1
Introduction
Implantable cardioverter-defibrillator (ICD) therapy is clearly an effective therapy
for selected patients in definable populations. The benefits and risks of ICD therapy
are directly impacted by programming and surgical decisions. This flexibility is both
a great strength and a weakness, for which there has been no prior official discussion
or guidance. It is the consensus of the 4 continental electrophysiology societies
that there are 4 important clinical issues for which there are sufficient ICD clinical
and trial data to provide evidence-based expert guidance. This document systematically
describes the greater than 80% (83%–100%, mean 96%) required consensus achieved for
each recommendation by official balloting in regard to the programming of (1) bradycardia
mode and rate, (2) tachycardia detection, (3) tachycardia therapy, and (4) the intraprocedural
testing of defibrillation efficacy. Representatives nominated by the Heart Rhythm
Society (HRS), European Heart Rhythm Association (EHRA), Asian Pacific Heart Rhythm
Society (APHRS), and the Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia
(SOLAECE-Latin American Society of Cardiac Pacing and Electrophysiology) participated
in the project definition, the literature review, the recommendation development,
the writing of the document, and its approval. The 32 recommendations were balloted
by the 35 writing committee members and were approved by an average of 96%.
The classification of the recommendations and the level of evidence follow the recently
updated ACC/AHA standard [1], [2]. Class I is a strong recommendation, denoting a
benefit greatly exceeding risk. Class IIa is a somewhat weaker recommendation, with
a benefit probably exceeding risk, and Class IIb denotes a benefit equivalent to or
possibly exceeding risk. Class III is a recommendation against a specific treatment
because either there is no net benefit or there is net harm. Level of Evidence A denotes
the highest level of evidence from more than 1 high-quality randomized clinical trial
(RCT), a meta-analysis of high-quality RCTs, or RCTs corroborated by high-quality
registry studies. Level of evidence B indicates moderate-quality evidence from either
RCTs with a meta-analysis (B-R) or well-executed nonrandomized trials with a meta-analysis
(B-NR). Level of evidence C indicates randomized or nonrandomized observational or
registry studies with limited data (C-LD) or from expert opinions (C-EO) based on
clinical experience in the absence of credible published evidence. These recommendations
were also subject to a 1-month public comment period. Each society then officially
reviewed, commented, edited, and endorsed the final document and recommendations.
All author and peer reviewer disclosure information is provided in Appendix A.
The care of individual patients must be provided in context of their specific clinical
condition and the data available on that patient. Although the recommendations in
this document provide guidance for a strategic approach to ICD programming, as an
individual patient’s condition changes or progresses and additional clinical considerations
become apparent, the programming of their ICDs must reflect those changes. Remote
and in-person interrogations of the ICD and clinical monitoring must continue to inform
the programming choices made for each patient. The recommendations in this document
specifically target adult patients and might not be applicable to pediatric patients,
particularly when programming rate criteria.
Please consider that each ICD has specific programmable options that might not be
specifically addressed by the 32 distinctive recommendations in this document. Appendix
B, published online (http://www.hrsonline.org/appendix-b), contains the writing committee’s
translations specific to each manufacturer and is intended to best approximate the
recommended behaviors for each available ICD model.
2
Bradycardia Mode and Rate Programming
2.1
Single- or Dual-Chamber Pacing Mode
2.1.1
Evidence
Because the ICD is primarily indicated for tachycardia therapy, there might be some
uncertainty regarding optimal bradycardia management for ICD patients. Data from clinical
studies adequately address only the programmed mode rather than the number of leads
implanted, the number of chambers stimulated, or how frequently the patients required
bradycardia support. It is of note that most information on pacing modes has been
collected from pacemaker patients, and these patients are clinically distinct from
ICD recipients. Dual-chamber pacing (atrial and ventricular) has been compared with
single-chamber pacing (atrial or ventricular) in patients with bradycardia in 5 multicenter,
parallel, randomized trials, in 1 meta-analysis of randomized trials, and in 1 systematic
review that also included 30 randomized crossover comparisons and 4 economic analyses
[3], [4], [5], [6], [7], [8], [9]. Meta analyses comparing dual- chamber to single-chamber
ICDs did not evaluate pacing modes [10], [11]. Compared with single-chamber pacing,
dual- chamber pacing results in small but potentially significant benefits in patients
with sinus node disease and/or atrioventricular block. No difference in mortality
has been observed between ventricular pacing modes and dual-chamber pacing modes.
Dual-chamber pacing was associated with a lower rate of atrial fibrillation (AF) and
stroke [12]. The benefit in terms of AF prevention was more marked in trials comprised
of patients with sinus node disease. Although trends in favor of dual-chamber pacing
have been observed in some trials, there was no benefit in terms of heart failure
(HF). In patients without symptomatic bradycardia, however, the Dual Chamber and VVI
Implantable Defibrillator (DAVID) trial in ICD recipients showed that one specific
choice of dual-chamber rate-responsive (DDDR) programming parameters led to poorer
outcomes than VVI backup pacing, most likely secondary to unnecessary right ventricular
(RV) pacing. The fact that RV stimulation was responsible was reinforced in the DAVID
II trial, in which AAI pacing was demonstrated to be noninferior to VVI backup pacing
[13].
Approximately a quarter of patients with either sinus node disease or atrioventricular
block develop “pacemaker syndrome” with VVI pacing usually associated with retrograde
(ventricular to atrial) conduction, which in turn is associated with a reduction in
the quality of life [14]. In crossover trials, symptoms of pacemaker syndrome (dyspnea,
dizziness, palpitations, pulsations, and chest pain) were reduced by reprogramming
to a dual-chamber mode [14]. Dual-chamber pacing is associated with better exercise
performance compared with single-chamber VVI pacing without rate adaptation, but produces
similar exercise performance when compared with rate-responsive VVIR pacing. Because
of the additional lead, dual-chamber devices involve longer implantation times, have
a higher risk of complications, and are more expensive. However, because of the additional
clinical consequences of pacemaker syndrome and AF (and its sequelae), the overall
cost difference between single- and dual-pacing systems is moderated.
In patients with persistent sinus bradycardia, atrial rather than ventricular dual-chamber
pacing is the pacing mode of choice. There is evidence for superiority of atrial-based
pacing over ventricular pacing for patients who require pacing for a significant proportion
of the day. The evidence is stronger for patients with sinus node disease, in whom
dual-chamber pacing confers a modest reduction in AF and stroke, but not in hospitalization
for HF or death compared with ventricular pacing. In patients with acquired atrioventricular
block, large randomized parallel trials were unable to demonstrate the superiority
of dual-chamber pacing over ventricular pacing with regard to hard clinical endpoints
of mortality and morbidity [4], [6], [7], [8]. The benefit of dual-chamber over ventricular
pacing is primarily due to the avoidance of pacemaker syndrome and to improved exercise
capacity [14]. Even if it is a softer endpoint, pacemaker syndrome is associated with
a reduction in quality of life that justifies the preference for dual-chamber pacing
when reasonable; thus, there is strong evidence for the superiority of dual-chamber
pacing over ventricular pacing that is limited to symptom improvement. Conversely,
there is strong evidence of nonsuperiority with regard to survival and morbidity.
The net result is that the indications for programming the dual- chamber modes are
weaker and the choice regarding the pacing mode should be individualized, taking into
consideration the increased complication risk and costs of dual- chamber devices.
Because ICD patients usually do not require bradycardia support, with the exception
of patients who require cardiac resynchronization, programming choices should avoid
pacing and in particular avoid single ventricular pacing, if possible [15], [16].
3
Programming of Rate Modulation
The benefit of rate response programming has been evaluated in patients with bradycardia
in 5 multicenter, randomized trials and in 1 systematic review that also included
7 single-center studies [17], [18], [19], [20], [21], [22]. Most of these data were
obtained from pacemaker studies and must be interpreted in that light.
Although there is evidence of the superiority of VVIR pacing compared with VVI pacing
in improving quality of life and exercise capacity, improvements in exercise capacity
with DDDR compared with DDD have been inconsistent. In 2 small studies on patients
with chronotropic incompetence comparing DDD and DDDR pacing, the latter had improved
quality of life and exercise capacity; however, a larger, multicenter randomized trial
(Advanced Elements of Pacing Randomized Controlled Trial [ADEPT]) failed to show a
difference in patients with a modest blunted heart rate response to exercise [17],
[18], [19]. In addition, DDDR programming in cardiac resynchronization therapy (CRT)
patients has the potential to impair AV synchrony and timing. It should be noted that
trials evaluating CRT generally did not use rate- responsive pacing, and many in fact
avoided atrial stimulation using atrial sensed and ventricular paced pacing modes
with a lower base rate. However, the Pacing Evaluation- Atrial Support Study in Cardiac
Resynchronization Therapy (PEGASUS CRT) trial is the exception and did not demonstrate
adverse impact on mortality and HF events [23].
4
Sinus Node Disease
In patients with persistent or intermittent sinus node dysfunction or chronotropic
incompetence, the first choice is DDDR with algorithms responding to intermittent
atrioventricular conduction. There is sufficient evidence for the superiority of VVIR
compared with VVI in improving quality of life and exercise capacity. The evidence
is much weaker in dual-chamber pacing (DDDR vs DDD).
Although only an issue when there is some concomitant AV block, the upper rate limit
should be programmed higher than the fastest spontaneous sinus rhythm to avoid upper
rate limit behavior. To avoid symptomatic bradycardia, the lower rate should be programmed
on an individual basis, according to the clinical characteristics and the underlying
cardiac substrate of the patient.
5
Atrial Fibrillation and Atrioventricular Block
Patients with permanent AF and either spontaneous or AV junctional ablation-induced
high-degree atrioventricular block have little to no chronotropic response to exercise;
thus, VVIR pacing is associated with better exercise performance, improved daily activities,
improved quality of life, and decreased symptoms of shortness of breath, chest pain,
and heart palpitations, compared with VVI [20], [21], [22], [24], [25], [26]. Therefore,
rate-adaptive pacing is the first choice of pacing mode; fixed-rate VVI pacing should
be abandoned in patients with permanent AF and atrioventricular block. It is the experts’
opinion that the minimum rate can be programmed higher (e. g., 70 bpm) than for sinus
rhythm patients, in an attempt to compensate for the loss of active atrial filling.
In addition, the maximum sensor rate should be programmed restrictively (e. g., 110–120 bpm)
to avoid “overpacing” (i.e., pacing with a heart rate faster than necessary), which
can be symptomatic, particularly in patients with coronary artery disease. In a small
study, however, it was found that rate-responsive pacing could be safe and effective
in patients with angina pectoris, without an increase in subjective or objective signs
of ischemia [25]. The lower rate should be programmed on an individual basis, according
to the clinical characteristics and the underlying cardiac substrate of the patient.
The clinical benefit of programming a lower resting rate at night based on internal
clocks has not been evaluated in ICD patients. There is some concern that atrioventricular
junction ablation and permanent ventricular pacing might predispose the patient to
an increased risk of sudden cardiac death (SCD) related to a bradycardia-dependent
prolongation of the QT interval. This risk might be overcome by setting the ventricular
pacing rate to a minimum of 80 or 90 bpm for the first 1-2 months following the atrioventricular
junction ablation, then reducing it to a conventional 60–70 bpm [27], [28]. Not all
patients with AF and milder forms of atrioventricular block will require a high percentage
of ventricular pacing or have a wide QRS. Physicians should consider the risk of increasing
preexisting left ventricular (LV) dysfunction with RV pacing vs improved chronotropic
responsiveness and the potential value of CRT.
