Download Long-Term Outcome After Catheter Ablation of Ventricular

Original Article
Long-Term Outcome After Catheter Ablation
of Ventricular Tachycardia in Patients With
Nonischemic Dilated Cardiomyopathy
Daniele Muser, MD*; Pasquale Santangeli, MD, PhD*; Simon A. Castro, MD;
Rajeev K. Pathak, MBBS, PhD; Jackson J. Liang, DO; Tatsuya Hayashi, MD;
Silvia Magnani, MD; Fermin C. Garcia, MD; Mathew D. Hutchinson, MD;
Gregory G. Supple, MD; David S. Frankel, MD; Michael P. Riley, MD, PhD;
David Lin, MD; Robert D. Schaller, DO; Sanjay Dixit, MD; Erica S. Zado, PA-C;
David J. Callans, MD; Francis E. Marchlinski, MD
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Background—Catheter ablation (CA) of ventricular tachycardia (VT) in patients with nonischemic dilated cardiomyopathy
can be challenging because of the complexity of underlying substrates. We sought to determine the long-term outcomes
of endocardial and adjuvant epicardial CA in nonischemic dilated cardiomyopathy.
Methods and Results—We examined 282 consecutive patients (aged 59±15 years, 80% males) with nonischemic dilated
cardiomyopathy who underwent CA. Ablation was guided by activation/entrainment mapping for tolerated VT and
pacemapping/targeting of abnormal electrograms for unmappable VT. Adjuvant epicardial ablation was performed for
recurrent VT or persistent inducibility after endocardial–only ablation. Epicardial ablation was performed in 90 (32%)
patients. Before ablation, patients failed a median of 2 antiarrhythmic drugs), including amiodarone, in 166 (59%)
patients. The median follow-up after the last procedure was 48 (19–67) months. Overall, VT-free survival was 69% at
60-month follow-up. Transplant-free survival was 76% and 68% at 60- and 120-month follow-up, respectively. Among
the 58 (21%) patients with VT recurrence, CA still resulted in a significant reduction of VT burden, with 31 (53%)
patients having only isolated (1–3) VT episodes in 12 (4–35) months after the procedure. At the last follow-up, 128 (45%)
patients were only on β-blockers or no treatment, 41 (15%) were on sotalol or class I antiarrhythmic drugs, and 62 (22%)
were on amiodarone.
Conclusions—In patients with nonischemic dilated cardiomyopathy and VT, endocardial and adjuvant epicardial CA is
effective in achieving long-term VT freedom in 69% of cases, with a substantial improvement in VT burden in many of
the remaining patients. (Circ Arrhythm Electrophysiol. 2016;9:e004328. DOI: 10.1161/CIRCEP.116.004328.)
Key Words: antiarrhythmic drug ◼ catheter ablation ◼ dilated cardiomyopathy
◼ electroanatomic mapping ◼ ventricular tachycardia
T
he management of recurrent ventricular tachycardia (VT)
in the setting of nonischemic dilated cardiomyopathy
(NIDCM) is challenging because of the complexity of the
underlying arrhythmic substrates, which are typically located
at the basal perivalvular regions and at the interventricular
septum, with a high prevalence of midmyocardial and subepicardial substrates.1–5 Prior experiences with CA have reported
worse arrhythmia-free survival after endocardial-only procedures, with a substantial improvement in short to mid-term
VT-free survival when a combined endocardial–epicardial
approach is adopted.1,4,6–11 However, data on long-term outcomes after catheter ablation (CA) are lacking, including
the impact on mortality and the use of antiarrhythmic drugs
(AAD). The aim of this study was to evaluate the long-term
outcome after CA of VT in a large series of patients with
NIDCM and VT undergoing endocardial and as needed adjuvant epicardial CA.
See Editorial by Della Bella and Trevisi
Methods
Patient Sample
The study sample consisted of 282 consecutive patients with
NIDCM and recurrent VT referred to the Hospital of the University
Received May 10, 2016; accepted August 25, 2016.
From the Cardiac Electrophysiology Section, Hospital of the University of Pennsylvania, Philadelphia.
*Drs Muser and Santangeli contributed equally as co-first authors to this work.
The Data Supplement is available at http://circep.ahajournals.org/lookup/suppl/doi:10.1161/CIRCEP.116.004328/-/DC1.
Correspondence to Francis Marchlinski, MD, Hospital of the University of Pennsylvania, 9 Founders Pavilion–Cardiology, 3400 Spruce St, Philadelphia,
PA 19104. E-mail [email protected]
© 2016 American Heart Association, Inc.
Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org
1
DOI: 10.1161/CIRCEP.116.004328
2 Muser et al Long-Term Outcome of VT Ablation in NIDCM
WHAT IS KNOWN
• The management of recurrent ventricular tachycar-
dia in the setting of nonischemic dilated cardiomyopathy is challenging due to the complexity of the
underlying arrhythmogenic substrates, typically located at the basal perivalvular regions and at the interventricular septum and with a high prevalence of
mid-myocardial and sub-epicardial substrates.
• Prior series with catheter ablation have reported
worse arrhythmia-free survival following endocardial-only procedures, with a substantial improvement
in short to mid-term VT-free survival when a combined endocardial–epicardial approach is adopted.
• Data on long-term outcomes following catheter ablation are insufficient, and the impact of catheter ablation on the long-term use of antiarrhythmic drug
therapy and mortality is unknown.
