(Circulation. 1995;92:3070-3081.)
© 1995 American Heart Association, Inc.
Articles |
Radiofrequency Catheter Modification of Sinus Pacemaker Function Guided by Intracardiac Echocardiography
From the Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco.
Correspondence to Jonathan M. Kalman, MBBS, PhD, Department of Medicine and Cardiovascular Research Institute, Room MU 428, University of California, San Francisco, Box 1354, San Francisco, CA 94143-0214.
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Abstract |
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Background The sinus P wave arises from a pacemaker complex distributed along the crista terminalis. We investigated the feasibility of modification of sinus pacemaker function using graded applications of radiofrequency energy along the crista terminalis in dogs to achieve sinus rate control.
Methods and Results Modification of sinus pacemaker function (30±5% reduction in intrinsic heart rate with retention of a normal P-wave axis) was performed in 11 dogs (group 1). Total sinus pacemaker ablation (>50% reduction in intrinsic heart rate with development of a low ectopic atrial or a junctional rhythm) was performed in 4 dogs (group 2). Intracardiac echocardiography was used to identify the crista terminalis as an anatomic marker of sinus node location. Sinus pacemaker modification caused a significant decrease in intrinsic heart rate (31% reduction, P<.001), heart rate responsiveness to isoproterenol (30% reduction, P<.0001), and average (20% reduction, P=.0002) and maximal (22% reduction, P=.0007) heart rates during 24-hour Holter monitoring. In 6 of the 11 animals, the targeted rate reduction of 30±5% was accurately achieved (mean, 31.6±4.3%; P<.001), and in the other 5, significant reduction of intrinsic heart rate was achieved but with greater variation (28.0±17.3%, P<.005). Corrected sinus node recovery time was not prolonged. After modification, earliest activation was mapped to the crista terminalis inferior to the lesion in all animals. In long-term follow-up (3.7±1.0 months), effects were maintained. After total sinus pacemaker ablation, junctional and low atrial escape pacemakers were unstable.
Conclusions This study demonstrates the feasibility of modification of sinus pacemaker function for sinus rate control using catheter-based radiofrequency ablation guided by intracardiac echocardiography. This can be done while pacemaker stability and attenuated responsiveness to autonomic influences are preserved. Intracardiac echocardiography accurately defined the crista terminalis and provided a reliable means to anatomically localize catheter position in relation to the sinus node.
Key Words: echocardiography • catheter ablation • pacemakers
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Introduction |
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The past decade has witnessed enormous advances in the use of radiofrequency catheter ablative procedures for cure or control of a variety of cardiac arrhythmias. However, no one has described a technique for reliable modification of the sinus rate. At present, this must be achieved with pharmacological therapy, which may frequently be limited by side effects, patient intolerance, or treatment failure related to an associated disease process.
The unique anatomic1 2 3 and functional4 5 characteristics of the sinus node have been well characterized. The sinus P wave arises from a pacemaker complex distributed over an area extending from the junction of the superior vena cava and right atrial appendage in the inferior direction along the sulcus terminalis almost to the inferior vena cava. A close correspondence between the change in heart rate and the change in sites of impulse origin within this complex in response to certain autonomic manipulations has been shown.4 5 This site-specific differential sensitivity to autonomic inputs allows the possibility of targeted modification of sinus pacemaker function. Indeed, successful modification of sinus pacemaker function by use of epicardial laser irradiation recently was described in dogs.6 However, this approach requires thoracotomy, epicardial mapping, and epicardial laser application and therefore, a clinical application has not been developed.
In the present study, we investigated the feasibility of modification of sinus pacemaker function using graded applications of radiofrequency energy along the crista terminalis in dogs. Chu et al7 recently demonstrated that intracardiac echocardiography can be used to guide anatomic placement of radiofrequency lesions. We hypothesized that intracardiac echocardiography could be used to accurately position the ablation electrode on the crista terminalis and supplemented this anatomic localization with endocardial activation mapping to define the sites of earliest activation during total autonomic blockade. We also performed total sinus pacemaker ablation in another group of animals to characterize any difference in lesion extent required for total ablation, to define the "margin for error" during an attempted modification procedure, and to compare the physiological characteristics of the escape pacemakers.
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Methods |
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Fifteen adult mongrel dogs of either sex were included in the study. Group 1 consisted of 11 animals that underwent sinus pacemaker modification, and group 2 consisted of 4 animals that had total sinus pacemaker ablation. All animals underwent the same series of pharmacological and electrophysiological tests both before and after ablation, as described below. All studies conformed to the "Position of the American Heart Association on Research Animal Use" adopted November 11, 1984, and the protocol was approved by the University of California Committee on Animal Research.
