Download Transcoronary Ethanol Ablation for Recurrent Ventricular

Transcoronary Ethanol Ablation for Recurrent Ventricular
Tachycardia After Failed Catheter Ablation
An Update
Michifumi Tokuda, MD; Piotr Sobieszczyk, MD; Andrew C. Eisenhauer, MD; Pipin Kojodjojo, MD;
Keiichi Inada, MD; Bruce A. Koplan, MD, MPH; Gregory F. Michaud, MD; Roy M. John, MD, PhD;
Laurence M. Epstein, MD; Frédéric Sacher, MD; William G. Stevenson, MD; Usha B. Tedrow, MD
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Background—Despite substantial progress, radiofrequency catheter ablation (RFCA) fails in some patients. After
encouraging results with transcoronary ethanol ablation (TCEA), we began offering TCEA routinely when endocardial
and epicardial RFCA failed or a deep intramural substrate was likely.
Methods and Results—Among 274 consecutive patients who underwent 408 ventricular tachycardia (VT) ablation
procedures, 27 patients (21 men; age, 63⫾13 years; left ventricular ejection fraction, 30⫾11%; ischemic cardiomyopathy, 14) had 29 TCEA procedures attempted. In 5 patients, TCEA was abandoned because of unfavorable anatomy. In
22 patients, a mean of 1.3⫾0.6 arteries (range, 1–3 arteries) were targeted for TCEA. After ablation, the targeted VT
was no longer inducible in 18 of 22 (82%) patients. Complete heart block occurred in 5 patients, and 3 patients with
advanced heart failure died within 30 days of the procedure. After the last TCEA procedure, a VT recurred in 64% of
patients, and overall, 32% of patients died. Of 11 patients with prior VT storm, 9 were free of VT storm. At repeat study
in 8 patients who had a recurrence, 7 had a new QRS morphology of VT originating from the same general substrate
region as the prior VT.
Conclusions—In patients with difficult-to-control VT in whom RFCA fails, TCEA prevents all VT recurrences in 36% and
improves arrhythmia control in an additional 27%. Inadequate target vessels, collaterals, and recurrence of modified VTs
limit efficacy, but TCEA continues to play an important role for difficult VTs in these high-risk patients. (Circ
Arrhythm Electrophysiol. 2011;4:889-896.)
Key Words: ventricular tachycardia 䡲 catheter ablation 䡲 ethanol 䡲 coronary artery 䡲 outcome 䡲 complication
R
adiofrequency catheter ablation (RFCA) plays an important and often life-saving role for patients with frequent
or incessant ventricular tachycardia (VT).1,2 Although percutaneous and surgical approaches to the pericardial space now
allow RFCA to target epicardial VTs, there are still a number
of patients in whom VT cannot be eliminated with both the
endocardial and the epicardial approach. Intramural ablation
appears to be required in some patients. Transcoronary
ethanol ablation (TCEA) was first performed experimentally3,4 and used to ablate postinfarction VT in the early
1990s.5,6 Subsequently, significant improvement and experience in interventional techniques for subselective targeting of
coronary vessels have occurred. In 2008, we reported encouraging results in 9 patients who had undergone TCEA between
January 1999 and May 2007.7 Based on this experience, we
began offering TCEA routinely when endocardial and epicar-
dial ablation failed or when endocardial ablation failed and a
deep intramural VT, such as in the septum, was believe to be
likely. This update provides the largest reported experience of
TCEA for VT to our knowledge and further clarifies its
limitations with present techniques.
Clinical Perspective on p 896
Methods
Patient Selection
From June 2007 to September 2010, 274 consecutive patients (217
men; age, 62⫾13 years) with structural heart disease underwent 408
VT ablations (1.4⫾0.7 times) at our institution and were included in
this analysis. Patients who had at least 1 RFCA for symptomatic
monomorphic VTs that were refractory to endocardial ablation,
epicardial ablation, or both were considered for TCEA. VT storm
was defined as ⬎3 separate VT episodes in a 24-hour period before
Received April 20, 2011; accepted September 16, 2011.
From the Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (M.T., P.S., A.C.E., P.K., K.I., B.A.K.,
G.F.M., R.M.J., L.M.E., W.G.S., U.T.), and Université Bordeaux II, Hôpital Cardiologique du Haut-Lévêque, Bordeaux-Pessac, France (F.S.).
Guest Editor for this article was Kenneth A. Ellenbogen, MD.
The online-only Data Supplement is available at http://circep.ahajournals.org/lookup/suppl/doi:10.1161/CIRCEP.111.966283/-/DC1.
Correspondence to Michifumi Tokuda, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail
[email protected]
© 2011 American Heart Association, Inc.
Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org
889
DOI: 10.1161/CIRCEP.111.966283
890
Circ Arrhythm Electrophysiol
December 2011
ablation. Written informed consent was obtained from all patients.
Procedures and review of medical records were conducted under
protocols approved by the institutional human subject protection
committee.
Transcoronary Ethanol Ablation
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Transthoracic echocardiography was performed before and after the
procedure in all patients to assess cardiac disease and function.
