depth >5 mm. The majority of the scar is located at a depth <5 mm. (C) Short-axis DE-CMR slice in a patient with an intramural scar located close to the left ventricular endocardium. The stepwise approach failed to eliminate VT. Picture A shows the intramural septal scar that is colored in red in picture B. The surface of the scar is projected onto the closest endocardial surface (here the left ventricular outflow tract) in picture C. Picture D shows the proportion of the scar surface located at a depth of 0 to 3 mm displayed in green. Picture E shows the proportion of the scar surface located at a depth of 3 to 5 mm, and picture F shows the proportion of the scar surface at a depth >5 mm. The majority of the scar is at a depth >3 to 5 mm.

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T A B L E 1 Patient Characteristics

Entire Stepwise Group (N ¼ 42)

Localized Ablation (n ¼ 13)

Extensive Ablation (n ¼ 26)

No Repeat PVS* (n ¼ 3)

Historical Cohort (N ¼ 19)

35 (83)

10 (77)

24 (92)

1 (33)

18 (95)

0.82

61 (55–69)

68 (59–70)

59 (52–69)

68 (58–69)

61.38 (48–69)

0.99

BMI, kg/m2

31 (28–35)

29 (28–32)

33 (30–35)

30 (27–30)

31 (25–35)

0.42

Left ventricular ejection fraction, %

36 (25–55)

55 (47–65)

30 (24–45)

25 (23–29)

25 (25–30)

0.15

Beta-blockers, n

42 (100)

13 (100)

26 (100)

3 (100)

19 (100)

1.0

ACE inhibitors or ARBs, n

25 (60)

7 (54)

15 (58)

3 (100)

10 (53)

0.97

Antiarrhythmic therapy, n

37 (88)

11 (85)

23 (89)

3 (100)

15 (78)

0.65

ICD before CMR imaging, n

34 (81)

NA

NA

Male, no. (%) Age, yrs

p Value

Continuous data are shown as medians and (1st to 3rd quartile), and nominal data are shown with n (%). Values of p are from comparisons between the extensive ablation group and the historical cohort group. *Programmed ventricular stimulation (PVS) was not performed at the end of the procedure. ACE ¼ angiotensin-converting enzyme; ARBs ¼ angiotensin receptor blockers; BMI ¼ body mass index; CMR ¼ cardiac magnetic resonance; ICD ¼ implantable cardioverterdefibrillator; NA ¼ not applicable.

STATISTICAL ANALYSIS. Variables were compared

patients had structural heart disease due to either

between the extended ablation group and the his-

ischemic (n ¼ 4) or nonischemic (n ¼ 38) cardiomy-

torical control group by using the Wilcoxon rank sum

opathy and were refractory to 2  1 antiarrhythmic

test for continuous data and the Fisher exact test or

medications. The indications for VT ablation were ICD

chi-square test for nominal data. Receiver-operating

discharges in 31 patients (74%), recurrent palpitations

characteristic curves were created to relate scar

in 17 (40%), and VT storm in 17 (23%). Twenty-eight

characteristics to acute procedural outcomes. The

patients (67%) had undergone a previous ablation

clinical long-term events of interest were ventricular

elsewhere. All patients had a predominantly intra-

arrhythmias, cardiac transplantation, or death. Sur-

mural scar, involving the left ventricular free wall in

vival time free from any of the events was analyzed,

13 patients and the interventricular septum in 29 pa-

and time was censored at the end of follow-up.

tients. An epicardial ablation using a subxiphoid ac-

Kaplan-Meier curves were created, and a log-rank

cess was performed in 8 patients with free wall

test was used to compare hazard of clinical outcome

scarring.

according to acute procedural outcomes. Cox regres-

The historic control cohort patients who had failed

sion was used to determine the independent associ-

a localized ablation approach consisted of 19 patients

ation between acute procedural outcome categories

(median age 61 years; 18 male patients; median left

and scar characteristics with the clinical events.

