(Circulation. 1997;96:2601-2611.)
© 1997 American Heart Association, Inc.
Articles |
Characterization of Low Right Atrial Isthmus as the Slow Conduction Zone and Pharmacological Target in Typical Atrial Flutter
Correspondence to Shih-Ann Chen, MD, Division of Cardiology, Department of Medicine, Veterans General Hospital-Taipei, 201 Sec 2, Shih-Pai Rd, Taipei, Taiwan, ROC.
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Abstract |
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Background Previous electrophysiological studies in patients with typical atrial flutter suggested that the slow conduction zone might be located in the low right atrial isthmus, which is a path formed by orifice of inferior vena cava, eustachian valve/ridge, coronary sinus ostium, and tricuspid annulus. The conduction characteristics during atrial pacing and responses to antiarrhythmic drugs of this anatomic isthmus were unknown.
Methods and Results Forty-four patients, 20 patients with paroxysmal supraventricular tachycardia (group 1) and 24 patients with clinically documented paroxysmal typical atrial flutter (group 2), were studied. A 20-pole halo catheter was situated around the tricuspid annulus. Incremental pacing from the low right atrium and coronary sinus ostium was performed to measure the conduction time and velocity along the isthmus and lateral wall in the baseline state and after intravenous infusion of procainamide or sotalol. In both groups, conduction velocity in the isthmus during incremental pacing was significantly lower than that in the lateral wall before and after infusion of antiarrhythmic drugs. Furthermore, gradual conduction delay with unidirectional block in the isthmus was relevant to initiation of typical atrial flutter. Compared with group 1, group 2 had a lower conduction velocity in the isthmus and shorter right atrial refractory period. Procainamide significantly decreased the conduction velocity, but sotalol did not change it. In contrast, sotalol significantly prolonged the atrial refractory period with a higher extent than procainamide. After infusion of procainamide, the increase of conduction time in the isthmus accounted for 52±19% of the increase in flutter cycle length, and 5 of 12 patients (42%) had spontaneous termination of typical flutter. After infusion of sotalol, typical flutter was induced in only 6 of 12 patients (50%) without significant prolongation of flutter cycle length.
Conclusions The low right atrial isthmus with rate-dependent slow conduction properties is critical to initiation of typical human atrial flutter. It may be the potentially pharmacological target of antiarrhythmic drugs in the future.
Key Words: atrial flutter • conduction • procainamide • sotalol
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Introduction |
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Previous mapping studies in patients with typical atrial flutter have demonstrated a macroreentrant circuit localized to the right atrium.1 2 3 More recently, some of the right atrial endocardial structures, such as crista terminalis and eustachian ridge/valve as the posterior barriers and tricuspid annulus as the anterior barrier, were proven to support the atrial flutter reentrant circuit.3 4 5 Furthermore, several investigators reported that radiofrequency catheter ablation of the inferior vena cava–tricuspid annulus or coronary sinus ostium–tricuspid annulus isthmus was effective in eliminating the typical atrial flutter.5 6 7 8 9 10 11 Recent animal studies using multielectrodes activation mapping have demonstrated slow conduction in the low right atrium during atrial flutter.12 13 14 Using entrainment pacing techniques, several investigators suggested that the slow conduction zone might be located in the low right atrium during human atrial flutter.15 16 However, the extent to which the slow conduction zone is related to anatomic architecture has not been delineated. In addition, the effects of antiarrhythmic drugs on this conduction zone in human atrial flutter were still unknown. Therefore, in the present study, we will test the hypotheses that (1) the low right atrial isthmus contiguous to the posterior triangle of Koch is the anatomic slow conduction zone during typical atrial flutter and (2) procainamide (class I) and sotalol (class III) have different effects on this electric isthmus and right atrial free wall.