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WHAT THE STUDY ADDS
• Catheter
ablation of ventricular tachycardia in patients with nonischemic dilated cardiomyopathy is
a safe and effective approach to achieve long-term
arrhythmia control in most patients.
• Endocardial with adjuvant epicardial ablation (in
case of persistent VT inducibility or clinical recurrence following endocardial-only procedure) provide
good long-term arrhythmia-free survival. The majority of patients have complete ventricular tachycardia
control, and most of the remaining patients have a
substantial improvement in ventricular tachycardia
burden with limited need for antiarrhythmic drugs.
• Recurrent VT is independently associated with increased risk of subsequent death/transplant. In these
patients, a more aggressive treatment of recurrent
VT may translate into a mortality benefit.
of Pennsylvania for radiofrequency CA between January 1999 and
December 2014. All patients had evidence of left ventricular (LV)
dilation and systolic impairment (LV ejection fraction [LVEF] <50%)
persistent for at least 9 months, despite optimal medical treatment
after the initial diagnosis.12,13 Patients with significant coronary artery disease (>50% stenosis, assessed by coronary angiography or
coronary artery computed tomography), congenital heart disease,
hypertrophic cardiomyopathy, arrhythmogenic right ventricular (RV)
cardiomyopathy, LV noncompaction, restrictive cardiomyopathy,
(sub)acute myocarditis, cardiac sarcoidosis, toxic cardiomyopathy,
tachycardia-induced cardiomyopathy, or primary valvular abnormalities were excluded. All patients were treated according to the institutional guidelines of the University of Pennsylvania Health System
and provided written informed consent.
Electrophysiological Study
All patients underwent the procedure in the fasting state. Ablation
was performed under conscious sedation whenever possible. General
anesthesia was used when necessary at the discretion of the operator
or anesthesiologist for ventilation, oxygenation, or patient comfort
and during epicardial mapping and ablation. AADs were routinely
discontinued ≥5 half-lives before the procedure, with the exception
of amiodarone, which was discontinued at least 3 days beforehand.
Recurrent unstable arrhythmias necessitated continued AAD therapy
in selected patients at the time of the procedure. Catheters were placed
under fluoroscopic guidance. A standard transvenous 6F quadripolar
catheter with 5-mm interelectrode distance (Bard Inc, Delran, NJ)
was placed at the RV apex. An 8F 64-element phased-array intracardiac echocardiography catheter (AcuNav; Acuson, Mountain View,
CA) was used routinely for cases after 2005 to assist catheter positioning, to assess tissue–catheter contact, and to monitor for complications. In 376 out of 442 (85%) procedures, a deflectable 3.5-mm
open-irrigated tip catheter (NaviStar ThermoCool; Biosense Webster,
Inc, Diamond Bar, CA) was used for mapping and ablation; a bidirectional closed-irrigated ablation catheter (Chilli; Boston Scientific,
Natick, MA) was used in 36 (8%) procedures. In the remaining 30
(7%) procedures (all before 2002), a nonirrigated 4-mm tip ablation
catheter (NaviStar; Biosense Webster, Inc) was used. The mapping/
ablation catheter was advanced to the RV (transvenous approach),
LV (retrograde aortic or transseptal approach), or epicardial space according to the presumed site of origin of the VT or the underlying
substrate. Programmed ventricular stimulation was delivered, with
triple extrastimuli from at least 2 RV or LV sites with at least 2 drive
cycle lengths (CLs). The 12-lead ECG morphology of all spontaneous VTs (when available) and the intracardiac near-field and far-field
electrograms of the implantable cardioverter defibrillator (ICD) were
collected and compared with the induced VT(s) during the procedure.
Induced VT(s) were identified as clinical if they matched the CL and
morphology of stored ICD electrograms (near-field and far-field) and
the 12-lead ECG when available. Isoproterenol was used in select
cases to facilitate induction of the clinical VT.
Endocardial Mapping
A high-density 3-dimensional electro-anatomic map (CARTO;
Biosense Webster, Inc) was created during sinus or paced rhythm,
maintaining a color and surface fill threshold of 15 mm to ensure
adequate sampling and representation of the entire endocardial surface area to identify low voltage areas and abnormal electrograms
consistent with scar. The bipolar signals were filtered at 30 to 400 Hz
(CARTO V.9 and V.7 systems; Biosense Webster, Inc.) or 16 to 500
Hz (CARTO-3 system; Biosense Webster, Inc.) and were displayed
at 100 mm/s speed. The peak-to-peak signal amplitude of the bipolar
electrogram was measured automatically and confirmed during manual review. The electrogram signals were displayed as color gradients
on a 3-dimensional computerized bipolar voltage map. Reference
values for identifying abnormal endocardial bipolar and unipolar and
epicardial bipolar electrogram signal amplitudes in the RV and LV
were defined according to previously established criteria.14–16 An endocardial bipolar signal amplitude >1.5 mV either in the RV or in the
LV and an endocardial unipolar signal amplitude >8.3 mV in the LV
and RV septum and >5.5 mV in the RV free wall were categorized as
normal and represented in the electro-anatomic map by purple color.