6
Intact Atrioventricular Conduction
6.1
Right Ventricular Pacing
The results of a number of large-scale, prospective randomized trials demonstrated
a significant reduction in AF in pacemaker patients with atrial-based pacing (AAI
or DDD) compared with patients with ventricular-based pacing [4], [8], [29]. In the
Mode Selection Trial, which enrolled 2010 patients with sick sinus syndrome, the risk
of AF increased linearly with the increasing percentage of RV pacing [30]. At the
same time, deleterious effects of RV pacing in patients with LV dysfunction (left
ventricular ejection fraction [LVEF] ≤40%) implanted with dual-chamber ICD systems
were observed in the Dual Chamber and VVI Implantable Defibrillator (DAVID) trial,
which included 506 ICD patients without indications for bradycardia pacing. Patients
within the DDDR-70 group (with paced and sensed atrioventricular delays of 170 and
150 ms, respectively, in most of the DDDR group patients) showed a trend toward higher
mortality and an increased incidence of HF compared with the patients programmed to
ventricular backup pacing—the VVI-40 group. Within the DDDR-70 group, there were more
cardiac events when the percentage of ventricular pacing exceeded 40% (P=.09) compared
with patients with 95% RV stimulation (DDDR-70) or [31], [32] However, a more detailed
post hoc analysis of the Inhibition of Unnecessary RV Pacing With Atrial-Ventricular
Search Hysteresis in ICDs (INTRINSIC RV) trial revealed that the most favorable clinical
results were not in the VVI groups with the least percentage of RV pacing but in the
subgroup that had DDD pacing with longer atrioventricular delays and 11%–19% of ventricular
pacing. This parameter selection probably helped patients to avoid exceedingly low
heart rates while preserving intrinsic atrioventricular conduction most of the time
[31], [33]. In the Second Multicenter Automated Defibrillator Implantation Trial (MADIT
II), a higher risk of HF was observed in patients who had a greater than 50% burden
of RV pacing [34]. In another large observational study of 456 ICD patients without
HF at baseline, a high RV pacing burden (RV pacing more than 50% of the time) was
associated with an increased risk of HF events and appropriate ICD shocks [35]. Optimally,
RV stimulation should be avoided, but the precise tradeoff between the percentage
of ventricular pacing and atrioventricular timing is unclear in non-CRT patients.
7
Non-CRT Devices: Algorithms to Reduce Right Ventricular Stimulation
The importance of reducing or avoiding RV pacing in ICD patients with LV dysfunction
was illustrated in the DAVID trial [31]. The feasibility of algorithms designed to
decrease the burden of unnecessary ventricular pacing has been demonstrated in patients
with dual-chamber pacemakers [36], [37], [38]. These algorithms usually provide functional
AAI pacing with monitoring of atrioventricular conduction and an automatic mode switch
from AAI to DDD during episodes of atrioventricular block. Some studies directly compared
various algorithms to decrease ventricular pacing, showing that a “managed ventricular
pacing” (MVP) algorithm resulted in greater ventricular pacing reduction than an “atrioventricular
search” algorithm [39], [40]: however, no randomized studies comparing these two algorithms
with respect to important cardiovascular endpoints (e.g., HF, cardiac death) have
been performed. The results of the studies on these pacing algorithms are summarized
in Table 1.
Unnecessary RV pacing should be minimized by using specific algorithms or programming
longer atrioventricular delays, and this process is more important for patients with
a higher risk of AF or who already have poorer LV function [49]. Patients with longer
baseline PR intervals have a higher risk of AF regardless of the percentage of ventricular
pacing or the length of the programmed atrioventricular interval [50]. Use of the
AAIR pacing mode with exceedingly long atrioventricular conduction times can lead
to “AAIR pacemaker syndrome” and actually increases the risk of AF compared with the
DDDR mode, as was shown in the Danish Multicenter Randomized Trial on Single Lead
Atrial versus Dual-Chamber Pacing in Sick Sinus Syndrome (DANPACE) [3], [51]. Therefore,
excessively long atrioventricular delays resulting in nonphysiologic atrioventricular
contraction patterns should be avoided. The potential harm of atrial pacing with a
prolonged atrioventricular delay was also demonstrated in the MVP trial. In the MVP
trial, dual- chamber pacing with the MVP algorithm was not superior to ventricular
backup pacing (VVI 40 bpm) with respect to HF events. After a follow-up of 2.4 years,
there was an apparent increase in HF events that was limited primarily to patients
with a baseline PR interval of >230 ms (mean PR of 255– 260 ms) [42]. Long atrioventricular
intervals also predispose the patient to repetitive atrioventricular reentrant rhythms,
“repetitive nonreentrant VA synchrony,” or “atrioventricular desynchronization arrhythmia,”
which manifest as mode switching but which also cause sustained episodes with poor
hemodynamics [52]. Thus, based on the available data, it appears that atrial pacing
with excessively long atrioventricular delays should be avoided.
Algorithms that minimize ventricular pacing sometimes lead to inadvertent bradycardia
or spontaneous premature, beat-related short-long-short RR interval sequences with
proarrhythmic potential [53], [54], [55]. However, in a study retrospectively analyzing
the onset of ventricular tachycardia (VT) in ICD patients, the MVP mode was less frequently
associated with the onset of VT compared with the DDD and VVI modes [54]. Atrioventricular
decoupling (greater than 40% of atrioventricular intervals exceeding 300 ms) was observed
in 14% of the ICD patients in the Marquis ICD MVP study, which might have a negative
effect on ventricular filling [56].
In ICD patients with structural heart disease, spontaneous atrioventricular conduction
can become prolonged instead of shortening, with increased atrial paced heart rates
[33]. This outcome frequently leads to a higher percentage of ventricular paced complexes.
In view of the results of the ADEPT trial, which failed to demonstrate the clinical
superiority of combined rate modulation and DDD pacing, the need for and aggressiveness
of sensor-driven rate responses should be individualized or eliminated [19]. Rate-dependent
shortening of atrioventricular delay could have the same effect and should usually
be avoided.
Patients with hypertrophic cardiomyopathy represent a small but intricate subset of
the ICD population for whom pacing has not been demonstrated to be a consistently
effective treatment for outflow tract obstruction. However, according to the 2011
ACCF/AHA Hypertrophic Cardiomyopathy Guideline, dual-chamber ICDs are reasonable for
patients with resting LV outflow tract gradients more than 50 mm Hg, and who have
indications for ICD implantation to reduce mortality [57]. In these patients, atrioventricular
delays should be individually programmed to be short enough to achieve RV preexcitation
and decrease LV outflow tract gradient, but not too short, which would impair LV filling;
usually in the ranges of 60–150 ms [58], [59]. There are few studies of pacing modes
in these patients, and they are limited by small numbers and the failure to quantify
important cardiac outcomes.
In conclusion, atrioventricular interval programming and choosing between DDDR and
MVP or other atrioventricular interval management modes should be performed on an
individual basis. The goal is to minimize the percentage of RV pacing and to avoid
atrial-based pacing with atrioventricular intervals exceeding 250–300 ms leading to
atrioventricular uncoupling. In patients with prolonged PR intervals and impaired
LV function, biventricular pacing can be considered.
8
Cardiac Resynchronization Therapy: Consistent Delivery of Ventricular Pacing
CRT in combination with a defibrillator device (CRT-D) improves survival and cardiac
function in patients with LV systolic dysfunction, prolonged QRS duration, and mild-to-
severe HF [60], [61], [62]. The beneficial effect of CRT-D compared with ICD is likely
to be derived from biventricular pacing, with a decrease in dyssynchrony and an improvement
in cardiac function. The percentage of biventricular pacing capture in the ventricles
can be negatively influenced by a number of factors, including atrial tachyarrhythmias,
premature ventricular complexes, and programming of the atrioventricular delay, giving
way to the intrinsic conduction of the patient and a reduced percentage of biventricular
pacing. Some large observational studies have investigated the optimal level of biventricular
pacing percentage and found a higher percentage to be associated with more pronounced
CRT benefits. An optimal CRT benefit was observed with a biventricular pacing percentage
as close to 100% as possible [63], [64], [65], [66].
In the analysis of the left bundle branch block population in the MADIT-CRT trial,
those patients with less than 90% biventricular pacing had similar rates of HF and
death compared with the patients randomized to no CRT. By contrast, biventricular
pacing exceeding 90% was associated with a benefit of CRT-D in terms of HF or death
when compared with ICD patients and no CRT. Biventricular pacing 97% and greater was
associated with a further reduction in HF or death and a significant reduction in
death alone. Consistently, every 1% increase in biventricular pacing percentage was
associated with a 6% risk reduction in HF or death, a 10% risk reduction in death
alone, and an increase in LV reverse remodeling [67]. Therefore, in ICD patients with
biventricular pacing, it can be beneficial to adjust the therapy to produce the highest
achievable percentage of ventricular pacing, preferably above 98%, to improve survival
and reduce HF hospitalization. Approaches to increasing the percentage of biventricular
pacing include programming shorter but hemodynamically appropriate atrioventricular
delays and minimizing atrial and ventricular ectopic activity and tachyarrhythmias.
Optimizing the location of ventricular pacing sites and the timing of the pacing pulses
can significantly improve cardiac hemodynamics in CRT patients. Echocardiographic
optimization of atrioventricular delays in CRT patients can alleviate HF symptoms
and increase exercise capacity compared with nominal programming, particularly when
approaching nonresponding populations [68]. However, echocardiographic optimization
in the PROSPECT study did not support this approach in a randomized trial, and the
Frequent Optimization Study Using the QuickOpt Method (FREEDOM) trials failed to provide
evidence supporting the benefit of CRT optimization and did not demonstrate superiority
of the respective algorithms over nominal or empiric programming [69], [70], [71].
There are limited data supporting the use of LV- only stimulation in a small subset
of patients who fail to respond to biventricular stimulation [72]. Adaptive CRT (aCRT)
is an algorithm that periodically measures intrinsic conduction and dynamically adjusts
CRT pacing parameters. The algorithm withholds RV pacing when intrinsic electrical
conduction to the RV is normal and provides adjustment of CRT pacing parameters based
on electrical conduction. A prospective, multicenter, randomized, double-blind clinical
trial demonstrated the safety and efficacy of the aCRT algorithm [73]. This algorithm
can increase the longevity of the implantable device and replace a manual device optimization
process with an automatic ambulatory algorithm, although echo optimization might still
be needed, at least in nonresponders. The Clinical Evaluation on Advanced Resynchronization
(CLEAR) study assessed the effects of CRT with automatically optimized atrioventricular
and interventricular delays, based on a peak endocardial acceleration (PEA) signal
system. PEA-based optimization of CRT in patients with HF significantly increased
the proportion of patients who improved with therapy during follow- up, mainly through
an improved New York Heart Association (NYHA) class [74].
Table
Bradycardia Mode and Rate Programming Recommendations
Class of Recommendation
Level of Evidence
In ICD patients who also have sinus node disease and guideline-supported indications
for a bradycardia pacemaker, it is beneficial to provide dual-chamber pacing to reduce
the risk of AF and stroke, to avoid pacemaker syndrome, and to improve quality of
life.
I
B-R
In single- or dual-chamber ICD patients without guideline-supported indications for
bradycardia pacing, adjusting the pacing parameters is recommended so that ventricular
stimulation is minimized to improve survival and reduce HF hospitalization.