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Methods |
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Patient Characteristics
Forty-four patients, 20 with paroxysmal supraventricular tachycardia (group 1) and 24 with clinically documented paroxysmal typical atrial flutter (group 2), were included. Group 1 had 11 men and 9 women; their mean age was 54±11 years (range, 39 to 72 years). Group 2 had 14 men and 10 women; their mean age was 56±16 years (range, 15 to 80 years). All patients were refractory to or intolerant of a mean of 3±1 (range, 2 to 5) antiarrhythmic drugs before referral. Ten patients had associated cardiovascular diseases, including rheumatic heart disease (n=1), hypertension (n=4), coronary heart disease (n=3), and mitral valve prolapse (n=2).
Catheter Positions
Each patient gave informed consent. Research protocols were
approved by the Human Research Committee at this institution. As
described previously, all antiarrhythmic drugs were discontinued for at
least five half-lives before the study.17 Both the
orifices of the inferior vena cava and coronary
sinus were identified by venograms. In all patients, a 7F, 20-pole,
deflectable "halo" catheter with 10-mm paired spacing
(Cordis-Webster) was positioned around the tricuspid annulus to
record the right atrial activation in the lateral wall and the low
right atrial isthmus simultaneously. We tried to put the
distal tip of halo catheter into the coronary sinus and let the
electrode poles 1,2 (H1) be located at the ostium in each patient (Fig 1A
and 1B). If the halo catheter could
not be placed into the coronary sinus, it was adjusted with the
distal tip against the septum, and poles 1,2 (H1) were located close to
the ostium of the coronary sinus in the left anterior oblique
(LAO) view. In the present study, the halo catheter could be placed
into the coronary sinus in 32 of the 44 patients (14 of 20
group 1 and 18 of 24 group 2 patients). A 7F, deflectable, decapolar
catheter with 2-mm interelectrode distance and 5-mm space between each
electrode pair was also inserted into the coronary sinus via
the internal jugular vein. Position of the proximal electrode pair at
the ostium of the coronary sinus was confirmed with contrast
injection. Three multipolar, closely spaced (interelectrode space,
2 mm) electrode catheters with a deflectable tip (Mansfield
Division of Boston Scientific Inc) were introduced from the right and
left femoral veins and placed in the high right atrium, low right
atrium (entrance of the low right atrial isthmus), and His bundle area
for recording and pacing.
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Baseline Electrophysiological Study
Each patient underwent a baseline
electrophysiological study in the fasting,
unsedated state. None of the patients had an episode of sustained
atrial flutter shortly before entering the study. A programmed digital
stimulator (DTU-210 or 215, Bloom Associate Ltd) was used to deliver
electrical impulses of 2.0 ms in duration at 10-mA current. The study
protocol included (1) incremental pacing from the low right atrium and
ostium of the coronary sinus at pacing cycle lengths of 500,
450, 400, 350, 300, and 250 ms to measure the conduction time in the
low right atrial isthmus and lateral wall; (2) burst atrial pacing from
the above sites at progressively shorter cycle lengths until 2:1 atrial
capture to induce atrial flutter; (3) atrial pacing using the cycle
length equal to flutter cycle length to compare the conduction time in
the low right atrial isthmus if typical atrial flutter was induced; and
(4) single extrastimulus testing with 300-ms drive cycle length at the
above pacing sites and high right atrium to determine the atrial
effective refractory periods.
Intracardiac bipolar electrograms were displayed
simultaneously with ECG leads V1 and
VII or aVF on a multichannel oscilloscopic recorder
(model VR-13, PPG Biomedical System, Cardiovascular
Division) and were recorded on paper at a speed of 200 mm/s.
The filter was set from 30 to 500 Hz. Measurement of electrograms was
made with the onset of the first sharp component that reached an angle
of 45° with the baseline. In the LAO view, the electric pairs located
in the medial sites of the right atrium–inferior vena cava
junction were considered located within the isthmus, while those
located in the lateral sites of the right atrium-inferior
vena cava junction were considered located within the lateral wall.