Abnormal voltage areas were represented by nonpurple range of colors, with the most abnormal signal amplitude (arbitrary defined as
<0.5 mV) represented by red color. Particular attention was paid to
define the valvular planes. Tricuspid and mitral valvular sites were
identified by the fluoroscopic catheter tip positions at the ventricular
base with discrete bipolar recordings that demonstrated both sharp
atrial and ventricular signals of approximately equal amplitude and
confirmed with the use of direct valve visualization with intracardiac
echocardiography (for cases after 2005). The pulmonic valve was
carefully identified by passing the mapping catheter into the pulmonary artery and slowly withdrawing it until an RV electrograms was
identified, and RV capture was possible and confirmed with the use of
direct visualization of the valve with intracardiac echocardiography
(for cases after 2005). Valvular sites were given a location-only tag to
preclude their influence on the voltage map color. Careful attention
was paid to record multiple endocardial electrograms around valvular
structures.
Epicardial Mapping
Epicardial mapping was performed when (1) the 12-lead ECG of the VT
suggested an epicardial origin; (2) there was evidence of epicardial substrate on imaging studies (eg, magnetic resonance, intracardiac echocardiography); (3) there was unipolar electrogram abnormality (<8.3
3 Muser et al Long-Term Outcome of VT Ablation in NIDCM
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Figure 1. Examples of typical distribution of endocardial ablation linear lesions across abnormal left ventricle to valve annulus in a patient
with multiple unmappable ventricular tachycardias (VTs). Linear lesions transecting the putative VT isthmuses were placed through the
sites of best pace maps with long stimulus to QRS and were anchored to the valve annulus.
mV) in the presence of no or minimal bipolar (<1.5 mV) electrogram
abnormality; and (4) there was failure of endocardial ablation (either
early VT recurrence or persistent inducibility of clinical VT). Access to
the pericardial space was obtained using the percutaneous subxiphoid
approach described by Sosa et al.17 An 8F sheath (or deflectable sheath)
was introduced into the pericardial space, and the mapping/ablation
catheter was advanced through the sheath. Detailed voltage mapping
was performed with a surface and color fill threshold maintained at 15
mm. The reference value for defining abnormal electrograms in the
epicardium was <1.0 mV, as previously reported.4 Dense scar was also
arbitrarily defined as <0.5 mV for display purposes for the epicardial
electroanatomic maps. To further limit the influence of epicardial fat
and small-vessel coronary vasculature (ie, vessels that cannot be directly appreciated by coronary angiogram) on the low-voltage region, the
contiguous low-voltage electrograms had to demonstrate not only low
amplitude but also discrete late potentials (recorded after the QRS of the
surface ECG) and demonstrate broad multicomponent or split signals.
Signals >1.0 mV that also demonstrated abnormal, multicomponent,
split or late potentials were also tagged and if adjacent to confluent areas
of low voltage typically included in substrate-based ablation targets.
Catheter Ablation
The primary ablation end point was elimination of the clinical VT(s)
and all mappable nonclinical VT(s). All induced VT(s) with a CL
Figure 2. Example of endocardial (A) and epicardial (B and C) substrate modification in a patient with minimal endocardial substrate.
Black dots (B and C) indicate abnormal electrograms. Coronary angiography was performed to confirm safe distance of the ablation sites
on the epicardium from the major coronary vessels.
4 Muser et al Long-Term Outcome of VT Ablation in NIDCM
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>250 ms were also considered potentially relevant and routinely
targeted for ablation. For hemodynamically tolerated VT(s), entrainment mapping was performed at sites showing diastolic activity to
identify critical sites of the VT re-entrant circuit. Sites with concealed QRS fusion and return cycle within 30 ms of the VT CL with
matching stimulus-QRS and electrogram-QRS intervals or where VT
terminated during pacing without global capture were considered
critical.18,19 Radiofrequency energy was delivered at these sites (see
below). For hemodynamically unstable VTs, substrate modification
was performed, with cluster/linear lesions targeting sites identified
by pace mapping, as well as abnormal electrograms.15 The putative
VT site of origin was defined using pace mapping to reproduce the
VT QRS complex and to identify sites with a long stimulus to QRS
interval. Limited activation and entrainment information were used
to corroborate the pace map information when possible. Typically,
lesions were delivered through the sites of best pace map with long
stimulus to QRS (>30 ms). The ablation lesions were extended to
target markedly abnormal fractionated split and late potentials and,
for endocardial ablation, were typically anchored to the valve annuli
(Figure 1). Specific emphasis was given to target abnormal potentials
recorded within a 2- to 3-cm radius of the region of interest, defined
by entrainment mapping or pace mapping techniques, with the end
point of signal modification or elimination (Figure 2). Epicardial
radiofrequency lesions always avoided large coronary vessels by at
least 1 cm based on cine angiography. If inducibility of monomorphic
VT persisted after ablation, residual inducible VTs were remapped
and targeted using the techniques described earlier.
Radiofrequency energy application with the 4-mm standard catheter was set at 50 W and 55°. Open-irrigated ablation targeted a maximum temperature of 42° and a maximum impedance drop of 12 to
15 Ohms with power 20 to 50 W. Closed-irrigated ablation was set
to deliver 20 to 50 W, targeting a maximum temperature of 45° and
maximum impedance drop of 12 to 15 Ohms. Lesion duration was
typically set for 60 to 90 seconds but was further increased to ≥3
minutes in duration at sites associated with transient suppression of
VT with monitoring to confirm stable impedance drop, particularly
at sites suspected of harboring intramural substrate. The amount of
fluid in the epicardial space associated with the open irrigated catheter was monitored with intracardiac echocardiography and continuous arterial blood pressure monitoring for evidence of hypotension
and drained intermittently or continuously to preclude hemodynamic
compromise. At the end of the ablation procedure, 2 to 3 mg/kg of
triamcinolone was routinely administered intrapericardially to reduce
inflammation.
