Safety and efficacy of programming a high number of antitachycardia pacing attempts for fast ventricular tachycardia: a prospective study
Safety and efficacy of programming a high number of antitachycardia pacing attempts for fast ventricular tachycardia: a prospective study
Raphae¨ l P. Martins 0
Hugues Blangy 0
Lucian Muresan 0
Luc Freysz 0
Laurent Groben 0
Pierre-Yves Zinzius 0
Je´ roˆ me Schwartz 0
Jean-Marc Sellal 0
Etienne Aliot 0
Nicolas Sadoul 0
0 CHU Nancy, Service de Cardiologie , 54511 Vandoeuvre les Nancy , France
Aims Little is known about the optimal number of antitachycardia pacing (ATP) attempts to programme in the fast ventricular tachycardia (FVT) zone. We sought to analyse the long-term efficacy and safety of programming a high number of ATP attempts for FVTs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methods All patients receiving an implantable cardioverter/defibrillator (ICD) for coronary artery disease or dilated cardiomyand results opathy for primary and secondary prevention between 2000 and 2009 were prospectively included. Implantable cardioverter/defibrillators were programmed to deliver 10 ATP attempts for FVT cycle lengths (CLs) of 250 - 300 ms (200 - 240 b.p.m.) before shock delivery (5 bursts, then 5 ramps; 8 - 10 extrastimuli at 81 - 88% FVT CL; minimal pacing CL 180 ms). Among 770 patients included and followed for 40.6 + 25.6 months, 137 (17.8%) experienced a total of 1839 FVTs, 1713 of which were ATP-terminated (unadjusted efficacy ¼ 93.1%, adjusted ¼ 81.7%), 106 ATP-accelerated (5.8%), and 20 ATP-resistant (1.1%). The majority of FVT episodes were successfully treated by one or two attempts (98.3%). However, patient-based analysis showed that 17 (12.4%), 8 (5.8%), and 5 patients (2.1%) had at least one episode treated by three or more, four or more, and five or more ATP attempts. The benefit of this strategy was reduced after five attempts. The majority of FVT episodes was asymptomatic and diagnosed at device interrogation during follow-up: syncope and pre-syncope occurred in only 0.2 and 0.4% of episodes, respectively. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion Programming a high number of ATP attempts (up to five ATP attempts) in the FVT zone is both safe and efficient and could prevent shocks in numerous ICD recipients. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Implantable cardioverter/defibrillator (ICD) is a cornerstone
therapy used in the primary or secondary prevention of sudden
cardiac death.1 The usefulness of antitachycardia pacing (ATP)
has been demonstrated in large studies: offering a painless
opportunity of terminating ventricular arrhythmias, reducing the
occurrence of defibrillation shocks and hospitalizations, improving
patients’ quality of life2 and acceptance of the device, and
improving battery life.
Programming ATP for fast ventricular tachycardia (FVT) was
initially limited for safety concerns until pioneer studies such as
PainFREE Rx3 and PainFREE Rx II4 were published. These studies
demonstrated both the safety and the efficacy of ATP for FVTs.
Further trials confirmed these initial results in patients implanted
for primary and secondary prevention for coronary artery
disease (CAD) or dilated cardiomyopathy (DCM).5 – 10 However,
in all published trials, the use of ATP was limited to mainly one
unique or rarely two ATP attempts before shock delivery. This
was explained by both the fact that most of FVTs are interrupted
by the first ATP attempt and by concerns of delaying successful
therapy in the case of ATP failure. The efficacy and safety of
programming more ATP attempts and the optimal number of attempts
to programme in the FVT zone remain unknown.
The objective of this study was to analyse if empiric ICD
programming with a high number of ATP attempts is both useful
and safe in patients with CAD or DCM, implanted for primary
or secondary prevention.
Consecutive patients with CAD and primary DCM scheduled for ICD
implantation in our institution from January 2000 to June 2009 were
included. Patients were selected for ICD implantation for primary or
secondary prevention according to the European Society of
Cardiology guidelines at the time of implantation.1,11 Each patient provided
written informed consent before enrolment.
Device implantation and programming
Market-released single-chamber, dual – chamber, and cardiac
resynchronization therapy-defibrillator (CRT-D) devices capable of
delivering ATP for FVTs were implanted (from Biotronik, Boston Scientific,
Medtronic, St Jude Medical and Sorin Group companies). Devices
were programmed to deliver 10 ATP attempts from the right
ventricular lead (including for CRT-D recipients) for ventricular arrhythmias up
to 240 b.p.m. before high-energy shock delivery (Figure 1).