Therefore, the relevant conduction velocity could be calculated by
measuring the respective conduction time and sparing distance between
two end dipoles within the isthmus and lateral wall. In the Fig 1B
, the
H1 electrode pair is located at the ostium of the coronary
sinus, H2 through H5 electrode pairs are located within the low right
atrial isthmus, and H6 through H10 electrode pairs are located within
the lateral free wall. Conduction velocity in the low right atrial
isthmus was measured from the septal portion to lateral portion (H1 to
H5) and from the lateral portion to septal portion (H5 through H1)
during pacing from the coronary sinus ostium and low lateral
right atrium (near the H6 electrode pair), respectively. Conduction
velocity in the lateral wall (H6 through H10) was measured only during
pacing from the low right atrium (near the H6 electrode pair), because
activation of the lateral free wall during pacing from the
coronary sinus ostium represents bidirectional
conduction via the interatrial septum and low right atrial isthmus with
collision of wave fronts in the midlateral free wall.
Pharmacological Study
Each group was further divided into two subgroups. After the
baseline study, groups 1A and 2A received intravenous
loading infusion of procainamide 15 mg/kg at a rate not
exceeding 50 mg/min, followed by a maintenance infusion
of 2 mg/min; groups 1B and 2B received intravenous
infusion of dl- sotalol 1.5 mg/kg over 10
minutes.18 19 The
electrophysiological study protocol and
measurement were repeated to observe the pharmacological effects on the
flutter reentrant circuit.
Definitions
The low right atrial isthmus was defined as a path formed by the
orifice of the inferior vena cava, eustachian valve/ridge,
coronary sinus ostium, and tricuspid annulus. Thus, the septal
portion (1 cm lateral to the coronary sinus ostium) of the
isthmus is contiguous to the posterior triangle of
Koch.5 20 21 The lateral portion (1 cm medial to the
orifice of inferior vena cava) of the isthmus merges into
the pectinate muscles. The residual part of the isthmus was defined as
the middle portion (Fig 1B). Counterclockwise (typical) atrial flutter
was defined as an atrial flutter with craniocaudal activation of the
anterior and lateral walls of the right atrium and caudocranial
activation of the atrial septum, inverted P waves in the
inferior leads, and positive P wave in lead V1.
Clockwise atrial flutter was defined as an atrial flutter with a
similar flutter cycle length and reverse activation sequence of the
counterclockwise flutter. Atypical atrial flutter was defined as an
atrial flutter other than the counterclockwise and clockwise
atrial flutters.
Statistical Analysis
Quantitative values are expressed as mean±SD. Student's paired
t test was used for statistical comparison of the conduction
velocity and effective refractory periods before and after infusion of
antiarrhythmic drugs and for comparison of conduction velocity at 500
ms versus other pacing cycle lengths. Student's unpaired t
test was used for statistical comparison of conduction velocity,
effective refractory periods, and drug responses between groups 1 and
2. Statistical analysis of conduction velocity in the septal,
middle, and lateral isthmus was performed with the use of ANOVA test.
2 test and Fisher's exact test were used for
analysis of relationship between the pacing site and type of
atrial flutter. A value of P<.05 was considered
statistically significant.
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Results |
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Group 1
Conduction Velocity
Conduction velocity from the septal isthmus to the lateral isthmus during pacing from the coronary sinus ostium and from lateral isthmus to septal isthmus during pacing from the low lateral right atrium at 500-, 450-, 400-, 350-, 300-, and 250-ms drive cycle lengths was significantly lower than that in the lateral wall during pacing from the low lateral right atrium before and after infusion of antiarrhythmic drugs (Figs 2A
, 2B, 3A, and 3B). Conduction velocity in the
lateral isthmus (0.842±0.045 and 0.886±0.051 m/s) during atrial
pacing from the low right atrium and coronary sinus ostium at
250-ms cycle length was significantly higher than that in the middle
(0.382±0.044 and 0.396±0.047 m/s) and septal (0.345±0.040 and
0.352±0.039 m/s) isthmus (P<.05). Procainamide
significantly decreased the conduction velocity at all pacing cycle
lengths in the isthmus and lateral wall in group 1A (Fig 2A and 2B),
but sotalol did not change the conduction velocity at any pacing cycle
length in group 1B (Fig 3A and 3B).
