Circulation

ORIGINAL RESEARCH ARTICLE

Does Timing of Ventricular Tachycardia Ablation

Affect Prognosis in Patients With an Implantable
Cardioverter Defibrillator? Results From the
Multicenter Randomized PARTITA Trial
Paolo Della Bella , MD; Francesca Baratto, MD; Pasquale Vergara, MD PhD; Patrizia Bertocchi, MD;
Matteo Santamaria, MD PhD; Pasquale Notarstefano, MD; Leonardo Calò , MD; Daniela Orsida, MD; Luca Tomasi, MD;
Marcello Piacenti, MD; Stefano Sangiorgio, MD; Francesco Pentimalli , MD; Etienne Pruvot , MD; João De Sousa, MD;
Frederic Sacher , MD; Massimo Tritto, MD; Luca Rebellato, MD; Thomas Deneke , MD; Salvo Andrea Romano, MD;
Martina Nesti, MD; Alessio Gargaro , MSc; Daniele Giacopelli , MSc; Giovanni Peretto , MD; Andrea Radinovic, MD

BACKGROUND: Optimal timing for catheter ablation of ventricular tachycardia is an important unresolved issue. There are no
randomized trials evaluating the benefit of ablation after the first implantable cardioverter defibrillator (ICD) shock.

METHODS: We conducted a 2-phase, prospective, multicenter, randomized clinical trial. Patients with ischemic or nonischemic
dilated cardiomyopathy and primary or secondary prevention indication for ICD were enrolled in an initial observational phase
until first appropriate shock (phase A). After reconsenting, patients were randomly assigned 1:1 in phase B to immediate
ablation (within 2 months from shock delivery) or continuation of standard therapy. The primary end point was a composite
of death from any cause or hospitalization for worsening heart failure. Amiodarone intake was not allowed except for
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documented atrial tachyarrhythmias. On July 23, 2021, phase B of the trial was interrupted as a result of the first interim
analysis on the basis of the Bayesian adaptive design.
RESULTS: Of the 517 patients enrolled in phase A, 154 (30%) had ventricular tachycardia, 56 (11%) received an appropriate
shock over a median follow-up of 2.4 years (interquartile range, 1.4–4.4), and 47 of 56 (84%) agreed to participate in phase
B. After 24.2 (8.5–24.4) months, the primary end point occurred in 1 of 23 (4%) patients in the ablation group and 10 of
24 (42%) patients in the control group (hazard ratio, 0.11 [95% CI, 0.01–0.85]; P=0.034). The results met the prespecified
termination criterion of >99% Bayesian posterior probability of superiority of treatment over standard therapy. No deaths
were observed in the ablation group versus 8 deaths (33%) in the control group (P=0.004); there was 1 worsening heart
failure hospitalization in the ablation group (4%) versus 4 in the control group (17%; P=0.159). ICD shocks were less
frequent in the ablation group (9%) than in the control group (42%; P=0.039).
CONCLUSIONS: Ventricular tachycardia ablation after first appropriate shock was associated with a reduced risk of the combined
death or worsening heart failure hospitalization end point, lower mortality, and fewer ICD shocks. These findings provide
support for considering ventricular tachycardia ablation after the first ICD shock.
REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01547208.

Key Words:  catheter ablation ◼ defibrillators, implantable ◼ tachycardia, ventricular

Editorial, see p XXX

 
Correspondence to: Paolo Della Bella, MD, Department of Cardiac Electrophysiology and Arrhythmology, IRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, Italy.
Email dellabella.paolo@hsr.it
This work was presented as an abstract at the American College of Cardiology Scientific Session, April 2–4, 2022.
Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCULATIONAHA.122.059598.
For Sources of Funding and Disclosures, see page XXX.
© 2022 American Heart Association, Inc.
Circulation is available at www.ahajournals.org/journal/circ