Definitions
Modification of sinus pacemaker function (group 1) was defined
by a targeted reduction of intrinsic heart rate of 30±5% with
retention of a normal P-wave axis in the frontal and horizontal planes
(Fig 1
, top).
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Total sinus pacemaker ablation (group 2) was defined by a reduction of
intrinsic heart rate of >50% with a low atrial (inverted P waves in
inferior leads II, III, and aVF) or a junctional (P waves
merged with the QRS complex) escape rhythm (Fig 1
, bottom).
Surgical Technique and Recordings
Animals were premedicated with Innovar-vet (0.1 mL/kg SC)
and anesthetized with sodium pentobarbital (7 to 15 mg/kg IV).
After intubation, animals were ventilated with room air, and the level
of anesthesia was continuously monitored. Body temperature
was maintained at 37°C with a heating mattress.
Venous access was obtained by cutdown technique over both femoral veins and over the right external jugular vein. Each vein was cannulated with appropriately sized hemostatic sheaths. Throughout the study, three surface ECG leads (I, II, and III) and five bipolar electrograms recorded from the decapolar catheter were displayed simultaneously on a multichannel oscilloscope. The distal bipolar recording from the ablation catheter was also displayed during endocardial mapping. Femoral arterial blood pressure was continuously monitored throughout the procedure. Recording was performed with an Electronics for Medicine recorder (PPG Inc) at a paper speed of 100 mm/s during autonomic testing and at 150 mm/s during activation mapping. A 12-lead ECG was recorded before and after each pharmacological manipulation at a paper speed of 50 mm/s.
Intracardiac Echocardiography
The intracardiac imaging system has been described
previously.7 The imaging catheter was introduced via a 10F
sheath in the right external jugular vein and positioned at the
junction of the superior vena cava and right atrial appendage to obtain
optimal images of the crista terminalis. When necessary, the ultrasound
catheter was advanced into the body of the right atrium to obtain
images from more caudal aspects of the crista terminalis and
recorded on super-VHS videotape for review.
Electrophysiological and
Pharmacological Evaluation
In both group 1 and group 2 dogs,
electrophysiological and pharmacological
evaluations of the sinus node pacemakers were performed under general
anesthesia before radiofrequency ablation and at a
follow-up study 14 days later. In addition, 3 group 1 animals
underwent repeat electrophysiological and
pharmacological evaluation at 
3-month follow-up to evaluate the
long-term effects of sinus pacemaker modification.
A 6F quadripolar catheter (0.5-cm interelectrode spacing) was
positioned in the right atrial appendage for pacing. A 7F decapolar
catheter (Elecath, 2-mm bipole spacing, 10-mm interbipole spacing) was
inserted via the femoral vein and positioned with the tip located in
the superior vena cava. The second bipole (electrodes 3 and 4) was
positioned at the superior vena caval–right atrial junction (Fig 2). In this manner, the decapolar catheter lay
approximately parallel to the crista terminalis. Positioning was
confirmed with intracardiac echocardiography, which
was used to accurately define the superior vena cava–right atrial
junction and was reconfirmed throughout the experimental procedure by
use of both echocardiographic and fluoroscopic
landmarks. Both intracardiac echocardiography and
fluoroscopy were used in positioning of the decapolar catheter at the
follow-up study to duplicate its location at the initial study.
Bipolar electrograms were recorded from each electrode pair and
displayed throughout the study. Simultaneous atrial
activation sequence mapping from the decapolar bipoles was performed
relative to the surface P wave recorded in three ECG leads. In
cases in which activation times appeared to be
simultaneous, the initial atrial activation vector was
analyzed, with the point of electrogram polarity
reversal8 noted to assist with definition of the pacemaker
location.
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Autonomic function testing with evaluation of heart rate, blood pressure, and site of earliest atrial activation on the decapolar catheter was then performed, both before ablation and at the follow-up study, in the following sequence, with time allowed for return to baseline after each intervention: (1) An intravenous infusion of nitroprusside in three incremental doses (1, 2, and 4 µg · kg-1 · min-1) was administered to evaluate the response of sinus node pacemaker cells to reflex sympathetic activation. (2) An intravenous infusion of isoproterenol in six incremental doses ranging between 1 and 6 µg/min was administered to evaluate the response of sinus node pacemaker cells to direct sympathetic stimulation. (3) Two incremental bolus doses of phenylephrine (0.2 and 0.4 mg) were administered to evaluate the pacemaker response during vagotonia. (4) Sequential intravenous administration of atropine (0.5 mg/kg) followed by propranolol (1.0 mg/kg) was performed to evaluate the maximum heart rate after vagolysis and then the intrinsic heart rate during total autonomic blockade.