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P<.05, 500 ms vs other pacing cycle lengths.
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Effective Refractory Period
At the baseline study, the effective refractory period at the
coronary sinus ostium was significantly longer than that at the
high and low right atrium (group 1A, 194±21 versus 175±23 versus
183±26 ms; group 1B, 198±20 versus 181±23 versus 187±22 ms;
P<.05). Procainamide significantly prolonged the
atrial effective refractory periods in group 1A (high right atrium,
201±31 ms, +15±6%; low right atrium, 212±24 ms, +16±6%;
coronary sinus ostium, 217±25 ms, +12±5%), and sotalol
significantly prolonged the effective refractory period in group 1B
with a higher extent (high right atrium, 222±32 ms, +22±5%; low
right atrium, 225±30 ms, +20±7%; coronary sinus ostium,
236±25 ms, +19±6%) (Fig 4A and 4B).
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Induction of Atrial Flutter
In group 1A, incremental pacing from the low lateral right atrium
reproducibly induced clockwise atrial flutter in 2 patients after
counterclockwise wave front produced gradual conduction delay with
block in the middle portion of the isthmus (Fig 5A). The flutter cycle lengths in these 2
patients were 200 ms. After procainamide infusion, clockwise
atrial flutter was still induced. Both flutter cycle lengths were
prolonged; one was 245 ms (+30 ms in the isthmus and +15 ms in the
residual atrial wall), and the other was 260 ms (+40 ms in the isthmus
and +20 ms in the residual atrial wall). Thus, most of the increase in
cycle length was due to an increase in conduction time in the low right
atrial isthmus. Incremental pacing from the coronary sinus
ostium induced counterclockwise atrial flutter in 4 patients after a
clockwise wave front produced gradual conduction delay with block in
the septal portion of the isthmus (Fig 5B). The mean flutter cycle
length was 220±15 ms. After procainamide infusion,
counterclockwise atrial flutter was still induced with the same
activation sequence in these 4 patients. The flutter cycle length was
prolonged to 278±21 ms. One cycle length was prolonged to 340 ms, and
1: 1 AV conduction with acceleration of ventricular
response occurred. There was more prolongation of conduction time
(50±10 ms) in the isthmus than in the residual atrial wall (18±12
ms).
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In group 1B, incremental pacing from the low lateral right atrium induced clockwise atrial flutter in 2 patients. One flutter cycle length was 245 ms and the other was 220 ms. After sotalol infusion, clockwise atrial flutter was not induced. Incremental pacing from the coronary sinus ostium induced counterclockwise atrial flutter in another 3 patients. The mean flutter cycle lengths was 197±12 ms. After sotalol infusion, counterclockwise atrial flutters were still induced with the same activation sequence, but mean cycle length was slightly prolonged to 207±12 ms. The increase in flutter cycle length was due to an increase in conduction time (13±6 ms) in the low right atrial isthmus without conduction delay in the residual atrial wall.
Direct induction of counterclockwise and clockwise atrial flutter was documented in 22 of 25 episodes (88%) in 9 patients, and 3 episodes (12%) had transitional atrial fibrillation induced by short pacing cycle length (190±26 ms). Eight episodes of clockwise atrial flutter were all induced from the low lateral right atrium, while 14 episodes of counterclockwise atrial flutter were all induced from the coronary sinus ostium. Thus, there was significant correlation between the pacing site and type of atrial flutter (P<.001).