Consequently, FVT cycle lengths (CLs) of 250 – 300 ms (i.e. 200 –
240 b.p.m.) were included in this zone and could benefit from ATP
Antitachycardia pacing consisted of five bursts (8 – 10 pulse bursts
pacing trains at 81 – 88% of the FVT CL), followed by five ramps (8 –
10 pulse ramp pacing trains at 85 – 91% of the FVT CL). The minimal
basic CL was programmed at 180 ms. For patients implanted with a
market-released ICD able to deliver only bursts or ramps ATP
therapies in the same zone (former models from St Jude Medical, St Paul,
Minnesota, USA), 10 bursts attempts were programmed. Detection
and redetection intervals were programmed to nominal settings. For
CL , 250 ms (i.e. .240 b.p.m.), high-energy shocks alone were
Supra-ventricular tachycardia (SVT) discriminators, defined as
stability (40 ms), sudden onset (100 ms or 12 – 15%), and morphology
(when available) algorithms, and AV relationship for dual chambers
and CRT-D devices were programmed up to 240 b.p.m.
Data collection and follow-up
Stored far-field electrograms were classified as SVT or FVT by
reviewers based on the spontaneous rhythm preceding the onset
and following the end of each episode. Only episodes with detailed
electrograms were included in the analysis. Acceleration was defined
as .10% decrease in tachycardia CL.
Two types of ventricular tachycardia (VT) terminations with ATP
have been described: the type-1 and the type-2 breaks. Type-1
breaks are characterized by a termination of VT immediately after
the last ATP pulse and are considered as ATP success. Conversely,
in the type-2 breaks, the same or a different VT persists for few
beats before spontaneous restoration of the underlying rhythm. There
is no agreement on the definition of FVT termination for type-2
breaks. Based on the results published by Wathen’s group,12 we
considered the therapy as successful if FVT lasted ,5 beats after the last
Patients were followed every 6 months as recommended by the
French health authorities13 or sooner if clinically indicated. The
characteristics of FVT episodes (rate, therapy delivered, and number of
ATP attempts necessary for the reduction or the acceleration of
FVT) occurring during follow-up were recorded for analysis.
Symptoms data were obtained by patients’ interrogation at this time. For
patients who died during the follow-up, post-mortem ICD removal
and interrogation were performed when possible.
Statistical analyses were performed using SPSS for Windows release
16.0 (SPSS Inc., Chicago, IL, USA). Continuous variables with normal
distributions were expressed as mean + SD. Categorical variables
were expressed as frequency (percentage). Exact confidence intervals
were estimated using binomial distribution. Comparison of categorical
measures was performed using the x2 tests. Survival curves were
performed using Kaplan – Meier analysis with log-rank test. To adjust for
multiple episodes per patient, the generalized estimating equations
(GEE) method was used. A value of P , 0.05 was considered
From January 2000 to June 2009, 807 patients met the inclusion
criteria and were enrolled in the study. Twelve months of
followup could not be obtained in 37 patients (4.6%) implanted in our
centre but followed in other institutions. These patients were
not included in the analysis. Clinical characteristics of the remaining
770 patients are summarized in Table 1. Most patients were on
optimal medical therapy at enrolment with 83.1% on b-blocker
and 91.2% on angiotensin-converting enzyme inhibitor or
angiotensin receptor blocker therapies. Amiodarone was prescribed in
26.0% of patients and up to one-third of patients were on
spironolactone or eplerenone.
Episodes of fast ventricular tachycardias detected
During a mean follow-up of 40.6 + 25.6 months (range ¼ 12 –
125 months), 137 patients (17.8%) experienced a total of 1839
episodes of FVTs (i.e. from 200 and 240 b.p.m.) treated by
ATP (1 – 516 episodes/patient, median ¼ 3 episodes/patient).
The mean rate of FVT episodes was 209.2 + 9.2 b.p.m.
(range ¼ 200 – 240 b.p.m.). The majority of patients (96.4%)
experienced from 1 – 20 episodes, but five patients (3.6%)
experienced a total of 1179 episodes (516, 238, 166, 130, and 129
episodes each, respectively) accounting for 64.1% of all the
Antitachycardia pacing efficacy
Out of the 1839 episodes of FVTs detected, 1713 were
successfully terminated by ATP [unadjusted efficacy ¼ 93.1%,
GEE-adjusted efficacy ¼ 81.7%; 95% confidence interval (CI),
76.2 – 86.3%]. The five patients who experienced the majority of
episodes had a high ATP efficacy (94.0 – 100%). Excluding these
five patients from the analysis led to a reduction in the unadjusted
efficacy to 83.8% with no change in the GEE-adjusted efficacy
(81.5%; 95% CI, 75.9 – 86.1%). Acceleration occurred in 106
episodes (5.8%) in 44 patients and the 10 ATP attempts were
unsuccessful in 20 episodes (1.1%) in 10 patients. All
unsuccessfully treated or ATP-accelerated FVTs were successfully
terminated by back-up programmed high-energy shocks.