I
B-R
In ICD patients who have sinus rhythm, no or only mild LV dysfunction, and atrioventricular
block where ventricular pacing is expected, it is reasonable to provide dual-chamber
pacing in preference to single-chamber ventricular pacing to avoid pacemaker syndrome
and to improve quality of life.
IIa
B-R
In ICD patients who have sinus rhythm, mild-to-moderate LV dysfunction, and atrioventricular
block where ventricular pacing is expected, it is reasonable to provide CRT in preference
to dual-chamber ventricular pacing to improve the combination of HF hospitalization,
LV enlargement, and death.
IIa
B-R
In ICD patients who have chronotropic incompetence, it can be beneficial to program
the ICD to provide sensor-augmented rate response, especially if the patient is young
and physically active.
IIa
B-NR
In dual-chamber ICD patients with native PR intervals of 230 ms or less, it can be
beneficial to program the mode, automatic mode change, and rate response so that the
patient’s native atrioventricular conduction minimizes ventricular pacing.
IIa
B-R
In biventricular pacing ICD patients, it can be beneficial to adjust the therapy to
produce the highest achievable percentage of ventricular pacing, preferably above
98%, to improve survival and reduce HF hospitalization.
IIa
B-NR
In biventricular pacing ICD patients, it can be reasonable to activate the algorithms
providing automatic adjustment of atrioventricular delay and/or LV-RV offset to obtain
a high percentage of synchronized pacing and reduce the incidence of clinical events.
IIb
B-R
9
Tachycardia Detection Programming
Following significant technological changes in ICDs in recent years, the concept of
optimal ICD programming has changed dramatically. From the dawn of this therapy in
the early 1980s to the first decade of the 21st century, the rapid detection and treatment
of VT and ventricular fibrillation (VF) have been stressed. The argument for rapid
detection of VT and VF derived from a number of factors. Initial skepticism regarding
the feasibility of sudden death prevention with ICDs, the fact that early ICD patients
had all survived one or more cardiac arrests, concern for undersensing and underdetection
(of VF in particular), demonstration of an increasing defibrillation threshold with
prolonged VF duration, and the increased energy requirement of monophasic defibrillation
all created a culture of programming for rapid tachycardia detection and the shortest
possible time to initial therapy [75], [76], [77]. The initial generations of ICDs
did not record and save electrograms (EGMs), leading to a reduced appreciation for
the frequency and impact of inappropriate shocks. With the advent and then dominance
of primary prevention indications, avoidable shocks assumed a relatively larger proportion
of total therapy [78], [79], [80], [81], [82], [83]. Gradually, publications have
increased awareness of the frequency and the diverse range of adverse outcomes associated
with avoidable ICD therapy, and have demonstrated that avoidable ICD shocks can be
reduced by evidence-based programming of the detection rate, detection duration, antitachycardia
pacing (ATP), algorithms that discriminate supraventricular tachycardia (SVT) from
VT, and specific programming to minimize the sensing of noise [81], [82], [83], [84],
[85], [86], [87], [88], [89], [90], [91], [92].
10
Duration Criteria for the Detection of Ventricular Arrhythmia
Until recently, default device programming used short- duration “detection” criteria
that varied by manufacturer and a tachycardia rate of approximately 2.8 to 5 seconds
before either ATP or charging (including detection time plus duration or number of
intervals) [82], [93]. With increased awareness of the potential harm from inappropriate
shocks and the realization from stored pacemaker EGMs that even long episodes of VT
can self-terminate, a strategy of prolonged detection settings has been explored.
This strategy allows episodes to self-terminate without requiring device intervention
and reduces inappropriate therapy for nonmalignant arrhythmias. The benefit of programming
a prolonged detection duration (30 of 40 beats) was first reported in the Prevention
Parameters Evaluation (PREPARE) study on exclusively primary prevention subjects (n=700),
and compared outcomes to a historical ICD cohort programmed at “conventional detection
delays” with about half programmed to 12 of 16 intervals within the programmed detection
zone and half to 18 of 24 intervals [94]. The programming in PREPARE demonstrated
a significant reduction in inappropriate shocks for supraventricular arrhythmia and
in avoidable shocks for VT. In addition, a composite endpoint was reduced as well:
the morbidity index, which consists of shocks, syncope, and untreated sustained VT.
Within the limitations of a nonrandomized study, it was concluded that extending detection
times reduces shocks without increasing serious adverse sequelae.
In 2009, the Role of Long-Detection Window Programming in Patients with Left Ventricular
Dysfunction, Non- Ischemic Etiology in Primary Prevention Treated with a Biventricular
ICD (RELEVANT) study confirmed and expanded the results of the PREPARE trial in a
cohort of 324 primary prevention CRT-D patients with nonischemic cardiomyopathy [95].
The subjects were treated with simplified VT management, which implies much longer
detection for VF episodes (30 of 40) compared with the control group (12 of 16) and
a monitor-only window for VT. As in PREPARE, the RELEVANT study group experienced
a significantly reduced burden of ICD interventions (81% reduction) without increasing
the incidence of syncope. Fewer inappropriate shocks and HF hospitalizations were
reported in the RELEVANT study group compared with the control group.
The Multicenter Automatic Defibrillator Implantation Trial: Reduce Inappropriate Therapy
(MADIT-RIT), a 3- arm study, compared a conventional programming strategy (a 1-second
delay for VF [equivalent to approximately 12 intervals including detection plus delay]
and a 2.5-second delay for VT detection [equivalent to approximately 16 intervals
including detection plus delay]) (Arm A) to both a high-rate cutoff with a VF zone
starting at 200 bpm (Arm B) (discussed in section Rate Criteria for the Detection
of Ventricular Arrhythmia and discussed as referenced in reference [96].) and to a
delayed therapy strategy with a 60- second delay for rates between 170 and 199 bpm,
a 12- second delay at 200 to 249 bpm, and a 2.5-second delay at 250 bpm (Arm C) [96].
The MADIT-RIT population was exclusively primary prevention and included approximately
an equal proportion of nonischemic and ischemic cardiomyopathy patients. All the patients
were implanted with either a dual-chamber ICD or a CRT-D programmed to deliver ATP
before charging. After a mean 1.4-year follow-up, the prolonged detection group (Arm
C) was associated with a reduction in treated VT/VF leading to a 76% reduction in
the primary endpoint of the first inappropriate therapy (P The Avoid Delivering Therapies
for Non-Sustained Arrhythmias in ICD Patients III (ADVANCE III) trial reported that
a long detection was associated with a highly significant reduction of overall therapies
(appropriate and inappropriate ATP and/ or shocks), inappropriate shocks, and all-cause
hospitalizations [97]. Importantly, like PREPARE, RELEVANT, and MADIT-RIT, the extended
detection duration used in the ADVANCE III trial (30 of 40) did not negatively impact
the rate of syncopal events. There was no significant difference in mortality between
the optimal and the conventional programming groups. Compared with the MADIT-RIT trial,
the ADVANCE III control group had a longer detection duration (primarily in the VF
zone), and enrolled a larger cohort of subjects covering all ICD types (single, dual,
and CRT with ATP delivered during charging) for both primary and secondary prevention
indications. Finally, the Programming Implantable Cardioverter-Defibrillators in Patients
With Primary Prevention Indication (PROVIDE) trial randomized 1670 patients to conventional
programming (12-beat detection in each of 2 zones) or experimental programming (2
VT and 1 VF zone requiring 25-, 18-, and 12-beat detection, respectively) [98]. PROVIDE
observed a significant 36% reduction in the 2-year all-cause shock rate and an improved
survival (hazard ratio [HR] 0.7; 95% confidence interval [CI] 0.50–0.98; P=.036).
Whereas PREPARE, RELEVANT, MADIT-RIT, and PROVIDE only enrolled primary prevention
patients, a subset of the ADVANCE III study evaluated the efficacy and safety of a
long-detection approach in secondary prevention patients who have a known higher burden
of arrhythmic episodes. In this particular subset of 25% of the enrolled patients,
ADVANCE III reported that a long detection duration reduced the overall therapies
delivered, primarily due to a significant 36% reduction in appropriate shocks [99].
Syncopal episodes related to arrhythmic events and deaths were similar between the
2 groups.Following shortly on the heels of these trials, 2 meta-analyses including
the above studies were published in 2014. Tan et al presented the data from the RELEVANT,
PREPARE, MADIT-RIT, ADVANCE III, PROVIDE, and EMPIRIC trials [100], [101]. A 30% reduction
in the risk of death was found in the therapy reduction group when including all 6
studies; however, similar results were observed when separately considering the 4
randomized trials and the 2 observational studies. Data on the appropriateness of
shocks were available only for RELEVANT, MADIT-RIT, ADVANCE III, and PROVIDE, and
a 50% reduction in inappropriate shock was observed without an increased risk of syncope
and appropriate shock.A meta- analysis evaluated the impact of a prolonged arrhythmia
detection duration on outcome [102]—thus excluding the EMPIRIC trial (which used 18
of 24 intervals for VF detection), the PREPARE trial (which used a historical control
group), and the high-rate therapy arm of the MADIT-RIT. Analyzing the cohort of patients
enrolled in RELEVANT, Arm C of MADIT-RIT, ADVANCE III, and PROVIDE, the meta-analysis
reported a reduction of overall burden of therapies, driven by the greater than 50%
reduction in appropriate and inappropriate ATP and the 50% reduction in inappropriate
shocks. A reduction in all-cause mortality was observed without an increase in the
risk of syncope.All the reports above clearly stress the necessity to consider a long
detection window setting as a “default” strategy for ICD programming. Moreover, they
underline the importance of choosing to reprogram the ICD rather than using the manufacturers’
out-of-the-box settings. A summary of the large comparative datasets of tachycardia
detection is presented in Table 2.
11
Limitations of Data on the Duration of Tachycardia Required for Detection
Although the findings on the effect of tachycardia detection duration are based on
roughly 7000 patients, there are limitations. Data on secondary prevention patients
are limited to 25% of the 1902 patients enrolled in the ADVANCE III trial (n=477).
Although this proportion is a fair representation of the real-world population receiving
an ICD, more data are needed to fully understand the impact of a long-detection strategy
in this subgroup of patients. MADIT-RIT and RELEVANT did not include single- chamber
ICDs, and MADIT-RIT excluded patients with permanent AF. The PROVIDE and MADIT-RIT
trials were designed to assess the time to first therapy and not the overall rate
of therapies. MADIT-RIT, ADVANCE III, RELEVANT, and PROVIDE used devices from 3 different
manufacturers with detection strategies leading to different detection times, intervals,
and definitions. Some manufacturers of ICDs are not represented at all in these trials.
Programming in the trial control groups was highly heterogeneous, with time until
ATP or charging for VF as varied as about 11–12 intervals (approximately 3.4 seconds
at 200 bpm) in MADIT-RIT and PROVIDE and 18 intervals (approximately 5.4 seconds)
in ADVANCE III. An approximate translation of the impact of the number of intervals
to detection and tachycardia cycle length (CL) are listed in Table 3. A further limitation
is the relatively short duration and lack of inclusion of the patients with the most
severe illness receiving an ICD. This limitation minimizes the exposure to relatively
rare events that might occur in nonclinical trial, “real-world” patients. Lastly,
as ICD batteries deplete, the charge time lengthens. The effect of such a delay to
shock therapy in addition to prolonged detection times has not been studied.
