Appropriate and Inappropriate Ventricular Therapies,
Quality of Life, and Mortality Among Primary and
Secondary Prevention Implantable Cardioverter
Defibrillator Patients
Results From the Pacing Fast VT REduces Shock ThErapies
(PainFREE Rx II) Trial
Michael O. Sweeney, MD; Mark S. Wathen, MD; Kent Volosin, MD; Ismaile Abdalla, MD;
Paul J. DeGroot, MS; Mary F. Otterness, MS; Alice J. Stark, RN, PhD
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Background—Implantable cardioverter defibrillators (ICDs) reduce mortality in primary and secondary prevention.
Quality of life, mortality, appropriate therapies for specific ventricular rhythms, and inappropriate therapies for
supraventricular tachycardia (SVT) were compared among 582 patients (primary prevention⫽248; secondary prevention⫽334) in PainFREE Rx II, a 634-patient prospective, randomized study of antitachycardia pacing or shocks for fast
ventricular tachycardia (FVT).
Methods and Results—ICDs were programmed identically with 3 zones (ventricular tachycardia [VT] ⬍188 bpm;
FVT⫽188 to 250 bpm; ventricular fibrillation [VF] ⬎250 bpm) but randomized to antitachycardia pacing or shock as
initial therapy for FVT. All treated episodes with electrograms were adjudicated. Primary prevention patients had lower
ejection fractions and more coronary artery disease. ␤-Blocker use, antiarrhythmic drug use, and follow-up duration
were similar. Over 11⫾3 months, 1563 treated episodes were classified as VT (n⫽740), FVT (n⫽350), VF (n⫽77), and
SVT (n⫽396). The distribution of VT, FVT, and VF was not different between primary and secondary prevention
patients (respectively, VT 52% versus 54%, FVT 35% versus 35%, and VF 14% versus 10%). More secondary
prevention patients had appropriate therapies (26% versus 18%, P⫽0.02), but among these patients, the median number
of episodes per patient was similar. Inappropriate therapies occurred in 15% of both groups and accounted for similar
proportions of all detected and treated episodes (46% in primary prevention patients versus 34% in secondary prevention
patients, P⫽0.09). Quality of life improved modestly in both groups, and mortality was similar.
Conclusions—Primary prevention patients are slightly less likely to have appropriate therapies than secondary prevention
patients, but episode density is similar among patients with appropriate therapies. SVT resulted in more than one third
of therapies in both groups, but quality of life and mortality were similar. (Circulation. 2005;111:2898-2905.)
Key Words: death, sudden 䡲 mortality 䡲 defibrillators, implantable 䡲 tachycardia, ventricular
䡲 tachycardia, supraventricular
I
mplantable cardioverter defibrillators (ICDs) reduce mortality among appropriately selected patients who have
survived an episode of life-threatening ventricular arrhythmia
(secondary prevention) or who are at risk for ventricular
arrhythmia (primary prevention).1–7 An important and unresolved issue is optimal application of ICDs in different
patient populations. In general, it has been postulated that
secondary prevention patients have a greater frequency of
spontaneous ventricular arrhythmia than primary prevention
patients; however, relatively little is known about the comparative incidence of appropriate therapies for specific ventricular arrhythmias, susceptibility to inappropriate therapies
due to supraventricular tachycardia (SVT), and quality of life
(QoL) and mortality outcomes. Although ⬎90% of all episodes of ventricular tachycardia (VT) can be terminated
painlessly by antitachycardia pacing (ATP), painful shocks
remain a significant problem. A correlation between poorquality QoL scores and ICD shocks has been shown.8 –10 We
Received November 30, 2004; revision received February 3, 2005; accepted March 1, 2005.
From Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (M.O.S.); Vanderbilt University Medical Center, Nashville, Tenn
(M.S.W.); University of Pennsylvania, Philadelphia, Pa (K.V.); Amarillo Heart Group, Amarillo, Tex (I.A.); and Medtronic, Inc, Minneapolis, Minn
(P.J.D., M.F.O., A.J.S.).
Guest Editor for this article is Douglas P. Zipes, MD.