Antitachycardia pacing efficacy in the different subsets of patients is
given in Table 2.
Successfully treated episodes had a slower rate compared with
ATP-accelerated episodes (209.1 + 8.8 vs. 212.3 + 13.5 b.p.m.,
P ¼ 0.02). Antitachycardia pacing efficacy was similar for FVT
rates ranging from 200 to 230 b.p.m. and significantly lower for
FVT rates between 230 and 240 b.p.m. (Figure 2).
Number of antitachycardia pacing attempts required to interrupt fast ventricular tachycardias
The vast majority of ATP-interrupted FVT episodes (1629 out of
1713 FVTs ¼ 95.1%) required one ATP attempt for termination.
Only 54 (3.2%) and 30 (1.7%) episodes needed two and from
three to nine ATP attempts for termination, respectively
(Figure 3). None of the terminated episodes required the delivery
of the 10 ATP attempts. The efficacies of the first and second ATP
attempts were 88.5 and 40.9%, respectively. The global efficacies of
the 3rd to 5th and 6th to 10th attempts were 35.9 and 22.6%,
respectively. The average number of ATP attempts required to
successfully terminate FVTs was 1.1 + 0.6 (Figure 3). For the five
patients who experienced the majority of FVT episodes (n ¼
1179), FVTs were successfully interrupted by only one
(n ¼ 1173) or two attempts (n ¼ 6).
Accelerated episodes occurred mainly after the first (67.9%) or
the second ATP attempt (18.9%) whereas subsequent ATP
3 – 10
) were less responsible for FVT acceleration
(13.2%). An average of 1.7 + 1.5 ATP attempts were delivered
for accelerated FVT episodes (Figure 3).
Although the vast majority of FVT episodes were successfully
interrupted by the first or the second ATP attempts, a large
number of patients had at least one episode treated by three or
more ATP attempts. In a patient-based analysis, 43 (31.4% of
patients; 95% CI, 23.7 – 39.9%), 17 (12.4% of patients; 95% CI,
7.4 – 19.1%), 8 (5.8% of patients; 95% CI, 2.6 – 11.2%), and 5
patients (3.6% of patients; 95% CI, 1.2 – 8.3%) had at least one
FVT episode treated by two or more, three or more, four or
more, and five or more ATP attempts, respectively. These patients
would have received at least one shock with a conventional ICD
programming. Thus, during follow-up, 84 shocks were avoided in
43 patients as compared with programming using one ATP
attempt for FVTs and 30 shocks were avoided in 17 patients as
compared with programming using two ATP attempts, respectively.
The benefit of programming numerous ATP attempts was lower
above five attempts.
Characteristics of patients with three or more antitachycardia pacing attempts
Seventeen patients (12.4% of FVT patients) had at least one
episode treated by three to nine ATP attempts. A comparison of
baseline characteristics between patients always treated by 1 – 2
ATP attempts and those treated at least once by three or more
ATP attempts showed no differences in terms of age at
implantation (62.8 + 11.7 vs. 67.4 + 13.3, P ¼ 0.147), indication for
implantation (secondary: 73.3 vs. 88.2%, P ¼ 0.153), heart disease
aetiology (CAD, 69.5 vs. 70.5%, P ¼ 0.588), left ventricular ejection
fraction (LVEF, 32.1 + 9.6 vs. 34.5 + 8.7%, P ¼ 0.335), and mean
FVT rates (209.3 + 9.0 vs. 208.6 + 10.1 b.p.m., P ¼ 0.390).
Safety of antitachycardia pacing programming
The vast majority of FVT episodes was asymptomatic and
diagnosed at device interrogation during routine follow-up. Twelve
of the 1839 episodes (0.6%, eight patients) were symptomatic.
Four patients experienced lightheadedness or pre-syncope (eight
episodes, 0.4%) whereas four other patients experienced
syncope (four episodes, 0.2%). All but three symptomatic episodes
were treated by only one ATP attempt: two symptomatic episodes
were treated by the two ATP attempts whereas the last
symptomatic episode was treated by six ATP attempts.