12
Rate Criteria for the Detection of Ventricular Arrhythmia
Ventricular tachyarrhythmia detection by implantable devices is primarily based on
heart rate. Heart rates can be extremely rapid during ventricular tachyarrhythmias,
and it is less likely that such rates are achieved during supraventricular tachyarrhythmias—thus
making rate a powerful component of arrhythmia discrimination. However, VT can also
present slower rates in the range of those of supraventricular tachyarrhythmias or
even of sinus tachycardia. Therefore, any rate cutoff will always imply a tradeoff
between maximizing sensitivity for ventricular tachyarrhythmia detection at the expense
of inappropriate detection of fast supraventricular tachyarrhythmias and maximizing
specificity at the expense of some slow VTs going undetected [103].
Because ICD therapy was initially employed in secondary prevention patients, the cutoff
rate was usually tailored to a rate slightly below that of the observed VT. With the
development of ICD use in primary prevention, the detection rate came into question
because there is no history of sustained tachycardia in these patients. The recognition
of a significant rate of inappropriate therapies in primary prevention studies, and
their potentially deleterious consequences, prompted the development of studies that
tested whether programming faster rate criteria reduced avoidable ICD therapies, particularly
shocks. In many of these studies, however, testing also involved programming parameters
other than rate, and those have been discussed as described below.
In the MADIT-RIT trial of primary prevention patients, conventional therapy (rate
cutoff 170 bpm, n=514) was compared with a “high-rate group” in which rate cutoff
was 200 bpm (n=500) [96]. The primary endpoint of first occurrence of inappropriate
therapy was observed in 20% of the conventional group and in 4% of the high-rate group
(P follow-up of 1.4 years. ICD shocks occurred in 4% and 2% of patients in the conventional
and high-rate groups, respectively. The proportion of patients with appropriate therapies
was also significantly different (22% vs 9% in the conventional and high-rate groups,
respectively). It is important to note that all-cause mortality in the conventional
group (6.6%) was approximately double that of the high-rate group (3.2%, P=.01).
In a single-center observational study, 365 primary prevention patients were prospectively
studied, with programming including a single shock-only zone over 220 bpm [104]. During
a mean follow-up of 42 months, 11% of the patients (7% in the first 2 years) experienced
appropriate shocks, and only 6.6% experienced inappropriate shocks. It was notable
that in the monitoring zone over 170 bpm, self- limiting VT episodes were detected
in 12% of the patients but were symptomatic in only 1.9%. The mortality rate was 17%,
with one case of unexplained sudden death.
A recent primary prevention study revealed that there was considerable overlap between
the ventricular rates of supraventricular and ventricular arrhythmias, and the majority
of inappropriate shocks occurred at rates between 181 and 213 bpm [98]. These data
also support the notion that for primary prevention patients it is safe to increase
the rate cutoff up to 200 bpm to reduce these potentially avoidable therapies, a practice
that was also supported by the results of the MADIT-RIT trial.
In secondary prevention patients, no trial has randomized the detection rate and compared
outcomes. However, the ADVANCE III Secondary Prevention substudy confirmed the safety
of not programming therapy for rates patient- years [105]. Previously published recommendations
suggest a VT zone starting at 10 to 20 bpm slower than the observed tachycardia rate,
usually including a 2- or 3-zone arrhythmia detection scheme (as discussed elsewhere)
[106]. Clinicians should allow a larger rate differential when starting a patient
on an antiarrhythmic drug that might slow the clinical tachycardia rate (e.g., amiodarone).
13
Single- or Multi-Zone Detection
Modern ICDs allow the rate to be classified into single or multiple zones. This classification
permits different criteria to be applied for detection (e.g., number of intervals)
and for tiered therapy (e.g., different adaptive CLs for slower vs faster VTs and
more sequences of ATP for slower and presumably hemodynamically more stable VTs).
Additionally, because some manufacturers tie SVT discrimination algorithms to specific
VT zones, programming more than one tachycardia zone allows for greater specificity
in discriminating VT from SVT (see online Appendix B). Although there are trials in
which arms differ in whether a single zone or multiple zones are used, this is typically
performed to allow programming of various detection, discrimination, or therapies
for comparison. Thus, the number of zones was not the randomization variable being
directly compared. Therefore, the concept of single- vs multizone programming as a
head-to-head comparison is not well tested. The MADIT-RIT study randomized primary
prevention ICD patients into 1 of 3 arms with single-, dual-, or triple-zone programming
(the single-zone arm also had a monitoring zone). Although the trial’s aim was to
compare conventional therapy with high-rate and delayed therapy, the outcome for the
single-zone arm (high-rate) was comparable to the triple-zone (delayed) arm and superior
to the dual-zone (conventional) arm, with regard to inappropriate shock [96]. This
study is consistent with multiple studies in ICD programming in which the use of multiple-zone
programming has allowed for flexibility in programming strategies with regard to detection,
discrimination, and therapy. Additionally, there are observational data from the ALTITUDE
Real World Evaluation of Dual-Zone ICD and CRT-D Programming Compared to Single-Zone
Programming (ALTITUDE REDUCES) study that show that dual-zone programming is associated
with fewer shocks than single- zone programming, at least for rates [64]. Therefore,
the authors conclude that using more than 1 detection zone can be useful for modern
ICD programming. It should be noted that ATP before or during charging was used in
the majority of studies described in both the tachycardia detection and therapy sections
and thus is recommended for longer detection.
14
Discrimination Between Supraventricular and Ventricular Arrhythmia
The SVT-VT discrimination process classifies a sequence of sensed EGMs that satisfies
rate and duration criteria as either SVT (therapy withheld) or VT/VF (therapy given).
Discriminators are individual algorithm components that provide a partial rhythm classification
or a definitive classification for a subset of rhythms. Discrimination algorithms
combine individual component discriminators to produce a final rhythm classification.
Discrimination algorithms vary among manufacturers and between individual ICD models
(see online Appendix B). The final rhythm classification can differ depending on the
technical details of how each individual discriminator is calculated, the nominal
or programmed threshold for each discriminator, the order in which discriminator components
are applied, and the logical connections between them (e.g., “and” vs “or”). In some
ICDs, rhythms classified as VT/VF undergo a subsequent sensing-verification step to
confirm that EGMs represent true cardiac activation.
15
SVT-VT Discriminator Components
Individual discriminators can be considered in relation to the EGMs analyzed as ventricular-only
or both atrial and ventricular, by the rhythm that they identify (e.g., AF, sinus
tachycardia, VT), or by the type of EGM information analyzed (intervals vs morphology).
Note that ventricular rate alone is a mandatory discriminator, as discussed in the
section above. We summarize the most commonly used discriminators. More comprehensive
discussions are available in the literature [107], [108], [109], [110], [111].
16
Rejection of Sinus Tachycardia by Onset
Several interval-based discriminators focus on differences in the onset of sinus tachycardia
(gradual and parallel acceleration of atrial and conducted ventricular intervals)
compared with VT (typically abrupt, with at least transient atrioventricular dissociation).
Sudden (abrupt) onset was one of the first single-chamber, interval-based discriminators.
It withholds therapy if acceleration across the sinus-VT rate boundary is gradual.
Because onset discriminators classify the rhythm only once, and thus cannot correct
misclassifications, they are now used infrequently and only with an override feature
and/or other discriminators [112], [113], [114], [115]. Chamber of onset is a related,
interval-based, dual-chamber discriminator that classifies a 1:1 tachycardia as SVT
if the atrial rhythm accelerates at the device-defined onset. A related “Sinus Tachycardiafi”
discriminator classifies a tachycardia as VT if either the RR or the PR intervals
deviate sufficiently from the range of the immediately preceding sinus intervals [116].
16.1
Rejection of AF by Ventricular Interval Regularity
Ventricular interval regularity (interval stability) is an explicit single-chamber,
interval-based discriminator that classifies the rhythm as AF if the ventricular intervals
are sufficiently irregular. Because interval variability in conducted AF decreases
at faster rates, stability becomes unreliable in discriminating VT from conducted
AF at ventricular rates greater than 170 bpm [112], [115]. Interval stability can
also fail if drugs (e.g., amiodarone) cause monomorphic VT to become irregular or
induce polymorphic VT to slow into the SVT-VT discrimination zone [114], [117].
16.2
Diagnosis of VT by Dual-Chamber Components: Atrial vs Ventricular Rate and Atrioventricular
Association
In contrast to the single-chamber discrimination algorithms above that diagnose SVT
when their criteria are fulfilled, 2 separate, interval-based, dual-chamber discrimination
algorithms diagnose VT. First,
atrial rate vs ventricular rate
diagnoses VT if the ventricular rate exceeds the atrial rate [118]. s,
atrioventricular dissociation
identifies isorhythmic VT during sinus tachycardia. Inversely, the atrioventricular
association
discriminator diagnoses SVT in the presence of N:1 (e.g., 2:1, 4:1) atrioventricular
association consistent with atrial flutter at a fixed conduction ratio.
16.3
The Ventricular Electrogram Morphology Discriminator
This versatile, single-chamber discriminator is the only algorithm component that
does not rely on inter-EGM intervals. It classifies tachycardias as SVT if the morphology
(shape) of the ventricular EGM is sufficiently similar to the morphology during a
conducted baseline rhythm. It can potentially discriminate any SVT from VT, including
SVTs that challenge other discriminators, such as abrupt-onset 1:1 SVTs and irregular
VT during AF. Contemporary ICDs (including subcutaneous ICD [S-ICD]) analyze EGMs
from the shock electrodes, which record a larger field of view than EGMs from pace-sense
electrodes [119]. They operate using a common series of steps and are susceptible
to common failure modes [111], [120], [121], [122], [123]. The first common step is
acquisition of a baseline rhythm template by mathematically extracting EGM features
and storing them. Both the acquisition of the initial template and the subsequent
template updating are automated in most ICDs. Nevertheless, physicians should confirm
that the conducted baseline beats match the template both at implant and during follow-up.
For CRT patients, the template must be manually collected. If the wavelet signal during
template acquisition appears clipped, adjustments specific to the manufacturer might
be necessary.
17
SVT-VT Discrimination Algorithms
Discrimination algorithms combine component discriminators to provide a final rhythm
classification of VT/VF or SVT. The morphology discriminator frequently forms the
primary component of single-chamber algorithms with stability playing a secondary
role and sudden onset used sparingly. By contrast, the cornerstone of most dual-chamber
algorithms is explicit or implicit comparison of atrial vs ventricular rates. Because
the ventricular rate is greater than the atrial rate in more than 80% of VTs, algorithms
that compare atrial and ventricular rates as their first step apply additional SVT
discriminators to fewer than 20% of VTs, reducing the risk that they will misclassify
VT as SVT [124], [125]. Most dual-chamber algorithms further restrict single- chamber
discriminators to tachycardias for which they offer the greatest benefit; thus, stability
is applied only if AF is confirmed by direct calculation of the atrial rate or the
atrial rate is greater than the ventricular rate. Similarly, sudden onset, chamber
of onset, or 1:1 atrioventricular association are applied only if the atrial rate
equals the ventricular rate. The use of discriminators in redetection varies among
manufacturers and has not been systematically studied.
18
Assessing Clinical Benefits and Risks
18.1
What Evidence Supports a Benefit?
Table
1.
The annual rate of inappropriate shocks has fallen dramatically from 37%–50% for SVT
alone in early studies to 1%–5% for all causes in modern clinical trials [97], [118],
[126], [127], [128]. This decrease is likely due to differences in both clinical populations
and the programming of multiple ICD parameters, including longer detection time and
higher rate cutoffs. Thus, it is difficult to isolate the differential effect of SVT-VT
discrimination algorithms using clinical data. These studies have programmed discrimination
algorithms to ON, however, so it seems reasonable to use them.