ventricular ejection fraction 25%). There were no

Hazard ratios (HRs) and the corresponding 95% con-

significant differences in baseline characteristics be-

fidence intervals (CIs) were obtained based on Cox

tween the historical cohort and the extensive ablation

regression models. Statistical significance was deter-

groups (Table 1). Thirteen of 19 patients had evidence

mined by using 2-sided 0.05 level tests. To assess the

of left ventricular free wall scarring, and 6 of 19 pa-

benefit of the extensive ablation step, subgroup

tients had evidence of septal scarring based on uni-

analysis was performed by using the combined data

polar voltage mapping. DE-CMR was not performed in

of the extensive approach cohort and the historical

the historical cohort; however, there were no differ-

control cohort. All statistical analyses were conduct-

ences between the areas of abnormal endocardial

ed by using R version 3.5.2 (R Foundation for Statis-

unipolar voltage maps between this group and the

tical Computing, Vienna, Austria).

study group that had also failed a localized ablation approach, suggesting a comparable scar burden (50.8

RESULTS

 19.7 cm 2 vs. 57.8  19.7 cm 2; p > 0.5). Mapping and ablation in the historic control group had been per-

PATIENT CHARACTERISTICS. Patient characteristics

formed by using a combined endocardial and epicar-

of the stepwise ablation group are shown in Table 1.

dial approach in 10 of 13 patients with evidence of

The subjects included 42 consecutive patients (me-

free wall scarring using a subxiphoid epicardial ac-

dian age 61 years; 35 male patients; median left ven-

cess. A combined left and right endocardial approach

tricular ejection fraction 36%). There were 5 patients

was used on both aspects of the interventricular

lost to long-term follow-up (2 of 19 in the historical

septum in the remaining 6 patients with evidence of

group, and 3 of 42 in the prospective group). The

septal scarring.

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F I G U R E 4 Survival Free of Ventricular Tachycardia or Cardiac Transplantation Stratified According to Acute Procedural Outcomes

Survival free of ventricular tachycardia (VT) or cardiac transplantation stratified according to acute procedural outcomes of the step-wise approach. The p value corresponds to the log-rank test.

CATHETER ABLATION. Sustained VT was inducible

patients, and no testing was performed post-ablation

in all 42 patients. A total of 258 VTs with a mean  SD

in 3 patients. The extensive ablation approach resul-

cycle length of 339.2  97.4 ms were inducible (6.1 

ted in non-inducibility of VT in 11 (42%) of 26 patients

4.2 VTs per patient); 147 VTs had a right bundle

and failed in 15 (58%) of 26 patients in whom PVS was

branch block morphology, and 111 VTs had a left

performed post-ablation (Figure 4).

bundle branch block morphology.

Median procedure time was 490.5 min (inter-

The ablation was performed and completed in all

quartile range [IQR] 437.8 to 570.5 min) and was

42 patients. A stepwise ablation approach was acutely

longer in patients undergoing extensive ablation

successful in 24 patients (57%) and unsuccessful in 15

(546.5 [477.8 to 595.0] min vs 425.0 [369.0 to

(36%); no PVS was performed in 3 patients (7%) due to

451.0]; p # 0.001). Median radiofrequency time was

concerns regarding hemodynamic instability during

75.0 min [47.75 to 95.0 min] and was longer in pa-

VT. An epicardial ablation was performed in 7 of 13

tients undergoing extensive ablation (85.5 [55.5 to

patients (all via a subxiphoid epicardial access) with

111.0] min vs. 48.0 [26.0 to 78.0] min; p ¼ 0.01).

free wall scarring who underwent an extensive abla-

There were no differences between the median

tion approach, and in 3 of 13 of the patients with a

radiofrequency and procedural times between pa-

localized approach (2 from within the coronary

tients in the historical cohort and those in the

venous system and 1 with a subxiphoid epicardial

stepwise approach cohort (81.0 [37.6 to 119.0] min

approach).

vs 75.0 [47.75 to 95.0] min, and 504.0 [402.0 to

A

localized

approach

resulted

in

non-inducibility of VT in 13 (31%) of 42 patients. An

600.0] min vs 490.5 [437.8-570.5] min; p > 0.05 for

extensive ablation was performed in the remaining 29

both).