The mortality rate during follow-up was 26.5%, mainly due to
non-arrhythmic cardiac deaths (Table 3). The arrhythmic mortality
accounted for 11.8% of all the deaths, which were related to
electrical storms due to incessant ventricular fibrillation (VF). No death
could be reported due to ATP failure since all unsuccessfully paced
FVTs were successfully interrupted by shock (see the paragraph on
ATP efficacy). Only five patients (2.4%) died from an unknown
cause. The mortality assessed by Kaplan – Meier analysis (Figure 4)
was similar in patients receiving one or two ATP attempts and
those treated at least once by more than two ATP attempts
(log-rank P ¼ 0.211).
To our knowledge, this is the first prospective study to
demonstrate that empirical programming of a large number of ATP
attempts is both safe and effective in terminating FVT episodes in
a large unselected population with CAD and DCM implanted for
primary and secondary prevention of sudden cardiac death. The
Figure 4 Survival curves in patients treated by only one or two
antitachycardia pacing attempts or at least once by three
antitachycardia pacing attempts. The mortality assessed by Kaplan –
Meier analysis was similar between patients using only one or
two antitachycardia pacing attempts and those using at least
once three or more attempts (log-rank P ¼ 0211).
adjusted efficacy of ATP was 81.7%, with a very low incidence of
pre-syncope or syncope. One interesting finding in this study
was that programming more than the usual one or two ATP
attempts in the FVT zone avoided the occurrence of 84 shocks
in 43 patients (31.4%) and 30 shocks in 17 patients (12.4%),
Antitachycardia pacing programming for the fast ventricular tachycardia zone
It is well established that ATP has a negligible battery drain, reduces
shocks delivery, and improves quality of life and hence acceptance
of the device.4,14 Since the publication of the pilots studies
PainFREE Rx3 and PainFREE Rx II,4 several trials have analysed the
safety and efficacy of ATP for FVTs,5 – 10 with a maximal unadjusted
efficacy up to 89%.7 However, ATP was used carefully in these
studies. Only one ATP attempt was used in the FVT zone in
PainFREE Rx II,4 PITAGORA ICD,6 AVANCE-D,9 and ADVANCE
CRT-D10 trials. Two attempts were used in PainFREE Rx,3
PROVE,8 Jimenez-Candil et al.,7 and Grimm et al.5 studies. This
attitude was related to concerns regarding (i) the haemodynamic
tolerance of FVT episodes and (ii) the risk of delaying the lifesaving
shock in the case of ATP failure. These concerns led to
incorporate in recent ICDs the capability to deliver ATP before or during
charging in order to prevent shock delay.15,16 However, this new
feature allows the delivery of only one or sometimes two ATP
attempts. There are no guidelines about optimal ICD
programming, but based on previously reported trials and some authors
recommendations,15,17 – 19 physicians empirically programme up
to a maximum of two ATP attempts in the FVT zone or
highenergy shock with ATP during capacitor charging.
Thus, the benefits and potential risks of programming many ATP
attempts are unknown. Only a retrospective small-size study
including 24 patients reported the efficacy of six ATP attempts in
a zone ranging from 140 to 220 b.p.m. One to three ATP attempts
reduced the majority of FVTs, and very few patients had episodes
requiring four or more ATP attempts. However, mean rate was
low (168 + 22 b.p.m.) and these results cannot be extrapolated
How many attempts to programme?
In this study, the majority of episodes were interrupted by the first
or the second ATP attempt. Since only 1.8% of episodes were
interrupted by 3 – 9 attempts, one can argue that programming
more than two ATP attempts is not necessary. This is true in an
episode-based analysis, but not in a patient-based analysis.
Indeed, a high proportion of patients had at least one episode
treated by three or more ATP attempts, and would have
experienced painful shocks even with modern ICD programming. In
comparison with PainFREE Rx,3 Jimenez-Candil et al.,7 and PROVE8
trials which programmed two ATP attempts, our programming
parameters avoided 30 shocks in 17 patients (12.4%) during
overall follow-up (Figure 5). The benefit of this strategy appeared
to be less in the case of more than five attempts.
The benefit of programming more than two ATP attempts may
be related to (i) pacing at faster CL (since after each failed ATP
attempt, pacing CL decreased by 10 ms) which can improve
circuit penetration both anterogradely and retrogradely, and FVT
termination;14 and (ii) programming a high number of ATP
attempts delays back-up high-energy shock in the case of ATP
failure; thus, some long-lasting non-sustained FVT episodes may
spontaneously terminate before shock delivery.