Outcomes
Table 1. Baseline Characteristics of the Study Sample
Age, y
Male sex, n (%)
59±15
227 (80)
Clinical characteristics
Family history of cardiomyopathy or sudden cardiac
death, n (%)
34 (12)
Hypertension, n (%)
95 (34)
Diabetes mellitus, n (%)
36 (13)
Hyperlipidemia, n (%)
65 (23)
Chronic kidney disease, n (%)
57 (20)
Chronic obstructive pulmonary disease, n (%)
26 (9)
Obstructive sleep apnea, n (%)
24 (8)
Previous cardiac arrest, n (%)
26 (9)
History of unexplained syncope, n (%)
64 (22)
History of atrial fibrillation, n (%)
66 (23)
NYHA class III/IV, n (%)
84 (30)
ICD, n (%)
Clinical presentation with VT storm, n (%)
240 (85)
71 (25)
Transthoracic echocardiography
LVEF, %
LVEF ≤ 35%, n (%)
36±13
137 (49)
Moderate to severe right ventricular dysfunction, n (%)
33 (12)
Moderate to severe diastolic dysfunction, n (%)
47 (17)
Clinical VT
Monomorphic with single morphology, n (%)
210 (75)
Monomorphic with multiple morphologies, n (%)
60 (21)
Polymorphic VT/ventricular fibrillation, n (%)
12 (4)
Medical therapy
Beta-blockers, n (%)
217 (77)
Angiotensin-converting enzyme-inhibitors/angiotensin
receptors blockers, n (%)
125 (44)
Spironolactone, n (%)
57 (20)
Long-term outcomes included (1) survival free of any VT (defined as
any sustained VT on ICD interrogation or 12-lead ECG) after single
or multiple procedures, (2) reduction of VT burden, and (3) survival
free of cardiac transplantation. The acute procedural outcomes consisted of noninducibility of any VT (excluding very fast [<250 ms]
nonclinical VTs/ventricular flutter). The acute efficacy was assessed
on the basis of inducibility of VT at the end of the ablation procedure
with a consistent stimulation protocol (up to triple extrastimuli from
≤2 ventricular sites with at least 2 drive CLs) and at the time of repeat programmed stimulation before hospital discharge noninvasively
from a single RV site via the ICD system (noninvasive programmed
stimulation or noninvasive programmed stimulation [NIPS]).
Continuous variables are reported as mean±SD or median (quartiles) and
categorical variables as counts and %. ICD indicates implantable cardioverterdefibrillator; LVEF, left ventricular ejection fraction; NYHA, New York Heart
Association; and VT, ventricular tachycardia.
Clinical Follow-Up
Statistical Analysis
Patients were evaluated at 4 to 8 weeks after ablation and then at 3- to
6-month intervals. For patients not followed at our institution, the referring cardiologists were contacted and ICD interrogations reviewed
to determine VT recurrence. Telephone interviews were performed at
6- and 12-month intervals with patients or family members to confirm
the absence of arrhythmias symptoms. The Social Security Death
Index database was queried for vital status.
Furosemide, n (%)
Failed antiarrhythmic drugs
Amiodarone before procedure, n (%)
Intravenous amiodarone before procedure, n (%)
Daily dose of amiodarone before the procedure, mg
123 (43)
2 (1–2)
166 (59)
29 (10)
290±148
Continuous variables are expressed as means±standard deviations if
normally distributed or medians (25th–75th percentile) if not normally
distributed. All continuous variables were tested for normal distribution using the 1-sample Kolmogorov–Smirnov test. Categorical data
are expressed as counts and percentages. Continuous variables were
compared using independent-sample parametric (unpaired Student’s
t test) or nonparametric (Mann–Whitney U) tests. Paired variables
5 Muser et al Long-Term Outcome of VT Ablation in NIDCM
Baseline characteristics of the study population are summarized
in Table 1. Two-hundred and eighty-two consecutive patients
with NIDCM (age 59±15 years, 80% males) underwent CA
after failure of 2 (1–2) AADs. Forty-five (16%) patients were
referred after a previous endocardial CA attempt at an outside
Institution. At baseline, 166 (59%) patients were receiving amiodarone therapy (intravenous infusion only in 29 cases). The
mean preprocedure daily oral amiodarone dose was 290±148
mg. In 37 (13%) patients, sotalol or at least one class I AAD had
been attempted before ablation (Figure 3). In 71 (25%) patients,
the clinical presentation was VT storm, defined as ≥3 appropriate ICD interventions in 24 hours or incessant VT.
stimulation or NIPS in the remaining 34/102 (33%) patients.
A total of 172/442 (38%) procedures were performed under
general anesthesia. In 21 (5%) procedures, mechanical
hemodynamic support was used because of periprocedural
hemodynamic instability (mostly after year 2010). The
majority of the procedures were performed via a retrograde
transaortic approach; an antegrade transseptal approach was
used in 31 (7%) cases.
During the procedure, a median number of 2 (1–4) different VTs were induced with a mean CL of 386±98 ms. At
least one hemodynamically unstable VT was induced in 239
(85%) patients. All patients underwent endocardial mapping
and ablation. The interventricular septum was identified as a
source of VT and targeted for ablation in 84 (30%) patients.