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 Della Bella et al
Clinical Perspective
ORIGINAL RESEARCH
What Is New?
ARTICLE
• Catheter ablation performed after the first implant-
able cardioverter defibrillator shock reduced the risk
of death or worsening heart failure hospitalization.
• Antitachycardia pacing predicted the occurrence
of appropriate implantable cardioverter defibrillator
shocks.
What Are the Clinical Implications?
• Catheter ablation for ventricular tachycardia may be
considered after the first implantable cardioverter
defibrillator shock in patients with ischemic or non-
ischemic cardiomyopathy.
• Therapeutic strategies should aim at reducing the
burden of antitachycardia pacing treatments.
Nonstandard Abbreviations and Acronyms
ATP antitachycardia pacing
CRT-D cardiac resynchronization therapy
defibrillator
HF heart failure
ICD implantable cardioverter defibrillator
VF ventricular fibrillation
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VT ventricular tachycardia
C
urrent guidelines recommend ventricular tachy-
cardia (VT) ablation in patients with structural
heart disease and recurrent VT episodes causing
implantable cardioverter defibrillator (ICD) interventions.1
It is known that the occurrence of appropriate shocks has
a negative effect on quality of life and survival.2–6 Retro-
spective observational studies indicated that freedom
from VT recurrence after catheter ablation was associ-
ated with improved survival.7 Other authors found, on the
basis of retrospective data, that an earlier ablation of VT,
both in ischemic and nonischemic cardiomyopathy, is
associated with a lower rate of VT recurrence, although
a survival benefit could not be demonstrated.8,9 Random-
ized controlled trials studying the importance of timing
addressed prophylactic catheter ablation at the time of
ICD implantation in ischemic cardiomyopathy, produc-
ing discordant results in terms of reduction of VT epi-
sodes or mortality.10–13 However, deferring the timing of
ablation to an undefined future increases the risk of VT
recurrence, with probable adverse effects on the clinical
course. It remains important to define when the ablation
procedure should be performed. The PARTITA trial (Does
Timing of VT Ablation Affect Prognosis in Patients With
an Implantable Cardioverter-Defibrillator?) was designed
to verify the prognostic effect of early VT ablation after
2 xxx xxx, XXX
VT Ablation Timing: The PARTITA Trial
the first ICD shock on the end points of mortality and
worsening heart failure (HF) and to provide data on the
natural history of VT after ICD implantation, including the
identification of specific arrhythmia patterns that may
predict a subsequent shock.
METHODS
The 2-stage, multicenter, randomized controlled trial PARTITA
was performed at 16 sites: 12 in Italy and 1 each in Switzerland,
Portugal, France, and Germany. The study was approved by the
institutional review committees of the participating centers.
Patients provided written informed consent. The trial is regis-
tered with ClinicalTrials.gov (URL: https://www.clinicaltrials.
gov; Unique identifier: NCT01547208). The data that support
the findings of this study are available from the corresponding
author on reasonable request.
Phase A
Patients with ischemic or nonischemic dilated cardiomyopathy
and primary or secondary prevention indication for ICD were
enrolled in the initial observational stage (phase A). Exclusion
criteria were general contraindication to transcatheter ablation
or antithrombotic therapy or chronic treatment with class I or
class III antiarrhythmic drugs (amiodarone was only allowed to
treat atrial fibrillation). The primary end point of phase A was
the occurrence of the first appropriate ICD shock. We also
evaluated whether ICD shocks were predicted by specific
arrhythmia patterns, such as nonsustained VT or sustained VT
treated with antitachycardia pacing (ATP) therapy (successfully
or unsuccessfully).
Patients received an ICD or a cardiac resynchronization
therapy defibrillator (CRT-D) manufactured by Biotronik. The
study protocol required a uniform ICD setting for the detection
and therapy of ventricular arrhythmias (Table S1). The follow-up
was on the basis of remote monitoring. Additional in-hospital
visits were scheduled according to the standard routine at
investigational sites. All episodes of ventricular tachyarrhythmia
were collected and classified as nonsustained VT (ie, lasting
<30 seconds and without ICD therapy), sustained VT, or ven-
tricular fibrillation (VF). Patients remained in phase A until the
first VT episode caused an appropriate ICD shock or until the
end of the study.
Phase B
After reconsenting, patients who received the first shock for VT
were randomly assigned 1:1 to VT ablation (within 2 months
of the ICD shock) or continuation of standard therapy with-
out undergoing any ablation procedure until an electrical storm
episode occurred. Patients were followed for 2 years after the
randomization or until the end of the study. In phase B, amioda-
rone was only allowed as a bridge to ablation after a VT storm.
