What Is the Minimal Pacing Rate that Prevents Permanent Pacemakers

Reprinted with permission from
JOURNAL OF PACING AND CLINICAL ELECTROPHYSIOLOGY, Volume 25, No. 11, November 2002
Copyright © 2002 by Futura Publishing Company, Inc., Armonk, NY 10504-0418.
What Is the Minimal Pacing Rate that Prevents
Torsades de Pointes? Insights from Patients with
Permanent Pacemakers
SERGIO L. PINSKI, LUIS E. EGUÍA, and RICHARD G. TROHMAN
From the Section of Cardiology, Rush-Presbyterian-St. Luke’s Medical Center and Rush Medical
College, Chicago, Illinois
PINSKI, S.L., ET AL.: What is the Minimal Pacing Rate that Prevents Torsades de Pointes? Insights From
Patients with Permanent Pacemakers. In the acquired long QT syndrome, torsades de pointes (TP) is invariably preceded by pauses or bradycardia. Thus, it has been proposed that out-of-hospital initiation of
drugs that prolong repolarization should be safe in patients with permanent pacemakers. However, a minimal protective pacing rate has not been identified. The authors reviewed published reports of acquired
TP in patients with permanent pacing. Those providing documentation of tachycardia onset and pacemaker programming were included in the analysis. Events occurring # 1 month after AV nodal ablation
were excluded. Eighteen cases were identified (age 74 6 5; 10 women). QT prolonging drugs were present
in 15 patients (quinidine 5, sotalol 3, disopyramide 3, amytriptiline, chloroquine, cisapride 1 haloperidol, and monopride 1 flecainide 1 each). Hypokalemia was present in eight patients. At the time of TP,
the programmed lower rate was 63 6 13 beats/min. However, the effective pacing rate was lower (55 6 11
beats/min) due to invocation of pause-promoting features (hysteresis [4 patients]; 1 PVARP extension on
PVC [1 patient]) or ventricular oversensing (2 patients). No patient developed TP with an effective pacing
rate . 70 beats/min. TP is possible in the presence of a functional permanent pacemaker. Programmed
lower rates # 70 beats/min are not protective. At programmed lower rates . 70 beats/min, TP may occur
only when facilitated by programmable pause-promoting features or oversensing. It remains to be seen if
rate smoothing algorithms can prevent TP when the baseline rate is programmed # 70 beats/min. (PACE
2002; 25:1612–1615)
pacemaker, artificial, torsades de pointes, proarrhythmia, quinidine; disopyramide, sotalol
Introduction
Torsades de pointes (TP) ventricular tachycardia occurring in the setting of acquired long QT
syndrome is almost invariably preceded by a
pause followed by a markedly prolonged QT interval.1– 3 An early beat (most often a premature
ventricular depolarization) arising from the prolonged T wave initiates torsades (i.e., the longshort sequence). Although the intimate electrophysiological mechanisms responsible for this
pattern are a matter of debate,4–6 it is well documented that temporary pacing, by suppressing the
pauses, can acutely prevent TP.7,8
Patients with permanent pacemakers, espe-
Address for reprints: Sergio L. Pinski, M.D., Cleveland Clinic
Florida, 2950 Cleveland Clinic Blvd., Weston, FL 33331. Fax:
(954) 659-5292; e-mail: [email protected].
Presented in part at the 22nd Annual Scientific Session of the
North American Society of Pacing and Electrophysiology
(NASPE), Boston, Massachusetts, May 2001.
Received August 16, 2001; revised September 28, 2001; accepted October 17, 2001.
1612
cially those with sick sinus syndrome, often require antiarrhythmic drug therapy for suppression
of concomitant atrial tachyarrhythmias. It has
been hypothesized that the risk of TP should be
low in patients with functional permanent pacemakers, making out-of-hospital initiation of antiarrhythmic drugs that prolong repolarization
safe in this population.9 In a large series of patients undergoing in hospital initiation of sotalol
for atrial tachyarrhythmias, the presence of a permanent pacemaker was the only variable that predicted freedom from proarrhythmic complications.10
To characterize the relation between pacing
rate and risk of TP (and hopefully identify a pacing rate that would make this arrhythmia unlikely), the authors searched the literature for reports of acquired TP in patients with permanent
pacemakers.9–21
Methods
Several strategies were used to identify the
relevant reports. Medline computerized searches
were conducted using the search words “torsade”
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PACE, Vol. 25, No. 11
MINIMAL PACING RATE TO PREVENT TP
and “pacemaker” and their variants (e.g., “polymorphic ventricular tachycardia,” “pacing,” etc).