In 28 (10%) cases, the coronary cusp region was targeted for
ablation. Epicardial mapping was performed in 168 (38%)
procedures (122 patients) and epicardial ablation in 118 (27%)
procedures (90 patients).
At the end of the last procedure, a total of 262 (92%)
patients underwent programmed ventricular stimulation; in
20 cases, this was not performed because of unstable patient
conditions. The clinical VT was still inducible in 32 (12%)
patients, and 46 (18%) patients had at least one nonclinical
VT still inducible. A total of 101 (36%) patients underwent
NIPS from the ICD a median of 3 (2–4) days after the last
procedure: the clinical VT was not inducible in 84/101 (83%)
patients while noninducibility of any VT was achieved in
63/101 (62%) patients.
CA and Acute Procedural Outcomes
Procedural Complications
among the same patients were compared using paired-sample parametric (paired t test) or nonparametric (paired Wilcoxon signed-rank
test) tests. Categorical variables were compared using chi-square test
or Fisher exact test when appropriate. Survival curves were generated
by the Kaplan–Meier method and compared with the log-rank test.
Univariable and multivariable Cox proportional hazards analysis (using the forward stepwise model selection procedure) was used to test
the association between the outcome event and baseline covariates.
VT recurrence over follow-up was included as a time-dependent covariate. Only variables with P value <0.1 at univariable analysis were
entered as covariates in the multivariable model. Two-tailed tests
were considered statistically significant at the 0.05 level. Analyses
were performed using IBM SPSS version 23.0 software (SPSS Inc,
Chicago, IL).
Results
Study Population
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Ablation characteristics are summarized in Table 2. A total
of 442 procedures were performed among the 282 patients
(median 1; range 1–8 procedures per patient). A second procedure was performed in 66 (23%) patients and 3 or more
procedures in 36 (13%). Among the 102 (36%) patients with
multiple procedures, the indication for repeat procedure
was VT recurrence in 68/102 (67%) patients and persistent
VT inducibility at postprocedure programmed ventricular
A total of 19 (4%) complications occurred during the 442
procedures (Table 2). Two patients had pericardial tamponade requiring open-chest surgery to control the bleeding. In
both cases, the event occurred during pericardial access: in
one because of a perforation of the middle cardiac vein and in
the other one because of laceration of the RV free wall. These
2 patients had concomitant epicardial cryo-ablation targeting
the perivalvular epicardium guided by endocardial unipolar
Figure 3. Reduction in antiarrhythmic drug
usage after the last ablation procedure.
6 Muser et al Long-Term Outcome of VT Ablation in NIDCM
Table 2. Procedural Characteristics and Acute Procedural
Outcomes (442 Procedures Among 282 Patients)
Multiple procedures, n (%)
102 (36)
Single ablation, n (%)
180 (64)
2 ablations, n (%)
66 (23)
3 or more ablations, n (%)
36 (13)
Indication for repeat ablation among 102 patients with multiple procedures
VT recurrence, n (%)
Time between repeated procedures, days
Persistent inducibility at the end of the procedure/NIPS
or early recurrence of VT within 48 h, n (%)
Time between repeated procedures, days
68/102 (67)
161 (39–569)
34/102 (33)
4 (2–5)
Procedural data
General anesthesia, n (%)
172/442 (38)
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Left ventricular hemodynamic support during the
procedure, n (%)
21/442 (5)
Transseptal access to the left ventricle, n (%)
31/442 (7)
Total procedural time, hours
8 (6–10)
Fluoroscopy time, min
60 (47–94)
Radiofrequency time, min
38 (24–61)
Mapping and ablation
Epicardial mapping, n (%)
168/442 (38)
Epicardial ablation, n (%)
118/442 (27)
Interventricular septum ablation, n (%)
148/442 (33)
Ablation in the coronary cusp region, n (%)
45/442 (10)
Ablation from the coronary venous system, n (%)
7/442 (2)
Number of VTs induced
2 (1–4)
Cycle length, ms
386±98
Acute procedural outcomes
Programmed stimulation at the end of the procedure, n (%) 262/282 (92)
Noninducibility of any VT at the end of the last
procedure, n (%)
216/262 (82)
NIPS performed after last procedure, n (%)
101/282 (36)
Noninducibility of any VT at postprocedure NIPS, n (%)
63/101 (62)
Complications, n (%)
19 (4)
without consequence. Two patients had an occlusion of a
small coronary artery branch during epicardial ablation (both
small obtuse-marginal branches). Finally, one patient had
phrenic nerve injury during epicardial ablation with transient
hemi-diaphragm paralysis.
Long-Term Outcomes
Events occurring during the follow-up period are summarized
in Table 3. After a median follow-up of 48 (19–67) months, 24
patients underwent heart transplantation and 43 died. Overall
transplant-free survival was 76% and 68% at 60- and 120month follow-up, respectively (Figure 4). Cumulative VT-free
survival after the last procedure was 69% at 60-month followup (Figure 5). Among the 58 patients with VT recurrences,
a significant reduction of VT burden was observed, with
31/58 (53%) patients having only isolated (≤3 VT) episodes
occurring during an average of 12 months after the procedure
(Figure 5).