Study Procedures
To obtain 12-lead ECG of the VT, baseline programmed ven-
tricular stimulation was performed (up to 4 extrastimuli from
2 ventricular sites) before general anesthesia. Endocardial
or endoepicardial ventricular high-density electroanatomic
Circulation. XXX;145:00–00. DOI: 10.1161/CIRCULATIONAHA.122.059598
 Della Bella et al
mapping was undertaken in sinus rhythm with the CARTO 3
(Biosense Webster) or NavX Ensite (Abbott) systems. Standard
voltage criteria were used to identify scar low-voltage areas
and activation maps were constructed to identify areas of late
potentials, defined as local ventricular potentials occurring after
the terminal portion of the surface QRS, and areas of early
potentials, either fractionated (electrogram containing >4 sharp
deflections) or isolated (≥2 sharp electrograms separated by
an isoelectric segment) within the QRS. Catheter ablation was
performed preferably in sinus rhythm with standard power set-
tings (50 W) aiming at abolition of late potentials when present
or early potentials when late potentials were absent. Remaps
were done to verify the abolition of abnormal electric potentials.
Programmed ventricular stimulation was repeated attempting
to reinduce VT after completing ablation in sinus rhythm. If the
VT was still inducible and hemodynamically tolerated by the
patient, activation mapping and ablation were done to termi-
nate the ongoing VT. The aim of the ablation procedure was the
combined procedural end point of abolition of late potentials
and VT noninducibility with the complete stimulation protocol.
End Points
The primary end point of phase A was the first appropriate
shock delivered for VT. The primary end point of phase B was
a composite of death from any cause or worsening HF that led
to hospitalization. Secondary outcome measures were death
resulting from cardiac causes, recurrences of sustained VT or
VF, appropriate ICD therapy, or electrical storm.
Statistical Analysis
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The study was powered to detect a 20% absolute difference
in the primary end point rate between groups during phase
B, assuming 0.05 type I error, 0.20 type II error (80% power),
exponential time to event distributions, and 2-year event-free
rates of 84% in the ablation group14 and 64% in the control
group.3 At a bilateral log-rank test, 88 patients per study group
would have been required to reject the null hypothesis of no
difference, including 15% patients declining randomization for
any reason and 10% dropouts during phase B follow-up. With
the further assumption of 20% shock incidence at 5 years in
primary prevention patients15 and 53% shock incidence at 2
years in secondary prevention patients,16 we estimated that
at least 586 patients were needed in phase A, 176 of whom
(30%) would have been potential candidates for phase B after
experiencing a shock for VT.
During the study, data from randomized clinical trials on
safety and efficacy of prolonged VT detection in ICD program-
ming became available,17 inducing a revision of the VT detec-
tion settings recommended in our clinical investigation plan. This
contributed to a lower than expected percentage of patients
experiencing shocks for VT, leading to an unrealistic prolonga-
tion of the study. In view of that, in December 2017 the clinical
investigation plan was amended to include an adaptive design
of the randomized study stage using a Bayesian approach.18
Two interim analyses were planned in 44 and 88 patients with
full follow-up, corresponding to 25% and 50% of the projected
176 sample size for phase B. For study success at the final
analysis, at least 98% probability of ablation superiority over
standard treatment was required to control ≤2.5% type I error
rate verified by 8000 study simulations (Supplemental Material).
Circulation. XXX;145:00–00. DOI: 10.1161/CIRCULATIONAHA.122.059598
VT Ablation Timing: The PARTITA Trial
According to the Bayesian adaptive design, after any interim
analysis the trial would be stopped and study success declared
ORIGINAL RESEARCH
if the predictive probability of superiority was ≥99% (including
+1% penalty). The study would be stopped for futility if the pre-
ARTICLE
dictive probability of superiority was <5%.
The primary end point of phase B was analyzed using the
Kaplan-Meier method with the intention-to-treat approach. We
used 2-sided log-rank test and Cox proportional hazards regres-
sion models to estimate the hazard ratio and the corresponding
95% CI. Multivariable Cox analysis was performed to identify
predictors of appropriate shocks in the registry phase and to
estimate adjusted hazard ratios and CIs. Multivariable models
were first obtained with automatic forward (P≤0.1 to enter),
backward (P≥0.2 to remove), and forward/backward stepwise
procedures. Then the model with the lowest Akaike information
criterion statistics was selected. The assumption of proportional
hazards was tested in all models with Schoenfeld residuals.
Continuous variables are presented as mean (SD) or median
(interquartile range) and compared using the Mann-Whitney U