Auxiliary searches were conducted using the
words “quinidine” and “pacemaker,” “sotalol”
and “pacemaker,” etc. Further searches included
all papers indicated as “related articles” in
PubMed for each relevant report. In addition, the
authors manually searched the bibliography of all
articles describing qualifying patients and of review articles on pharmacological proarrhythmia
or TP. Cases with clearly documented acquired TP
in the presence of a permanent pacemaker (or implantable defibrillator with pacing capabilities)
were included if information on the programmed
settings of the device plus a description of the intervals leading to arrhythmia initiation or electrocardiographic (ECG) documentation of its onset
were available. Good quality copies of ECG
recordings were magnified to allow measurement
of the relevant intervals with hand held calipers.
Cases were not included if the diagnosis of congenital long QT (Romano-Ward) syndrome could
be made on the basis of available information.22
Because the relationship between pacing rate and
QT duration is altered shortly after ablation of the
AV junction,23 cases occurring within 1 month of
this procedure were not included in the analysis.24
Results
Eighteen patients (10 women, 8 men) were
identified (Table I). Their age was 74 6 5 years
(range 64–82). Fifteen patients were taking drugs
known to prolong ventricular repolarization
(quinidine 5, sotalol 3, disopyramide 3, amytriptiline, chloroquine, cisapride 1 haloperidol, and
monopride 1 flecainide 1 each). Hypokalemia (#
3.5 mM/L) was present in at least eight patients
(information on potassium level was not provided
in six case reports).
The mean programmed lower rate at time of
TP was 63 6 13 beats/min (range 40–85). In 15
(88%) cases the pacemaker lower rate was set at #
70 beats/min. However, the effective pacing rate at
time of TP was lower, 55 6 11 beats/min (range
40–70), due to the operation of pause-promoting
algorithms (hysteresis in four patients; premature
ventricular atrial refractory period [PVARP] 1 in
premature ventricular contraction [PVC] in patient) or oversensing (myopotentials in 1 patient;
T wave in 1 patient). In no instance did TP occur
with an effective pacing rate . 70 beats/min. Figure 1 displays the distribution of programmed and
effective pacing rates at the onset of TP. In all the
patients reported, increasing the pacing rate or
disabling the pause promoting algorithms when
appropriate prevented arrhythmia recurrence.
Table I.
Clinical Characteristics and Pacemaker Programming
First Author
Age
Sex
Mode
Medication
Thompson (1976)11
Thompson (1976)11
Speca (1978)1 2
Iesaka (1982)13
79
77
70
64
M
M
M
M
VVI
VVI
VVI
VVI
Quinidine
Quinidine
None
Quinidine
Delia Bella (1990)14
Kimura (1994)1 5
Kimura (1994)1 5
Kimura (1994)1 5
Alt (1996)1 6
Kurita (1996)17
Chung (1998)10
Chung (1998)10
Goldman (1998)18
Pardo (1998)1 9
Pinski (1999)9
Pinski (1998)9
Ng (2000)2 0
Ohki (2000)2 1
75
71
77
69
82
74
78
74
71
81
75
70
81
68
M
F
F
F
F
F
F
M
F
F
F
M
F
M
VVI
VVI
VVI
VVI
VVI
DDI
DDD
VVI
DDD
VVI
DDD
VVI
VVI
DDD
Quinidine
Disopyramide
Disopyramide
Disopyramide
Chloroquine
None
Sotalol
Sotalol
None
Amytriptiline
Quinidine
Sotalol
Cisapride1haloperidol
Mosapride1flecainide
K
(mM/L)
LRL
(bpm)
Effective
Rate
(bpm)
N/A
N/A
3.2
N/A
70
70
72
85
60
60
60
30
Normal
3.2
2.6
2.9
3.5
3
3.4
Normal
N/A
3.6
N/A
N/A
Normal
3.2
70
50
60
70
40
70
60
40
85
70
50
44
70
60
50
50
60
70
40
70
60
40
61
70
50
44
60
60
Pause-Promoting
Feature
Hysteresis (60 bpm)
Hysteresis (60 bpm)
Hysteresis (50 bpm)
Oversending of
myopotentials
Hysteresis (50 bpm)
PVARP 1 on PVC
T wave overspending
bpm 5 beats per minute; LRL 5 programmed lower rate limit; N/A 5 not available; PVARP 5 premature ventricular atrial refractory
period; PVC 5 premature ventricular contraction.
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November 2002
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PINSKI, ET AL.
Figure 1. Histogram showing distribution of
programmed lower rates (LRL) and effective pacing rates
at the time of torsades de pointes in 18 patients.