Patients were studied in a fasted state with all antiarrhythmics except
amiodarone stopped for ⬎5 half lives. Patients receiving warfarin
were transitioned to heparin, which was then discontinued 6 hours
before arrival in the electrophysiology laboratory. The details of the
initial mapping, RFCA, and TCEA procedure have been described
previously.7,8 Surface ECG leads and intracardiac electrograms were
stored in digital format (Prucka CardioLab EP System; GE Healthcare; Waukesha, WI). Nonfluoroscopic electroanatomic mapping
was performed using a 3D mapping system (CARTO; Biosense
Webster, Inc; Diamond Bar, CA). Morphological analysis of VT,
location of scar from low-voltage areas on electroanatomical mapping, pace mapping, and entrainment mapping were used to identify
ablation target locations.
At least 1 quadripolar electrode catheter was positioned through a
femoral vein in the right ventricle. When VT was not incessant,
programmed stimulation using up to 3 extrastimuli from 2 right
ventricular sites was performed for VT induction. The operators for
each procedure included both an electrophysiologist and an interventional cardiologist experienced in the TCEA. After clinical VT
was induced and terminated, selective coronary angiography was
performed through a femoral arterial sheath. Patients were heparinized, and the activated clotting time was maintained at ⬎250 s. The
ostium of the relevant coronary artery was selectively intubated
using an angioplasty wire (Graphix Intermediate; Boston Scientific
Corporation; Natick, MA). An 8-mm over-the-wire balloon sized to
be slightly larger than the angiographic diameter of the target vessel
(HighSail; Guidant Corporation; Santa Clara, CA) was deployed in
the ostium of the target branch vessel and fully inflated to prevent
backwash of ethanol into other coronary vessels, and occlusion was
verified using contrast injection after guidewire removal. A sonography contrast agent (Optison; Amersham Health; Buckinghamshire,
UK) was injected in the targeted coronary artery, and its territory was
verified by echocardiography in some patients. Next, the VT was
reinduced, and with the balloon fully inflated, iced saline (2–3 mL)
was injected through the central lumen in an attempt to terminate
VT. Alcohol injection was performed only if VT terminated during
iced saline infusion in the vessel (19 patients) or if VT that had been
inducible before subselective cannulation of the vessel was no longer
inducible when blood flow was interrupted in the vessel by the
cannulation and balloon inflation (3 patients).
If the VT continued, another branch was targeted. In addition, the
territory of perfusion was assessed, seeking arterial branches believed to be sufficiently distal and without supplying collateral flow
to adjacent areas such that they were deemed unlikely to cause
significant collateral ventricular damage. Once an appropriate target
site had been identified, 1 mL of sterile absolute alcohol was injected
with the balloon inflated for 10 minutes. After deflation of the
balloon, contrast was injected to assess target vessel patency. If
perfusion was present, a second 1 mL of additional ethanol was
infused, and the balloon inflation was maintained for 10 minutes
after that infusion. This could be repeated up to a maximum of 5 mL
of ethanol in 1 artery.
After TCEA, programmed right ventricular stimulation as described previously was performed. If the targeted VT remained
inducible, we sought an adjacent target vessel using the same
method.
Serum creatine kinase (CK), CK-MB, and troponin I were
measured at least daily after each procedure until they peaked and
declined. Renal function was assessed from serum creatinine within
24 hours before and 24 and 72 hours after the TCEA. Estimated
glomerular filtration rate was calculated using a modified equation to
predict the glomerular filtration rate from the serum creatinine
value.9 Contrast-induced acute kidney injury was defined as an
Table 1.
Patient Characteristics
TCEA (⫺)
(n⫽247)
Characteristic
TCEA (⫹)
(n⫽27)
P
Age, y
62⫾13
63⫾13
0.87*
Male sex
196 (79)
21 (78)
0.51†
Ischemic cardiomyopathy
149 (60)
14 (52)
0.41†
Major coronary vessels stenosed
0.69*
1.3⫾1.3
1.2⫾1.3
1
68 (28)
4 (15)
2
38 (15)
3 (11)
3
30 (12)
7 (26)
History of cardiac surgery
94 (38)
13 (48)
History of CABG
78 (32)
9 (33)
0.83†
0.5⫾0.7
2.0⫾1.7
⬍0.001*
25 (10)
13 (48)
⬍0.001†
I
117 (47)
7 (26)
II
52 (21)
15 (56)
III
65 (26)
3 (11)
No. of previous ablations
ⱖ2
NYHA class
0.31†
0.58‡
13 (5)
2 (7)
LV ejection fraction, %
IV
34⫾15
30⫾11
VT storm
49 (20)
11 (41)
0.02†
Failed AAD
2.0⫾1.3
2.8⫾1.3
0.003*
0.39†
0.23*
␤-blocker
207 (84)
25 (93)
ICD
210 (85)
27 (100)
0.03†
CRT
63 (26)
9 (33)
0.37†
Data are presented as mean⫾SD or n (%). AAD indicates antiarrhythmic
drug; CABG, coronary artery bypass graft; CRT, cardiac resynchronization
therapy; ICD, implantable cardioverter-defibrillator; LV, left ventricular; NYHA,
New York Heart Association; TCEA, transcoronary ethanol ablation; VT,
ventricular tachycardia.
*Student t test.
†Chi-square test.