test. Categorical variables are presented by absolute and relative
frequencies and compared with the χ2 test or Fisher exact test.
The median missing data value for the baseline variables
was 2.3% (interquartile range, 1.2%–8.1%). Multiple imputation
chained equations were used with predictive mean matching (for
numeric data) and logistic regression imputation (for binary data)
under the missing-at-random assumption. Imputed datasets
were pooled thereafter for analysis. All tests were considered
significant with P<0.05. Analyses were performed with Stata/
MP 17.0 software (StataCorp LLC) and R Studio 4.0.3.
Interim Analysis
By July 2021, the number of randomized patients required for
the first planned interim analysis completed their follow-up. This
analysis showed that the predictive probability of success was
99.9% (Supplemental Material). This was more than the proto-
col-specified boundary of 99%, allowing an immediate claim of
study success (ie, superiority of immediate ablation over stan-
dard therapy). The investigators were asked to terminate study
procedures and competent ethics committees were informed.
RESULTS
Study Population
Figure 1 shows the trial profile. From September 2012
to July 2021, a total of 517 patients were enrolled at
16 sites. The median age at enrollment was 67.3±10.7
years and 449 (87%) patients were men. A total of
107 (21%) of the patients were implanted for sec-
ondary prevention and the prevalence of CRT-Ds was
24%. The most frequent cause was ischemic cardio-
myopathy (78%). Complete baseline characteristics
are reported in Table 1.
Phase A
During a median follow-up of 2.4 years (interquartile
range, 1.4–4.4), 246 (48%) patients had any VT epi-
sodes, 154 (30%) had sustained VT episodes, and 56
xxx xxx, XXX 3
 Della Bella et al
ORIGINAL RESEARCH
ARTICLE
Figure 1. Patient allocation and analysis.
Patients completing all study-related procedures were regular study terminations. ITT indicates intention-to-treat; PARTITA, Does Timing of VT
Ablation Affect Prognosis in Patients With an Implantable Cardioverter-Defibrillator?; and VT, ventricular tachycardia.
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(11%) received a first appropriate shock for VT, which
was preceded by ATP therapies in 49 of 56 (88%) pa-
tients. Among secondary prevention patients, 50% did
not have VT episodes. The shock incidence was 0.30 (CI,
0.22–0.40) per patient-month in primary prevention pa-
tients and 0.34 (CI, 0.18–0.56) per patient-month in sec-
ondary prevention patients, with an overall rate of 0.31
(CI, 0.23–0.40) per patient-month. The proportions of
patients with ventricular arrhythmias and ICD therapies
are summarized in Table 2. During phase A, there were 3
strokes, 65 worsening HF hospitalizations in 37 patients,
and 45 deaths. Fifteen deaths were cardiovascular, in-
cluding 11 from worsening HF, 21 noncardiac, and 9 of
unknown cause.
At univariable analysis (Table 3), none of the patient-
or disease-related variables listed in Table 3 predicted
appropriate shock delivery for VT (except for left ventric-
ular ejection faction <35%), whereas each ATP delivery
and successful ATP were associated with 5% and 4%
increased risk of subsequent appropriate shocks, respec-
tively. At multivariable analysis, appropriate shocks for VT
were best predicted by the cumulative number of suc-
cessful ATP and previous myocardial infarction (Table 3).
Any additional ATP successfully terminating a VT epi-
sode was independently associated with 4% increased
risk of subsequent shock (adjusted hazard ratio, 1.04 [CI,
1.02–1.06]; P<0.001). Nonsustained VT episodes were
4 xxx xxx, XXX
VT Ablation Timing: The PARTITA Trial
not significant. At Schoenfeld test, no evidence of non-
proportional hazards was obtained in survival models.
Phase B
Forty-seven patients were randomized to ablation (n=23)
or standard therapy (n=24) and were included in the in-
tention-to-treat analysis. The mean age of these patients
was 68.4±9.3 years, 81% had a previous myocardial in-
farction, and 74% had received an ICD for primary pre-
vention (Table 1). There were no significant differences
between the 2 groups, despite a trend to older age in the
ablation group (P=0.059).
At the time of the first interim analysis (median fol-
low-up, 24.2 months [interquartile range, 8.5–24.4]),
the composite primary end point of death or worsen-
ing HF hospitalization occurred in significantly fewer
patients in the ablation group as compared with stan-
dard therapy (1 patient [4%] vs 10 patients [42%]; log-
rank P=0.010). The Kaplan-Meier curves for the primary
analysis are shown in Figure 2 (hazard ratio, 0.11 [CI,
0.01–0.85]; P=0.034). The difference was also observed
after excluding noncardiac deaths (1 patient [4%] vs 6
patients [25%]; P=0.053). Five patients in the ablation
group did not undergo the procedure (patient refusal)
and 1 in the standard therapy group underwent ablation
9 months after randomization because of an electrical
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 Della Bella et al VT Ablation Timing: The PARTITA Trial