At the last follow-up, 128 (45%) patients were only on
β-blockers or no treatment, 41 (15%) were on sotalol or class
I AADs, and 62 (22%) were on amiodarone (Figure 3). The
daily dose of amiodarone at last follow-up was 247±103 mg.
Table 4 shows the results of the univariable and multivariable Cox proportional hazards analysis of correlates of events
during follow-up. In multivariable analysis, LVEF≤35% (hazard ratio [HR] 2.60, 95% confidence interval [CI] 1.06–6.38;
P=0.04) and inducibility of any VT with CL>250 ms at postprocedural NIPS (HR 3.53, 95% CI 1.42–8.80; P=0.007) were
the only variables independently associated with VT recurrence during follow-up.
Recurrent VT over follow-up was independently associated with subsequent mortality or transplant in multivariable
analysis (HR 12.12, 95% CI 4.58–32.05; P<0.001), as was
New York Heart Association (NYHA) functional class III/IV
(HR 2.97, 95% CI 1.10–7.98; P=0.031) and LVEF≤35% (HR
4.70, 95% CI 1.33–16.55; P=0.016).
Kaplan–Meier survival curves for transplant and VT
recurrence are presented in Figures 4 and 5.
Discussion
The present study reports the long-term results of CA of drugrefractory VT in the largest series of patients with NIDCM
to date. The major findings are as follows: (1) CA of VT in
patients with NIDCM is a safe and effective approach to
achieve long-term arrhythmia control in most patients; (2)
Pericardial effusion successfully drained by
pericardiocenthesis
10
Pericardial tamponade with need for open-chest surgical
repair of perforation
2
Coronary artery occlusion during epicardial ablation
2
Follow-up, months
48 (19–67)
Phrenic nerve injury during epicardial ablation
1
VT recurrence after the last procedure, n (%)
58 (21)
Vascular access site complications
4
Death, n (%)
43 (15)
Heart transplant, n (%)
24 (9)
Amiodarone at last follow-up, n (%)
62 (22)
Continuous variables are reported as mean±SD or median (quartiles) and
categorical variables as counts and %. NIPS indicates noninvasive programmed
stimulation; and VT, ventricular tachycardia.
voltage abnormalities and ECG morphology of the induced
VT. In 10 patients, a pericardial effusion occurred during mapping/ablation and was successfully drained percutaneously
Table 3. Long-Term Outcomes
Amiodarone dose at last follow-up, mg
248±103
Sotalol or class I arrhythmic drugs at last follow-up, n (%)
41 (15)
Continuous variables are reported as mean±SD or median (quartiles) and
categorical variables as counts and %. VT indicates ventricular tachycardia.
7 Muser et al Long-Term Outcome of VT Ablation in NIDCM
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Figure 4. Kaplan–Meier survival curves showing transplant-free
survival in the whole population (A) and stratified according to left
ventricular ejection fraction (LVEF; B) and New York Heart Association (NYHA) class (C).
severely depressed LVEF (≤35%) and persistent inducibility
of any VT at postprocedure NIPS were the only clinical factors independently related to VT recurrence after ablation; (3)
VT recurrence over follow-up was strongly associated with an
increased risk of subsequent death or transplant.
The management of recurrent VT in the setting of
NIDCM is challenging, and evidence supporting the benefit of CA mainly stems from small retrospective studies,
with discordant outcomes and arrhythmia-free survivals
ranging from 30% to 71%.1,4,7–11,15,20–22 Our findings confirm
and extend the results of the prior studies and show that
endocardial with adjuvant epicardial mapping and ablation when indicated (ie, early recurrence of VT or persistent inducibility after endocardial-only ablation) provides
good long-term outcomes, with 69% of patients having no
VT at 60-months follow-up and infrequent or isolated recurrent episodes in most of the remaining patients (Figure 5).
Moreover, arrhythmia control was achieved without requiring long-term AAD therapy with amiodarone in the majority of patients (Figure 3). The possibility to discontinue
amiodarone after CA seems particularly attractive, considering that 75 (27%) patients in our series were <50 years old
and given the risk of toxicity related to long-term exposure
to this drug.23 In addition, in a recent pooled analysis of randomized controlled trials comparing CA versus AADs, we
have shown that treatment with amiodarone was associated
with increased risk of mortality.24
Although the acute procedural end points evolved during
the 15-year period of the study, the ablation approaches were
uniform and always started with endocardial-only procedures,
reserving adjuvant epicardial mapping and ablation in patients
with VT recurrence or persistent VT inducibility after endocardial-only ablation. Of note, all of the major complications
observed in our study occurred during pericardial access or
epicardial mapping/ablation (Table 2). This finding is in line
with prior reports on endocardial–epicardial ablation and further highlights the concept that pericardial access is definitively associated with increased risks, albeit small, supporting
the notion that epicardial mapping/ablation should be reserved
for select cases and not as a first-line approach in every
patient with NIDCM.25 The occurrence of pericardial adhesions preventing future pericardial accesses, even if reduced
by the administration of intrapericardial steroids, should also
be taken into account. These considerations justify the need
for a comprehensive substrate ablation whenever pericardial
access is obtained to minimize the need for repeated epicardial
procedures.
As previously reported by our group and others, the
arrhythmic substrate in patients with NIDCM frequently
involves the basal interventricular septum.2,22,26 In our series,
the interventricular septum was identified as a source of VT
and targeted for ablation in 84 (30%) patients, and in additional 28 (10%) cases, the coronary cusp region was also targeted. Our data confirm the importance of the interventricular
septum and LV ostium region as a common site of origin of
VT in patients with nonischemic cardiomyopathy.