Group 2
Conduction Velocity
Conduction velocity from the septal isthmus to the lateral isthmus
during pacing from the coronary sinus ostium and from the
lateral isthmus to the septal isthmus during pacing from the low
lateral right atrium at 500-, 450-, 400-, 350-, 300-, and 250-ms drives
was significantly lower than that in the lateral wall during pacing
from the low lateral right atrium before and after infusion of
antiarrhythmic drugs (Figs 6A, 6B, 7A and 7B). Conduction velocity in the
lateral isthmus (0.769±0.038 and 0.782±0.044 m/s) during atrial
pacing from the low right atrium and coronary sinus ostium at
the 250-ms cycle length was significantly higher than that in the
middle (0.336±0.045 and 0.341±0.046 m/s) and septal (0.297±0.033 and
0.315±0.042 m/s) isthmus (P<.05). Procainamide
significantly decreased the conduction velocity at all pacing cycle
lengths in the isthmus and lateral wall in group 2A (Fig 6A and 6B),
but sotalol infusion significantly decreased the conduction velocity
only at pacing cycle lengths of 300 and 250 ms in group 2B (Fig 7A and 7B).
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Effective Refractory Period
At baseline study, the effective refractory period at the
coronary sinus ostium was significantly longer than that at the
high and low right atriums (group 2A, 210±34 versus 160±25 versus
165±24 ms; group 2B, 202±16 versus 164±22 versus 177±18 ms;
P<.05). Procainamide significantly prolonged the
atrial effective refractory periods in group 2A (high right atrium,
186±27 ms, +16±5%; low right atrium, 194±30 ms, +18±5%;
coronary sinus ostrum, 237±40 ms, +13±5%), and sotalol
significantly prolonged the effective refractory period in group 2B to
a higher extent (high right atrium, 208±22 ms, +27±7%; low right
atrium, 219±21 ms, +25±6%; coronary sinus ostium,
241±18 ms, +20±7%) (Fig 8A and 8B).
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Induction of Atrial Flutter
In group 2A, incremental pacing from the coronary sinus
ostium induced clinical counterclockwise atrial flutter in all patients
after a clockwise activation wave front produced gradual conduction
delay with block in the septal or middle portion of the isthmus. The
mean flutter cycle length at baseline study was 246±27 ms. Conduction
time (96±14 ms) in the low right atrial isthmus accounted for 40±8%
of the flutter cycle length. Conduction time in the low right atrial
isthmus during pacing from the low lateral right atrium using a cycle
length equal to that of typical flutter was 90±12 ms. Incremental
pacing from the low lateral right atrium could induce counterclockwise
atrial flutter in 2 patients and clockwise atrial flutter in 6
patients. The mean cycle length of the clockwise atrial flutter was
238±19 ms. After procainamide infusion, pacing from the
coronary sinus ostium still induced all the counterclockwise
atrial flutters with prolongation of the flutter cycle length to
320±35 ms. Procainamide also increased conduction time in the
low right atrial isthmus during atrial flutter (128±15 ms) and atrial
pacing (116±12 ms). The increase in conduction time in the low right
atrial isthmus accounted for 52±19% of the increase in flutter cycle
length. Furthermore, 5 patients (42%) had gradual conduction delay in
the isthmus, culminating in conduction block and termination of
counterclockwise atrial flutter (Fig 9A and 9B). After procainamide infusion,
low lateral right atrial pacing still induced clockwise atrial flutter
in 6 patients with prolongation of mean cycle length to 308±35 ms.
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In group 2B, incremental pacing from the coronary sinus ostium induced clinical counterclockwise atrial flutter in all patients after a clockwise activation wave front produced gradual conduction delay with block in the low right atrial isthmus. The mean flutter cycle length at baseline study was 240±22 ms. Conduction time (95±15 ms) in the low right atrial isthmus accounted for 42±6% of the flutter cycle length. Conduction time in the low right atrial isthmus during pacing from the low lateral right atrium using a cycle length equal to that of typical flutter was 89±14 ms. Incremental pacing from the low lateral right atrium also induced counterclockwise atrial flutter in 1 patient and clockwise atrial flutter in 5 patients. The cycle lengths of the clockwise atrial flutter were 230±15 ms. After sotalol infusion, pacing from the coronary sinus ostium induced counterclockwise atrial flutters in only 6 patients without significant prolongation of the flutter cycle length (248±20 ms). Sotalol did not significantly increase conduction time in the low right atrial isthmus during atrial flutter (96±12 ms) and atrial pacing (90±18 ms), nor did it produce spontaneous termination of counterclockwise atrial flutter in any patient. After sotalol infusion, pacing from the low lateral right atrium did not induce counterclockwise or clockwise atrial flutter but induced atypical atrial flutter in another 2 patients.