‡Mann-Whitney U test.
increase from the baseline serum creatinine concentration of at least
0.5 mg/dL or at least 25% within 48 to 72 hours after angiography.10
Patients were seen by the investigator or referring physician after
discharge, and implantable cardioverter-defibrillator interrogation
was obtained. Survival was assessed from referring physicians and
the Social Security Death Index. VT improvement was defined as the
absence of sustained VT or no recurrence of preexisting VT storm or
incessant VT.
Statistical Analysis
Continuous variables are expressed as mean⫾SD or median. Student
t test was chosen for continuous variables, and Mann-Whitney U test
was chosen for ordinal outcome variables. Categorical variables,
expressed as numbers or percentages, were analyzed using ␹2 tests
(Table 1), unless the number of values in any cell was ⬍5, in which
case, Fisher exact test was used. Left ventricular ejection fractions
before and after the TCEA procedure were compared with the paired
t test. All tests were 2-tailed, and P⬍0.05 was considered to be
statistically significant. Statistical analysis were performed using
SPSS version 18.0.0 (SPSS Inc; Chicago, IL) software. The authors
had full access to the data and take full responsibility for the integrity
of the data.
Results
Patient Characteristics
A total of 29 TCEA procedures were performed for 27
patients (21 men; age, 63⫾13 years) at our institution from
Tokuda et al
Transcoronary Ethanol Ablation for VT
891
Figure 1. Flow chart of patients and outcomes. Of 27 patients, planned TCEA
was aborted in 5. Fourteen patients
experienced ventricular tachycardia recurrence after the first TCEA. RFCA indicates radiofrequency catheter ablation;
TCEA, transcoronary ethanol ablation.
Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017
June 2007 to September 2010. Two patients had 2 TCEA
procedures. All 27 patients had structural heart disease as
follows: ischemic cardiomyopathy, 14 (52%); dilated cardiomyopathy, 10 (37%); hypertrophic cardiomyopathy, 2 (7%)
(previously reported)11; and valvular heart disease, 1 (4%).
Prior cardiac and coronary artery bypass graft surgery had
been performed in 48% and 33% of these patients, respectively. All patients had VT attributed to scar-related reentry,
and 20 of the 22 had a mean of 2.0⫾1.7 failed RFCA
attempts.
Prior endocardial ablation was not attempted in 1 patient
with left ventricular thrombus and 1 patient with recent
biventricular assist device placement because of concerns
about potential embolization of thrombus from the recent
surgery in the latter (patients 1 and 3, online-only Data
Supplement). Epicardial ablation had been attempted in 13
(48%) patients. Initial RF ablation was attempted for all 20
patients with an initially failed ablation elsewhere. RFCA was
performed first in 18 patients; in 2 patients, mapping without
ablation was performed because a desirable endocardial
target region was not identified. The median duration from
the last RF ablation to the first TCEA was 32 days. All
patients had an implantable cardioverter-defibrillator had
been implanted; 9 (33%) had cardiac resynchronization therapy. One patient had a biventricular assist device. In Table 1,
patient characteristics are compared with those of the 247
patients with structural heart disease who underwent RFCA
but did not undergo attempted TCEA during the same period.
That the TCEA group had VT that was more difficult to
control is supported by the fact that more had VT storm (41%
versus 20%, P⫽0.02) and had failed a greater number of
antiarrhythmic drugs (2.8⫾1.3 versus 2.0⫾1.3, P⫽0.003)
and previous ablation attempts (2.0⫾1.7 versus 0.5⫾0.7,
P⬍0.001). First-degree atrioventricular (AV) block was present in 13 (48%) patients, and 3 (11%) patients had complete
heart block with ventricular pacing. Of 24 patients with intact
AV conduction, 8 had complete left bundle branch block, and
4 had complete right bundle branch block. There were a mean
of 3.2⫾3.7 VTs (median, 2 VTs) inducible during the
procedure.
Transcoronary Ethanol Ablation
Outcomes are summarized in the flow chart in Figure 1.
Coronary angiography showed no coronary artery stenosis
deemed to require revascularization. Of 27 patients undergoing catheterization for the procedure, administration of alcohol was not performed in 5 (19%) patients because of the
absence of a sufficiently sized coronary artery perfusing the
target region in 2 patients, extensive collaterals in 2, and no
effect of saline injection on VT in 1. Of these 5 patients,
RFCA was subsequently performed in 2, and the remaining 3
received only drug therapy. Patients for whom TCEA was
judged to be not feasible had a larger number of stenosed
major epicardial arteries (2.4⫾1.3 versus 0.6⫾1.0, P⫽0.007),
and none had presumptive septal arteries as possible targets
compared with those with targets (0% versus 68%, P⫽0.02)
but were otherwise similar to those in whom TCEA could be
performed (Table 2).
In 22 initial TCEA procedures, ethanol was injected into 28
coronary arteries (1.3⫾0.6 arteries/person; range, 1–3 arteries/person). Coronary artery segments (according to the
American Heart Association classification)12 targeted for
TCEA are shown in Figure 2; 64% were branches of the left
anterior descending coronary artery, 14% were branches of
the left circumflex coronary artery, and 22% were branches to
the left ventricle from the right coronary artery. In total, 57%
of the targeted arteries supplied the septum (including collateral flow). Of the 15 patients with TCEA performed for
presumed septal VT, 8 had prior RFCA performed at sites on
both sides of the septum. Of the 7 patients with nonseptal
coronary targets, 6 had failed endocardial ablation, and 4 had
failed epicardial ablation. Of these, 3 had coronary artery
disease, 2 nonischemic dilated cardiomyopathy, 1 hypertrophic cardiomyopathy, and 1 valvular disease. Of the 14
892
Table 2.