After completion of autonomic function testing (with total autonomic blockade established), the maximal sinus node recovery time and maximal corrected sinus node recovery time were evaluated by right atrial pacing for periods of 30 seconds at decreasing pacing cycle lengths (decrements of 20 ms) commencing 20% below resting.
Ablation Procedure
Radiofrequency catheter ablation was performed during autonomic
blockade to allow evaluation of the effects of each radiofrequency
application on heart rate without the variations produced by autonomic
innervation. Ablation was performed with a 7F catheter with an 8F,
custom-designed, 10-mm distal ablation electrode with a thermistor
tip (EP Technologies). On the basis of previous
studies,6 9 we assumed that the area of ablation required
to produce modification of sinus pacemaker function with changes in
maximal and average heart rate of 30% would be between 2 and 3
cm2. This is a much greater area of tissue desiccation than
that provided by conventional ablation catheters with a 4- or 5-mm tip.
If the power output is increased to maintain sufficient current density
at the distal electrode, then lesion size will increase in proportion
to electrode surface area.10
Radiofrequency energy (500 kHz) was delivered between the distal electrode and a large surface area backplate from a generator providing continuous closed-loop temperature feedback control of energy output (EP Technologies). This was programmed to adjust power to achieve an electrode tip and tissue temperature of 70°C. Energy was limited to a maximum output of 100 W and was delivered for a period of 60 seconds. Electrode temperature, power, and impedance were monitored during each application. If a temperature of 50°C was not achieved within 15 to 20 seconds, endocardial contact was considered inadequate and energy application was discontinued.
Intracardiac echocardiography was used to accurately position the ablation electrode tip, marked by a characteristic fan-shaped artifact,7 on the crista terminalis at the lateral junction of the superior vena cava with the right atrial appendage. The catheter tip was then moved in the anterosuperior or inferior direction along this ridge to locate the site of earliest endocardial activation as assessed by recording from the distal ablation bipole relative to the surface P wave in three ECG surface leads. Activation mapping was also performed from other right atrial sites to confirm that the earliest activation times were located on the crista terminalis. During each energy application, catheter tip position was monitored continuously with intracardiac echocardiography. After each application, a shift in the pacemaker site was detected by a change in the endocardial activation sequence and/or from a change in the surface ECG P-wave morphology. Right atrial endocardial mapping was repeated after each application.
Holter Monitoring
In both group 1 and group 2 dogs, 24-hour Holter monitoring was
performed for 2 consecutive days before the ablation procedure and for
2 consecutive days after the procedure in the second postoperative
week. In three group 1 animals, Holter monitoring was also performed
for 2 consecutive days before the long-term follow-up study.
The average and maximum heart rates were determined for each 1-hour
period and for the full 24 hours by a Zymed Holter analyzer.
Assessment was also made of the duration of time for which the heart
rate was >110 beats per minute (prospectively defined as
tachycardia) during the 24-hour period. The
analysis of minimum heart rate and development of pauses is
complicated by the fact that normal dogs may demonstrate pauses of >2
seconds at times of high vagal tone. Therefore, we evaluated the
maximal pause duration and the number of pauses of >2 seconds in a
24-hour period.
Pathological Evaluation
All hearts were fixed in 10% buffered formalin. Before
dissection, lesions created by the ablation were identified on the
epicardial aspect and measured. The chambers were opened in standard
fashion along the lines of blood flow. The thickness of the damage
within the atrial wall, as well as the endocardial extent, was also
measured. Representative full-thickness pieces of
the heart across the junction between the superior vena cava and right
atrium laterally (both at the lesion and more caudally where the
myocardium appeared normal) were taken and submitted for
histology. For localization of sympathetic nerves, a block of fresh
tissue from the same area was fixed in 4% buffered
paraformaldehyde for 4 hours and then kept in 30%
sucrose buffer until the immunohistochemical procedure, performed on
floating thick sections according to previously described
methods.11
Statistical Analysis
All results are given as mean±SD in the text and as mean±SEM
in the figures. Statistical analyses were made using a paired
t test for two-group comparisons and with ANOVA for
comparisons involving three or more groups. Between-group
analysis was by Scheffé's F test. Statistical
significance was accepted at P<.05. In all figures, the
preablation data from animals in groups 1 and 2 are pooled for the sake
of visual clarity. There were no significant differences between the
two groups in any of the preablation parameters.
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Results |
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Preablation Study: Pharmacological Evaluation (Groups 1 and 2)
There was no statistically significant difference in heart rate, blood pressure, or decapolar activation sequence between group 1 and group 2 dogs during any of the preablation autonomic interventions, and these parameters are presented as pooled data in this section.
