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From the Division of Cardiology, Department of Medicine, National
Yang-Ming University School of Medicine (S.-H.L.), and Veterans General
Hospital-Taipei, Taipei, Taiwan.
Correspondence to Shih-Ann Chen, MD, Division of Cardiology, Veterans General Hospital-Taipei, 201 Sec 2, Shih-Pai Rd, Taipei, Taiwan. E-mail sachen{at}vghtpe.gov.tw
Methods and Results—Seventy adult patients without structural
heart disease were included. For the first part of the study, right
atrial ERP was measured with a drive cycle length of 500 ms before and
after 10 minutes of rapid atrial pacing using five pacing cycle lengths
(450, 400, 350, 300, and 250 ms) in 10 patients. For the second part of
the study, the remaining 60 patients were included to study the effects
of antiarrhythmic drugs on changes in atrial ERP induced by AF. Atrial
ERP was measured with a drive cycle of 500 ms before and after an
episode of pacing-induced AF. After the patients were randomized to
receive one of six antiarrhythmic drugs (procainamide,
propafenone, propranolol, dl-sotalol,
amiodarone, and verapamil), atrial ERP was measured
before and after another episode of pacing-induced AF. In the first
part of the study, atrial ERP shortened significantly after 10 minutes
of rapid atrial pacing, and the degree of shortening was correlated
with pacing cycle length. The second part of the study showed that
atrial ERP shortened after conversion of AF (172±15 versus 202±14 ms,
P<0.0001) and that ERP shortening was attenuated after
verapamil infusion (-4.6±1.2% versus -15.1±3.4%,
P<0.001) but was unchanged after infusion of the other
antiarrhythmic drugs. Furthermore, all of these antiarrhythmic drugs
could decrease the incidence and duration of secondary AF.
Conclusions—The atrial ERP shortening induced by
tachycardia was a rate-dependent response.
Verapamil, but not other antiarrhythmic drugs, could
markedly attenuate this effect. However, verapamil and the
other drugs could decrease the incidence and duration of secondary AF.
Electrophysiological Testing
Study Protocol
The mean atrial capture threshold was 0.58±0.20 and 0.56±0.22 mA for
the right atrial appendage and high lateral free wall, respectively.
Pacing was performed at twice the diastolic threshold.
Atrial ERP was measured by an incremental technique, with 2-ms steps at
basic drive cycle lengths of 500 ms for eight beats. Atrial ERP was
defined as the longest
S1-S2 coupling interval
that failed to result in atrial capture. The baseline atrial ERP was
measured three times and averaged. In the present study, atrial ERP
refers to the effective refractory period of the right atrial
appendage.
Rate Dependency Study
Antiarrhythmic Drug Study to Assess Changes in Atrial ERP
After AF
Statistical Analysis
Changes in ERP After AF
Recovery of the Atrial ERP Change
To assess the effect of a secondary episode of AF on the course of
recovery of atrial ERP, the temporal recovery curves of ERP were
plotted for patients with and without a secondary episode of AF (Figure 2
Effects of Antiarrhythmic Drugs
Effects of Antiarrhythmic Drugs on Post-AF ERP
Change
Inducibility of Secondary AF After Antiarrhythmic Drugs
After infusion of antiarrhythmic drugs, 26 secondary episodes of AF
were unintentionally induced in 17 patients while their post-AF atrial
ERP was being measured (1.6±1.1 episodes per patient). The onset of
the first episode of secondary AF was 40±34 ms after termination of
AF. The duration of secondary AF was shorter than that before drug
infusion (32±26 versus 55±73 seconds, P<0.001). In
addition, the A1-A2
coupling interval that induced secondary AF was longer than that before
drug infusion (187±26 versus 169±19 ms, P=0.005). Thus,
antiarrhythmic drug infusion reduced the inducibility of secondary AF.
The results also showed that the patients with secondary AF after
antiarrhythmic drugs were the same patients who had experienced
secondary AF before antiarrhythmic drug infusion.