Circ Arrhythm Electrophysiol
December 2011
TCEA Possible Versus Not Feasible
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Age, y
Male sex
Ischemic cardiomyopathy
History of cardiac surgery
History of CABG
No. of previous ablations
ⱖ2
Major coronary vessels stenosed
1
2
3
NYHA class
I
II
III
IV
LV ejection fraction, %
LVDd, cm
IVSd, cm
VT storm
Failed AAD
No. of induced VTs
VT cycle length, ms
Fast VT, cycle length ⬍400 ms
Septal origin
Possible
(n⫽22)
Not Feasible
(n⫽5)
62⫾13
16 (73)
10 (46)
10 (46)
6 (27)
1.9⫾1.8
10 (45)
0.6⫾1.0
4 (18)
3 (14)
3 (14)
66⫾17
5 (100)
4 (80)
3 (60)
3 (60)
2.2⫾1.9
3 (60)
2.4⫾1.3
0
0
4 (80)
6 (27)
12 (55)
2 (9)
2 (9)
31⫾11
6.1⫾0.9
1.0⫾0.2
11 (50%)
2.6⫾1.3
3.3⫾4.1
429⫾105
15 (68)
15 (68)
1 (20)
3 (60)
1 (20)
0
29⫾10
6.9⫾0.2
1.4⫾0.3
0 (0%)
3.4⫾1.5
2.6⫾1.3
446⫾168
3 (60)
0 (0)
P
0.68*
0.55†
0.33†
0.65†
0.30†
0.76*
0.92†
0.007*
0.93‡
0.73*
0.14*
0.34*
0.06†
0.25*
0.71*
0.80*
1.00†
0.02†
Data are presented as mean⫾SD or n (%). IVSd indicates interventricular
septal thickness in diastole; LVDd, left ventricular diastolic dimension. Other
abbreviations as in Table 1.
*Student t test.
†Fisher exact test.
‡Mann-Whitney U test.
patients without prior epicardial ablation, in 10 (71%), VT
was believed to originate from the septum, and a septal artery
was targeted. All of the targeted sites were related to prior
detected scar. In 1 patient, initial coronary angiography
revealed a patent stent in the left anterior descending coronary artery located over the first septal branch that was the
target vessel, but this septal branch was successfully engaged
and cannulated. In 2 patients, the target vessel was accessed
through a coronary artery bypass graft (posterior descending
branch through saphenous vein graft to right coronary artery
and distal septal branch through left internal mammary artery
graft to distal left anterior descending coronary artery). Of the
13 patients with prior epicardial ablation, RF application was
limited by proximity of a coronary artery to a target region in
1, with a circumflex marginal branch in proximity to a VT
exit. This branch was successfully occluded in the following
TCEA procedure.
The 22 patients who had initial TCEA received a total dose
of ethanol of 3.2⫾2.4 mL (range, 1–9 mL; median, 3 mL) and
received 165⫾79 mL (range, 75–275 mL; median, 200 mL)
of angiographic contrast. The saline injection test was not
performed in 3 patients because targeted VT terminated with
balloon inflation in the target vessel and was not inducible.
After TCEA, no VT was inducible in 10 (46%) patients
(acute success). Eight (36%) patients had inducible monomorphic VT that was different from the VT targeted for
TCEA (modified). In 3 patients, postablation attempts to
reinduce VT were not performed to avoid aggravating their
poor hemodynamic status. In 1 patient, the targeted VT
remained inducible. No VT was inducible in 60% and 14% of
the patients with septal and nonseptal targets, respectively.
Early Outcome and Complications
Of 13 patients with intact AV conduction who had undergone
TCEA to arteries that supplied the septum, complete heart
block occurred in 5 (38%). All 5 patients had an AV block of
more than first degree and a bundle branch block present
before ablation (left bundle branch block in 3, right bundle
branch block in 2). Patients receiving septal alcohol embolization who developed heart block were similar to those who
did not develop heart block (Table 3). AV conduction
subsequently recovered in 1 patient 2 days after the procedure. Complete heart block persisted in the other 4 patients,
Figure 2. Summary of coronary arteries
targeted for ethanol ablation (American
Heart Association classification of coronary artery segmental anatomy12). Coronary artery segments are numbered 1
through 15. AC indicates atrial circumflex branch; AM, acute marginal branch;
AV, atrioventricular node; CB, conus
branch; D1, first diagonal branch; D2,
second diagonal branch; LAD, left anterior descending coronary artery; LCX, left
circumflex coronary artery; OM, obtuse
marginal branch; PD, posterior descending branch; PL, posterolateral branch;
RCA, right coronary artery; RPD, right
posterior descending branch; RV, right
ventricle; SN, sinus node.
Tokuda et al
Table 3.