2.
Although clinical trials that reported dramatic reductions in shocks for SVT programmed
discrimination algorithms consistently, they have been programmed inconsistently in
clinical practice, and the rate of inappropriate shocks for SVT has been higher in
observational studies of remote- monitoring ICD databases. In the ALTITUDE REDUCES
study on 15,991 patients in the Latitudefi database, SVT was the most common cause
of shocks when the detection rate was ≤180 bpm [129]. For detection rates ≤170 bpm,
the rate of inappropriate shocks at 1 year was significantly lower with dual-zone
programming, which permits SVT- VT discrimination, than single-zone programming, which
does not (9.6% vs 4.3%). Similarly, Fischer et al [130] analyzed shocks in 106,513
patients in the CareLinkfi database; programming SVT-VT discrimination ON was associated
with a 17% reduction in all-cause shocks.
3.
Sophisticated simulations indicate that SVT-VT discrimination algorithms have substantial
benefit. For example, the SCD-HeFT study on primary prevention patients did not use
discriminators. A validated Monte Carlo simulation predicted that use of single- or
dual-chamber SVT- VT discriminators alone would have reduced inappropriate shocks
for SVT by 75.5% and 78.8%, respectively [131].
18.2
Which Patients are Most Likely to Benefit, and Which are Least Likely to Benefit?
Despite limited direct evidence, it seems clear that patients will benefit most if
the rates of their VTs and SVTs overlap. This includes patients with slower monomorphic
VT, those at risk for AF with rapid ventricular rates, or those capable of exercising
to sinus rates in the VT zonev [103], [132]. In secondary prevention patients with
slower VT, older discrimination algorithms reduced shocks for SVT compared with rate-only
detection. The benefit is less for primary prevention patients, secondary prevention
patients at risk only for VF, and those who cannot sustain rapid atrioventricular
conduction. Patients with permanent complete atrioventricular block do not benefit.
18.3
What are the Risks?
The risk of the misclassification of either VT or VF as SVT by the discrimination
algorithms can either prevent VT detection or delay the time to therapy (underdetection),
as documented in clinically significant situations [112], [113], [115], [125]. When
modern algorithms are programmed to recommended parameters, clinically significant
underdetection is rare. Large clinical trials on multiple shock-reduction strategies
(including SVT-VT discrimination) report no or minimal and statistically insignificant
increases in syncope [95], [97], [126], [133]. Most reports do not include the causes
of syncope and thus do not permit identification of whether discrimination algorithms
contributed to any of the syncopal episodes by prolonging detection. However, in the
PREPARE study, no syncopal episode was caused by untreated tachycardia [133]. In general,
discriminators that re-evaluate the rhythm classification during ongoing tachycardia
reduce the risk of underdetection compared with those that withhold therapy if the
rhythm is misclassified by the initial evaluation (e.g., onset, chamber of origin
algorithms).
19
Additional Considerations
19.1
SVT Limit
SVT-VT discrimination applies from the VT detection rate to the SVT limit rate, which
is programmable independently of the VT/VF therapy zones with some manufacturers (preferable),
but which might be linked to one of the zone boundaries in others. The minimum CL
for SVT-VT discrimination should be set to prevent clinically significant delays in
the detection of hemodynamically unstable VT. PREPARE, EMPIRIC, and MADIT-RIT all
support the safety of empirical programming at 200 bpm [96], [101], [134]. In MADIT-II,
approximately 50% of SVT episodes were faster than 170 bpm, and a few were as fast
as 250 bpm [82] In INTRINSIC RV, SVT comprised 19% of episodes, with rates between
200 and 250 bpm [135]. More limited and preliminary data from PainFree SST support
programming up to 222–230 bpm [116], [136]. We suggest the SVT limit not exceed 230 bpm
in adults without a patient-specific indication, based on the low incidence of SVTs
in this rate range among ICD patients and the potential—however small—for misclassifying
hemodynamically unstable VT.
19.2
Duration-Based “Safety-Net” Features to Override Discriminators
These features deliver VT/VF therapy if a tachycardia satisfies the ventricular rate
criterion for a sufficient duration, even if the discrimination algorithm indicates
SVT. The premise is that the ventricular rate during transient sinus tachycardia or
AF will decrease to below the VT rate boundary before the override duration is exceeded.
In one study, an override duration of 3 minutes delivered inappropriate therapy to
10% of SVTs [112]. Because SVT is much more common than VT, programming an override
duration of less than 5–10 minutes results primarily or solely in inappropriate SVT
therapy [122]. Although more data would be useful, in the absence of a documented
benefit, we recommend programming this feature OFF or long (minutes) without a patient-specific
or device-specific indication.
19.3
Dual-Chamber vs Single-Chamber Algorithms
Clinical trials and simulated testing of induced arrhythmias that compared single-
vs dual-chamber discriminators have reported inconsistent results [10], [33], [137],
[138], [139]. Two meta-analyses found no superiority of dual-chamber ICDs in terms
of mortality or inappropriate therapies [11], [140]. Any benefit of dual-chamber discrimination
is likely restricted to specific patient groups [103], [138]. For example, the Dual
Chamber and Atrial Tachyarrhythmias Adverse Events (DATAS) trial of predominantly
secondary prevention patients with slower VTs reported modest benefit from dual-chamber
discrimination, while the recent Reduction and Prevention of Tachyarrhythmias and
Shocks Using Reduced Ventricular Pacing with Atrial Algorithms (RAPTURE) trial of
primary prevention patients programmed to a fast detection rate (>182 bpm) and long
detection duration (30/40 intervals) did not [103], [138], [139]. Inappropriate therapy
for SVT occurred in only 2% of the patients in each group. Recent data from PainFree
SST notes very low rates of inappropriate shocks (3.7% for single chamber; 2.8% for
dual and triple chamber after 2 years). The choice of device was not randomized, suggesting
that when physicians chose a dual- or triple- chamber device (perhaps due to known
atrial arrhythmia or bradycardia), inappropriate shock rates were minimized [136].
The Optimal Anti-Tachycardia Therapy in Implantable Cardioverter-Defibrillator Patients
Without Pacing Indications (OPTION) trial randomized 462 patients to single- or dual-chamber
programming and noted inappropriate shock rates of 10.3% for single chamber vs 4.3%
for dual chamber after 27 months (P=.015). Atrial lead-related complications were
1.3%, therapy was delivered from 170 bpm (VT) and 200 bpm (VF), and no difference
in ventricular pacing percentage was noted [141]. Dual-chamber algorithms probably
reduce the risk of underdetection compared with single- chamber algorithms because
more than 80% of VTs with a ventricular rate greater than the atrial rate undergo
no further analysis [103], [124], [125]. However, the rate of clinically significant
underdetection with modern programming is so low that this difference is rarely of
clinical significance. In most patients, improved SVT-VT discrimination should not
be considered an indication for a dual- vs single-chamber ICD. Even if a dual-chamber
ICD is implanted, dual-chamber discrimination should be programmed only if the atrial
lead becomes chronic or if atrial sensing is unreliable. Accurate sensing of atrial
EGMs is essential for dual-chamber SVT-VT discrimination. Atrial lead dislodgments,
oversensing of far-field R waves, or undersensing due to low-amplitude atrial signals
can cause misclassification of VT/SVT. On implant, it is important to position the
atrial lead to minimize far-field R waves.
19.4
Ventricular Oversensing
Excluding recalled leads, ventricular oversensing accounts for less than 10% of inappropriate
shocks, but it often results in repetitive shocks and severe symptoms [82], [142],
[143], [144]. Recently introduced features reduce inappropriate therapies from oversensing
of physiologic T waves and nonphysiologic signals related to pace-sense lead failures
as discussed below.
20
Programming to Reduce T-Wave Oversensing
The problem of T-wave oversensing relates to the basic requirement that ICDs reliably
sense VF, which is characterized by RR intervals shorter than the normal QT interval
and some EGMs with low amplitudes and slew rates. Approaches to minimizing T-wave
oversensing include reprogramming ventricular sensitivity, altering sensing bandwidth,
and changing the sensing bipole [109], [123], [145]. One manufacturer provides an
algorithm that withholds therapy after rate and duration criteria for VT/VF are fulfilled
if a specific pattern of T-wave oversensing is identified [146]. T- wave oversensing
rates vary based on device design; using an appropriate high band-pass filter results
in very low rates of T-wave oversensing [142]. Because T-wave oversensing is unpredictable,
features that minimize T-wave oversensing should be enabled proactively at implant,
providing they do not cause undersensing in VF [146].
21
Lead-Related Oversensing
Oversensed signals caused by pace-sense lead failure have specific interval patterns
and EGM characteristics [145], [147], [148]. Present algorithms identify three features:
(1) intervals can be too short to represent successive ventricular activations; (2)
such short intervals are often transient and can be repetitive; and (3) in true bipolar
leads, oversensed signals are absent on the shock EGM. Algorithms can provide warning
alerts, withhold shocks after spurious detection of VT/VF, or both. All 3 criteria
can provide alerts, but only the third is applied to withhold shocks. The present
algorithms were developed to identify impending lead failures on recalled leads, notably
the Sprint Fidelis. These algorithms might not be appropriate for detecting failures
in other leads [144]. There is a high false-positive rate when using these algorithms,
and caregivers must carefully review the device data that caused the alert to ensure
the lead experienced a true failure [145].
Alerts that combine both oversensing and abrupt changes in impedance trends provide
earlier warning of lead failure than a fixed impedance threshold [144], [145], [149].
Such alerts can be delivered via wireless remote monitoring and/or by notifying the
patient via vibration or an audible tone. Caregivers must respond rapidly to alerts
to minimize inappropriate shocks [144], [149]. Wireless remote monitoring has been
reported to reduce response time [150]. The principal disadvantage of lead alerts
is false-positive triggers. The principal risk of shock-withholding algorithms is
a failure to shock VF, which is extremely rare [151]. In addition to algorithmic approaches,
oversensing due to failure of the cable leading to the ring electrode can be prevented
by changing the programming of the sensing configuration from true bipolar to integrated
bipolar. This approach is appropriate prophylactically or as temporary programming
after a ring electrode cable failure; it is not a permanent solution, however, because
increased rates of high-voltage cable fractures have been documented after sensing
cable fractures [152].
22
The Subcutaneous Defibrillator (S-ICD)
The novel S-ICD follows many of the same principles as intravascular ICDs but is considered
here separately for duration criteria, rate criteria, and discrimination algorithms.
Candidates for the S-ICD must initially be screened with a modified tri-channel surface
electrocardiogram that mimics the sensing vectors of the S-ICD system. This test is
designed to assess the R-wave to T-wave ratio for appropriate signal characteristics
and relationships. If the screening is not satisfactory for at least 1 of the 3 vectors
supine and standing, an S-ICD should not be implanted. On implant, the S-ICD automatically
analyzes and selects the optimal sensing vector.
Detection of VT or VF by the S-ICD is programmable using a single or dual zone. In
the single-zone configuration, shocks are delivered for detected heart rates above
the programmed rate threshold: the “shock zone” [134]. In the dual-zone configuration,
arrhythmia discrimination algorithms are active from the lower rate: the “conditional
shock zone.” In this latter zone, a unique discrimination algorithm is used to classify
rhythms as either shockable or nonshockable. If they are classified as supraventricular
arrhythmias or nonarrhythmic oversensing, therapy is withheld.