Comparison among the different groups before administration of drugs
showed that the number of patients with secondary episode of AF, the
number of AF episodes per patient, the onset of the first episode of
secondary AF, and the duration of secondary episodes of AF were
similar. Furthermore, comparison among the different groups after
administration of drugs showed that the aforementioned
parameters were also similar.
Rate Dependency of ERP Shortening of the Atria
Effects of Antiarrhythmic Drugs on Tachycardia-Induced
Change in Atrial ERP and Secondary AF
On the other hand, potassium channels play a critical role in
repolarization, and changes in potassium channel function can affect
the measurement of ERP.31 In this study, we
demonstrated that class III antiarrhythmic drugs (dl-sotalol
and amiodarone), despite their effects on prolongation of ERP,
could not prevent the change in ERP induced by short-duration AF. These
data suggested that potassium channels might not play a critical role
in the change in ERP induced by AF of short duration.
Effects on Secondary AF
The results of the current study and of the one by Daoud et
al30 both showed that verapamil could
significantly decrease the incidence of secondary AF. In contrast to
the study of Daoud et al, we found that procainamide also
significantly prevented secondary AF. In the study by Daoud et al, they
set the prolongation of atrial ERP at
Study Limitations
Clinical Implications
Conclusions
Received September 9, 1997;
revision received January 20, 1998;
accepted February 4, 1998.
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© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Tachycardia-Induced Change of Atrial Refractory Period in Humans
Rate Dependency and Effects of Antiarrhythmic Drugs
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Background—Atrial fibrillation (AF)
has been shown to shorten the atrial effective refractory period (ERP)
and make the atrium more vulnerable to AF. This study investigated the
effect of atrial rate and antiarrhythmic drugs on ERP shortening
induced by tachycardia.
Key Words: antiarrhythmia agents • atrium • fibrillation • electrophysiology
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
Atrial fibrillation
(AF) is a common cardiac arrhythmia. It is frequently
associated with disabling symptoms and has been shown to increase
cardiovascular morbidity and mortality, even in
patients without underlying heart disease.1 2 3 4
Epidemiological studies have shown that paroxysmal AF can progress to
chronic AF in patients with or without underlying structural heart
disease.5 6 In addition, the incidence of
successful restoration and maintenance of sinus rhythm was
higher in patients with recent-onset AF than in those with chronic
AF.7 8 These findings suggested that AF was a
progressive disease and that AF might be self-perpetuating. Wijffels et
al9 demonstrated that maintenance of AF
by pacing in the normal goat heart resulted in the development of
sustained AF within 1 to 3 weeks; these findings suggested that
shortening of the effective refractory period (ERP; the so-called
"electrical remodeling") was the main underlying
electrophysiological change. In humans, AF
of <10 minutes' duration has also been shown to shorten the ERP of
the atrium.10 Goette et
al11 demonstrated that the atrial ERP shortening
induced by rapid pacing could be blocked with verapamil
infusion in an animal study. As shown in these studies, rapid atrial
pacing as well as AF can cause significant shortening of atrial
ERP.9 10 11 Whether atrial ERP shortening is a
specific response to AF or a common response to a rapid atrial rate is
not clear. On the other hand, antiarrhythmic drugs are still the
mainstay therapy for patients with AF. In patients with paroxysmal AF,
class IA, class IC, or class III antiarrhythmic drugs are frequently
used to restore and maintain sinus rhythm.12 13 14 15 16
For patients with AF and rapid ventricular response,
ß-blockers and calcium channel blockers are commonly used to control
the symptomatic rapid ventricular
response.17 18 However, the effects of different
classes of antiarrhythmic drugs on AF-induced ERP shortening have not
been fully elucidated. The purposes of this study were to investigate
the rate dependency of atrial ERP change and to evaluate the effects of
different antiarrhythmic drugs on tachycardia-induced
changes in atrial ERP.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
Patient Population
This study included 70 patients referred to our laboratory for
electrophysiological testing and
radiofrequency catheter ablation of paroxysmal
supraventricular tachycardia. There were 37 men
and 33 women with a mean age of 48±18 years. They were all free from
structural heart disease, as assessed by transthoracic
echocardiography and coronary angiography.