Heart Block After TCEA for Septal Arteries
Transcoronary Ethanol Ablation for VT
Table 4.
Heart Block
(⫹) (n⫽5)
Heart Block
(⫺) (n⫽8)
P
Age, y
67⫾13
61⫾13
0.40*
Male sex
5 (100)
4 (50)
0.11†
Ischemic cardiomyopathy
1 (20)
5 (63)
893
Recurrence After TCEA
No Recurrence
(n⫽8)
Recurrence
(n⫽14)
P
Age, y
66⫾9
60⫾14
0.33*
Male sex
5 (63)
11 (79)
0.62†
0.27†
Ischemic cardiomyopathy
4 (50)
6 (43)
1.00†
History of cardiac surgery
0 (0)
4 (50)
0.11†
History of cardiac surgery
5 (63)
5 (36)
0.38†
AH interval, ms
143⫾36
118⫾48
0.30*
History of CABG
2 (25)
4 (29)
1.00†
HV interval, ms
64⫾24
61⫾13
0.76*
No. of previous ablations
1.0⫾0.5
2.4⫾2.0
0.07*
First-degree AV block
5 (100)
4 (50)
0.20†
Prior epicardial ablation
1 (13)
8 (57)
0.07†
2
LBBB
3 (60)
4 (50)
0.83†
eGFR, mL/min per 1.73 m
57⫾11
63⫾8
0.55*
RBBB
2 (40)
1 (13)
0.24†
LV ejection fraction, %
29⫾11
31⫾11
0.69*
Ablated ⬎1 septal artery
1 (20)
1 (13)
1.00†
LVDd, cm
6.0⫾1.1
6.3⫾0.9
0.44*
LV ejection fraction, %
37⫾10
29⫾9
0.18*
IVSd, cm
1.0⫾0.3
1.0⫾0.2
0.85*
␤-blocker
5 (100)
7 (88)
1.00†
VT storm
Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017
Data are presented as mean⫾SD or n (%). LBBB indicates left bundle branch
block; RBBB, right bundle branch block. Other abbreviations as in Table 1.
*Student t test.
†Fisher exact test.
and 3 patients underwent additional left ventricular lead
implantation for implantable cardioverter-defibrillator upgrade to cardiac resynchronization therapy. None of these 5
patients had heart block during balloon occlusion or saline
injection in the vessel that received ethanol injection. Another
patient had transient severe hypotension after ethanol injection that required intraaortic balloon counterpulsation. Temporary coronary spasm occurred in 1 patient. There were no
coronary artery dissections or perforations or other complications related to catheter manipulation in the coronary
circulation.
CK, CK-MB, and troponin I at their maximum values after
TCEA were 597⫾380 U/L (normal reference value, 27–218
U/L), 68⫾40 ng/mL (0.0 –5.0 ng/mL), and 14⫾10 ng/mL
(0.0 – 0.04 ng/mL), respectively. There was no significant
relationship between the cardiac enzyme increase and the
number of arteries targeted for ablation.
Estimated glomerular filtration rate 24 and 72 hours after
the procedure were not significantly different from preprocedure (24 hours, 61⫾24 versus 66⫾23 mL/min per 1.73 m2,
P⫽0.29; 72 hours, 61⫾24 versus 66⫾23 mL/min per 1.73
m2, P⫽0.37). However, 4 patients met criteria for contrastinduced nephropathy. In all 4 patients, renal function recovered without additional therapy or long-term consequences.
Overall echocardiographic assessment a median of 8 days
after TCEA did not show a statistically significant change in
left ventricular ejection fraction (P⫽0.35), although some
individual changes were observed (online-only Data Supplement Figure). This comparison is limited, however, by
variable time of assessment among different patients in
relation to VT and cardiac arrest episodes. No unanticipated
new wall motion abnormalities were noted.
Three patients died within 30 days of the procedure
(online-only Data Supplement). All had a history of ischemic
heart disease and heart failure. Deaths were attributed to
continued VT and hemodynamic deterioration in 1 patient,
cholesterol embolization syndrome with multiorgan failure in
3 (38)
8 (57)
0.66†
Failed AAD
2.6⫾1.4
2.6⫾1.2
0.98*
VT cycle length
397⫾90
449⫾112
0.32*
6 (75)
9 (64)
1.0†
Total amount of ethanol, mL
1.6⫾0.6
4.1⫾2.7
0.03*
No. of ablated coronary arteries
1.0⫾0.0
1.4⫾0.6
0.07*
Max CK
703⫾653
557⫾276
0.60*
Max CK-MB
54⫾9
72⫾46
0.53*
Max troponin I
11⫾5
15⫾11
0.53*
Septal origin
Data are presented as mean⫾SD or n (%). CK indicates creatine kinase;
eGFR, estimated glomerular filtration rate. Other abbreviations as in Tables 1
and 2.
*Student t test.
†Fisher exact test.
the second patient, and failure to recover from prior strokes
associated with biventricular assist device placement before
ablation in the third patient (online-only Data Supplement).
Another patient had a heart transplant 110 days after the
procedure. The median time from TCEA to discharge was 7
days.