Baseline heart rate (71.1±19.1 beats per minute) showed considerable beat-to-beat variation in cycle length, consistent with vagal predominance. At this heart rate, the site of earliest activation in the decapolar catheter was usually located between the second and third bipoles, and spontaneous shifts frequently occurred. At this time, P-wave morphology in the 12-lead ECG typically demonstrated low amplitude in the inferior leads.
With incremental infusion of nitroprusside, there was a shift in site
of earliest activation on the decapolar catheter to a more superior
location (between the first and second bipoles; Fig 3)
and a peaking of P waves in inferior ECG leads. Blood
pressure decreased significantly (20.2±8.0%, P<.0001) and
was accompanied by a progressive increase in heart rate (maximum
93±43% increase, P<.0001; Fig 3). The effects of
isoproterenol infusion on heart rate, activation sequence, and P-wave
morphology were similar to those observed with nitroprusside (215±79%
increase in maximal rate, P<.0001; Fig 3). In contrast,
phenylephrine produced an increase in blood pressure
(19.1±7.5% increase, P<.0001) accompanied by a
significant decrease in heart rate (34±11% reduction,
P<.0001, Fig 3). Earliest activation shifted in the
inferior direction toward the region of the third bipole
(Fig 3), and P-wave morphology was of low amplitude in the
inferior ECG leads. After autonomic blockade, the earliest
activation site was again shifted in the superior direction (Fig 3),
with a significant increase in heart rate compared with baseline
(154.5±36.8 versus 71.1±19.1 beats per minute, P<.0001),
confirming the marked vagal predominance in the anesthetized
animals. An example of the effects of autonomic interventions on the
decapolar activation sequence and P-wave morphology is shown in Fig 4.
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Ablation Procedure (Groups 1 and 2)
In all dogs, the initial targeted site during ablation was on the
crista terminalis at the lateral junction of the superior vena cava
with the right atrial appendage. This was accurately localized with
intracardiac echocardiography (Fig 5), and earliest activation in this region after
complete autonomic blockade was confirmed with right atrial endocardial
mapping in all animals. A general correspondence between decreasing
heart rate and progressively inferior pacemaker activity
was noted. However, this was not a simple linear relation. To achieve
the first decrease in heart rate, it was necessary to apply a mean of
3.8±1.8 energy applications in the region of the lateral junction of
the superior vena cava with the right atrial appendage in group 1
animals and 4.2±2.2 energy applications in group 2 animals
(P=NS). In two group 1 animals, it was also necessary
to extend the lesion medially along the crista terminalis,
anterior to the superior vena cava. Successful ablation of cranial
pacemaking groups was marked by a variable initial reduction in
heart rate associated with a shift of the pacemaker in the
inferior direction along the crista terminalis. To achieve
the target heart rate reduction for animals in each of the two groups,
further energy applications needed to be delivered for a variable
distance in the inferior direction along the crista
terminalis. This distance was 2 to 3 cm for sinus pacemaker
modification and 3 to 4 cm (virtually extending to the junction of the
right atrium with the inferior vena cava) for total sinus
pacemaker ablation.
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In group 1 dogs, after sinus pacemaker modification, earliest
endocardial activation was at the crista terminalis
inferior to the radiofrequency lesion in the vicinity of
the third and fourth decapolar bipoles (Figs 3 and 4D). With this
shift, there was also a flattening of P waves in the
inferior ECG leads. In no group 1 animals did an
atrioventricular junctional rhythm emerge. The
intrinsic heart rate decreased from an initial 154.5±36.8 to
107.0±26.2 beats per minute (30.5±11.6% reduction,
P<.001) immediately after the ablative procedure and to an
intrinsic heart rate of 94.7±23.2 beats per minute (38.7±12.0%
reduction, P<.001) at the 2-week follow-up study (Fig 6). The difference between the intrinsic heart rate
immediately after the procedure with that at the follow-up study
was not statistically significant (P=NS, Scheffé's
F test). The narrow prospective definition of heart rate
reduction (30±5%) was achieved in 6 of the 11 animals undergoing
sinus pacemaker modification (31.6±4.3% reduction immediately and
38.6±10.1% reduction at the 2-week follow-up study; by ANOVA,
P<.001 compared with baseline). In the other 5 animals,
there was also a highly significant reduction in intrinsic heart rate,
although results were more variable (28.0±17.3% reduction
immediately and 37.6±15.1% reduction at the 2-week follow-up
study; by ANOVA, P<.005 compared with baseline). These more
variable results occurred in the initial animals during development
of the technique. The prospective heart rate definition was achieved in
5 of the last 6 consecutive animals in which sinus pacemaker
modification was attempted.
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, sinus
pacemaker modification; 
, total sinus pacemaker ablation).