Ten patients (4 men and 6 women; mean age, 48±19 years) were included
in the first part of the investigation to study the rate dependency of
atrial ERP shortening; the other 60 patients (33 men and 27 women; mean
age, 49±18 years) were included in the second part to study the
effects of antiarrhythmic drugs on atrial ERP shortening induced by AF.
These latter 60 patients were randomized into six groups, and the age
and sex distributions among the groups were similar
(Table
).
View this table:
[in a new window]
Table 1. Characteristics of Atrial Fibrillation (AF) Before (B) and
After (A) Antiarrhythmic Drugs
All patients were studied in the postabsorptive, nonsedated
state after giving written, informed consent, and the antiarrhythmic
drugs were discontinued for >5 half-lives. Three quadripolar electrode
catheters, which had an interelectrode spacing of 2 to 5 to 2 mm
(Mansfield EP), were positioned in the high right atrium, the His
bundle position, and the right ventricular apex,
respectively. One decapolar electrode catheter (Daig Corp) was inserted
into the coronary sinus via the right internal jugular vein.
ECG leads I, aVF, and V1 and the intracardiac
electrograms were recorded (Cardiolab, Prucka Engineering, Inc, or
PPG MIDAS 2500). Pacing was performed with a programmable stimulator
(DTU-215, Bloom Associates, Ltd).
Determination of Atrial ERP
The study protocol was approved by the Committee of Human
Subject Research at this institute. After successful radiofrequency
ablation of supraventricular tachycardia, one
quadripolar electrode catheter was positioned in the right atrial
appendage; electrodes 1 and 2 were used for pacing, and electrodes 3
and 4 were used to record the local right atrial electrogram. This
electrode catheter was used for determination of ERP. Another electrode
catheter was positioned at the high lateral wall of the right atrium;
this electrode was used for rapid atrial pacing or induction of AF.
Ten patients were included in this part of the study. After
baseline ERP determination, the right atrium was paced for 10 minutes
with cycle lengths of 450, 400, 350, 300, and 250 ms. The sequences of
pacing cycle length were randomized in this study. Atrial ERP was
measured repeatedly at the termination of each pacing session until it
returned to within 2 ms of the baseline value. Furthermore, we compared
the effects of verapamil on pacing-induced and AF-induced
ERP shortening in an attempt to evaluate whether the
electrophysiological mechanism behind ERP
shortening is similar. Eight of the 10 patients underwent atrial pacing
with a 250-ms cycle length after infusion of verapamil
(0.15 mg/kg of body weight for a loading dose for 10 minutes and 0.3
mg · kg-1 ·
h-1 for maintenance). Ten minutes after
the loading dose, atrial ERP was measured again and then measured
repeatedly at the termination of another pacing episode until it
returned to within 2 ms of the prepacing value.
Sixty patients were included in this part of study. After the
baseline atrial ERP measurement, AF was induced by burst atrial pacing
at cycle lengths of 160 to 190 ms (18 patients needed a 10-mA current
for pacing to induce AF). After at least 7 minutes of AF (including the
duration of rapid, atrial burst pacing for inducing AF and the duration
of induced AF), the AF was allowed to spontaneously convert to sinus
rhythm. Immediately on conversion to sinus rhythm, atrial ERP was
measured repeatedly until it returned to within 2 ms of the baseline
value. Three patients experienced sustained AF (>30 minutes) during
the baseline study; they were cardioverted and excluded from further
antiarrhythmic drug study. Then the remaining patients were randomly
assigned to receive an infusion of 1 of 6 antiarrhythmic drugs:
procainamide (15 mg/kg of body weight for the loading dose at a
rate of 50 mg/min and 4 mg/min for maintenance), propafenone (2
mg/kg of body weight for the loading dose over 10 minutes and 0.4
mg · kg-1 ·
h-1 for maintenance),
propranolol (0.2 mg/kg of body weight for the loading dose
over 10 minutes and 0.04 mg · kg-1
· h-1 for maintenance),
amiodarone (5 mg/kg of body weight for the loading dose over 30
minutes and 30 mg/h for maintenance), dl-sotalol
(1.5 mg/kg of body weight for the loading dose over 10 minutes and 0.2
mg · kg-1 ·
h-1 for maintenance), or
verapamil (0.15 mg/kg of body weight for the loading dose
over 10 minutes and 0.3 mg · kg-1
· h-1 for maintenance). Ten minutes
after the loading dose was given, atrial ERP was measured as in the
baseline study. AF was again induced and allowed to convert to normal
sinus rhythm, also with the same method as in the baseline study. In
addition, post-AF ERP was determined as described in the baseline
study.