Recurrent VT
Fourteen (64%) patients experienced VT recurrence, which
occurred at a median of 16 days after the first TCEA
procedure. However, 8 of the 14 had a history of VT storm or
incessant VT, and 6 remained free of VT storm or incessant
VT and were therefore classified as improved. Thus, 14
(63.6%) patients were free of recurrent VT or had improved
VT control.
Patients with recurrent VT had a larger number of previous
ablation attempts (2.4⫾2.0 versus 1.0⫾0.5, P⫽0.07), had
more ablated coronary arteries (1.4⫾0.6 versus 1.0⫾0.0,
P⫽0.07), and received a greater amount of injected ethanol
(4.1⫾2.7 versus 1.6⫾0.6, P⫽0.03) compared with patients
who remained free of VT (Table 4). VT recurred in 9 of 15
(60%) patients with septal artery targets and 5 of 7 (71%)
with nonseptal artery targets. Of 14 patients with VT recurrence after TCEA, 7 received additional RFCA (including
RFCA after the second TCEA procedure in 1 patient). Three
of these 7 patients remained free of VT, and VT was
improved in another 2 patients. A second TCEA procedure
894
Table 5.
Circ Arrhythm Electrophysiol
December 2011
Patients With Repeat Procedures
First TCEA Procedure
Repeated Procedure
Case
VT
Origin
Coronary Artery
Injected
VT Termination by
Saline Injection Test
Induction Test
Postprocedure
1
Septal
First septal
Yes
Nonclinical VT
Septal*
RFCA
Yes
2
Septal
First septal
Yes
No VT
Septal*
Second TCEA for
second septal
Yes
3
Posterior
Second OM
Yes
Nonclinical VT
Posterior*
Second TCEA for
third OM
No
4
Posterior
OM⫹diagonal
Yes
Nonclinical VT
Posterior*
RFCA
No
5
Septal
Distal septal⫹diagonal
Yes
No VT
Septal*
RFCA
Yes
6
Septal
First septal
Yes
No VT
Septal*
RFCA
Yes
VT Origin
Therapy
Outcome
Recurrence
7
Septal
First septal
Yes
No VT
Septal*
RFCA
Yes
8
Septal
First septal
Yes
No VT
Distal septal
inferior
RFCA
Yes
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OM indicates obtuse marginal branch; RFCA, radiofrequency catheter ablation. Other abbreviation as in Table 1.
*Same as first TCEA.
was performed in 2 patients 32 and 42 days after the first
TCEA, respectively. Coronary angiography revealed that
total occlusion of the vessel initially ablated was still present
in both patients. In 1 patient who had initial occlusion of a
first septal branch, the second septal branch was targeted for
ablation. He had prior complete heart block. VT recurred
after the second procedure, and further RF ablation was
performed in the left ventricular outflow region but also
failed (Figure 1). In the second patient, TCEA was performed
in a third obtuse marginal branch after prior ablation in the
second obtuse marginal branch. He subsequently remained
free of VT.
Of 8 patients who underwent repeated electrophysiological
study (during TCEA, 2; RFCA, 6) for recurrent VT, VT
originated from the same region as was targeted at the prior
TCEA in 7 patients (Table 5). In all patients, however, the
recurrent VT had a different QRS morphology than observed
at the first TCEA, suggesting that the substrate had been
modified.
After a mean follow-up of 20⫾11 months after the last
ablation procedure, total mortality was 32%, early mortality
(within 30 days) was 14%, and late mortality (beyond 30
days) was 18%. Peak serum cardiac enzymes after TCEA
were not statistically different comparing the patients with
early mortality and late mortality (CK-MB, 78⫾47 versus
69⫾29 ng/mL, P⫽0.80; troponin I, 23⫾10 versus 13⫾8
ng/mL, P⫽0.36). In univariate analysis, mortality was
associated with a history of cardiac surgery (P⫽0.02) and
worse New York Heart Association functional class score
(P⫽0.006). Peak CK-MB and troponin I levels after TCEA
procedure were not different between the 2 groups. At the
end of follow-up, 13 patients who had TCEA were alive
and free of VT or had improved control of VT.
Discussion
Although RFCA for recurrent VT due to structural heart
disease usually reduces VT recurrences, it continues to fail in
a significant number of patients. The presence of intramural
or epicardial arrhythmogenic substrates is an important cause
of failure for which ablation options are limited. This report
demonstrates that TCEA can prevent recurrent VT and VT
storm or control incessant VT in more than one half of such
patients. These results are more impressive considering that
TCEA was largely a last-resort therapy after previous failed
ablation and drug therapy. However, there are a number of
concerns and problems that these data highlight.
Based on ours and other series of ablation,5–7 we routinely
consider TCEA when RFCA fails. However, use of percutaneous epicardial mapping and ablation has continued to
increase. TCEA was considered before epicardial ablation in
cases where a deep intramural substrate was suspected, as
when there is earliest activation at the interventricular septum. Patients with cardiac surgery that renders pericardial
access more difficult also would likely be considered for
TCEA rather than a surgical epicardial ablation.
We anticipated that TCEA may be most useful for those
septal VTs that do not have an endocardial origin and cannot
be approached from the epicardium. Although the majority of
target vessels identified were septal, TCEA was also feasible
for some nonseptal VTs.