Correspondence to Michael O. Sweeney, MD, Cardiac Arrhythmia Service, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail
[email protected]
© 2005 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/CIRCULATIONAHA.104.526673
2898
Sweeney et al
ICD Therapies in Primary and Secondary Prevention
compared appropriate and inappropriate ventricular therapies,
QoL, and mortality according to primary or secondary prevention ICD indication in PainFREE Rx II, a prospective,
randomized study of ATP or shocks for fast ventricular
tachycardia (FVT).11
Methods
Study Design
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The study design was a retrospective subgroup analysis derived from
the Pacing Fast VT REduces Shock ThErapies (PainFREE Rx II)
trial, a prospective, randomized, multicenter study that tested
whether empirical ATP is as safe and effective for FVT as shocks
and affords a better QoL in a general ICD population.11 Only patients
believed unlikely to have substrate for stable monomorphic VT
susceptible to pace termination (eg, long-QT syndrome, Brugada
syndrome, or hypertrophic cardiomyopathy) were excluded. Six
hundred thirty-four patients were randomized at implantation to
either ATP (n⫽313) or shock (n⫽321) as the first therapy for FVT.
All patients were seen every 3 months over a mean follow-up
duration of 11⫾3 months (including patients who died). Stored ICD
data were transferred to a central database for analysis.
Device Description and Programming
A detailed description of the PainFREE Rx II study design and
device programming has been described.11 Device programming was
standardized with the exception of the initial randomized therapy for
FVT. Defibrillation thresholds (DFTs) were determined by binary
search at implantation. Only Medtronic ICDs capable of programming an FVT detection zone defined within the ventricular fibrillation (VF) zone (FVT via VF) for a cycle length of 240 to 320 ms
(250 to 188 bpm) were used. In the ATP arm, the first therapy in the
FVT zone was a single burst of 8 pacing pulses; failed ATP was
followed by shock at a DFT of 10 J, then by maximal energy shocks
as necessary. In the shock arm, first therapy was a DFT of 10 J
followed by maximal energy shocks. A VT zone with a cycle length
of 320 to ⱖ360 ms (ⱕ167 to 188 bpm) was programmed in all
patients, and the first therapy was 3 sequences of ATP. SVT
discrimination was programmed “on” in the VT zone of all dualchamber ICDs but was left to the discretion of the investigator for
single-chamber ICDs.
Definition of Primary and Secondary Prevention
ICD Indications and Specification of Subgroups
for Analysis
Primary prevention indication for ICD therapy was defined as (1)
coronary artery disease (CAD), nonsustained VT, ejection fraction
(EF) ⬍40%, and inducible sustained VT/VF4,5; (2) CAD, prior
myocardial infarction, and EF ⬍30%12; or (3) other (CAD, nonsustained VT, EF ⱖ40%, and inducible VT/VF). Secondary prevention
indication was defined as (1) VF or cardiac arrest without transient
or reversible cause,1–3 (2) spontaneous sustained VT with structural
heart disease,1,3 or (3) spontaneous syncopal VT or syncope of
unknown etiology and inducible sustained VT/VF.3
Of 634 patients randomized, 248 had a primary prevention
indication, 334 had a secondary prevention indication, and 52 had a
nonstandard indication for ICD therapy. Therefore, 582 patients were
the subjects of the present analysis.
Rhythm Classification and Definitions
All spontaneous episodes with stored electrograms that resulted in
ventricular therapies were reviewed and classified by the principal
investigator at each site and by at least 1 member of an episode
review committee that consisted of 5 electrophysiologists.11 The
present analysis was restricted to only adjudicated episodes that
resulted in ventricular therapies. True ventricular detections were
defined as device-detected VT/VF episodes that were confirmed to
be ventricular in origin after adjudication by the episode review
committee.
2899
QoL Assessment
Self-reported health-related QoL was measured at baseline and at 12
months with the Medical Outcomes Study 36-item Short-Form
General Health Survey (SF-36) that included 8 subscales and 2
summary measurements.13 SF-36 scores range from 0 to 100, with
higher scores representing better QoL. The change in score from
baseline to 12 months was compared between ICD-indication groups
for each scale.