All parametric data were expressed as mean±SD.
Nonparametric data were analyzed by the
2 test with Yates' correction or Fisher's
exact test. The postpacing and post-AF atrial ERP measurements and
comparison among the six groups of patients in the second part of the
study were analyzed by ANOVA with repeated measures. The
effects of different pacing cycle lengths on the shortening of atrial
ERP were analyzed by linear regression. Paired Student's
t test was used to compare the change in ERP after
antiarrhythmic drugs. The effects of antiarrhythmic drugs on the
incidence of secondary AF was analyzed with the sign test. A
value of P<0.05 was considered statistically
significant.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Changes in Atrial ERP
Changes in ERP After Atrial Pacing With Different Pacing Cycle
Lengths
Atrial ERP was similar before each episode of atrial pacing
(197±10, 197±11, 196±12, 198±16, and 198±12 ms before pacing with
a cycle length of 250, 300, 350, 400, and 450 ms, respectively;
P>0.05 by ANOVA). The first atrial ERP measured immediately
after termination of 10 minutes of pacing with a cycle length of 250 ms
was 173±8 ms (-12.4±2.0%, P<0.001 versus prepacing
ERP). Shortening of atrial ERP persisted for 6 minutes, 5 seconds after
termination of pacing. Similarly, pacing of the right atrium with a
cycle length of 300, 350, or 400 ms significantly shortened the first
postpacing ERP: the values decreased from 197±11 to 176±9 ms
(-10.9±2.4%, P<0.001), 196±12 to 180±12 ms
(-8.0±3.7%, P=0.002), and 198±15 to 186±11 ms
(-6.3±3.8%, P=0.02), respectively. However, pacing of the
right atrium with a cycle length of 450 ms did not shorten the first
postpacing ERP (198±11 versus 195±13 ms, P>0.05). The
degree of ERP shortening was correlated with pacing cycle length
(r=0.7, P<0.001).
Data from the 57 patients in the second part of the study were
pooled to construct the effect of AF on ERP before antiarrhythmic
drugs. Before induction of AF, the right atrial ERP was 202±14 ms,
which was not significantly different from those before each pacing
session. The duration of induced AF, including the time required for
atrial burst pacing, was 10.4±1.9 minutes (range, 7.5 to 15.1
minutes). The first atrial ERP measured immediately after conversion of
AF was 172±15 ms (-15.1±3.2%, P<0.0001 versus pre-AF
ERP). Comparison of the degree of ERP shortening induced by atrial
pacing and AF showed that AF tended to cause more shortening of ERP
than did atrial pacing with a cycle length of 250 ms (-15.1±3.2%
versus -12.4±2.0%, P=0.04).
Recovery of ERP Change After Atrial Pacing and
AF
The temporal recovery of atrial ERP after each pacing cycle length
is shown in Figure 1. The postpacing
atrial ERP remained significantly reduced for 6.1±0.2, 5.2±0.2,
4.6±0.3, and 3.2±0.1 minutes after termination of pacing with a
pacing cycle length of 250, 300, 350, and 400 ms, respectively.
Comparison of these data showed that the duration of postpacing ERP
shortening lasted longer after pacing with a shorter cycle length. A
significant shortening of the post-AF atrial ERP persisted for 6.1±0.3
minutes after termination of AF. The temporal recovery of atrial ERP
after AF was not different from that after atrial pacing with a cycle
length of 250 ms (Figure 1).