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T A B L E 2 CMR Scar Data According to Overall Acute Ablation Success in Entire Stepwise

Cohort (N ¼ 42)

respectively. A gradual decrease in SDI 0–3mm was observed between patients with an effective localized approach,

patients

with

an

effective

extensive

Ablation Acutely Effective (n ¼ 24)

Ablation Failed or No Repeat PVS* (n ¼ 18)

p Value

approach, and patients with a failed extensive

Scar volume, cm3

11.52 (5.72–13.65)

8.58 (6.55–24.7)

0.90

approach. In contrast, SDI 3–5mm and SDI >5mm were

Border zone volume, cm3

7.49 (3.80–13.01)

6.36 (4.54–14.90)

0.96

both found to gradually increase between these same

Core volume, cm3

4.87 (1.74–7.89)

2.59 (1.99–9.80)

0.92

patient populations. Overall, compared with patients

SDI at 0–3 mm (%)

72.00 (56.75–82.25)

32.00 (20.0–46.75)

<0.001

with procedural failure (n ¼ 18), those with an effec-

SDI at 3–5 mm (%)

21.50 (11.75–29.25)

38.00 (33.00–48.00)

0.002

SDI at >5 mm (%)

22.0 (8.50–42.50)

<0.001

tive procedure (n ¼ 24) reported higher SDI 0–3mm (72%

4.50 (2.00–12.25)

Data are shown as medians and 1st to 3rd quartile. Percent values are shown in parentheses. *Patients who did not have PVS at the end of the procedure. SDI ¼ scar depth index; other abbreviations as in Table 1.

vs. 32%; p < 0.001), lower SDI3–5mm (21% vs. 38%; p ¼ 0.002), and lower SDI >5mm (4% vs. 22%; p < 0.001). An SDI 0–3mm higher than 52.5% accurately predicted procedural success (AUC: 0.86; 95% CI: 0.75 to 0.98; sensitivity of 0.83; specificity of 0.79). An SDI >5mm higher than 16.5% accurately predicted pro-

Complications occurred in 5 patients. Two patients (both with existing ICDs, and either a preprocedural biventricular pacing system in place or a preprocedural indication for biventricular pacing) developed complete heart block, 2 patients developed vascular pseudoaneurysms requiring thrombin injection, and 1 patient developed a lower extremity deep venous thrombosis post-procedurally. Both patients with AV block were in the extensive ablation group.

cedural failure (AUC: 0.84; 95% CI: 0.71 to 0.97; sensitivity of 0.67; specificity of 0.92). FOLLOW-UP. The median follow-up time was 17 [IQR

8 to 36] months, and there were no differences in follow-up times among the outcome groups in patients undergoing a stepwise ablation (p > 0.5 for all comparisons). Among the 8 patients who did not have ICDs before the ablation procedure, 4 patients underwent device placement before hospital discharge,

FINDINGS ON DE-CMR AND ABLATION RESULTS. The

1 underwent ICD placement shortly after discharge, 1

median total scar volume was 9.3 cm 3 [IQR 6.1 to

received an implantable loop recorder, and 2 did not

12.6 cm 3; range 1.9 to 36.7 cm 3]. The volume of the

receive any devices over the follow-up period. Ejec-

scar border zone was 6.7 cm 3 [IQR 3.9 to 14.9 cm 3;

tion fraction was assessed echocardiographically 3 to

range 1.1 to 240 cm 3], and the volume of the core scar

6 months’ post-ablation. It was found to have

was 3.6 cm3 [IQR 1.7-8.6 cm 3; range 0.5 to 12.7 cm3 ].