Direct induction of counterclockwise and clockwise atrial flutter was documented in 43 of 50 episodes (86%) in 24 patients, and 7 episodes (14%) had transitional atrial fibrillation induced by a short pacing cycle length (186±24 ms). All of the 16 episodes of clockwise flutter (100%) were induced from the low lateral right atrium, while 22 of 27 episodes (82%) of counterclockwise flutter was induced from the coronary sinus ostium. Thus, there was significant correlation between the pacing site and type of atrial flutter (P<.001).
Comparisons Between Groups 1 and 2
Group 2 patients had a lower conduction velocity at all paced
cycle lengths in the low right atrial isthmus and a shorter effective
refractory period at the high and low right atrium than group 1
patients (Figs 10 and 11). There was no significant
difference in response to procainamide with respect to
conduction velocity and effective refractory period between the two
groups. Comparing groups 1 and 2 shows no significant difference in the
effects of sotalol on effective refractory period, while sotalol
decreased conduction velocity in the isthmus at short drive cycle
lengths in group 2 but not in group 1 patients.
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Discussion |
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Major Findings
The present study was the first to demonstrate that incremental pacing from the low lateral right atrium and coronary sinus ostium during sinus rhythm produced rate-dependent conduction delays in the low right atrial isthmus, especially the middle and septal isthmus contiguous to the posterior triangle of Koch. Furthermore, gradual conduction delay with unidirectional block in the isthmus was relevant to development of counterclockwise and clockwise atrial flutters. Patients with clinical atrial flutter had much slower conduction in the low right atrial isthmus and shorter effective refractory periods in the right atrium than those without clinical flutter. The prolongation of atrial flutter cycle length after procainamide infusion was due to a predominant increase of conduction time in the low right atrial isthmus. In contrast, sotalol had less effect on atrial flutter cycle length and slow conduction zone, although it produced a greater prolongation in atrial effective refractory period.
Role and Site of Slow Conduction in Atrial Flutter
Klein et al1 have performed intraoperative atrial
epicardial mapping during common atrial flutter in 2 patients and
reported that relatively slow conduction was found at the low right
atrial tissue between the tricuspid valve ring and the orifices of the
inferior vena cava and proximal coronary sinus,
respectively. Saumarez et al20 used multielectrode
endocardial mapping preoperatively and demonstrated slow, tortuous
conduction in the "mouth" of the Koch's triangle associated with
common atrial flutter. Olshansky et al15 showed slow
conduction associated with fractionated electrogram and missing
interval of electrical activity during human type I atrial flutter in
the inferior right atrium using endocardial catheter
mapping and pacing techniques. Cosio et al8 and Chen et
al16 also used entrainment pacing in the IVC-TA isthmus to
show rate-dependent conduction delays in orthodromic activation during
human common atrial flutter. In the present study, incremental
pacing from the low lateral right atrium and coronary sinus
ostium during sinus rhythm produced rate-dependent conduction delays in
the low right atrial isthmus, especially near the posterior triangle of
Koch (middle and septal isthmus). Furthermore, atrial pacing resulted
in unidirectional conduction block in the low atrial isthmus and then
induced counterclockwise or clockwise atrial flutter in patients with
or without clinical atrial flutter. These findings proved that the low
right atrial isthmus has slow conduction properties and it is critical
to development of the human atrial flutter.