In this study, there was a very low incidence of symptoms (0.6%).
This incidence is similar to those reported in previously published
studies, i.e. 2 and 0.7% in PainFree Rx I3 and II,4 respectively, 1.7
and 1.1% in ADVANCE-D9 and ADVANCE CRT-D10 trials,
respectively, or 0.97% in PITAGORA ICD trial.6 Programming a
high number of ATP attempts does not seem to increase the
risk of symptoms since all, but one, symptomatic episodes were
treated by the first or the second ATP attempt. All ATP-resistant
or -accelerated episodes were terminated by ICD shock.
The 26.5% mortality rate during the follow-up was similar to
other clinical studies.21,22 No deaths were related to the study
programming and only five patients (2.4%) died from unknown
cause. Although one can argue that these deaths could be
related to the large number of ATP attempts programmed, one
should keep in mind that this rate is similar to those reported in
clinical trials in ICD recipients for secondary23 or primary
This study is a single-centre evaluation of ATP for FVTs. However,
our population is similar, in age, sex, and LVEF, to the other
populations of the main studies that evaluated ATP for the treatment of
Another limitation is the lack of control group with the usual
one or two ATP attempts programmed.
We also used a variable ATP scheme in the FVT zone: each
attempt was composed by 8 – 10 pulse bursts pacing trains at
81 – 88% of the FVT CL, or 8 – 10 pulse ramp pacing trains at
85 – 91% of the FVT CL. This is related to the enrolment of
patients implanted with any market-released ICDs, each having
specific ATP parameters. This limitation can be conversely
considered as a strong point, as this represents ATP programming in ‘real
life’. Furthermore, only a limited number of episodes were treated
or accelerated by 6 – 10 ATP attempts (11 among 1839 episodes,
0.59% of episodes), limiting the bias of using ramp pacing trains
from the 6th to the 10th attempt. Furthermore, as described in
Figure 1, only two zones were programmed, i.e. one VT zone
and one VF zone (FVTs were detected in the VT zone
programmed up to 240 b.p.m. and not in a ‘FVT via VF’ zone). Thus,
detection and redetection settings were different from those
programmed in PainFREE Rx studies.
As reported in the PREPARE study, some FVT episodes could
have been non-sustained and self-terminated if not treated by
ATP, possibly overestimating the ATP success rate.
The majority of FVT episodes (1179 out of 1839 episodes)
occurred in only five patients. This affects the unadjusted efficacy but
not the GEE-adjusted efficacy of ATP, as demonstrated by the
similar adjusted efficacy (81.5 vs. 81.7%) found in our study
when these five patients are not included in the analysis.
In this study, a low incidence of symptomatic FVT episodes was
found (0.6%). Symptoms data were obtained by patients’
interrogation during routine ICD follow-up every 6 months. Although
patients were systematically asked about syncopal or pre-syncopal
episodes, the real incidence of symptomatic FVT episodes is
To our knowledge, this is the first large-scale study evaluating the
long-term follow-up safety and efficacy of programming a high
number of ATP attempts. The main implication of this study is
that in CAD or DCM patients implanted with an ICD for
primary or secondary prevention, programming more than one or
two ATP attempts is both safe and efficient in terminating a large
number of life-threatening FVT episodes thus avoiding painful
shocks. Since only few patients did benefit from 6 to 10 attempts,
programming 10 attempts is probably not necessary. However,
programming up to five attempts could be a reasonable
compromise between ATP efficacy and therapy safety. One of the main
benefits of this strategy is that this easy programming can be used in all
This strategy, in addition to lessons learned from the PREPARE
study24 (associating increased tachycardia detection rate and
increased number of intervals to detect, SVT discriminators, and
high-energy first shock) and from computer modelling,25 could
reduce shock incidence and ICD-associated co-morbidities.
The impact of programming a high number of ATP attempts in
the case of erroneous SVT detection leading to inappropriate
therapy is unknown and has not been evaluated in this study.
Programming a high number of ATP attempts could probably allow
SVT to terminate spontaneously but also SVT detection algorithm
to operate in fast rate since SVT discriminators were programmed
up to 240 b.p.m.
This study suggests that programming a high number of ATP
attempts (up to five ATP attempts) is useful and prevents
numerous painful shocks for FVTs in ICD recipients implanted in primary
and secondary prevention of sudden cardiac death in CAD and
DCM. This strategy is also safe with a very low incidence of
rhythm accelerations, pre-syncope, or syncope.
Conflict of interest: None declared.
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