increased in patients who underwent the localized

Median SDI 0–3mm was 56.5% [IQR 35.8% to 77.8%],

approach (55 [IQR 47 to 65] before the ablation vs. 60

median SDI3–5mm was 30.0% [IQR 17.8% to 38.8%],

[55 to 65] post-ablation; p ¼ 0.03) and similarly in the

and median SDI >5mm was 8.5% [IQR 3.0% to 21.8%].

patients who underwent the extensive ablation

There was no correlation between the total scar

approach, although not statistically significant (30%

volume and SDI 0–3mm , SDI 3–5mm , or SDI >5mm (p > 0.05

[24% to 45%] before the ablation vs. 40% [30% to

for all).

55%] after the ablation; p ¼ 0.23).

Procedural outcomes did not correlate to total scar,

A stepwise ablation approach resulted in 1-year

border zone, or core scar volumes. In contrast, scar

freedom from recurrent VT, death, or cardiac trans-

depth was closely associated with procedural failure.

plantation in 32 (76%) of 42 patients. During a median

Tables 2 and 3 show the SDI at various depths (0 to

follow-up of 17 [IQR 8-36] months, recurrent ven-

3 mm, 3 to 5 mm, and >5 mm) stratified according to

tricular

ablation

plantation occurred in 16 (38%) of 42 patients

approaches

and

procedural

outcomes,

arrhythmias,

death,

or

cardiac

trans-

T A B L E 3 Characteristics of Intramural Scar Based on Procedural Outcomes

Localized Approach Effective (n ¼ 13)

Localized Approach Failed (n ¼ 26)

p Value*

Extensive Approach Effective (n ¼ 11)

Extensive Approach Failed (n ¼ 15)

p Value†

SDI at 0–3 mm (%)

81 (59–92)

40 (25.–58.25)

<.001

61 (48–74)

25 [18.5–39.5]

<0.001

SDI at 3–5 mm (%)

16 (5–22)

35 (27.25–48)

0.002

27 (21.5–30.5)

39 (34.5–49)

0.02

SDI at >5 mm (%)

2 (1.1–4)

16 (7.25–32)

<0.001

9 (5.5–14.5)

27 (12.5–48.5)

<0.007

Data are shown as medians and 1st to 3rd quartiles. *p value reflects comparison between the Localized Approach Effective and Localized Approach Failed groups. †p value reflects comparison between the Extensive Approach Effective and Extensive Approach Failed groups. SDI ¼ scar depth index.

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F I G U R E 5 Survival Free of Ventricular Tachycardia or Cardiac Transplantation Based on Procedural Success of the Different Steps

Compared With a Historical Control Group

Survival free of ventricular tachycardia (VT)or cardiac transplantation based on procedural success of the different steps compared with a historical control group. The p value corresponds to the Global Log-Rank test.

(Figure 4). One patient who had an unsuccessful

transplantation 2 months after the index procedure.

extensive ablation presented with VT storm and un-

The third patient had no VT recurrence.

derwent a repeat ablation 20 months after the index procedure. In the stepwise ablation group, there were

EXTENSIVE APPROACH COHORT VERSUS HISTORICAL

3 patient deaths: 1 patient with a successful acute

CONTROL PATIENTS. In those treated with an exten-

outcome died of complications from metastatic mel-

sive approach, 1-year freedom from recurrent VT,

anoma 28 months after the index procedure, and 2

death, or cardiac transplantation was 69% (18 of 26)

patients who both had unsuccessful ablations died of

compared with 37% (7 of 19) in the historical control

progression of their underlying heart failure 3 months

group (Figure 5). In the historical cohort group, 1 pa-

and 7 months after their index procedures.

tient died 2 weeks after the ablation due to cardio-

Antiarrhythmic medications were continued in

genic shock, and 3 others died of progression of their

patients with unsuccessful ablations. Previously

underlying heart failure at 5, 12, and 15 months after

ineffective antiarrhythmic agents were continued

the index procedure.