The mechanism of slow conduction in the isthmus was not clear. Spach et al22 have demonstrated that conduction velocity of atrial impulses is faster parallel to the long axis of myocyte fibers and slower along the plane transverse to myocyte fiber orientation. This phenomenon was explained by higher axial resistance caused by scant cell-to-cell coupling encountered when impulses propagated perpendicular to the long axis of muscle fibers.22 23 With aging or atrial dilatation, intercellular fibrosis can change the density of gap junctions and produce nonuniform anisotropic conduction through the trabeculations of the low right atrial isthmus.23 This hypothesis is supported by histological analysis of slow conduction areas during atrial flutter in animal models. Boineau et al12 have concluded that fiber directions, packing density, and dimensions of groups of fibers exerted a significant influence on the conduction velocity.
Atrial Properties in Patients With Clinical Atrial Flutter
Rensma et al24 have shown that induction of rapid
repetitive responses, atrial flutter and atrial fibrillation in normal
dogs was closely related to the wavelength of the initiating premature
impulse. The wavelength of an impulse is defined as the product of
conduction velocity and refractory period. They found that most of
atrial flutter was induced at a critical wavelength between 9.7 and 7.8
cm.24 Josephson,25 Attuel et
al,26 and Buxton et al,27 have systematically
measured atrial refractory periods in patients with a history of atrial
flutter and/or fibrillation and compared them with control subjects.
The results of these series revealed that atrial refractory periods in
patients with atrial flutter and/or fibrillation were significantly
shorter than those of control subjects. Furthermore, when compared with
control subjects, patients with a history of atrial flutter could
manifest an exaggerated degree of intraatrial conduction delay in
response to premature stimulation over a greater zone of coupling
intervals. Papageorgiou et al21 also reported that atrial
premature stimulation from high right atrial lateral wall induced much
more fractionation and conduction delay in the posterior triangle of
Koch than distal coronary sinus stimulation in patients with
induced atrial fibrillation. In the present study, group 2 patients
(with clinical typical atrial flutter) had a lower conduction velocity
in the low right atrial isthmus (especially at the middle and septal
portions) and a shorter effective refractory period at the high and low
right atrium than group 1 patients (without clinical atrial flutter).
These findings confirmed the previous studies and supported the
hypothesis that slow conduction and short refractory periods may foster
the initiation of atrial flutter in the human right atrium by allowing
the establishment of a sufficiently short critical wavelength.
Pharmacological Effects on Atrial Flutter
In the animal model of Y-shaped atrial lesion, Wu and
Hoffman28 have reported that procainamide could
terminate sustained atrial flutter around the tricuspid ring.
Termination was preceded by a marked increase in cycle length and
correlated with depression of conduction rather than prolongation of
refractoriness. In the canine sterile pericarditis model, Schoels et
al29 have shown that procainamide slowed
conduction in the slow zone of atrial flutter more than it prolonged
refractoriness. Termination of circus movement atrial flutter was
typically preceded by a large increase in cycle length, which
predominantly resulted from further slowing of conduction in the slow
zone. Thus, they concluded that procainamide has differential
effects on the components of the reentrant pathway. Stambler et
al18 used antiarrhythmic drugs to characterize the human
type I atrial flutter. Although they did not measure the conduction
velocity in the area of slow conduction, they found that the increase
in atrial flutter cycle length induced by procainamide was
significantly greater than the increase in monophasic action potential
duration; furthermore, a change in atrial flutter cycle length did not
correlate with a change in monophasic action potential. In the
present study, procainamide decreased conduction velocity
predominantly in the low right atrial isthmus during atrial flutter and
atrial pacing, and the increase in conduction time in the isthmus
accounted for 52±19% of the increase in flutter cycle length.
Furthermore, procainamide produced gradual conduction delay,
culminating in conduction block in the isthmus and termination of the
typical atrial flutter. In contrast, procainamide only
prolonged the atrial effective refractory periods by 12% to 18%.
Therefore, these finding suggested that procainamide might
terminate human type 1 atrial flutter by causing failure of impulse
propagation through the low right atrial isthmus, although other
mechanisms might also play a role. Furthermore, a possible explanation
for failure of wave-front propagation would be a reduction in safety
factor for conduction as suggested by Cha et al30 in their
animal model of atrial flutter.