Planned TCEA was aborted in 19% patients usually because of anatomic constraints. Technical limitations to TCEA
are more likely to be encountered in patients with multivessel
coronary artery disease and prior coronary artery bypass graft
surgery. Paradoxically, TCEA is more likely to be of interest
in this subgroup because percutaneous epicardial mapping
often is not possible after cardiac surgery. In some patients
with ischemic heart disease, a coronary vessel perfusing the
target region identified from catheter mapping could not be
identified or was not accessible because it was perfused only
by a network of multiple collateral vessels. We also observed
that extensive collateral vessels from a possible target vessel
can be present, perfusing more distant myocardium, which
would presumably create a risk of larger infarction beyond
the VT substrate. In such cases, we deferred ablation.
Anatomic variations are important considerations. Because
the septum is the most common target region, septal perforators from the left anterior descending coronary artery were
Tokuda et al
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important targets. In 1 patient, a right superior septal perforator from a conus branch of the right coronary artery was
found and successfully occluded. An ectopic origination of
the septal branch is infrequent, occurring in 3% of patients.13
What is the mechanism of VT recurrence? At repeat electrophysiological studies in 8 patients, the recurrent VT seemed
to originate from the same general region targeted at the first
TCEA in 88% of patients. In all of these patients, saline
injection or interruption of blood flow in the targeted vessel
had terminated VT, and TCEA was acutely successful. It is
possible that small collateral vessels developed over time in
some14; however, VT recurred earlier than 24 hours in some
patients. Persistent coronary occlusion without clear collaterals was observed in 2 patients who had repeat angiography
after VT recurrence. Interestingly, the VT substrate did seem
to be modified because the VTs that recurred had a different
QRS morphology than the initially targeted VT. Thus, it
seems likely that the lesion created by TCEA was insufficient
to damage all of the VT substrate and that there may have
been some recovery in the border region.
The mortality of 32% during 20⫾11 months of follow-up
remains concerning in this sample. Although these patients
had depressed ventricular function and uncontrollable VT,
which is a marker for increased mortality and heart failure,
before ablation, damage to contracting myocardium is a
potential contributing factor. Single-point measurement of
serum troponin I in the early phase after myocardial infarction performs well for estimation of final infarct size and is a
well-established prognostic marker after myocardial infarction.15,16 In the present study, CK-MB and troponin I levels
after TCEA were not related to mortality. We did not
appreciate measurable change in left ventricular function
after ablation, but this is difficult to assess in patients with
frequent episodes of VT and without blinded review of
changes in ventricular function. We believe that it remains
prudent, however, to take precautions to minimize the size of
the infarction.
Complications
AV block is an anticipated complication when the septum is
targeted for TCEA. Furthermore, the location of the arrhythmia substrate in this region and prior catheter ablation may
impair AV conduction. Thus, almost two thirds of patients
had some degree of AV block, and one half had bundle
branch block. Complete heart block occurred in 38% of
patients who underwent TCEA of the septum. TCEA for
hypertrophic cardiomyopathy causes complete heart block in
⬇11% of patients and is more likely if preexisting heart
disease is present and if ⬎1 septal artery is injected.17,18 In a
previous series, Kay et al6 reported on 4 (36%) patients with
complete heart block after 11 TCEA procedures for VT.
Interestingly, heart block could not be predicted by balloon
occlusion or saline infusion into the target vessel, suggesting
that the area of injury produced by ethanol injection is larger
than the area of ischemia produced by saline injection.
Limitations
This study has several limitations. These patients are largely
referred to our tertiary center and undoubtedly are a selected
Transcoronary Ethanol Ablation for VT
895
group. Because the study sample is small, statistical power is
very low and the chance of type I error may be very high
because of small sample sizes in subgroups combined with
multiple testing at a fixed 5% significance level. Further
studies are required to better identify patient groups most
likely to benefit and that are at risk for complications. To our
knowledge, however, these data comprise the largest series of
patients treated with TCEA. VTs were often documented by
implantable cardioverter-defibrillator interrogation, and 12lead ECG morphologies of spontaneous VTs were often
absent. This descriptive study of TCEA was from an experienced center. It is important to note that these findings may
not be applicable to less-experienced operators or centers.
Conclusions
In patients with difficult-to-control VT who fail RFCA,
TCEA prevents all VT recurrences in 36% and improves
arrhythmia control in an additional 27%. With attempted
broader use, we found that inadequate target vessels, collaterals, and recurrence of modified VTs limit efficacy but that
TCEA continues to play an important role for difficult VTs in
high-risk patients with failed RFCA.
Sources of Funding
Dr Kojodjojo was funded by a British Heart Foundation Travel
Fellowship (FS/09/047).
Disclosures
Dr Koplan is a consultant of Boston Scientific, St Jude Medical, and
Sanofi Aventis. Dr John is a consultant of St Jude Medical and
Spectranetics Inc. Dr Epstein is a consultant of Boston Scientific, St
Jude Medical, and Medtronic. Dr Stevenson is a coholder of a patent
for needle ablation consigned to Brigham and Women’s Hospital. Dr
Tedrow is a consultant of St Jude Medical.