Although there is some variability in heart rate reduction, this
occurred in the initial animals during development of the technique.
Compared with preablation, P<.001 both immediately after
ablation and at the 2-week follow-up study.
In group 2 dogs, after total ablation, the rhythm was either junctional
(n=2) or arose from the vicinity of the low right atrium (n=2) and was
associated with deeply inverted P waves in the inferior ECG
leads. The prospective definition of total ablation was met in all four
animals. The intrinsic heart rate decreased from 161.0±6.3 beats per
minute initially to 68.0±11.5 beats per minute immediately after the
procedure (57.8±7.8% reduction) and to 56.0±20.5 beats per minute
(65.3±12.1% reduction) at the 2-week follow-up study
(P<.001, ANOVA; Fig 6). As in group 1, the difference
between intrinsic heart rate immediately after the procedure and that
at the 2-week follow-up study was not statistically significant
(P>.05, Scheffé's F test).
In no instance in group 1 or 2 animals was it necessary to apply radiofrequency energy to sites not located on the crista terminalis to achieve the required heart rate reduction.
The mean number of radiofrequency applications required was 6.2±3.2 in group 1 (range, 2 to 14) and 9.8±3.0 in group 2 (range, 7 to 14, P=.01). In none of the group 2 animals was a total ablation achieved without the criteria for modification having first been observed on a preceding application. In these group 2 animals, the mean additional number of radiofrequency applications required to achieve a total ablation after a sinus pacemaker modification had been observed was 2.8±0.5 applications (range, 2 to 4). An initial increase in sinus rate occurred during 81% of radiofrequency energy applications. This was followed by a decrease in heart rate during energy delivery in 23% of applications. The mean activation time for radiofrequency applications that caused heart rate reduction was -21±9 ms before onset of the surface P wave.
Intracardiac Echocardiographic
Observations
Intracardiac echocardiography clearly
demonstrated the prominent ridge of the crista terminalis at the
junction of the superior vena cava and right atrial appendage in all
animals (Fig 5). This ridge became less prominent as it extended in the
inferior direction along the posterolateral right atrium
but could still be clearly defined as the junction of the posterior
smooth-walled atrium with the anterior trabeculated
atrium. Direct imaging of the electrode catheter tip–tissue
contact was successful in 93% of energy applications. Interference of
the imaging catheter with the ablation catheter necessitating removal
of the imaging catheter did not occur in any animals.
The site of lesion formation could be detected after most
radiofrequency applications by the appearance of local irregular
swelling that produced ultrasound shadowing artifact (Fig 5).
Subsequent pathological examination demonstrated superficial adherent
thrombus at the endocardial lesion site that was presumed to be partly
responsible for the swelling and ultrasound artifact observed (Fig 7).
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Follow-up Study
Autonomic Interventions
Group 1. In group 1 dogs, after sinus pacemaker
modification, the heart rate remained responsive to both
reflex-mediated and direct sympathetic activation but with the peak
attainable heart rate significantly reduced. Nitroprusside infusion
caused a decrease in blood pressure similar to that at the initial
study but with a reflex-mediated increase in heart rate at both 2
and 4 µg · kg-1 · min-1,
which was significantly less than before ablation (24±21% reduction,
P=.04, and 27±18% reduction, P=.006,
respectively; Fig 3). Similarly, although heart rate remained
responsive to isoproterenol infusion, the maximal attainable rate was
significantly less than that observed before sinus pacemaker
modification (30±9% reduction, P<.0001, Fig 3).
Right atrial activation mapping in the baseline state demonstrated that
earliest endocardial activation occurred on the crista terminalis in
the region of the third and fourth bipolar pairs of the decapolar
catheter in all group 1 animals (Fig 3). With sympathetic activation
(either direct or reflex mediated), in contrast to before ablation,
there was no cranial shift along the crista terminalis in the site of
earliest activation.
Phenylephrine caused an increase in systolic blood
pressure associated with a decrease in heart rate that was not
significantly different from the premodification response (Fig 3). In
no instance did sinus pauses or sinus arrest occur during
administration of phenylephrine in group 1 animals. The
site of earliest endocardial activation on the crista terminalis was
similar to the preablation site after administration of
phenylephrine (Fig 3).
During complete autonomic blockade, intrinsic heart rate (94.7±23.2 beats per minute) was significantly greater than the baseline rate (62.8±18.1 beats per minute, P=.01) at the commencement of the follow-up study. However, the magnitude of the increase (50±16%) was significantly attenuated compared with the preablation increase (145±26%, P<.01).