Spinelli and Hoffman31 and Boyden and Graziano32 have shown that d-sotalol slightly prolonged the flutter cycle length (+10% to +15%) and terminated atrial flutter by producing complete conduction block of the reentering impulse within the critical area or inducing failure of the lateral boundary of the circuit path in the canine model of Y-shaped atrial lesion. In the tricuspid regurgitation model of atrial flutter, Boyden33 has demonstrated another mode of termination by d-sotalol, which was preceded by a prolongation and then a period of shortened atrial cycle lengths; ie, the regular reentrant activity of the flutter rhythm became unstable (fibrillatory) in the presence of d-sotalol. In the crush injury model of atrial flutter, Feld et al34 and Inoue et al35 have suggested that the class III antiarrhythmic drugs (including d-sotalol and E-4031) selectively prolonged atrial refractoriness with little effect on conduction velocity or flutter cycle length, and they were highly effective in termination and suppression of atrial flutter by abolishing the excitable gap and eliminating the dispersion of refractoriness. However, in a randomized human study, intravenous infusion of d,l-sotalol (1.0 to 1.5 mg/kg) was not effective in converting atrial flutter to sinus rhythm, while intravenous ibutilide (a pure class III agent) was very effective in terminating atrial flutter.19 36 In the present study, d,l-sotalol did not significantly decrease conduction velocity in the low right atrial isthmus during atrial flutter, nor produce spontaneous termination of the typical atrial flutter although it significantly prolonged the atrial refractory periods by 19% to 27%. In contrast, it could prevent reinduction of the typical atrial flutter in 6 patients. Furthermore, several studies have shown that sotalol was effective in preventing the recurrence of atrial flutter after patients had restored sinus rhythm previously.37 38 39
Study Limitations
The atrial refractory periods were not determined during atrial
flutter and might be overestimated. However, the drive cycle length of
300 ms is close to the flutter cycle length, and the difference may be
small. Because some patients with clinical atrial flutter required high
current (10 mA) electric stimulation for induction of
tachycardia, we used this intensity of electric impulses to
perform atrial pacing for measurement of conduction velocity and
effective refractory period. Papageorgiou et al21 reported
that atrial fibrillation was more readily inducible by premature
stimulation from the high right atrium than the distal coronary
sinus because of increased anisotropy in Koch's triangle. However, in
the present study, atrial flutter was more readily induced by rapid
pacing from the low right atrium and coronary sinus ostium.
Whether different pacing sites and pacing modes result in different
electrophysiological characteristics that
are related to the type of atrial tachyarrhythmia is
unknown and deserves further study.
Conclusions
The low right atrial isthmus near the posterior triangle of
Koch is the anatomic slow conduction zone during typical atrial
flutter. Gradual conduction delay with unidirectional block in this
isthmus was relevant to initiation of counterclockwise and clockwise
atrial flutter. Procainamide prolongs the atrial flutter cycle
length by predominantly diminishing conduction velocity in the slow
conduction zone and terminates atrial flutter by inducing conduction
block in the low right atrial isthmus. Sotalol prolongs the atrial
flutter cycle length minimally by increasing atrial refractoriness but
cannot terminate atrial flutter; however, it can prevent reinduction of
atrial flutter.
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Acknowledgments |
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This work was supported in part by grants from the National Science Council (NSC 85-2331-B-075-071, 85-2331-B-010-047, 85-2331-B-010-048, 86-2314-B-010-048, 86-2314-B-075-034, and 86-2314-B-075-098) and Tzou's Foundation (VGHYM-S4-30 and VGHYM-S4-31), Taipei, Taiwan, ROC.
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Footnotes |
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Division of Cardiology, Department of Medicine, National Yang-Ming University, School of Medicine, Veterans General Hospital-Taipei and Kaoshiung, Taiwan, ROC.
Dr S.-H. Lee is from Shin-Kong Memorial Hospital, and Dr J.-L. Huang is from Veterans General Hospital-Taichung, Taiwan, ROC.
Received February 10, 1997; revision received May 2, 1997; accepted May 15, 1997.
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References |
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