Statistical Methods
To adjust for multiple episodes per patient, the generalized estimating equations method was used in calculations of detection, therapy
delivery, and cycle lengths unless otherwise noted.14 Baseline QoL
and change in QoL over time were compared between randomization
groups with a Wilcoxon test. Paired nonparametric exact methods
were used to compare the change in QoL over time for each patient.
Mortality and shock survival were compared between ICD indication
groups by Kaplan-Meier estimation. All tests were performed at the
5% type I error level. The Hochberg method was used to adjust the
testing levels for demographic comparisons, to account for multiple
comparisons.15 Statistical analyses were performed with SAS (version 8).
Results
Description of ICD-Indication Groups and
Baseline Characteristics
Primary Prevention Indication
The majority of primary prevention patients had CAD,
nonsustained VT, EF ⬍40%, and inducible sustained VT/VF
(195/248, 79%). Only 17 (7%) of 248 had CAD and EF
⬍30% but no electrophysiology study, because enrollment
was largely completed before adoption of the Multicenter
Automatic Defibrillator Implantation Trial II indication.12 A
slightly larger subset (36/248, 15%) had CAD, nonsustained
VT, and inducible sustained VT/VF but EF ⱖ40%.
Secondary Prevention Indication
The majority of secondary prevention patients had spontaneous sustained VT (with or without syncope) and EF ⬍40% or
syncope, inducible sustained VT/VF, and EF ⬍40% (257/
334, 77%). The remaining patients (77/334, 23%) were
cardiac arrest survivors.
Primary prevention patients had lower EF and more CAD.
␤-Blocker use, antiarrhythmic drug use, and length of
follow-up were similar between groups (Table 1).
Spontaneous Ventricular Detections
Among the 3806 spontaneous episodes retrieved from ICD
counters that satisfied ventricular detection criteria, 1563
(41%) had complete data that included electrograms and were
analyzed. Missing data were due to ICD memory limitations,
incomplete interrogation, or cleared memory. The proportion
of patients with missing electrograms for spontaneous episodes was similar between primary (13%) and secondary
(18%) prevention groups. After generalized estimating equation adjustment for multiple episodes in some patients, there
was also no difference in the number of missing episodes
between primary and secondary prevention groups (22%
versus 25%, P⫽0.45).
Of the 1563 spontaneous episodes with stored electrograms, 396 (25%, unadjusted) were determined to be inappropriately detected SVT. The remaining 1167 (75%, unad-
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June 7, 2005
TABLE 1.
Patient Demographics and Baseline Characteristics of Study Population
Baseline Characteristic
Primary Prevention
Group (n⫽248)
Secondary Prevention
Group (n⫽334)
All Patients
(n⫽582)
P
Age, y
70⫾10
67⫾11
68⫾11
⬍0.01
Male, n (%)
207 (83)
253 (76)
460 (79)
0.02
242 (98)
287 (86)
529 (91)
⬍0.001
6 (2)
47 (14)
53 (9)
Cardiac substrate, n (%)*
CAD
Non-CAD
Previous revascularization, n (%)
CABG*
PCI
Ejection fraction, %*
145 (58)
149 (45)
294 (51)
0.001
83 (33)
113 (34)
196 (34)
NS
29⫾10
33⫾13
31⫾12
⬍0.001
NYHA class, n (%)
I
18 (7)
30 (9)
48 (8)
NS
145 (58)
153 (46)
298 (51)
⬍0.01
1 (0)
8 (2)
9 (2)
NS
69 (28)
70 (21)
139 (24)
NS
6 (2)
2 (1)
8 (1)
NS
16 (6)
9 (3)
25 (4)
0.04
SMVT*
0
156 (47)
156 (27)
⬍0.001
PMVT/VF*
0
81 (24)
81 (14)
⬍0.001
154 (62)
197 (59)
351 (60)
NS
1 (0)
2 (1)
3 (1)
NS
Digoxin
91 (37)
92 (28)
183 (32)
0.02
Amiodarone
0.02
II–III*
IV
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Prior SVT, n (%)
Atrial fibrillation
Atrial tachycardia
Other SVT
Spontaneous ventricular arrhythmia, n (%)
Cardiac medications, n (%)
␤-Blockers
Calcium channel blockers
30 (12)
66 (20)
96 (16)
Sotalol
9 (4)
10 (3)
19 (3)
NS
Class I antiarrhythmics
2 (1)
6 (2)
8 (1)
NS
NS
ICD system, n (%)
Single chamber
Dual chamber
Follow-up, mo
59 (24)
90 (27)
149 (26)
189 (76)
244 (73)
433 (74)
11⫾3
11⫾3
11⫾3
NS
PCI indicates percutaneous coronary intervention; NYHA, New York Heart Association; SMVT, sustained
monomorphic VT; PMVT, polymorphic VT; and class I antiarrhythmics, procainamide, quinidine, or disopyramide.