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Figure 1. Temporal recovery of effective refractory period
(ERP) shortening after atrial (A) pacing and atrial fibrillation (AF).
Ordinate is percent shortening of atrial ERP, and abscissa is time.
Data are presented as mean±SEM. AF causes more shortening of
atrial ERP than does atrial pacing. Pacing with shorter cycle length
causes more shortening of atrial ERP. PCL indicates pacing cycle length
(ms). *P<0.001, **P<0.01, and
P<0.05 versus baseline ERP.). There was no significant difference
in the temporal recovery course between these two groups of
patients.
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Figure 2. Effect of secondary atrial fibrillation (AF) on
temporal recovery of effective refractory period (ERP) shortening after
AF. Ordinate is atrial (A) ERP in milliseconds and abscissa is time.
Data are pooled from 57 patients in second part of study and are
presented as mean±SD. Temporal recovery curves of patients
with (filled circle) and without (open circle) secondary episodes of AF
are plotted. There are no significant differences in atrial ERPs
between patients with and without secondary episodes of AF at any
period.
Effects of Antiarrhythmic Drugs on Postpacing ERP
Change
Before verapamil infusion, the prepacing and
postpacing ERPs were 197±11 and 172±10 ms, respectively (-12.7%,
P<0.001). After verapamil infusion, the
prepacing and postpacing ERPs were 203±15 and 194±13 ms, respectively
(-4.4%, P<0.01). Verapamil infusion markedly
attenuated the effect of ERP shortening induced by rapid atrial pacing
(-12.7% versus -4.4%, P<0.001; Figure 3). In addition, the recovery of ERP
shortening became more rapid after verapamil infusion
(3.0±0.3 versus 6.0±0.1 minutes, P<0.001).
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Figure 3. Effect of verapamil on effective
refractory period (ERP) change induced by rapid atrial (A) pacing.
Ordinate is ERP in milliseconds and abscissa is time.
Verapamil infusion significantly reduced ERP shortening
induced by atrial pacing with cycle length of 250 ms and shortened time
course of recovery. *P<0.001, **P<0.01,
and P<0.05 versus baseline ERP.
Baseline atrial ERPs were similar among the six groups; however,
atrial ERP obtained after verapamil infusion was shorter
than those after other antiarrhythmic drugs. However, the first post-AF
measurement of atrial ERP after verapamil was similar to
those of other groups. The effects of antiarrhythmic drugs on post-AF
ERP change and its temporal recovery are shown in Figure 4. After antiarrhythmic drug infusion,
pre-AF and post-AF ERPs were 227±16 and 193±18 ms, respectively, for
the procainamide group; 223±14 and 191±16 ms for the
propafenone group; 209±15 and 183±15 ms for the
propranolol group; 242±29 and 205±25 ms for the
dl-sotalol group; 231±15 and 196±13 ms for the
amiodarone group; and 198±14 and 189±14 ms for the
verapamil group. The degree of atrial ERP shortening was
similar before and after infusion of procainamide
(-14.6±4.2% versus -15.0±2.3%, P>0.05), propafenone
(-14.2±3.3% versus -14.3±3.5%, P>0.05),
propranolol (-14.0±3.1 versus -12.4±1.9%,
P>0.05), dl-sotalol (-14.0±3.2% versus
-15.3±2.2%, P>0.05), and amiodarone (-16.0±2.4
versus -15.2±1.0%, P>0.05). The temporal recovery curves
were also similar before and after infusion of these five drugs.
However, atrial ERP shortening was significantly reduced after
verapamil infusion (-4.6±1.2% versus -15.1±3.4%,
P<0.001). Furthermore, the time course of recovery was also
significantly shortened: post-AF ERP shortening persisted for 6.1±0.3
minutes before verapamil infusion but lasted for only
3.1±0.2 minutes after verapamil infusion
(P<0.001).