Group 2. All group 2 dogs showed a return of some periods of
sinus rhythm with a normal P-wave axis at the follow-up study. The
pacemaker site was usually located on the crista terminalis in the
vicinity of the third or fourth decapolar bipole. However, this rhythm
was inherently unstable, with pacemaker shift, most frequently to
a low atrial or a junctional site, occurring either spontaneously or in
response to autonomic interventions (Fig 8). Although
heart rate response to either nitroprusside or isoproterenol was not
significantly different from that in group 1 animals (Fig 3), this was
due to responsiveness of a junctional or low atrial focus leading to
sympathetically mediated junctional or atrial tachycardia
(Fig 8). In two group 2 animals, phenylephrine produced
prolonged pauses during the follow-up study.
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At the follow-up study, intrinsic heart rate (56.0±10.3 beats per minute) did not increase significantly from the baseline heart rate (60.3±12.7 beats per minute). The intrinsic heart rate at follow-up study was significantly slower in group 2 than in group 1 animals (P<.05).
Sinus Node Recovery Time
Group 1. In group 1, maximum sinus node recovery time
at the follow-up study (939.0±280.2 ms) was significantly longer
than the maximum preablation recovery time (579.5±123.6 ms,
P=.001). However, when expressed as a percentage of the
resting cycle length, there was no significant difference (135.7% and
134.7%, respectively, P=NS).
Group 2. The maximum preablation sinus node recovery time in group 2 animals (541.7±86.9 ms) was not significantly different from that in group 1 (579.5±123.6 ms, P=NS). However, after total ablation, prolonged postpacing pauses (range, 5.5 to 8.4 seconds; mean, 6.8±0.7 seconds) occurred in all group 2 animals.
Holter Monitoring (Groups 1 and 2)
Holter monitoring data from dogs in both groups are
presented in Table 1. In both groups, there were
highly significant reductions in maximum and average heart rates and
also in time spent in tachycardia. A comparison of Holter
parameters after total ablation in group 2 animals with
parameters after sinus pacemaker modification in group 1
animals demonstrated a significantly shorter time spent in
tachycardia (P=.003) and a nonsignificant trend
toward a lower maximum heart rate (P=.07) in the group 2
animals. There was no difference in average heart rate. In group 1
animals, there was no significant increase in the maximal pause
duration after sinus pacemaker modification (3.1±1.2 seconds
premodification versus 3.8±1.0 seconds postmodification;
P=NS), in the number of pauses of >2 seconds in
duration during the 24-hour period of monitoring (7.2±5.6 versus
10.1±10.1, respectively, P=NS), or in the minimum heart
rate (32.7±19.3 versus 28.7±13.4 beats per minute, respectively,
P=NS). Holter recordings from group 2 animals were
characterized by prolonged episodes of junctional rhythm and frequent
changes in the P-wave morphology. In addition, group 2 animals
demonstrated a significant increase in both the maximal pause duration
(2.7±0.6 seconds preablation versus 5.0±0.5 seconds postablation;
P<.01) and in the number of pauses of >2 seconds in the
24-hour period of monitoring (4.8±2.1 versus 16.5±7.8,
P<.05). None of the animals in either group died suddenly
during the follow-up period.
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Long-term Follow-up
In the three group 1 animals followed for a mean period of
3.7±1.0 months, there were no significant differences at the late
study compared with the 2-week follow-up study for intrinsic heart
rate, maximal heart rate on isoproterenol, maximal heart rate or
average heart rate on 24-hour Holter monitor, or time spent in
tachycardia on 24-hour Holter monitor. Intrinsic heart rate
was decreased by 39% at 2 weeks and by 35% at the long-term
follow-up study (P=NS). Maximal heart rate on
isoproterenol was decreased by 31% at 2 weeks and by 36% at the
long-term follow-up study (P=NS). Maximal heart rate
on Holter monitor was decreased by 27% at 2 weeks and by 25% at the
long-term follow-up study (P=NS). Average heart rate
on Holter monitor was decreased by 17% at 2 weeks and 19% at the
long-term follow-up study (P=NS). Time in
tachycardia on 24-hour Holter monitor was decreased by 80%
at 2 weeks and 88% at the long-term follow-up study
(P=NS).
All three animals demonstrated a stable sinus pacemaker P-wave morphology, with earliest atrial activation mapped to the mid–crista terminalis (earliest activation at the third [n=1] or fourth [n=2] bipole of the decapolar catheter at the long-term follow-up study), and overdrive pacing did not cause abnormal sinus node pauses. There was no cranial shift of the activation focus with sympathetic activation.
Pathology
In all dogs from groups 1 and 2, pathological examination
demonstrated that lesions were accurately located at the lateral right
atrial–superior vena caval junction and extended a variable
distance along the crista terminalis (Fig 9). In the two
animals that required radiofrequency applications to be extended
medially along the crista terminalis, lesions in this location were
demonstrated at pathological examination.