after successful ablations in 14 patients. Three pa-

In a Cox regression analysis, patients who under-

tients taking sotalol continued on the same dose post-

went an extensive ablation had a lower risk of clinical

ablation. The remaining 11 patients either stopped 1 of

events than patients in an historical cohort who did

multiple antiarrhythmic drugs (n ¼ 6) or underwent a

not undergo extensive ablation after a failed local

dose reduction of a single agent (n ¼ 5). The dose of

approach (HR: 0.30; 95% CI: 0.13 to 0.68; p < 0.004)

amiodarone was reduced from a mean of 400  0 mg

(Figure 5). In a Cox regression analysis of the exten-

daily to a mean of 180  140 mg daily.

sive approach cohort and the historical control

In the 3 patients who had no programmed stimu-

cohort, hazards of long-term clinical events were

lation was performed at the end of the procedure,

lower in patients who underwent a successful

1

extensive ablation (HR: 0.18; 95% CI: 0.05 to 0.63;

had

recurrent

VT

and

1

underwent

cardiac

9

10

Ghannam et al.

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Ventricular Tachycardia and Magnetic Resonance Imaging

required, targeting the entire scar projecting on the

T A B L E 4 Univariate Predictors Of Recurrent VT, Death, Or Cardiac

adjacent endocardial or epicardial surface. Patients

Transplantation (N ¼ 42)

who were noninducible for VT after this stepwise Age (yrs) EF (%)

HR [95% CI]

p Value

0.99 (0.96–1.04)/yr

0.93

0.93 (0.89–0.98)/% 3

Total scar volume (cm )

0.002 3

ablation strategy had favorable outcomes. A novel imaging parameter based on scar depth (i.e., the SDI) was found to be associated with the acute and

1.008 (0.95–1.07)/cm

0.76

Border zone scar volume (cm3)

1.01 (0.98–1.10)/cm3

0.78

long-term

Core zone scar volume (cm3)

1.02 (0.88–1.18)/cm3

0.75

(Central Illustration).

outcomes

of

the

ablation

procedure

SDI <3 mm %

0.97 (0.85–0.99)/%

0.02

SDI 1–3 mm%

0.98 (0.99–1.05)/%

0.11

SDI >5 mm%

1.03 (1.01–1.06)/%

0.03

VTs. The stepwise strategy is a departure from pre-

1.16 (1.04–1.3)/VT induced

<0.01

vious clinical practice in that areas superficial to the

0.17 (0.04–0.57)

<0.01

scar were targeted because of their proximity to the

VT induced pre-ablation (n) Acute procedural success

STEPWISE ABLATION APPROACH FOR INTRAMURAL

intramural scar, not based on mapping data. This CI ¼ confidence interval; EF ¼ ejection fraction; HR ¼ hazard ratio; SDI ¼ scar depth index; VT ¼ ventricular tachycardia.

approach was only performed if VT remained inducible after a localized approach had failed. In about one-half of the patients who did not respond to a

p ¼ 0.007) but were not lower in patients who un-

localized approach, extensive ablation helped to

derwent an unsuccessful extensive ablation (HR:

eliminate inducible VTs. Compared with a historical

0.043; 95% CI: 0.17 to 1.04; p ¼ 0.06) compared with a

control group with a failed localized approach, we

historical control group who only underwent a failed

showed that a successful extensive ablation approach

localized approach.

resulted in improved outcomes.

FACTORS ASSOCIATED WITH LONG-TERM OUTCOMES.