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Figure 4. Effects of antiarrhythmic drugs on atrial
effective refractory period (AERP) change induced by atrial
fibrillation (AF). There are no significant differences in degree of
ERP shortening or time course of ERP recovery after
procainamide, propafenone, propranolol,
dl-sotalol, or amiodarone infusion. However,
verapamil infusion significantly reduced degree of ERP
shortening induced by AF and shortened its time course of recovery.
*P<0.001, **P<0.01, and
P<0.05 versus baseline ERP.
The characteristics of secondary AF induced during determination
of post-AF ERP are summarized in the Table
. During the baseline study,
54 secondary episodes of AF were unintentionally induced in 20 patients
while their post-AF atrial ERP was being measured (2.7±1.3 episodes
per patient). The first episode of secondary AF was induced at a mean
interval of 56±51 seconds after spontaneous conversion of AF.
Secondary episodes of AF lasted 55±73 seconds (ranging from 4 seconds
to 4.4 minutes). The mean
A1-A2 coupling interval
that induced secondary episodes of AF was 169±19 ms
(P<0.005 versus pre-AF atrial ERP). The atrial ERP measured
immediately after spontaneous conversion of secondary episodes of AF
was not significantly different from the
A1-A2 that induced
secondary episodes of AF (166±30 versus 169±19 ms,
P>0.05).
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
Main Findings
In this study, we demonstrated that both short-duration, rapid
atrial pacing and AF shortened atrial ERP. The atrial ERP shortening
induced by rapid atrial pacing was a rate-dependent response: the
shorter the pacing cycle length, the greater the decrease in atrial
ERP. Also, the time course of atrial ERP recovery was similar between
rapid atrial pacing and AF. In addition, verapamil infusion
attenuated the change in atrial ERP, and the commonly used class IA,
IC, II, and III antiarrhythmic drugs had no effect on the change in
atrial ERP. However, all antiarrhythmic drugs tested did decrease the
incidence and duration of secondary AF.
Mapping of the activation pattern of AF has confirmed the
hypothesis that AF is a multiple-wavelet reentrant
tachycardia.19 20 21 The wavelength of
the wavelets, which is defined as the product of ERP and conduction
velocity, plays a critical role in the induction and
maintenance of AF.22 23 Previous studies
have demonstrated that high-frequency atrial pacing and sustained AF
lead to shortening of atrial ERP, without a significant change in
conduction velocity.9 10 11 24 25 26 A shorter ERP
can create a shorter wavelength, which makes AF easier to be induced
and sustained. In other words, AF might beget AF. However, there were
great variations in tachycardia cycle lengths used to
induce ERP shortening in these published studies: two studies used
pacing-induced AF, and the other four used rapid atrial pacing with
cycle lengths ranging from 50 to 200
ms.9 10 11 24 25 26 In the present study, we
demonstrated that atrial pacing with a cycle length ranging from 250 to
400 ms for 10 minutes could cause significant shortening of atrial ERP
and that ERP shortening induced by tachycardia was a
rate-dependent response. Rapid atrial pacing with a cycle length of 250
ms for 10 minutes had an effect on atrial ERP that was comparable to a
10-minute AF episode. The time course of ERP recovery after termination
of pacing and the response to verapamil were also similar
between rapid atrial pacing and AF. These data suggested that
tachycardia-induced ERP shortening was not a specific
response to AF. Achieving at a critical rate, atrial tachyarrhythmia
could also shorten atrial ERP as did AF.
Effects on Atrial ERP
Antiarrhythmic drugs have been commonly used to convert AF or
prevent its recurrence. However, long-term treatment has not
been satisfactory: as much as a 50% recurrence has been
reported.27 A breakthrough AF, if it persists
long enough, may have a significant effect on atrial electrophysiology.