Discussion
From this review of published cases of acquired TP in the presence of permanent pacing it
can be concluded that a pacemaker cannot provide reliable protection against this arrhythmia if
the programmed lower rate is # 70 beats/min. A
“protective” rate could not be identified, although
the limited available evidence suggests that at programmed rates . 70 beats/min, TP may be possible only after activation of device algorithms that
allow for the occurrence of pauses longer than the
lower rate limit or in case of ventricular oversensing. These findings have implications for patient
care. Initiation of antiarrhythmic drugs that prolong repolarization cannot be assumed absolutely
safe solely on the basis of a functional pacemaker
programmed at the usual lower rates of 60–70
beats/min.
One can speculate regarding why a heart rate
of $ 70 beats/min may be necessary to prevent TP.
Most drugs that prolong the QT interval do so more
at slow rates than at fast ones, a phenomenon
termed reverse use-dependence and this phenomenon probably contributes to the bradycardia
dependence of TP.25 There are few human studies
assessing the effects of Class III drugs on ventricular repolarization over a wide range of cardiac
rates. Visual inspection of the graph plotting QT
interval versus RR interval in a study of sotalol
suggests that the effect becomes more marked at
rates , 80 beats/min.26 Other evidence also indicate that the protective pacing rate may be slightly
. 70 beats/min. In a placebo-controlled trial of
dofetilide in patients with ICDs, pause dependent
polymorphic ventricular tachycardia (presumably
TP) was seen in stored electrograms in 15 (17%) of
87 patients assigned to dofetilide.27 The pro1614
grammed pacing rate was , 70 beats/min in 14 patients, and 70 beats/min in 1 patient. No detail was
provided regarding the effective pacing and initiating intervals. Among patients with congenital long
QT syndrome treated with a permanent pacemaker, recurrent arrhythmic events with pacing
rates , 75 beats/min are well documented.28
Several idiosyncratic or programmable functions can result in pacing at rates below the lower
rate limit. Hysteresis is the most obvious, and it
was operative in four of the patients in this study.
Although some investigators have recommended
hysteresis in patients with sinus node dysfunction
and single chamber ventricular pacemakers to
promote atrioventricular (AV) synchrony,29 it may
not reduce pacemaker use or improve patient
well-being.30 Circadian functions that automatically drop the stimulation rate during night hours
or patient inactivity are also a frequent cause of
lower rate limit overriding. Less known idiosyncratic features including, for example, atrial-based
timing after a late-coupled ventricular premature
beat, and the programmable “1 PVARP on PVC”
feature in Pacesetter/St. Jude (Sylmar, CA, USA)
pacemakers can result in pauses longer than the
programmed lower rate limit. In general, all these
algorithms should be avoided in patients with a
history of TP or risk factors for its development,
especially drugs that prolong repolarization.
The risk of TP is higher after a sudden drop
from persistently fast ventricular rates. Electrical
remodeling due to potassium channel down-regulation has been implicated.31 TP during pacing at
“usual” rates shortly after AV junction ablation in
patients with supraventricular tachyarrhythmias
is well documented, and faster pacing rates are
recommended for the first few days thereafter. In
addition, the authors have recently demonstrated
a high risk of ventricular tachyarrhythmia immediately after pacemaker reprogramming to usual
rates in patients “tracking” atrial tachyarrhythmias at rapid rates.32 The available clinical descriptions allowed them to rule out the role of a
preexistent fast ventricular rate in promoting TP
in most of the patients included in this analysis.
A relatively high baseline pacing rate (i.e., .
80 beats/min) could be programmed to prevent TP
in patients at risk. However, such fast rates can be
detrimental to patient well-being and, if maintained for long periods, can provoke myocardial
dysfunction.33 Alternatively, rate stabilization algorithms available in newer pacemakers and implantable defibrillators can eliminate post ectopic
pauses without the need to program fast baseline
rates.34 Early data suggest that they may be highly
effective in preventing TP in patients with congenital long QT syndrome.35 Given the common
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MINIMAL PACING RATE TO PREVENT TP
mechanisms that underlie the congenital and acquired long QT syndromes (including similar
molecular targets and frequent existence of mutations or polymorphisms in ion channel genes in
patients with otherwise “acquired” long QT36,37 )
the algorithms could also be efficacious in pre-
venting acquired TP. Prospective validation of this
hypothesis would be highly desirable. It should be
remembered that in some dual chamber pacemakers and defibrillators rate smoothing algorithms
may become inactive during mode switching in response to atrial tachyarrhythmias.38
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