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Table 2 demonstrates a comparison of lesion size in
group 1 versus group 2 animals. The mean endocardial lesion length in
group 2 animals was significantly greater than in group 1 animals, but
there was no significant difference in maximal lesion width.
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In addition, pathological examination demonstrated the accuracy of
lesion localization (Fig 9). The maximal distance from the edge of the
crista terminalis that lesions were found was 0.8±0.2 cm.
Histological examination confirmed that radiofrequency
lesions were transmural. No residual sinus node pacemaker cells were
seen in any sections from the right atrial–superior vena caval
junction (Fig 7). In addition, none of the sections taken through the
crista terminalis at sites inferior to the lesion
demonstrated typical sinus node pacemaker cells. Neural staining did
not demonstrate any sympathetic nerve terminals in the lesion area,
although these were present in normal appearance from sections
taken immediately inferior to the lesion (Fig 7).
Histological evaluation in the 3 animals undergoing
long-term follow-up also demonstrated that lesions were
transmural with fibrosis and accurately targeted to the crista
terminalis. In 2 of these animals, there was some cartilaginous
metaplasia.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Our results demonstrate the feasibility of modification of sinus pacemaker function for sinus rate control using catheter-based radiofrequency ablation guided by intracardiac echocardiography. This can be done while pacemaker stability and responsiveness to autonomic influences are preserved. The effects of sinus pacemaker modification were maintained during long-term follow-up of 3 months.
Anatomic and Physiological
Considerations
Using endocardial mapping, we were able to demonstrate that under
autonomic influences, the origin of the dominant sinus pacemaker group
may be shifted over a distance of up to 3 cm along the region of the
sulcus terminalis. Sympathetic activation caused a shift to a cranial
pacemaker location, usually at the lateral junction of the superior
vena cava with the right atrial appendage but also extending medially
along the crista terminalis in two cases. Reflex vagal stimulation
caused a shift of the pacemaker site to a more caudal location on the
crista terminalis. The demonstration of shifts in origin of the sinus
node impulse along the sulcus terminalis under autonomic influences was
first observed by Lewis et al12 and by Meek and
Eyster13 early in the century and has since been reported
by other investigators using either mapping or microelectrode
techniques.14 15 16 17 Most recently, Boineau et
al5 18 used a computerized epicardial mapping system to
show that over a physiological range of spontaneous
heart rates, the dominant pacemaker may occur over a wide distribution,
as far cranially as the right atrial–superior vena caval junction
or as far caudally as the right atrial–inferior vena
caval junction. These sites of origin were centered about the long axis
of the sulcus terminalis and, as in our study, produced a P-wave axis
on the surface ECG within the normal sinus spectrum. In addition, in
response to autonomic manipulations, a close correspondence existed
between the heart rate and the site of impulse origin within the sulcus
terminalis, consistent with a graduated site-specific
differential sensitivity to autonomic inputs.4 5 19 Vagal
stimulation produced an increase in cycle length associated with change
in location of the dominant pacemaker to a lower atrial site.
Isoproterenol infusion resulted in dominance of a more cranial and
anterior pacemaker with associated decrease in cycle length. The
existence of a widely distributed pacemaker complex initially shown in
dogs has more recently also been demonstrated in
humans.20
This widely distributed physiological pacemaker
complex contrasts with the more localized and constant anatomic
location of the histologically defined sinus
node.3 21 The human sinus node lies immediately beneath
the epicardium within the sulcus terminalis of the right atrium at the
junction of the anterior trabeculated appendage with the
posterior smooth-walled venous component.3 21 The
endocardial aspect of the sulcus terminalis is marked by the crista
terminalis. In most cases, the node lies lateral to the crest of the
atrial appendage, and specialized cells extend in the
inferior direction in the sulcus terminalis for 10 mm.
In up to 10% of cases, the node extends across the crest of the
appendage anterior to the superior vena cava.3 In most
respects, the anatomy of the sinus node of the dog is very
similar to that of the sinus node of humans.1 2 In our
study and those of Boineau et al,5 19 the spatial
distribution of the physiologically defined
pacemaker complex exceeded the dimensions of the
histologically defined sinus node by a factor of 3 to
4.