CMR-GUIDED ABLATION APPROACH AND SDI. CMR

Clinical factors associated with long-term outcomes

is the gold standard for characterizing the precise

are shown in Table 4. Acute procedural success was

extent of intramural scarring, and several previous

associated with greater survival free from VT or car-

studies have shown the utility of a CMR-guided/

diac transplantation (HR: 0.17; 95% CI: 0.04 to 0.57;

aided approach for VT ablation targeting DE-CMR–

p ¼ 0.01) (Figure 4). Based on a Cox regression, pa-

defined areas (1,3,13,18–20). This study shows how a

tients with a successful extensive ablation had similar

stepwise ablation approach guided by image-derived

long-term clinical events as those with a successful

scar depth can be successfully conducted in patients

localized ablation (HR: 4.2; 95% CI: 0.44 to 41;

with predominantly intramural scarring. In the

p ¼ 0.22); however, those with a failed extensive

absence of CMR, different endocardial voltage cutoff

ablation had higher rates of recurrent VT outcomes

values have been reported (11,21,22) to indicate

(HR: 10.1; 95% CI: 1.25 to 82.6; p ¼ 0.02).

deeper

scarring.

Validation

studies

with

CMR-

A higher SDI >5mm was associated with long-term

defined scar, however, revealed that there is a sub-

clinical events on univariate analysis (HR: 1.03;

stantial overlap of unipolar low voltage between scar

95% CI: 1.01 to 1.06/%; p ¼ 0.03) and remained

zones and regions without scar (11,22), hence a CMR-

significantly associated with long-term clinical events

guided approach may be preferable to avoid unnec-

after adjusting for total scar volume (HR: 1.04;

essary ablation and potential collateral damage.

95% CI: 1.01-1.08/%; p ¼ 0.01).

Furthermore, in this study we showed that the location of the scar within the myocardium affected

DISCUSSION

outcomes. The ability to render a patient with predominantly intramural scar noninducible depends on

MAIN FINDINGS. The current study introduces a safe

the depth of the scar containing the circuit of the

and effective CMR-guided stepwise ablation strategy

intramural VT. The deeper the scar, the lower the

to treat patients with VT and intramural scar. In one-

probability of being able to reach the circuit with the

half of the patients with successful ablation, a local-

ablation lesions. The larger the portion of the scar

ized approach targeting VT from the myocardial sur-

located at a depth >5 mm, the higher the likelihood of

face closest to the CMR-defined scar was able to

a failed ablation procedure. The larger the portion of

eliminate VT; these patients had favorable long-term

the scar located at a depth <3 mm, the more likely the

outcomes with no additional empirical substrate

ablation was successful. The SDI indicates the dis-

modification. In the remaining patients, a more

tance of the scar to the nearest surface that can be

extensive ablation approach with endocardialization

reached by the ablation catheter. The association of

and/or epicardialization of the intramural scar was

this imaging parameter with ablation outcomes

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Ventricular Tachycardia and Magnetic Resonance Imaging

C ENTR AL I LL U STRA T I O N Delayed Enhanced–Cardiac Magnetic Resonance–Guided Stepwise Ablation

A 2

3

C

DE-CMR used in 42 patients to measure scar depth index (SDI) and guide catheter ablation of ventricular tachycardia.

B 1 Total scar area

4

1.00 0.75 0.50 0.25 p < 0.0001 0.00 0

m

5m

m>

epth

rdiu

oca

my

m

epth

rdiu

md

md

5m

oca

3m

end

2

Survival Free of VT or Transplant

1

Scar area at 0-3 mm SDI 0-3 = 55% of total scar area

3 Scar area at 3-5 mm SDI 3-5 = 31% of total scar area

4 Scar area at >5 mm SDI >5 = 14% of total scar area

250

500 Time

Successful Localized Unsuccessful Extensive

750

Successful Extensive Historical Cohort

• One year freedom from VT, death or transplant achieved in 32/42 patients (76%). • Higher SDI>5 mm associated with worse long term outcomes (HR 1.04 [1.01-1.08]/%, p = 0.01). • Extensive DE-CMR guided ablation had improved outcomes compared to a historical cohort without image guidance (HR = 0.30 95%CI [0.13-0.68], p < 0.004)

Ghannam, M. et al. J Am Coll Cardiol EP. 2020;-(-):-–-.