*Difference is significantly different after adjustment for multiple comparisons.
justed) episodes were true ventricular arrhythmias that were
detected as VT (740 episodes [47%], unadjusted), FVT (350
episodes [22%], unadjusted), and VF (77 episodes [5%],
unadjusted).
Among the 191 patients with 1 or more detected VT/VF
episodes (median 3, 75th percentile 9, 95th percentile 35,
range 1 to 91), we found that 12 (16%) of 73 of the primary
prevention patients and 32 (27%) of 118 of the secondary
prevention patients had episode counts over the collective
75th percentile (P⫽0.09), whereas 1 (1%) of 73 of the
primary prevention patients and 7 (6%) of 118 of the
secondary prevention patients had episode counts above
the collective 95th percentile (P⫽0.16). Thus, we found no
evidence of a difference in proportion of patients with large
episode counts between the 2 indication groups.
Rhythm Classification by ICD-Indication Group
The distribution of VT, FVT, and VF was similar between
primary and secondary prevention groups (VT 150/315
[52%] versus 590/852 [54%], P⫽NS; FVT 134/315 [35%]
versus 216/852 [35%], P⫽NS; VF 31/315 [14%] versus
46/852 [10%], P⫽NS; Figure 1).
Shocks by Rhythm Classification and
ICD-Indication Group
The rhythm classification of true ventricular detections with
stored electrograms that resulted in shocks by ICD-indication
group are shown in Figures 2 and 3. The proportion of true
ventricular detections that resulted in shocks was similar
between primary and secondary prevention groups (40%
versus 32%, respectively). The proportion of inappropriate
Sweeney et al
ICD Therapies in Primary and Secondary Prevention
2901
Figure 1. Classification of true ventricular detections by ICD
indication.
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ventricular detections due to SVT that resulted in shocks was
also similar between primary and secondary prevention
groups (44% versus 42%, respectively).
Cycle Lengths of VT, FVT, and VF by
ICD-Indication Group
After adjustment for multiple episodes per patient, there were
no significant differences in cycle lengths of VT, FVT, or VF
between groups (Table 2).
Figure 3. Percent of true ventricular detections shocked in primary (top) and secondary (bottom) prevention patients by
rhythm classification. Percentages are generalized estimating
equation–adjusted and thus are not necessarily additive.
Relative Frequency of Appropriate and
Inappropriate Ventricular Therapies by
ICD-Indication Group
3), but among all patients with appropriate therapies, the
median number of episodes per patient was similar between
groups. Similarly, the proportion of patients with at least 1
episode that resulted in inappropriate therapy was not different. The relative proportion of inappropriate episodes that
The proportion of patients with at least 1 appropriate therapy
was slightly higher in the secondary prevention group (Table
Figure 2. Raw data for all detected and
treated episodes by primary (top) and
secondary (bottom) prevention patients
(pts).