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CLINICAL PERSPECTIVE
Catheter ablation of scar-related ventricular tachycardias (VTs) still fails in some patients, usually because of an inability
to reach the arrhythmia substrate. Transcoronary ethanol ablation (TCEA) offers an alternative for these patients. We began
offering TCEA routinely at our institution when endocardial and epicardial ablation fail or when a deep intramural
substrate, such as in the septum, is anticipated. To our knowledge, this update provides the largest reported experience of
TCEA for VT and further clarifies its limitations with present techniques. In 19% of patients, TCEA was considered but
not performed because of unsuitable coronary anatomy. Of the 22 patients who received TCEA, VT recurrences were
completely prevented in 36%, and arrhythmia control was improved in an additional 27%. Complete heart block occurred
in 5 patients, and 1 patient with advanced heart failure died 5 days after the procedure. Thus, TCEA is a useful treatment
option when catheter ablation fails but has significant limitations.
Transcoronary Ethanol Ablation for Recurrent Ventricular Tachycardia After Failed
Catheter Ablation: An Update
Michifumi Tokuda, Piotr Sobieszczyk, Andrew C. Eisenhauer, Pipin Kojodjojo, Keiichi Inada,
Bruce A. Koplan, Gregory F. Michaud, Roy M. John, Laurence M. Epstein, Frédéric Sacher,
William G. Stevenson and Usha B. Tedrow
Downloaded from http://circep.ahajournals.org/ by guest on May 12, 2017
Circ Arrhythm Electrophysiol. 2011;4:889-896; originally published online October 7, 2011;
doi: 10.1161/CIRCEP.111.966283
Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville
Avenue, Dallas, TX 75231
Copyright © 2011 American Heart Association, Inc. All rights reserved.
Print ISSN: 1941-3149. Online ISSN: 1941-3084
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circep.ahajournals.org/content/4/6/889
Data Supplement (unedited) at:
http://circep.ahajournals.org/content/suppl/2011/10/07/CIRCEP.111.966283.DC1
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SUPPLEMENTAL MATERIAL
Figure in online data supplement
Figure in online data supplement
Individual changes of left ventricular (LV) ejection fraction before and
after transcoronary ethanol ablation (TCEA) are shown for patients who
survived ablation and follow-up (left panel) and those who died early
(within 30 days) or late (right panel).
Details of Post-Procedure Mortality
The first patient was a 60-year-old male with ischemic cardiomyopathy
with prior coronary artery bypass surgery and stenting, and left ventricular
(LV) ejection fraction 10 – 15% that had improved after biventricular
implantable cardiac defibrillator placement. He was admitted with
frequent episodes of polymorphic and monomorphic ventricular
tachycardia (VT) with syncope despite amiodarone that had been increased
to 800mg daily. Echocardiography (15 days prior to ablation) showed LV
ejection fraction of 30%, with a 4.8 cm apical LV thrombus; LV ejection
fraction on positron emission tomography imaging was 22%. Episodes of
VT increased despite therapy with lidocaine, amiodarone, mexiletine,
quinidine and metoprolol. Angiography showed no targets for
revascularization. He was evaluated, but felt not to be an option for
cardiac transplantation or destination left ventricular assist device. Due to
the LV thrombus transcoronary ethanol ablation (TCEA) procedure of the
distal left anterior descending artery (LAD) branch was performed without
LV endocardial mapping, targeting a right bundle branch block
configuration VT with a cycle length of 340 ms. TCEA of the distal LAD
abolished VT1, but other VTs remained inducible. After TCEA
procedure he remained on intraaortic balloon counter pulsation and
inotropic support. Episodes of VT continued with further hemodynamic
deterioration. Subsequently comfort measures were instituted and
antiarrhythmic therapy withdrawn as the family wished and he died 3 days
after the TCEA.
Patient #2 was a 73-year-old female with prior anterior wall infarction,
hypertension, aortic aneurysm, and coronary artery bypass surgery. She
was transferred to us for management of recurrent monomorphic VT
despite amiodarone and mexiletine and prior endocardial radiofrequency
catheter ablation attempt. LV ejection fraction the day of the procedure was
35%. RF ablation at the infero-septal LV slowed and terminated VT, but
VT remained inducible. TCEA of a septal branch of the apical LAD was
performed after balloon catheter placement in the vessel terminated VT.
She initially tolerated the procedure well, and had no VT, but over the next
24 hours developed oligura, hypotension, progressive acidosis, and
multi-organ failure subsequently attributed to cholesterol embolization
syndrome, followed by death. Echocardiogram 1 day after the procedure
showed no change in estimated LV ejection fraction of 35%.
Patient #3 was a 62-year-old female, with prior infero-septal myocardial
infarction and heart failure, resection and primary closure of a mid inferior
wall left ventricular pseudoaneurysm and placement of a biventricular
assist device (BiVAD), followed by embolic strokes. She had continued to
have episodes of VT and VF with acceptable, but diminished VAD flows.
Ablation was requested in the hope of achieving some improvement
hemodynamic stability after VT and VF increased despite medical therapy
with quinidine. Due to the recent BiVAD placement, there was concern
about potential risk of embolization of thrombus. TCEA of the 1st septal
branch of the LAD was performed without LV endocardial mapping.
TCEA abolished VT, but her neurologic status and general condition failed
to improve. She was transitioned to comfort measures only and died 28
days after the TCEA procedure.