In the present study, we demonstrated that the commonly used class
IA (procainamide), class IC (propafenone), class II
(propranolol), and class III (dl-sotalol and
amiodarone) antiarrhythmic drugs could not prevent the
shortening of ERP induced by short-duration AF. Only
verapamil, a class IV antiarrhythmic drug, could attenuate
the shortening of atrial ERP. Furthermore, lesser shortening of ERP
after termination of AF would permit a more rapid recovery of ERP. This
effect was also observed in the verapamil-treated group
only. One study on ventricular fibrillation showed that
increases in calcium transients and calcium overload were associated
with postfibrillation ventricular
dysfunction.28 Similarly, atrial dysfunction was
noted after a short duration of AF, and this dysfunction was prevented
by verapamil infusion and exaggerated by a calcium channel
agonist.29 Previous animal and human studies have
shown that verapamil infusion can block ERP changes induced
by high-frequency atrial pacing or AF.11 26 30
These data suggested that calcium overload was the underlying mechanism
of the tachycardia-induced ERP change. However, other
possible mechanisms about intracellular calcium handling merit further
investigation.
Inducibility and sustenance of AF depend on the presence of a
critical number of reentrant wavelets in the
atrium.22 23 The product of atrial ERP and
conduction velocity (defined as wavelength) determines how many
wavelets can exist in the atrium; therefore, a shorter atrial ERP may
lead to a greater number of wavelets and thus, make AF easier to be
sustained. In contrast, a greater prolongation of atrial ERP could
result in a lower incidence of secondary AF because the wavelengths of
reentry wavelets are increased by prolongation of ERP. In this study,
the first episode of secondary AF usually occurred at the first several
ERP determinations. This finding was compatible with the wavelength
hypothesis, because the first several ERPs were the shortest post-AF
ones in each patient. A shorter ERP would produce a shorter wavelength,
which would increase inducibility of AF. 
10% (14.1% in this study),
and the total dose of procainamide (344±155 mg) was lower than
usual. In our current study, a larger dose of procainamide and
a greater increase in atrial ERP than those in the study of Daoud et al
might account for the different results.
First, this study population consisted of patients with
structurally normal hearts and no clinically documented AF, and the
response in patients with paroxysmal or chronic AF or in patients with
structural heart disease may be different. Second,
verapamil infusion attenuated the effect of ERP shortening
induced by short-duration tachycardia. Whether this result
could be extrapolated to tachycardia of longer duration or
chronic AF needs further investigation. Third, that
verapamil infusion slowed a ventricular
response during AF may have been associated with a more favorable
hemodynamic response and may have contributed to its
effect in the prevention of ERP shortening. However, similar
ventricular rate and blood pressure changes were observed
after infusion of propafenone, propranolol,
dl-sotalol, and amiodarone; however, these drugs
could not prevent ERP shortening. Thus, prevention of ERP shortening by
verapamil may not be due to its slowing effect on
ventricular rate during AF. Fourth, we did not use total
autonomic blockade during this study; we think that this condition
would be more like the clinical one, and propranolol,
propafenone, dl-sotalol, and amiodarone already have
a ß-adrenergic–blocking effect.
This study demonstrated that a brief episode of
tachycardia or AF significantly shortened atrial ERP, which
might make the atrium more vulnerable to future AF. Furthermore,
previous studies have demonstrated that a short duration of AF can
impair atrial contractile function.29 The
tachycardia-induced electrical and mechanical dysfunction
can be attenuated by verapamil infusion. Early intervention
to terminate AF should be considered a therapeutic goal, because such
intervention disrupted the process of tachycardia-induced
atrial dysfunction.
The atrial ERP shortening induced by tachycardia is a
rate-dependent response. The shorter the tachycardia cycle
length, the greater the decrease in atrial ERP. Verapamil
infusion can markedly blunt this effect, but class IA, IC, II, and III
antiarrhythmic drugs have no effect. However, verapamil and
the other drugs can decrease the incidence and duration of secondary
AF.
Acknowledgments
This study was supported in part by grants from the National
Science Council (NSC-86-2314-B-010-030, 86-2314-B075-034, and
86-2314-B-075-098) and Tzou's Foundation (VGHYM-S4-30 and
VGHYM-S4-31), Taipei, Taiwan.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
1.
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