Table 1.  Patient Characteristics

ORIGINAL RESEARCH
Characteristics Overall (n=517) Randomized (n=47) Ablation (n=23) Standard therapy (n=24) P value*
Male 449 (87) 40 (85) 19 (83) 21 (88) 0.7

ARTICLE
Age, y 67.3 (10.7) 68.4 (9.3) 71.2 (8.1) 65.6 (9.6) 0.059
NYHA class 0.5
 I 95 (20) 8 (18) 3 (13) 5 (24)
 II 291 (62) 29 (66) 17 (74) 12 (57)
 III 82 (17) 7 (16) 3 (13) 4 (19)
 IV 1 (0.2) 0 (0) 0 (0) 0 (0)
LV ejection fraction, % 34.0 (9.5) 32.2 (8.6) 31.9 (9.0) 32.4 (8.3) >0.9
QRS duration, ms 120.8 (31.1) 123.6 (30.1) 126.3 (35.0) 120.9 (25.2) >0.9
Device 0.5
  Single-chamber ICD 177 (35) 13 (28) 5 (22) 8 (33)
  Dual-chamber ICD 209 (41) 19 (40) 11 (48) 8 (33)
 CRT-D 123 (24) 15 (32) 7 (30) 8 (33)
ICD indication 0.5
  Primary prevention 403 (79) 35 (74) 16 (70) 19 (79)
  Secondary prevention 107 (21) 12 (26) 7 (30) 5 (21)
Cardiomyopathy 0.5
 Ischemic 397 (78) 38 (81) 20 (87) 18 (75)
  Idiopathic dilated 114 (22) 9 (19) 3 (13) 6 (25)
Comorbidities
 Hypertension 355 (77) 32 (74) 17 (81) 15 (68) 0.3
 Diabetes 165 (36) 13 (30) 4 (19) 9 (41) 0.12
  Chronic renal failure 66 (14) 9 (21) 3 (14) 6 (27) 0.5
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 COPD 50 (11) 7 (16) 2 (9.5) 5 (23) 0.4

 Stroke/TIA 37 (8.1) 3 (7.0) 2 (9.5) 1 (4.5) 0.6
  Liver disease 28 (6.1) 3 (7.0) 1 (4.8) 2 (9.1) >0.9
  History of atrial fibrillation 144 (29) 18 (38) 9 (39) 9 (37) 0.7
Drug therapy
  ACE inhibitors 327 (67) 34 (72) 17 (74) 17 (71) 0.8
 ARB 79 (16) 8 (17) 3 (13) 5 (21) 0.7
 Aspirin 326 (67) 32 (68) 16 (70) 16 (67) 0.8

  β-blockers 423 (97) 47 (100) 23 (100) 24 (100) —

 Diuretics 381 (78) 40 (85) 20 (87) 20 (83) >0.9

 Statins 343 (70) 36 (77) 17 (74) 19 (79) 0.7
 Amiodarone 56 (13) 5 (12) 1 (5) 4 (21) 0.2

Values are mean (SD) or n (%). ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; COPD, chronic obstructive pulmonary disease;
CRT-D, cardiac resynchronization therapy defibrillator; ICD, implantable cardioverter defibrillator; LV, left ventricle; NYHA, New York Heart Association; and TIA,
transient ischemic attack.
*Wilcoxon rank sum test, Pearson χ2 test, or Fisher exact test.

storm. The results of the per protocol analysis were con-
sistent with the results of the primary analysis (Figure 2
and Table S4).
Among secondary outcomes (Table 4), the propor-
tions of patients with all-cause death (0% vs 33%;
P=0.004) and recurrent VT with shocks (9% vs 42%;
P=0.039) were significantly lower in the ablation group.
Besides a trend in reduction of cardiac deaths (0%
vs 13%; P=0.087), we did not observe significant dif-
ferences in worsening HF hospitalization rate (4% vs
17%; P=0.159), recurrences of any VT (30% vs 50%;
P=0.434), recurrences of VT successfully treated with
ATP (30% vs 46%; P=0.639), or electrical storms (0%
vs 8%; P=0.280). All patients in the control group with
a primary end point event also had VT recurrences with
device therapies. Figure 2 shows the Kaplan-Meier
curves for all-cause deaths and worsening HF hospital-
izations; Figure 3 shows VT recurrences with ICD shock.

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 Della Bella et al VT Ablation Timing: The PARTITA Trial

Table 2.  Ventricular Arrhythmias and Device Therapies Dur- days of hospitalization, 1 patient had a fatal cardiac
ing Phase A arrest outside the hospital, 3 died from noncardiac
ORIGINAL RESEARCH

Characteristics Overall (n=517) causes (2 malignant tumors [sarcoma and squamous

cell carcinoma of the skin], 1 sepsis), and 2 died from
ARTICLE

Any VT 246 (47.6)