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June 7, 2005
TABLE 2. Cycle Lengths of Detected Ventricular
Tachyarrhythmias by Primary or Secondary Prevention
ICD Indication*
TABLE 4. Relative Frequency of Shocks by Primary or
Secondary Prevention ICD Indication
Primary
Prevention
(n⫽248)
Primary
Prevention
(n⫽248)
Secondary
Prevention
(n⫽334)
P
Mean VT CL
351⫾3
362⫾6
NS
Total shocks, mean/patient (total)
Mean FVT CL
289⫾5
299⫾5
NS
Shocked patients, n (%)
All VT/FVT CL
324⫾6
334⫾6
NS
Shocks/shocked patient, n
Mean VF CL
231⫾3
222⫾4
0.10
Appropriate detections shocked*
Mean SVT CL
338⫾5
352⫾6
NS
Total shocks, mean (total)
Ventricular detections shocked*
CL indicates cycle length (in milliseconds).
*Statistics reported are the generalized estimating equation–adjusted mean
and SE.
Shocked patients, n (%)
Shocks/shocked patient, mean
Inappropriate detections shocked*
P
NS
43%
38%
0.77 (190)
1.24 (414)
NS
49 (20)
78 (23)
NS
3.88
5.31
NS
40%
32%
NS
0.40 (98)
0.66 (221)
NS
28 (11)
50 (15)
NS
3.5
4.42
NS
NS
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44%
42%
0.37 (92)
0.58 (193)
NS
Shocked patients, n (%)
23 (9)
30 (9)
NS
Shocks/shocked patient, mean
4.00
6.43
NS
resulted in spurious therapy was greater in the primary
prevention group, but the difference was not significant.
Total shocks, mean (total)
Relative Frequency of Shocks by
ICD-Indication Group
More shocks were delivered in the secondary prevention
group (total shocks n⫽414, 1.24 shocks/patient) than in the
primary prevention group (total shocks n⫽190, 0.77 shocks/
patient); however, the proportion of true and spurious ventricular detections that resulted in shocks was not different
(primary 43% versus secondary 38%; Table 4). Similarly,
there was no difference between groups in the proportion of
patients who received any shocks (appropriate or
inappropriate).
Secondary
Prevention
(n⫽334)
*Generalized estimating equation adjustment to account for multiple episodes in some patients.
Quality of Life
Baseline or 12-month QoL surveys were missing in 156
(27%) of 582 study patients, including 55 patients who died.
QoL was analyzed in the remaining 426 patients who were
alive at 12 months (primary prevention 186 [44%] of 426,
secondary prevention 240 [56%] of 426). There were no
Time to First Shock for VT/VF by
ICD-Indication Group
The time from enrollment to first appropriate shock was not
different between groups, nor was time to first inappropriate
shock (Figure 4).
TABLE 3. Frequency of Appropriate and Inappropriate
Ventricular Detections in Primary and Secondary Prevention
ICD-Indication Patients*
Primary
Prevention
(n⫽248)
Secondary
Prevention
(n⫽334)
P
Percentage of patients with
ⱖ1 appropriate detection
18
26
0.02
Percentage of patients with
ⱖ1 inappropriate detection
15
15
NS
2
3
NS
VT
52
54
NS
FVT
35
35
NS
VF
14
10
NS
46
34
0.09
Median number of appropriate
detections†
Subclassification of appropriate
detections, %‡
Proportion (%) of detections that
were inappropriate‡
*Includes detected and treated episodes only, excluding self-terminating
episodes. Treatment includes shocks and ATP.
†Among patients with ⱖ1 appropriately detected episodes.
‡Generalized estimating equation adjustment to account for multiple episodes in some patients.
Figure 4. Top, Time to first appropriate shock by ICD indication.
Bottom, Time to first inappropriate shock by ICD indication.
Sweeney et al
ICD Therapies in Primary and Secondary Prevention
2903
Figure 5. Change in QoL scores at 12
months by ICD-indication groups. P1
indicates physical functioning; P2, role
physical; P3, bodily pain; P4, general
health; M1, vitality; M2, social functioning; M3, role emotional; and M4, mental
health.
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significant differences in baseline demographic variables
between patients with or without complete QoL data.
There were no significant baseline differences in any of the
10 components of the SF-36 between groups. Both primary
and secondary prevention groups experienced a significant
improvement in 7 of 10 components of the SF-36 between
baseline and 12 months. The improvement in physical and
mental health summary scores over 12 months was similar
(Figure 5).