With dual-zone programming, the shock zone uses rate as the sole method for rhythm
analysis. In contrast, the conditional shock zone uses a stepwise discrimination algorithm
to distinguish shockable from nonshockable rhythms. The conditional shock zone has
a morphology analysis process based on a normal rhythm transthoracic QRS:T wave template.
The template uses up to 41 fiduciary points to reconstruct morphology for the template
as well as the programmed targeted heart rate zones. The comparison of the template
to the high-rate rhythm electrocardiogram for discrimination constitutes the static
waveform analysis. A good template match designates a sensed beat as supraventricular,
thereby preventing a shock. A poor match to the static QRS:T morphology template moves
the algorithm to a dynamic waveform analysis that compares single-beat morphologies
in groups of 4 beats for uniformity. A consistent dynamic waveform match adjusts the
sensing to evaluate QRS width. If a tachycardia has a prolonged QRS width compared
with the template width (>20 ms) and is of sufficient duration, it will lead to a
shock.
The system uses an initial 18 of 24 duration criteria (nonprogrammable) prior to initiating
capacitor charging; however, this duration is automatically extended following nonsustained
ventricular tachyarrhythmia events. A confirmation algorithm is also used at the end
of capacitor charging to ensure persistence of the ventricular arrhythmia prior to
shock delivery. Shocks for spontaneous (noninduced) episodes are delivered at a nonprogrammable
80 J regardless of the therapy zone of origination.
When programmed to include a conditional shock zone, the S-ICD VT detection algorithm
has been demonstrated to be more effective than transvenous ICD systems programmed
at nominal settings to prevent the detection of induced supraventricular arrhythmias
[153]. Furthermore, in the clinical evaluation of the conditional shock zone, the
S-ICD system was strongly associated with a reduction in inappropriate shocks from
supraventricular arrhythmias and did not result in prolongation of detection times
or increased syncope [154].
23
Integrating Tachycardia Detection Data Into Programming Recommendations
When taking data from specific single-manufacturer studies and producing generic guidelines
applicable across all ICDs, some compromises and potential pitfalls have been encountered.
Nevertheless, it is our intention to convey the general principles of good quality
evidence (e.g., extending detection time) to apply to ICD programming in general.
Thus, attempts have been made to translate interval-based detection to time-based
detection and to provide a range of reasonable heart rate cutoffs that are inclusive
of those proven in good- quality trials. We encourage programming ICDs to manufacturer-specific
therapies of proven benefit; however, when evidence is lacking, the guidelines provide
a framework for programming within the evidence base. See online Appendix B for manufacturer-specific
examples of optimal ICD programming.
Table
Tachycardia Detection Programming Recommendations
Class of Recommendation
Level of Evidence
For primary prevention ICD patients, tachyarrhythmia detection duration criteria should
be programmed to require the tachycardia to continue for at least 6–12 seconds* or
for 30 intervals before completing detection, to reduce total therapies.
I
A
*Tachyarrhythmia detection duration is directly related to the tachyarrhythmia rate.
Direct evidence to support a delay >2.5 seconds for rates over 250 bpm is not available,
but can be inferred from evidence that 30 detection intervals are safe at that rate.
For primary prevention ICD patients, the slowest tachycardia therapy zone limit should
be programmed between 185 and 200 bpm*, to reduce total therapies.
I
A
*Higher minimum rates for detection might be appropriate for young patients or for
those in whom SVT-VT discriminators cannot reliably distinguish SVT from VT, provided
there is no clinical VT below this rate.
For secondary prevention ICD patients, tachyarrhythmia detection duration criteria
should be programmed to require the tachycardia to continue for at least 6–12 seconds*
or for 30 intervals before completing detection, to reduce total therapies.
I
B-R
*Tachyarrhythmia detection duration is directly related to the tachyarrhythmia rate.
Direct evidence to support a delay >2.5 seconds for rates over 250 bpm is not available,
but can be inferred from evidence that 30 detection intervals are safe at that rate.
Discrimination algorithms to distinguish SVT from VT should be programmed to include
rhythms with rates faster than 200 bpm and potentially up to 230 bpm (unless contraindicated*)
to reduce inappropriate therapies.
I
B-R
*Discrimination algorithms and/or their individual components are contraindicated
in patients with complete heart block or if the algorithm/component is known to be
unreliable in an individual patient. Dual-chamber discriminators that misclassify
VT as SVT if the atrial lead dislodges are discouraged in the perioperative period.
Dual-chamber discriminators are contraindicated in patients with known atrial lead
dislodgment, atrial undersensing or oversensing of far field R waves, and in those
with permanent AF.
It is recommended to activate lead-failure alerts to detect potential lead problems.
I
B-NR
For secondary prevention ICD patients for whom the clinical VT rate is known, it is
reasonable to program the slowest tachycardia therapy zone at least 10 bpm below the
documented tachycardia rate but not faster than 200 bpm*, to reduce total therapies.
IIa
C-EO
*Higher minimum rates for detection might be appropriate for young patients or for
those in whom SVT-VT discriminators cannot reliably distinguish SVT from VT, provided
there is no clinical VT below this rate.
It can be useful to program more than one tachycardia detection zone to allow effective
use of tiered therapy and/or SVT-VT discriminators and allow for a shorter delay in
time-based detection programming for faster arrhythmias.
IIa
B-R
When a morphology discriminator is activated, it is reasonable to reacquire the morphology
template when the morphology match is unsatisfactory, to improve the accuracy of the
morphology discriminator.
IIa
C-LD
It is reasonable to choose single-chamber ICD therapy in preference to dual-chamber
ICD therapy if the sole reason for the atrial lead is SVT discrimination, unless a
known SVT exists that may enter the VT treatment zone, to reduce both lead-related
complications and the cost of ICD therapy.
IIa
B-NR
For the S-ICD, it is reasonable to program 2 tachycardia detection zones: 1 zone with
tachycardia discrimination algorithms from a rate ≤200 bpm and a second zone without
tachycardia discrimination algorithms from a rate ≥230 bpm, to reduce avoidable shocks.
IIa
B-NR
Programming a nontherapy zone for tachycardia monitoring might be considered to alert
clinicians to untreated arrhythmias.
IIb
B-NR
It may be reasonable to disable the SVT discriminator timeout function, to reduce
inappropriate therapies.
IIb
C-EO
It may be reasonable to activate lead “noise” algorithms that withhold shocks when
detected VT/VF is not confirmed on a shock or other far-field channel to avoid therapies
for nonphysiologic signals.
IIb
C-EO
It may be reasonable to activate T-wave oversensing algorithms, to reduce inappropriate
therapies.
IIb
C-LD
It may be reasonable to program the sensing vector from bipolar to integrated-bipolar
in true-bipolar leads at risk for failure of the cable to the ring electrode to reduce
inappropriate therapies.*
IIb
C-EO
*This is not intended as a long-term solution when a cable fracture has been identified.
24
Tachycardia Therapy Programming
Although therapies delivered by the ICD can abort SCD, appropriate and inappropriate
ICD shocks have been associated with a considerable increase in the risk of mortality
[82], [83], [155], [156], [157], [158]. In the Sudden Cardiac Death in Heart Failure
Trial (SCD-HeFT), the risk of mortality was 5-fold higher in patients who received
appropriate ICD shocks and 2-fold higher in patients who received inappropriate shocks
[83]. Similarly, pooling data from 4 studies of 2135 ICD patients, shocked VT was
associated with a 32% increase in the risk of mortality. In that analysis, shocked
patients had poorer survival than patients treated with ATP only [155]. ICD shocks
are likely a marker of more advanced heart disease and subsequent death, but defibrillation
therapies have been associated with troponin release and increased LV dysfunction
with the potential of further mortality risk.
The incidence of appropriate and inappropriate ICD shocks depends on the patient’s
characteristics, including the indication for the device, concomitant medical therapies
including antiarrhythmic medications, programming of the ICD, and the duration of
follow-up. With regard to ICD programming, faster VT/VF detection rates, longer detection
durations, use of a single zone, use of SVT discriminators, and delivery of ATP have
been shown to reduce both appropriate and inappropriate shocks and to improve quality
of life [91], [101], [126], [129], [130], [133], [159], [160]. This programming might
improve survival [126]. Indeed, several studies have shown that ATP is effective at
terminating slow and fast VT with exceedingly low rates of adverse events like syncope
[93], [135], [161], [162], [163], [164], [165]. The initial bias of the ICD community
was to reserve ATP therapy for those patients in whom the therapy was demonstrated
to be effective, usually during an electrophysiologic study. However, the approach
of physician-directed programming based on the knowledge of induced arrhythmias was
found to be significantly inferior to the routine strategic (EMPIRIC) programming
of ATP. It is not reflective of the arrhythmias experienced outside the electrophysiology
laboratory for primary and secondary prevention patients with ischemic and nonischemic
substrates [101], [166]. Although the ideal number of ATP bursts has not been definitively
determined, current data support the use of up to 2 ATP attempts, given additional
attempts yield very little additional efficacy [93], [135], [161], [162], [163], [164],
[165], [167], [168]. In one study, up to 5 attempts were found to be safe [168]. The
most effective ATP duration is likewise uncertain; however, in the ATP Delivery for
Painless ICD Therapy (ADVANCE-D) trial—a prospective RCT of 925 patients—8-pulse ATP
was as effective and safe as 15-pulse ATP [169]. The PITAGORA ICD clinical trial randomized
206 patients with an ICD to 2 ATP strategies: an 88% coupling interval burst vs a
91% coupling interval ramp. The results of the trial showed that over a median follow-up
of 36 months and compared with ramp pacing, burst pacing was more effective for terminating
fast VT episodes (between CL 240 and 320 ms) [170]. In a prospective study of 602
patients, a strategy of tiered ATP and low-energy shock was efficacious and safe in
patients with VT CL greater than 250 ms, with extremely low syncope rates [171]. However,
a “real-world” retrospective study on 2000 patients with 5279 shock episodes from
the LATITUDE remote monitoring system showed that the success rate of first shock
as first therapy was approximately 90%, but the success rate was lower after failed
ATP. Therefore, that study recommended programming a higher level of energy after
ATP [172]. Finally, a substudy of the Effectiveness and Cost of ICD Follow-Up Schedule
with Telecardiology (ECOST) study, which randomly assigned 433 patients to remote
monitoring (n=221; active group) vs ambulatory follow-up (n=212; control group), showed
that remote monitoring was highly effective in the long-term prevention of inappropriate
ICD shocks through early detection and prevention of AF with a rapid ventricular rate,
nonsustained VT, or diverted VT episodes [173].
25
Benefits and Risks
The goal of ICD therapy is to prolong life while causing as little morbidity as possible.
Although survival is quantifiably objective, morbidity is more subjective and includes
both physical and emotional components. Clearly, shocks are usually painful to the
patient, whereas ATP is typically not uncomfortable. However, there can be other morbidities
related to both therapies, including mild to extreme emotional distress, syncope,
palpitations, and proarrhythmia yielding more therapies and occasionally leading to
death. Paradoxically, the need for life-saving therapies, including shocks and potentially
ATP, might also be associated with increased mortality; however, the causal relationships
are unclear. Also, the prevalence of tachycardia amenable to ATP or hemodynamic significance
varies with the mechanism of the risk (e.g., long QT vs ischemic cardiomyopathy).
In addition, although the risk of having a hemodynamically important or life-threatening
arrhythmia can vary from patient group to patient group, the largest proportion of
patients in whom ICD therapy is applied has yet to have a previously recorded arrhythmia,
and we must therefore strategically choose on the basis of other factors how we will
treat the first event and subsequent events.