  Nonsustained VT 145 (28.0)
an unknown cause. There were 5 worsening HF hos-
pitalizations (1 patient in the ablation group and 4 in
  Sustained VT 154 (29.8)
the control group); all patients were treated by opti-
   With no device therapy* 36 (7.0)
mizing medical therapy. No stroke events occurred in
   Treated with ATP only 62 (12.0) phase B.
   Treated with shock only 6 (1.2)
   Treated with ATP and shock 50 (9.7)
  Ventricular fibrillation 29 (5.6)
DISCUSSION
Inappropriate shock 19 (3.7) Main Study Findings
Values are n (%). ATP indicates antitachycardia pacing. The PARTITA trial is the first prospective randomized
*Ventricular tachycardia (VT) episodes in the VT1 monitor zone (<167 bpm,
study to demonstrate a benefit of catheter ablation of VT
as reported in the Supplemental Material). All these patients underwent subse-
quent implantable cardioverter defibrillator reprogramming. on the composite end point of death or worsening HF
in patients with ischemic or nonischemic cardiomyopa-
Catheter ablation was performed in 18 patients in the thy who have an implanted ICD compared with a control
ablation group. An endocardial approach was uniformly population. The benefit reported for the composite end
adopted. Nine patients had an inducible VT (median, 1 point was derived by the lower number of deaths and
[range, 1–2]), 2 of whom had a nontolerated arrhythmia. HF episodes in the ablation group. These results were
Late potential abolition was achieved in all patients and observed in both the intention-to-treat and per protocol
VT was still inducible in one. There were no procedure- analyses (Figure 1). After 24 months, 95% of the pa-
related complications among patients who underwent VT tients in the ablation arm were free of death or worsening
ablation during the study. HF, compared with 57% of patients in the control arm. In
Among patients in phase B, there were 8 deaths addition, there was a significant reduction in recurrent
in the control group (Table S3). Two of these patients VT episodes treated with shock: 9% in the ablation arm
died of heart failure during follow-up after 5 and 10 compared with 42% in the control group.
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Table 3.  Cox Proportional Hazard Models for Occurrence of Appropriate Shock on Ventricular Tachycardia

Univariable analysis Multivariable analysis*

Characteristics HR 95% CI P value HR 95% CI P value

Patient-dependent
  Age, y 1.01 0.99–1.04 0.330 — — —
 Male 0.84 0.39–1.81 0.650 — — —
 Diabetes 0.89 0.49–1.60 0.688 — — —
  Chronic renal failure 1.45 0.66–3.19 0.342 — — —
Disease-dependent
  Secondary prevention 1.14 0.61–2.11 0.683 — — —
  Previous infarction 1.70 0.89–3.28 0.107 2.40 1.19–4.82 0.014
  LV ejection fraction <35% 1.77 1.00–3.14 0.049 1.70 0.97–3.00 0.064
  QRS duration >120 ms 0.91 0.47–1.79 0.782 — — —
  Cardiac resynchronization therapy 1.53 0.85–2.74 0.153 1.79 0.99–3.21 0.052
  History of AF 1.18 0.54–2.58 0.652 — — —
Arrhythmic findings
  Number of NSVT episodes 1.00 0.99–1.01 0.612 — — —
  Number of VT episodes treated with ATP† 1.05 1.04–1.07 <0.001 — — —
  Number of VT episodes terminated with ATP 1.04 1.02–1.05 <0.001 1.04 1.02–1.06 <0.001

AF indicates atrial fibrillation; HR, hazard ratio; LV, left ventricular; and NSVT, nonsustained ventricular tachycardia.
*In the multivariable analysis, selection of model variables was on the basis of automatic stepwise procedures and Akaike information cri-
terion.
†Removed for collinearity with the number of ventricular tachycardia (VT) episodes terminated with antitachycardia pacing (ATP).