Total Mortality Rates
There was no difference in total mortality rates between
groups. Twenty-two (9%) of the primary prevention patients
died, whereas 33 (10%) of the secondary prevention patients
died within 12 months of enrollment.
Modification to ICD Detection Programming
Ventricular Detection
Because ventricular rate and duration thresholds are the
primary determinants for recognition of spontaneous
tachycardia, these were standardized at enrollment. Modification of detection parameters owing to changing patient
conditions could result in reporting bias between comparison
groups. Accordingly, changes in detection parameters were
tracked during the study. VF and FVT detection parameters
were modified in an equivalently small percentage of patients
(9% of both primary and secondary prevention patients)
during follow-up.
VT detection parameters were modified more frequently in
secondary versus primary prevention groups (15% versus 9%,
P⫽0.04). Twenty-two patients (9%) in the primary prevention group had at least 1 change in the VT detection interval
during follow-up. Of these, the VT detection interval was
decreased in 18 patients (7%) and increased in 9 (4%). Five
patients (2%) had both an increase and a decrease. Forty-nine
patients (15%) in the secondary group had at least 1 change
in VT detection interval. Of these, the VT detection interval
was decreased in 29 patients (9%) and increased in 28 (8%).
Eight patients (2%) had both an increase and a decrease.
SVT Discrimination
There was no difference in single-chamber (24% versus 27%)
or dual-chamber (76% versus 73%) ICD systems between
primary versus secondary prevention groups, respectively.
SVT discrimination was programmed “on” during follow-up
in all dual-chamber ICD patients, in compliance with required
study programming. SVT discrimination was programmed
“on” at the investigator’s discretion in 16% of all singlechamber ICD patients.
Discussion
The 3 main findings of the present study are that (1) primary
prevention patients are slightly less likely to have appropriate
therapies than secondary prevention patients, (2) inappropriate detection of SVTs accounts for more than one third of
therapies in both groups, and (3) QoL and mortality are
similar between groups. Although primary prevention patients received statistically fewer appropriate therapies for
ventricular arrhythmias within the first year of follow-up, the
difference was slight (18% versus 26%). Furthermore, among
patients in either group with at least 1 appropriate therapy,
there was no difference in median number of episodes per
patient. The absolute rate of appropriate ventricular therapies
was less in primary versus secondary prevention patients,
consistent with an analysis of Multicenter InSync RAndomized CLinical Evaluation ICD (MIRACLE ICD).16
The majority of true ventricular episodes in both groups
were due to VT and FVT. VF accounted for only ⬇12% of
total episodes in both groups. There was no difference in the
relative frequency of VT, FVT, or VF between primary and
secondary prevention groups. Furthermore, there was no
difference in cycle lengths of VT, FVT, VF, or SVT between
groups. This is notably different from the analysis by Wilkoff
et al,16 in which primary prevention patients had a significantly higher percentage of device-classified VF than secondary prevention patients (40% versus14%). They also showed
that the median cycle length of true ventricular rhythms was
significantly shorter in primary versus secondary prevention
patients (303⫾53 versus 367⫾54 ms). There are several
possible explanations for these differences. Because an FVT
zone was not used in MIRACLE ICD, it is likely that many
episodes of potentially pace-terminable rapid monomorphic
VT were detected as VF. Additionally, 44% of patients in the
primary prevention group had nonischemic dilated cardiomyopathy and no history of sustained VT or syncope and
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June 7, 2005
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therefore did not meet existing guidelines for ICD therapy
during the time the study was conducted. This patient
population has a lower event rate than the ischemic cardiomyopathy population, and mortality reductions with ICD
therapy have been either impossible to demonstrate17,18 or
more modest7,19 than in ischemic cardiomyopathy. Our observation that VT and FVT occur with similar frequency in
primary and secondary prevention patients is important because we have previously demonstrated that the majority of
these rhythms can be terminated by ATP.11,20 Furthermore,
reduction of painful shocks by ATP may improve QoL.