In line with previous reports, we found that severely
depressed LVEF and persistent VT inducibility at postprocedure
NIPS were the only independent predictors of VT recurrence
8 Muser et al Long-Term Outcome of VT Ablation in NIDCM
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ablation.6,7,27 In contrast, we found that programmed stimulation
at the end of the procedure was not associated with increased
risk of VT recurrence over follow-up. The predictive role of
programmed stimulation at the end of the ablation procedure
in patient with NIDCM has been investigated in few prior studies with conflicting results.6,7,28 Several previous reports failed
to demonstrate predictive value of noninducibility at the end
of the procedure for VT recurrence, which is consistent with
our results.28 The lack of predictive value of postprocedure programmed ventricular stimulation despite the strong association
between inducibility at NIPS and arrhythmia-free survival may
be explained by the imperfect reproducibility and probabilistic
nature of VT induction with programmed stimulation, residual
effect of AAD medications at the end of the procedure, alterations in the autonomic tone, and procedural sedation/anesthesia.
The overall transplant-free survival in our study population was of 68% at 120 months. Freedom from recurrent VT
after CA was independently associated with a significant
reduction in all-cause mortality/transplant. This observation
confirms and expands prior single-center observational studies,29–31 as well as the results of a recent multicenter VT ablation registry.20 In addition, advanced NYHA class and severely
depressed LVEF were associated with higher risk of transplant
in multivariable analysis. Although the latter 2 factors cannot be modified significantly by therapeutic interventions, the
finding of an independent association between VT recurrence
and subsequent mortality regardless of underlying comorbidities and severity of heart failure status is of particular interest
and would suggest that a more aggressive treatment with early
consideration of repeat ablation procedures to eliminate recurrent VT may translate into a mortality benefit.
Study Limitations
Figure 5. Kaplan–Meier survival curves showing survival free
from any sustained ventricular tachycardia (VT) after the last
procedure in the whole population (A) and stratified according to
left ventricular ejection fraction (LVEF; B). Catheter ablation still
resulted in a significant reduction of VT burden among patients
experiencing VT recurrence (C).
at follow-up, confirming postprocedure NIPS as an important
prognostic tool to identify patients with not only ischemic
cardiomyopathy but also NIDCM who may need additional
This was a single-center observational study summarizing a
15-year experience with CA in patients with NIDCM. The outcomes we reported reflect the experience of our tertiary referral
center and may not be generalized to lower volume Institutions
with less experience with endocardial and epicardial VT CA.
The choice for the specific ablation approach (ie, endocardialonly versus endocardial–epicardial ablation) and the additional
therapeutic strategies implemented during follow-up (including
repeat CA and continuation/discontinuation of AADs, such as
amiodarone) was not randomized, and as expected, the acute
ablation end points evolved over the multiyear study period.
However, given the single center nature of the study, the ablation
approaches and protocols adopted were uniform. In this regard,
the decision to perform endocardial–epicardial mapping and
ablation was driven by 4 criteria, namely, (1) the 12-lead ECG of
the VT suggested an epicardial origin; (2) evidence of epicardial
substrate on imaging studies (eg, magnetic resonance, intracardiac echocardiography); (3) endocardial unipolar electrogram
abnormality (<8.3 mV) in the presence of no or minimal bipolar
(<1.5 mV) electrogram abnormality; and (4) failure of endocardial ablation (VT recurrence or persistent inducibility of VT
after endocardial ablation). Patients, who underwent endocardial-only ablation, were enrolled earlier in the experience and,
as a result, also had a longer follow-up, which may potentially
act as a bias. Furthermore, the year of enrollment may also have
influenced the decision to perform epicardial ablation because
9 Muser et al Long-Term Outcome of VT Ablation in NIDCM
Table 4. Univariable and Multivariable Cox Proportional Hazards Analysis of Baseline Covariates in Relation to Outcome Events
VT Recurrence
Univariable
Death/Heart Transplant
Multivariable
HR (95% CI)
P Value
Male
1.91 (0.86–4.21)
Age
Univariable
P Value
0.111
1.60 (0.79–3.23)
0.192
1.02 (1.00–1.04)
0.111
1.02 (1.00–1.04)
0.044
Family history of
sudden cardiac death/
cardiomyopathy
1.36 (0.66–2.77)
0.402
1.13 (0.54–2.38)
0.742
Diabetes mellitus
1.21 (0.52–2.83)
0.655
2.33 (1.29–4.23)
0.73 (0.42–1.25)
0.250
1.90 (1.06–3.39)
0.030
Chronic obstructive lung
disease
1.69 (0.82–3.46)
0.153
History of atrial fibrillation
1.85 (1.07–3.19)
0.027
…
…
2.37 (1.43–3.94)
0.001
…
…
NYHA class III/IV
2.44 (1.46–4.10)
0.001
…
…
5.67 (3.40–9.45)
<0.001
2.97 (1.10–7.98)
0.031
LVEF ≤35%
3.18 (1.82–5.55)
<0.001
2.60 (1.06–6.38)
0.037
9.45 (4.51–19.83)
<0.001
4.70 (1.33–16.55)
0.016
Moderate to severe right
ventricular dysfunction
2.44 (1.33–4.48)
0.004
…
…
3.99 (2.34–6.83)
<0.001
…
…
VT storm
3.51 (2.10–5.89)
<0.001
…
…
3.95 (2.42–6.47)
<0.001
…
…
History of unexplained
syncope
0.82 (0.41–1.62)
0.564
1.29 (0.74–2.24)
0.368
Amiodarone
discontinuation at
follow-up
1.25 (0.72–2.16)
0.432
0.61 (0.38–0.99)
0.049
…
…
Beta blockers therapy
1.11 (0.60–2.08)
0.748
1.10 (0.61–1.96)
0.756
Any VT inducible at the
end of the procedure
1.75 (1.00–3.07)
0.050
…
…
1.73 (1.04–2.90)
0.036
…
…
Any VT inducible at NIPS
2.59 (1.09–6.16)
0.031
3.53 (1.42–8.80)
0.007
2.42 (0.97–6.03)
0.057
…
…
…
…
12.06 (7.17–20.29)
<0.001
12.12 (4.58–30.05)
<0.001
Chronic kidney disease
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VT recurrence
…
P Value
Multivariable
HR (95% CI)
Hypertension
HR (95% CI)
…
HR (95% CI)
P Value
…
…
0.005
…
…
1.99 (1.23–3.25)
0.006
…
…
4.51 (2.76–7.37)
<0.001
…
…
2.86 (1.58–5.18)
0.001
…
…
CI indicates confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction; NIPS, noninvasive programmed stimulation; NYHA, New York Heart
Association; and VT, ventricular tachycardia.