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 Della Bella et al
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Figure 2. Primary end point and its components.
A, Survival free from the primary end point—death at any time or worsening heart failure (HF)—among patients treated with catheter ablation or
standard therapy at the intention-to-treat analysis. B, Survival free from the primary end point at per protocol analysis. C, Rates of death. D, Rates
of worsening HF.
Linking VT Reduction to Enhanced Survival:
Comparison With Published Trials
Previously published randomized trials on the timing of
ablation were mainly focused on prophylactic catheter
ablation.10–13 The results were heterogenous in terms
of VT recurrences and there was no benefit in terms of
mortality. The SMASH-VT (Substrate Mapping and Abla-
tion in Sinus Rhythm to Halt Ventricular Tachycardia)10
findings supported the hypothesis that a decreased rate
of VT recurrences may have an effect on subsequent
mortality. There was a trend in the reduction of mortality
although it was not significant. Two later studies, VTACH
(Substrate Modification in Stable Ventricular Tachycar-
dia in Addition to Implantable Cardioverter Defibrillator
Therapy)11 and SMS (Substrate Modification Study),12
failed to prove a survival benefit, also because the rate
of VT recurrences was significantly higher in both arms,
compared with SMASH-VT and our own data. SMS did
not demonstrate a benefit in VT recurrence rate in the
active arm. These discordant results may be explained
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VT Ablation Timing: The PARTITA Trial
ORIGINAL RESEARCH
ARTICLE
by the different ablation strategy that did not include
substrate modification as an end point and the fact that
the ablation protocol was heterogenous, allowing varia-
tions among centers. BERLIN VT (Preventive Ablation of
Ventricular Tachycardia in Patients With Myocardial In-
farction)13 ultimately demonstrated the lack of benefit of
preventive ablation, as it was interrupted for futility when
the primary end point (all-cause death or hospitalization
for worsening HF or arrhythmia) increased sufficiently in
the prophylactic treatment arm. The reasons why prophy-
lactic catheter ablation failed to prove a net benefit were
probably multiple. One of the main explanations could be
that a truly prophylactic ablation strategy may include pa-
tients who would not have arrhythmia recurrences in the
future. From this standpoint, our study randomized to ab-
lation patients with an active arrhythmia pattern, as docu-
mented by the finding that 88% of patients had multiple
episodes of VT treated by ATP before the first shock. The
inclusion of patients with secondary prevention does not
warrant a higher rate of shock, as among 107 patients
included for secondary prevention in our series, 50% had
xxx xxx, XXX 7
 Della Bella et al VT Ablation Timing: The PARTITA Trial

Table 4.  Percentage of Patients With Secondary Outcomes Although no complications were observed in our study
and Comparison Between Ablation and Standard Therapy patients, VT ablation is a complex procedure that can be
ORIGINAL RESEARCH

Group by Log-Rank Test

associated with complications and risks. From this per-
spective, the time selection proposed in our study pro-
ARTICLE

Ablation Standard therapy

Outcomes (n=23) (n=24) P value
vides an efficient indication to treatment for patients with
All-cause death 0 (0) 8 (33.3) 0.004 an active arrhythmia pattern while avoiding potentially
Worsening HF hospitalization 1 (4.3) 4 (16.7) 0.159 unnecessary prophylactic VT ablation procedures.
Worsening HF hospitalization 1 (4.3) 6 (25.0) 0.053
or cardiac death
Cardiac death 0 (0) 3 (12.5) 0.087
Role of ICD Programming
Recurrent VT 7 (30.4) 12 (50.0) 0.434 Despite the high incidence (48%) of any ventricular ar-
rhythmia in the study population, a striking minority was
Recurrent VT with ATP 7 (30.4) 11 (45.8) 0.639
treated with an ICD shock (11%). The incidence of non-
Recurrent VT with shock 2 (8.7) 10 (41.7) 0.039
sustained VT was fairly high (28%), as a consequence
Electrical storm 0 (0) 2 (8.3) 0.280 of the long-time detection criteria that were uniformly
Values are n (%). ATP indicates antitachycardia pacing; HF, heart failure; and adopted and strictly observed on the basis of previously
VT, ventricular tachycardias. published trials.17,20 Furthermore, the extensive use of
ATP, both bursts and ramps, led to a very high number
no ventricular arrhythmias and the rate of shock was sim- of ATP therapies that successfully terminated VT epi-
ilar to that of the patients included for primary prevention. sodes without shocks. Aside from previous myocardial
In addition to the different selection criteria, other trials infarction, the only predictor of subsequent shocks was
did not always report strict ICD programming,10 or had effective ATP therapy (delivery of any ATP was omitted
drug management fluctuations,12 whereas mapping and for collinearity). Among clinical variables, we found that
ablation strategies were not uniform among centers.11,12 atrial fibrillation was not associated with VT shocks, nor
An alternative design was proposed in the VANISH were nonsustained VT episodes. The occurrence of non-
study (Ventricular Tachycardia Ablation or Escalated Drug sustained VT with long detection intervals seems to be a
Therapy),19 where patients with ischemic cardiomyopathy benign finding that does not require specific treatment.
were randomized to catheter ablation or escalated drug On the other hand, any appropriate ATP or successful
therapy after failing amiodarone treatment, showing a ATP were strong predictors of subsequent shock. It is
Downloaded from http://ahajournals.org by on May 6, 2022

significant benefit in the composite end point of death,
VT storm, or ICD shock in the ablation arm. Results were
mainly driven by a reduction in VT recurrences. This trial
targeted a population with a more advanced arrhythmia
pattern, despite similar left ventricular ejection fraction, as it
included only patients in whom antiarrhythmic drug therapy
failed, whereas in our group it was substantially banned.
estimated that every ATP intervention increased the risk
of a shock by 4%.
Clinical Implication
The PARTITA trial provides evidence that catheter abla-
tion should be considered after the first ICD shock in

Figure 3. Kaplan-Meier survival

curves of first recurrence of
ventricular tachycardia with shock.
VT indicates ventricular tachycardia.