26
Classification of Therapy
The literature uses definitions of therapies that differ from each other and that
impact their results and conclusions. The occurrence rates of these events not only
are dependent on their definition but also are highly dependent on the programming
of the defibrillation system. Both shock and nonshock therapies can be categorized
as being appropriate, inappropriate, and avoidable. Whereas appropriate and inappropriate
therapies refer to therapies that were actually delivered, avoidable therapies are
theoretical events in the future. These potential future tachycardia therapies, delivered
for either appropriately or inappropriately detected events, can frequently be avoided
by establishing programming to either prevent the initiation of the arrhythmia or
to allow the condition to pass without therapy.
27
Appropriate
A response to a sustained ventricular arrhythmia (VT, VF) or hemodynamically poorly
tolerated arrhythmias (e.g., associated with syncope, rate over 200 bpm, or hemodynamically
compromising supraventricular arrhythmias).
28
Inappropriate
A response to signals generated by something other than sustained ventricular arrhythmias
or hemodynamically poorly tolerated arrhythmias. Possible signals include supraventricular
rhythms such as sinus tachycardia, AF, atrial flutter, reentrant SVT, atrial tachycardia,
or instances of signal misinterpretation. Signal misinterpretation includes multiple
counting of single events (e.g., atrial, T-wave or R- wave), environmental signals
such as electromagnetic interference, frequent premature ventricular contractions
(PVCs) and nonsustained ventricular arrhythmias, extracardiac physiologic signals
(e.g., diaphragmatic or pectoral myopotentials), other implantable electronic devices
(e.g., pacemakers, LV assist devices, nerve stimulators), inappropriate lead placement
or dislodgment, conductor or insulation failures, header connection instability, and
pulse generator failure.
29
Avoidable
Programming of detection and therapy parameters and algorithms so that shock or ATP
therapy is withheld from arrhythmias that would be expected to be hemodynamically
tolerated. Examples include self-terminating ventricular arrhythmias, ATP-susceptible
ventricular arrhythmias, and overdrive suppression responsive rhythms. Many appropriate
and most inappropriate therapies are also potentially avoidable.
30
Phantom
These are not true therapies; however, there is the patient’s perception that a therapy
was delivered. Interrogation of the ICD and/or coincident rhythm monitoring does not
identify a tachycardia or therapy.
31
Unintended Consequences of ICD Therapy and ICD Therapy Programming
In the SCD-HeFT and MADIT II trials, inappropriate shocks more than doubled the risk
of death. Mortality rates were substantially higher after shocks: 10% within days
after the first shock, 25% within 1 year, and 40% by 2 years. The leading cause of
death was progressive HF. In an analysis of the MADIT-CRT trial, the patients with
appropriate shocks experienced increased mortality when compared with the patients
without ICD shocks, after accounting for mechanical remodeling effects; this was not
the case for patients who received appropriate ATP only [156]. ICD shocks have also
been associated with independent predictors of mortality in the large ALTITUDE registry
of 3809 ICD recipients and in a meta-analysis of ICD trials in which ATP was applied
[155], [157]. Emotional morbidities associated with ICD shocks are well recognized
and include anxiety, depression, and posttraumatic stress disorders [174], [175],
[176]. Phantom shocks can result from fear and/or anxiety and have a reported incidence
of 5% in a European study of ICD recipients over 35 months of follow-up [177]. If
possible, and when safe, it is best to avoid both the discomfort and psychological
impact of shocks for ventricular arrhythmias, supraventricular arrhythmias, noise
events including lead failures, and for self-terminating arrhythmias, as is discussed
in the section on tachycardia detection. The 1500-patient MADIT-RIT study demonstrated
a mortality reduction by changing both tachycardia detection criteria and tachycardia
therapy (shocks and ATP). Therefore, it is difficult to assign the outcome result
to ATP, shocks, or both when compared with older, more conventional programming [126].
In addition, in a randomized study of remote follow-up of ICDs, home monitoring showed
an incidence of 52% fewer inappropriate shocks, 72% fewer hospitalizations due to
inappropriate shocks, 76% fewer capacitor charges, and a significant positive impact
on battery longevity [178].
31.1
ATP
Several large clinical trials have established the safety and efficacy of ATP as a
first-line therapy to treat even very fast VTs [93], [95], [101], [133]. The use of
first-line ATP involving VT at rates between 188 and 250 bpm in the PainFREE Rx II
trial resulted in a 71% relative shock reduction [93]. In the PREPARE study, a primary
prevention cohort of 700 patients was programmed with 30 of 40 detection intervals
with ATP- first for VT between 182 and 250 bpm with SVT discriminators active up to
200 bpm. The results demonstrated a robust absolute risk reduction for shocks at 1
year from 17% to 9% without an increase in arrhythmic syncope when compared with historical
controls [133]. Similar findings were noted in the RELEVANT study, which evaluated
a cohort of patients with nonischemic heart disease and cardiac resynchronization
defibrillators [95]. In the earlier EMPIRIC study, standardized VT detection and ATP
therapy parameters demonstrated a reduction in shocks when compared with physician-tailored
treatment in a randomized assessment of 900 primary prevention patients [101]. The
use of ATP during ICD capacitor charging has been clinically validated as safe and
effective [163]. It is important to recognize that inappropriate therapies including
inappropriate ATP, delivered primarily in the setting of supraventricular arrhythmias,
have been associated with increased mortality in the MADIT-RIT and MADIT-CRT trials
[156], [179]. However, the overall safety of ATP and its role as a contributor to
improved survival are well established, particularly in terms of preventing avoidable
ICD shocks.
31.2
Customized vs Strategic Programming
Because primary prevention patients have no prior ventricular arrhythmias, programming
individual devices on implant is largely empiric. There are more data for secondary
prevention patients, but how the patient will behave in the future is still uncertain.
The ability to individualize the antitachycardia programming for patients with both
primary and secondary prevention indications was tested in the EMPIRIC trial and found
to be an inferior approach to prevent these therapy events [101]. The application
of standardized programming and borrowing data from the PainFREE Rx II and PREPARE
studies resulted in a comprehensive review of programming and its application across
manufacturers.
31.3
Secondary Prevention
For the secondary prevention ICD patient, specific knowledge of the patient’s arrhythmia
history facilitates the creation of an effective antitachycardia programming strategy.
Using what is known about the ventricular arrhythmia, including any electrocardiograms,
available telemetry strips, and EMS recordings, provides insight into the arrhythmia
mechanism. In cases of monomorphic VT, discerning the rate (CL) and the hemodynamic
impact is useful in making choices, particularly for detection at a minimum; the device
must be programmed with active VT detection zones sufficient to cover the clinical
arrhythmia. Slower, monomorphic VT that is better tolerated hemodynamically favors
a robust approach using ATP termination with at least 2–3 sequences and at least 8
pulses. The use of a second burst of ATP has also been shown to increase effectiveness
from 64% to 83% in the fast VT range of 188 to 250 bpm [167]. Although a second burst
has clear value, value beyond 2 bursts is limited, except in rare situations [101].
The use of ICDs in patients with implanted LV assist devices allows prolongation of
detection times and programming of multiple ATP attempts without significant risk
to the patient, and it reduces the opportunity for shock therapies. Adjunct medications
and ablation of VT (or SVT) might also be considered for cases in which slow VT occurs
or if there is an overlap between the SVT and VT rates, leading to ICD therapies.
Table
Tachycardia Therapy Programming Recommendations
Class of Recommendation
Level of Evidence
It is recommended in all patients with structural heart disease and ATP-capable ICD
therapy devices that ATP therapy be active for all ventricular tachyarrhythmia detection
zones to include arrhythmias up to 230 bpm, to reduce total shocks except when ATP
is documented to be ineffective or proarrhythmic.
I
A
It is recommended in all patients with structural heart disease and ATP-capable ICD
therapy devices that ATP therapy be programmed to deliver at least 1 ATP attempt with
a minimum of 8 stimuli and a cycle length of 84%–88% of the tachycardia cycle length
for ventricular tachyarrhythmias to reduce total shocks, except when ATP is documented
to be ineffective or proarrhythmic.
I
A
It is indicated to program burst ATP therapy in preference to ramp ATP therapy, to
improve the termination rate of treated ventricular tachyarrhythmias.
I
B-R
It is reasonable to activate shock therapy to be available in all* ventricular tachyarrhythmia
therapy zones, to improve the termination rate of ventricular tachyarrhythmias.
IIa
C-EO
*Rarely, to limit patient discomfort and anxiety, hemodynamically stable slow VT can
be treated without programming a backup shock.
It is reasonable to program the initial shock energy to the maximum available energy
in the highest rate detection zone to improve the first shock termination of ventricular
arrhythmias unless specific defibrillation testing demonstrates efficacy at lower
energies.
IIa
C-LD
32
Intraprocedural Testing of Defibrillation Efficacy
The efficacy of the ICD for the primary and secondary prevention of SCD has been well
established in several landmark clinical trials [180], [181], [182], [183], [184],
[185]. Most of these trials have required induction, detection, and termination of
VF at the time of implantation as a measure of defibrillation efficacy and as a surrogate
of the ICD’s ability to prevent SCD. Testing defibrillation efficacy has been considered
an integral part of ICD implantation for many years, and it is performed to establish
the appropriate connection of high-voltage electrodes and to test the ability of the
ICD to detect and terminate VF with a shock. However, identifying system failures
or high defibrillation thresholds is difficult, mainly due to the low prevalence,
which also depends on the definition employed, about 5% combined. Significant improvements
over the past 2 decades have reduced energy requirements for defibrillation [186],
[187], [188], [189]. Similarly, current transvenous ICD technology is capable of delivering
energies of 35–40 J, raising the question of the value of routine defibrillation testing
(DT). Physicians have therefore gravitated to implanting ICDs with minimum or no DT
with wide variability in practice, despite a paucity of rigorous data. DT is currently
being performed during ICD implant in only about half the procedures [190], [191],
[192], [193], [194], [195]. Studies evaluating DT are summarized in Table 4.
One of the most important reasons to avoid DT at the time of ICD implantation is that
testing might result in complications or even death. The risks of DT include (1) those
related to VF itself, which can lead to circulatory arrest and hypoperfusion, (2)
risks related to the shocks delivered to terminate VT, and (3) risks related to anesthetic
drugs that are required for heavier sedation, which are used to provide patient comfort
during testing.
33
Periprocedural Mortality
Although improved ICD technology has led to the need for fewer inductions of VF at
the time of implantation testing, procedure-related mortality has not been completely
eliminated. Using modern ICD technology with transvenous systems and biphasic waveforms,
the perioperative mortality rate within 30 days of implantation is reported to be
0.2% to 0.4% [191], [196]. Recent data from the National Cardiovascular Data Registry
(NCDR) demonstrated an in-hospital mortality of 0.03% following ICD implantation,
with death occurring in the laboratory in 0.02% [196]. A Canadian report from 21 implanting
centers estimates that 3 of 19,067 deaths (0.016%) are related to DT.
34
DT-Related Complications
Complications occurring during ICD implantation procedures are infrequent, and many
can be directly or indirectly related to DT. Adverse effects related to DT include
myocardial injury, depression of contractile function leading to worsening of HF,
persistent hypotension, central nervous system injury, thromboembolic events, or respiratory
depression.