our threshold for proceeding with an epicardial ablation became
lower starting in year 2004 (only 20% of the epicardial ablations
were performed before 2004 in our series). Given the observational nature of the study, we could not fully assess the impact of
evolving mapping technologies, including the adoption of unipolar voltage mapping and multielectrode high-density mapping
on the outcomes. However, we did not find a significant interaction between year of enrollment and procedural outcomes (Data
Supplement). Finally, our survival analysis shown in Figure 5
is referenced to the date of the last procedure, which can only
be determined retrospectively. However, because good arrhythmia control frequently requires more than a single procedure
in patients with nonischemic cardiomyopathy and VT, it was
appropriate to establish a reference point regarding outcome that
recognized this frequent requirement.
The majority of patients have complete VT control, and
most of the remaining patients have a substantial improvement in VT burden with limited need for AADs. However,
given the significant burden of associated comorbidities
and severity of heart failure, up to one third of patients died
or required heart transplant over follow-up. Recurrent VT
was found to be independently associated with increased
risk of subsequent death/transplant. Further studies are
necessary to evaluate whether a more aggressive treatment of recurrent VT may translate into a mortality benefit in these patients.
Source of Funding
Supported by the Richard T. and Angela Clark Innovation Fund and
the F. Harlan Batrus Research Fund in Cardiac Electrophysiology.
Conclusions
Endocardial with adjuvant epicardial ablation of VT in
NIDCM provides good long-term arrhythmia-free survival.
Disclosures
None.
10 Muser et al Long-Term Outcome of VT Ablation in NIDCM
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Long-Term Outcome After Catheter Ablation of Ventricular Tachycardia in Patients
With Nonischemic Dilated Cardiomyopathy
Daniele Muser, Pasquale Santangeli, Simon A. Castro, Rajeev K. Pathak, Jackson J. Liang,
Tatsuya Hayashi, Silvia Magnani, Fermin C. Garcia, Mathew D. Hutchinson, Gregory G.
Supple, David S. Frankel, Michael P. Riley, David Lin, Robert D. Schaller, Sanjay Dixit, Erica
S. Zado, David J. Callans and Francis E. Marchlinski
Downloaded from http://circep.ahajournals.org/ by guest on May 2, 2017
Circ Arrhythm Electrophysiol. 2016;9:
doi: 10.1161/CIRCEP.116.004328
Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville
Avenue, Dallas, TX 75231
Copyright © 2016 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/9/10/e004328
Data Supplement (unedited) at:
http://circep.ahajournals.org/content/suppl/2016/10/12/CIRCEP.116.004328.DC1
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Supplemental Material
Supplemental Table 1. Long-Term Outcomes according to Baseline LVEF
LVEF>35%
LVEF≤35%
(164 patients)
(184 patients)
VT recurrence after the last procedure, n (%)
35 (21)
79 (43)
Death, n (%)
5 (3)
38 (28)
Heart transplant, n (%)
3 (2)
22 (16)
categorical variables are reported as counts and %. LVEF: left ventricular ejection fraction; VT:
ventricular tachycardia
Evolution of Ablation Outcomes Over the Years
Considering that there has been considerable evolution in mapping strategies and ablation technologies over the
16-years spam of our study, we performed an analysis evaluating the ablation outcomes before and after year
2010. In particular, a total of 167/442 (38%) procedures in 98 patients were performed before 2010, while the
remaining 275/442 (62%) procedures in 184 patients were performed between years 2010 to 2014. Following
the last procedure, 19/98 (18%) patients treated before 2010 had VT recurrence [median follow-up 64 (19-112)
months], compared to 40/184 (21%) patients treated between years 2011 and 2014 [median follow-up 46 (1957) months]. This accounted for a non-significant difference in the cumulative 60-months VT free between the
two groups (Log-rank p=0.297). Due to limitations in the manuscript word count, we included these additional
analyses in the Supplemental Material.
1