8 xxx xxx, XXX Circulation. XXX;145:00–00. DOI: 10.1161/CIRCULATIONAHA.122.059598

 Della Bella et al
patients with ischemic and nonischemic cardiomyopa-
thy. Because the number of ATP treatments is strongly
predictive of subsequent shock treatment, future studies
may aim at the evaluation of a threshold of ATP treat-
ments that might warrant an ablation procedure.
Limitations
There was a small number of randomized patients ow-
ing to the lower-than-expected number of ICD shocks,
which did not allow us to demonstrate a benefit for all
the secondary end points. In particular, the study could
not show a net benefit on cardiac mortality induced by
reduction of arrhythmias. The study population did not
include disorders other than ischemic and nonischemic
cardiomyopathy. The rate of amiodarone therapy was
very low; however, it was prescribed in cases of atrial ar-
rhythmia, which might have affected the natural history of
VT episodes and ICD therapy. The relatively small num-
ber of catheter ablation procedures does not allow us to
draw conclusions about safety.
Conclusions
VT ablation after the first appropriate shock was associ-
ated with a reduced risk of the combined death or wors-
ening HF hospitalization end point. Catheter ablation was
also associated with lower recurrence of VT episodes
treated by shock and with lower mortality. These find-
Downloaded from http://ahajournals.org by on May 6, 2022
ings warrant further adequately powered clinical trials to
prove a net benefit of VT ablation after a first ICD shock
over alternative timings and strategies.
ARTICLE INFORMATION
Received February 11, 2022; accepted March 4, 2022.
Affiliations
Department of Cardiac Electrophysiology and Arrhythmology, San Raffaele Uni-
versity Hospital, Milan, Italy (P.D.B., F.B., P.V., G.P., A.R.). Cardiology Department,
Ospedale di Desio, Italy (P.B., S.A.R.). Cardiology Department, Ospedale Gemelli
Molise, Campobasso, Italy (M.S.). Cardiology Department, Ospedale San Donato,
Arezzo, Italy (P.N., M.N.). Cardiology Department, Policlinico Casilino, Rome, Italy
(L.C.). Cardiology Department, A.O. Sant’Antonio Abate, Gallarate, Italy (D.O.).
Cardiology Department, Azienda Ospedaliera Universitaria Integrata Verona,
Italy (L.T.). Cardiology Department, Fondazione G. Monasterio, Pisa, Italy (M.P.).
Cardiology Department, A.O. Valtellina e Valchiavenna, Sondrio, Italy (S.S.). S.S.
di Elettrofisiologia Cardiaca, S.C. di Cardiologia, Ospedale S. Paolo–Savona,
Italy (F.P.). Lausanne Hospital, Switzerland (E.P.). Cardiology Department, Santa
Maria University Hospital, Lisboa, Portugal (J.D.S.). Hôpital Cardiologique du
Haut-Lévêque, Bordeaux, France (F.S.). Istituto Clinico Humanitas Mater Domini,
Castellanza, Italy (M.T.). Azienda Sanitaria Universitaria Friuli Centrale (ASUFC),
Udine, Italy (L.R.). Herz-und Gefäss-Klinik, Bad Neustadt, Germany (T.D.). Clini-
cal Unit, Biotronik Italia, Milan, Italy (A.G., D.G.). Department of Cardiac, Thoracic,
Vascular Sciences & Public Health, University of Padova, Italy (D.G.).
Acknowledgments
The authors thank Dejan Danilovic for text revision and Gianluca Ceravolo for
assistance during the study.
Sources of Funding
Supported by unrestricted grants from Biotronik Schweiz AG and Biotronik
Italia SpA.
Circulation. XXX;145:00–00. DOI: 10.1161/CIRCULATIONAHA.122.059598
VT Ablation Timing: The PARTITA Trial
Disclosures
Dr Della Bella is a consultant for Abbott and Biosense and has received research
ORIGINAL RESEARCH
grants from Abbott, Biosense, Biotronik, and Boston Scientific. Dr Deneke re-
ceived speaker honoraria from Biotronik and Abbott and served as a consultant
ARTICLE
to Imricor, InHeart, Farapulse, and Galaxy Medical. Dr Sacher received speaking
honoraria from Biosense Webster, Abbott, Boston Scientific, Microport, and Bayer
Healthcare and is a stockholder of InHeart. A. Gargaro and D. Giacopelli are em-
ployees of Biotronik Italia. The other authors report no conflicts.
Supplemental Material
Expanded Methods
Figures S1–S3
Tables S1–S4
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