Transient central nervous system hypoperfusion and cerebral ischemic changes can be
demonstrated during intraoperative electroencephalographic (EEG) monitoring at the
time of DT. However, EEG recovery occurs within less than 30 seconds, with a slightly
longer time to the return of middle cerebral blood flow [197], [198], [199]. However,
the clinical relevance of this transient finding is unclear because DT does not appear
to cause cognitive dysfunction 24–48 hours following ICD implantation [200], [201].
Although an increase in biochemical markers of myocardial injury can be observed during
ICD implantation or after spontaneous clinical shocks, true intraoperative myocardial
infarction (MI) is rare, even when extensive DT is performed [202], [203], [204],
[205]. In 2 recent studies using transvenous ICDs and a more abbreviated testing protocol,
there was no significant increase in CK, CK-MB, myoglobin, and NT-proBNP before and
after DT, whereas elevated levels of high-sensitive troponin T were observed after
DT [206], [207]. In the NCDR ICD Registry, the incidence of MI during ICD implantation
was reported to be 0.02% [196].
Defibrillator shocks and VF transiently depress contractile function, although fatal
pulseless electrical activity is rare at the time of ICD implantation [202], [206],
[208], [209], [210]. Refractory VF has been reported to occur during DT, but this
is also uncommon, particularly with contemporary devices. One study reported that
all tested ICD shocks failed and at least 3 external rescue shocks were required in
0.5% of patients [203]. A Canadian study reported that 27 of 19,067 implants (0.14%)
required prolonged resuscitations during DT [211].
Thromboembolic complications can occur during DT in the presence of intracardiac thrombus
or when there are less than 3 weeks of therapeutic and uninterrupted anticoagulation
in the setting of AF. Stroke or transient ischemic attack (TIA) is reported to occur
in 0.026%–0.05% of cases [204], [211]. Multiple strategies have been employed, but
none were documented to reduce the incidence of thromboembolism, including the avoidance
of DT. These include preprocedure transesophageal echocardiography to exclude left
atrial appendage thrombus and deferring testing when a thrombus is identified, or
using transthoracic echocardiography to detect LV thrombi.
Anesthetic agents can contribute to complications related to a depressant effect on
myocardial contractility or can lead to respiratory depression if oversedation occurs.
Heavier sedation is typically used in patients undergoing DT. Although patients with
underlying chronic obstructive pulmonary disease or sleep apnea might be at increased
risk, oversedation and respiratory depression could occur in any patient. Randomized
trial data can help to identify which adverse events are directly (or indirectly)
related to DT. For example, stroke or TIA might be “directly” related to DT due to
dislodgment of intracardiac thrombus during conversion of AF in the absence of therapeutic
anticoagulation, and an episode of prolonged hypotension could result in reduced cerebral
perfusion. Respiratory depression, respiratory failure requiring intubation, or hypotension
might be direct results of DT or might be due to the drugs required to perform testing.
Pulseless electrical activity or even death can occur with hemodynamic complications
related to induction of VF or multiple external shocks. In contrast, DT can indirectly
increase the risk for pneumothorax, perforation, tamponade, lead dislodgment, or infection
as more leads are inserted, or the procedure might be prolonged due to the system
modifications required to improve defibrillation efficacy; however, all these complications
can also occur in the absence of DT. In addition, due to the rates and types of adverse
events reported in the literature, it appears that overall complication rates are
primarily driven by mechanical complications or infection, most of which are not related
to DT.
In a substudy of the Resynchronization for Ambulatory Heart Failure Trial (RAFT),
in which 145 patients were randomized to DT compared with no DT at the time of initial
ICD implantation, the risk of perioperative complications was extremely low, regardless
of DT performance [212]. There was, however, a nonsignificant increase in the risk
of death or HF hospitalization in the group that underwent DT. Likewise, no significant
difference in implant-related complications was demonstrated in DT compared with the
groups without DT in the Safety of Two Strategies of ICD Management at Implantation
(SAFE-ICD) study, a prospective observational study of 2120 patients performed at
41 centers [213]. Similar findings were observed in the prospective randomized Test-No
Test Implantable Cardioverter Defibrillator (TNT-ICD) pilot study on 66 patients,
in which there was no difference in adverse events between patients who underwent
testing compared with those who did not [214].
The Shockless Implant Evaluation (SIMPLE) trial is the largest randomized study assessing
the effect of DT on clinical outcomes [215]. This large-scale study randomized 2500
patients to DT or not at the time of ICD implantation; 1253 patients were randomly
assigned to DT and 1247 were assigned to no-testing, and were followed for a mean
of 3.1 years (SD 1.0). The primary outcome of arrhythmic death or failed appropriate
shock was noninferior (90 [7% per year]) in the no-testing group compared with patients
undergoing DT (104 [8% per year]; HR 0.86; 95% CI 0.65–1.14; P noninferiority P=.33).
The second, prespecified safety composite outcome, which included only events most
likely to be directly caused by testing, occurred in 3.2% of patients with no testing
and in 4.5% with DT (P=.08). Heart failure needing intravenous treatment with inotropes
or diuretics was the most common adverse event (in 20 of 1236 patients [2%] in the
no-testing group vs 28 of 1242 patients [2%] in the testing group, P=.25). In summary,
routine DT at the time of ICD implantation is generally well tolerated without a statistically
significantly increased rate of complications, but it also does not improve shock
efficacy or reduce arrhythmic death.
Finally, the No Regular Defibrillation Testing In Cardioverter Defibrillator Implantation
(NORDIC-ICD) trial, another prospective randomized parallel group multicenter noninferiority
trial conducted in 48 centers in Europe, assessed the effects of DT at the time of
ICD implantation on first shock efficacy [216]. The primary endpoint was different
from the SIMPLE trial and assessed the average first- shock efficacy for all true
VT and VF episodes occurring in any patient during follow-up. NORDIC-ICD randomized
540 patients to DT and 537 to no DT at the time of ICD implantation. During a median
follow-up of 22.8 months, the first shock efficacy was demonstrated to be noninferior
in the patients undergoing ICD implantation without DT, with a difference in first
shock efficacy of 3.0% in favor of the no- DT test group (95% CI 3.0%–9.0%; P noninferiority
procedure-related serious adverse events were reported within 30 days of ICD implantation
in 94 patients (17.6%) undergoing DT compared with 74 patients (13.9%) not undergoing
DT (P=.095). The authors concluded that defibrillation efficacy without DT was noninferior
to ICD implantation with DT in left-sided ICD implants. Because no major benefit or
harm associated with DT was detected, in patients with a left-sided pectoral implantation
it is reasonable to omit routine VF induction and DT during ICD implantation, assuming
stable ICD lead position and good sensing and capture function [217], [218], [219],
[220]. This approach is particularly applicable to patients with ischemic and idiopathic
dilated cardiomyopathy, given these entities were well represented in the studied
cohort. Patients well represented within the cohort included those with implantation
in the left pectoral location, those indicated for primary and secondary prevention
of SCD, and patients with ischemic and nonischemic cardiomyopathies. Fewer data are
available regarding other cardiomyopathies, such as patients with hypertrophic obstructive
cardiomyopathy, congenital channelopathies, patients undergoing generator replacement,
and procedures in the right pectoral location. In these instances, and when there
is any question of the adequacy of the lead position or function, DT is reasonable.
It is worth emphasizing that a nontesting strategy requires an anatomically well-
positioned defibrillation lead in the RV with adequate sensing of intrinsic R waves
(>5–7 mV), adequate pacing thresholds, and a thorough verification of proper lead
connection.
Other important considerations include the use of alternative RV defibrillation lead
sites such as the mid-septum. Pooled data from 2 randomized studies do not indicate
a clinically relevant elevation of energy required for defibrillation with mid-septal
sites. Positioning of the RV defibrillation lead in other positions such as the RV
outflow tract has not been systematically addressed [221].
The SIMPLE trial data were consistent between subgroups, both from patients with single-
or dual-coil ICD leads and with or without the use of amiodarone. More recently, the
Multicenter Comparison of Shock Efficacy Using Single vs Dual-Coil Lead Systems and
Anodal vs Cathodal Polarity Defibrillation in Patients Undergoing Transvenous Cardioverter-Defibrillator
Implantation (MODALITY) study was reported [222]. This was a multicenter registry
that prospectively followed 469 consecutive patients undergoing DT at the time of
implant; 158 (34%) had dual- coil and 311 (66%) had single-coil lead systems configuration,
254 (54%) received anodal shock, and 215 (46%) received cathodal shock. In 35 patients
(7.4%), the shock was unsuccessful. No significant differences in the outcome of DT
using a single- vs dual-coil lead were observed, but the multivariate analysis showed
an increased risk of shock failure using cathodal shock polarity (odds ratio [OR]
2.37; 95% CI 1.12–5.03). These and other registry data support the use of either single-
or dual-coil leads, preferably programmed to deliver anodal shocks [211], [213], [223].
Performing DT has not been determined to be harmful or inappropriate. One reason to
perform DT in specific populations is that high defibrillation thresholds have been
reported in 2.2% to 12% of subjects undergoing DT. The probabilistic nature of DT
with the failure of a single shock 10 J below the maximum ICD output does not necessarily
imply long-term ICD failure. Determinations of DT using multiple shock protocols have
reported that a safety margin of only 5.2–1.1 J has a 97.3% rate of successful VT/VF
conversion [224]; however, the inability to convert VF at maximum output occurs in
approximately 1% of procedures during DT. The long-term outcomes of these patients
have not been evaluated without modification of the lead system. Further supporters
of DT suggest that routine testing is necessary to identify system integrity and sensing
failures. R-wave amplitude ≤5–7 mV at implant almost invariably reliably sense VF
[190], [221]. Failure to sense and some inner insulation failures might only be detected
by DT. This situation has not been systematically evaluated.
35
Contraindications to Defibrillation Threshold Testing
A great paucity of systematic data limits the assessment of the literature regarding
contraindications to DT. Most implanters tend to avoid DT in patients perceived to
be at high risk. Information derived from an NCDR-ICD registry identified advanced
age, impaired LVEF, NYHA Class IV HF, atrial fibrillation/flutter, need to withhold
warfarin, and several other factors as high-risk situations. Unfortunately, the strength
of these associations was weak, given the ORs were under 2 [223]. Other registries
have identified patients with broader QRS durations, advanced NYHA class, and CRT
as reasons for not performing DT [213]. There are no convincing data to identify high-risk
patients, and clinical judgment has likely kept the highest-risk patients, particularly
those who were hemodynamically unstable, from being tested in the current literature.
36
S-ICD
Patients receiving a nontransvenous ICD system should routinely undergo DT, given
there are no current data regarding the safety and efficacy of not performing DT with
this lead configuration and device.
37
Conclusion
In providing focused recommendations for ICD programming and DT of patients implanted
with a device we have intentionally left many questions unanswered. There are hundreds
of choices for which there are inadequate data to provide evidence or consensus-based
recommendations. This document is a long overdue effort to provide analysis and guidance
to the clinician as to how to make strategic programming choices in the implementation
of ICD therapy. The four continental electrophysiology societies limited the discussion
and recommendations to four areas for which there was sufficient consensus and data.
In the review process, clearly articulated opinions pointed out that additional recommendations
are desirable. However, there is an information gap of insufficient data filled with
opinions and logical arguments. Generalizations and inferences were made from the
existing data, e.g., taking data from pacemaker trials and applying to this to ICD
bradycardia programming, logical arguments bridging the differences between primary
and secondary prevention patients for tachycardia detection and therapy, and the use
of noninferiority data to make decisions about DT. This document is a beginning, necessary
because there are now sufficient data to support recommendations that improve the
safety, morbidity, and mortality of patients with ICDs.