(A) Delayed enhanced–cardiac magnetic resonance (DE-CMR) images are merged with electroanatomical mapping data. Mapping and ablation are performed by using traditional electrogram-guided approaches (localized approach). If patients remained inducible for ventricular tachycardia, further ablation was performed with the aim of voltage reduction over the entire DE-CMR–defined scar (extensive ablation). (B) The scar depth index (SDI) was measured to determine the proportion of the scar surface area overlaying scar at a given depth from the endocardial surface (<3 mm, 3 to 5 mm, and >5 mm). Patients with greater SDI>5mm (i.e., relatively more scar at depths >5mm) had worse long-term outcomes post-ablation. (C) Non-inducibility of ventricular tachycardia (VT) (successful ablation) was associated with improved arrhythmia-free survival. Patient outcomes were improved compared with an historical cohort group that did not undergo an image-guided extensive ablation. MA ¼ mitral annulus.

targeting this compartment (from surface to scar)

needle ablation (28), may be required. These tech-

supports the hypothesis of compartmentalization of

niques have the potential for collateral damage and

the myocardium by intramural scarring (23,24).

should be used with caution. Patients who may

In patients in whom the scar is too deeply seated,

benefit from these techniques can be identified based

alternative techniques, including the use of half-

on preprocedural imaging, and these techniques

normal saline irrigation (25), bipolar ablation (26),

might be selectively used when imaging indicates a

transcoronary ethanol ablation (27), and retractable

deeper SDI.

11

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Ventricular Tachycardia and Magnetic Resonance Imaging

ABLATION IN AREAS WITH PRESERVED BIPOLAR

maps were similar in size when maps of study pa-

VOLTAGE. Ablation in areas of preserved bipolar

tients with previous imaging were compared versus

voltage in patients with impaired left ventricular

the maps of patients in the historical control group.

function has the potential to worsen left ventricular function. However, it is unclear whether tissue

CONCLUSIONS

interposed between intramural scar and endocardium or epicardium contributes critically to left ventricular

A stepwise ablation strategy guided by CMR imaging

function. Although this is a small series of patients, it

of intramural scar is feasible and helpful in patients

is reassuring that the ejection fraction did not change

with VT and predominantly intramural scar. The re-

significantly in patients undergoing extensive abla-

sults of this pilot series support further prospective

tion and that patients included in this series did not

analysis of this novel approach to ablation.

have heart failure exacerbations post-ablation. STUDY

LIMITATIONS. This

observational,

single-

center study included a small patient population that was retrospectively analyzed. A predefined protocol, however, was used for enrollment of all patients. Larger, prospective studies are needed to further determine the safety and efficacy of this approach. The creation of pre-ablation high-density voltage mapping was not specified in this protocol, preventing an accurate comparison between DE-

ADDRESS FOR CORRESPONDENCE: Dr. Frank Bogun,

University of Michigan, Cardiovascular Center, Internal Medicine, Division of Cardiology, SPC 5853, 1500 E. Medical Center Drive, Ann Arbor, Michigan 48109-5853. E-mail: [email protected]. PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: Scar

CMR–defined scar and voltage-defined scar. Alterna-

depth can negatively affect outcomes in patients with

tive ablation strategies to target intramural scar, such

intramural scar undergoing catheter ablation for VT.

as the use of bipolar ablation, were not used. This protocol relied upon noninducibility of VT as a procedural endpoint, and this approach has known limitations; however, we obtained favorable long-term outcomes with this strategy. The control group was a historical cohort of patients, and the presence of intramural

scarring

in

those

patients

was

not

TRANSLATIONAL OUTLOOK: DE-CMR imaging provides details on scar characteristics that are useful for cardiac ablation procedures. Prospective, randomized studies incorporating image-guided ablation approaches will better clarify the utility of these techniques.

confirmed by imaging. However, unipolar voltage

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KEY WORDS cardiac magnetic resonance, cardiomyopathy, catheter ablation, delayed enhancement, intramural scar, radiofrequency ablation, ventricular tachycardia

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