Numerous variables may affect the rate of inappropriate
ventricular therapies in ICD patients, including prior history
of SVT, atrioventricular conduction status, use of drugs that
may slow atrioventricular conduction or suppress SVT, and
tachycardia detection and therapy programming. Of these, the
latter is probably the most important. Longer VT detection
cycle lengths will increase the probability of inappropriate
detections due to rapidly conducted SVTs, and the cycle
lengths of inappropriately detected SVTs may be different
between primary and secondary prevention patients, possibly
related to mechanism of SVT.16 Additionally, some studies
have reported that the cycle lengths of appropriately detected
VT may be longer in secondary than in primary prevention
patients16 and that the difference in cycle lengths between
appropriately detected VT and inappropriately detected SVT
may be greater in primary prevention patients.16,21 One
possible interpretation of these data are that rate-based
programming to achieve the optimal balance between VT
detection and SVT rejection is different between primary and
secondary prevention patients. This is not supported by the
present study. We observed no difference in detected VT
cycle lengths between the primary and secondary prevention
groups. The zeal for reducing the probability of inappropriate
therapies by eliminating a slow-VT detection zone must be
balanced against the risk of failing to treat unanticipated VT.
Arbitrarily choosing a shorter VT detection interval in the
primary prevention group could have been hazardous for
individual patients, because undetected slow VT may result in
hemodynamic collapse.22
Inappropriate therapies due to misclassification of rapidly
conducted SVTs occurred in 15% of both patient groups and
accounted for more than one third of all therapies and ⬇40%
of all shocks in both groups. Although SVT discrimination
was equivalently underutilized in the minority of patients
with single-chamber ICDs in both groups, this is consistent
with the reported rates of inappropriate therapies in other
trials of secondary16,23,24 and primary16,19,21 prevention. These
observations emphasize that despite increasingly sophisticated enhancements to single- and dual-chamber ICD systems that rely on rate-based detection, rejection of SVT while
maintaining high sensitivity for true ventricular arrhythmias
remains elusive.25–27 Because there were fewer patients with
appropriate ventricular episodes in the primary prevention
group, inappropriate episodes accounted for a higher proportion of all episodes than in the secondary prevention group. A
similar pattern was reported by Wilkoff et al,16 although the
difference in proportion of inappropriate episodes between
primary and secondary prevention groups was not significantly different in the present study.
This issue is important, because one of the principal
limitations of ICD therapy is the discomfort associated with
shocks. A direct correlation between poor QoL scores and
shocks has been described in ICD trials of primary9 and
secondary8,10 prevention; however, none of these studies
compared QoL between primary and secondary prevention
indication groups. We found no difference in measures of
QoL between primary and secondary prevention patients.
Similarly modest improvements in QoL occurred in both
groups over 12 months. This may reflect the reduction in
appropriate shock burden due to ATP, although further
investigation is necessary to confirm this hypothesis.
Study Limitations
This was a retrospective (not prospectively defined) subgroup
analysis; the study was not originally designed to evaluate
differences between ICD-indication groups. Results are thus
hypothesis generating rather than confirmatory in nature.
Follow-up was only 1 year, perhaps not long enough to
validly measure and compare the proportion of patients with
appropriately detected episodes by ICD-indication group. The
small sample size might account for a failure to detect
important differences between groups, particularly for QoL
and episode distributions.
Conclusions
Although primary prevention patients are slightly less likely
to experience at least 1 appropriate detection, we detected no
difference in episode density among primary and secondary
prevention patients who experienced at least 1 appropriately
detected episode. SVT accounts for more than one third of all
therapies in both groups but a higher proportion of total
therapies in primary prevention patients. Despite this, QoL
improved modestly in both groups, and mortality was similar.
Disclosure
Dr Sweeney has served as a paid consultant to and participated in
clinical trials for Medtronic, Inc. Dr Wathen has served as a
consultant to Medtronic, Inc., and has conducted research for
Medtronic, Guidant, and St. Jude Medical. Dr Volosin has conducted
research and given lectures for Medtronic, Guidant, and St. Jude
Medical. Mary Otterness, Dr Alice Stark, and Paul DeGroot are
employed by Medtronic.
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