Sinus Pacemaker Modification
After selective ablation of the cranial pacemakers, the sinus node
pacemaker was located in a more caudal position along the crista
terminalis. With adrenergic stimulation, the heart rate was
significantly less responsive than before ablation and was no longer
accompanied by cranial movement of pacemaker origin. The pacemaker
cells at this site were stable, and the relation between sinus node
recovery time and prepacing cycle length was unchanged from the
preablation study. Changes in heart rate parameters during
autonomic manipulation were also paralleled by similar
reductions in ambulatory heart rate indexes. The feasibility of
modification of sinus pacemaker function was first demonstrated in dogs
by surgical excision.9 22 23 24 Randall et
al9 23 found that surgical modification of sinus pacemaker
function required excision of a block of tissue 2.0 cm long by 1.5
cm wide, dimensions similar to those required in our study. The escape
rhythm was localized to the sulcus terminalis at the caudal end of the
excised area. This rhythm was considered to arise from subsidiary
atrial pacemakers that were shown to be stable and responsive to
autonomic maneuvers but with a significant reduction in the maximal
attainable heart rate. The description of these pacemakers as
"subsidiary atrial" is consistent with
histological studies showing that the specialized sinus
node pacemaker tissue is relatively localized.3 21 In our
study, histological sections taken through the crista
terminalis immediately inferior to the ablative lesion at
the presumed site of postablation pacemaking failed to demonstrate the
characteristic histological appearance of the sinus
node in any animal. However, this does not preclude cells in this
region from having pacemaker function.
Recently, the feasibility of modification of sinus pacemaker function with epicardial laser irradiation in open-chest dogs has been demonstrated.6 In this study, epicardial laser photocoagulation was applied to the earliest site of activation (defined by epicardial mapping) during isoproterenol infusion and repeated to remapped activation points until a 30±5% decrease in heart rate occurred. After ablation, the rhythm was shown to arise from a site within the sulcus terminalis immediately caudal to the ablative lesion. Pacemaker cells in this region produced a stable rhythm responsive to autonomic inputs but with a significant reduction in maximal, average, and intrinsic heart rates of a magnitude similar to those we observed. In contrast to Randall et al,9 the authors of Reference 6 characterized the pacemaker cells in this region of the sulcus terminalis as part of the sinus node pacemaker complex. This characterization is well supported by the physiological studies of Boineau et al4 5 and by our observations of changes in sinus node pacemaker origin in the present study.
In all 11 animals in group 1, we were able to achieve sinus pacemaker modification without inadvertently causing a total sinus node ablation. In 6 animals, the narrow prospective intrinsic heart rate definition was achieved. In 5 others, there was more variability, although in these 5, intrinsic, maximal, and average heart rates were all significantly decreased without a total sinus node ablation being produced. This variability reflected the learning curve during development of the technique. The effects of sinus pacemaker modification were maintained during long-term follow-up of up to 3 months.
Total Ablation of the Sinus Pacemaker
In this study, total ablation of sinus pacemaker function required
creation of an extensive lesion extending along the length of the
crista terminalis from the right atrial junction with the superior vena
cava caudally to its junction with the inferior vena cava.
Both the number of radiofrequency energy applications and the
pathological lesion size were significantly greater than those required
for sinus pacemaker modification. The escape pacemaker was initially
located in the junctional or low right atrial region, and atrial
overdrive pacing produced prolonged pauses. At the follow-up study
2 weeks later, the rhythm had returned to the caudal aspect of the
crista terminalis near the inferior vena caval junction,
but it was unstable, and pacemaker shift occurred spontaneously and in
response to autonomic manipulations. Euler et al25
demonstrated that complete removal of the sinus node and crista
terminalis in dogs required excision of a block of tissue 4.0 cm
long by 1.5 cm wide, dimensions similar to those required for total
ablation in this study. The characteristics of the escape pacemaker
were also similar.
Modification Versus Total Ablation: Characteristics of the
Escape Pacemaker
Despite the difference in lesion extent between animals in the two
groups, there was no significant difference in heart rate response to
sympathetic stimulation or in maximum or average heart rate on
ambulatory monitoring. Although the sinus pacemaker was unable to
respond to adrenergic stimulation in group 2 animals, junctional and
low atrial pacemakers remained responsive. The implication is that the
degree of heart rate control achievable with sinus pacemaker ablation
may be limited by the sympathetic responsiveness of junctional (or
other atrial) foci and is likely to be on the order of 20% to 30%, a
rate reduction similar to that achieved with ß-adrenergic
blockade. Therefore, substantial additional rate control may not be
achieved by total ablation rather than a more limited modification.
Differentiation between these two outcomes is of obvious importance, in
view of the noted difference in stability of the escape rhythm.
Ablation of Pacemaker Tissue or of Sympathetic
Inputs?
The sinus node is richly innervated with both
sympathetic and parasympathetic nerve fibers. Recent evidence has
suggested that cardiac autonomic neural inputs may be modified by
radiofrequency lesions, with consequent effects on sinus
rate.26 Thus, it is feasible that changes in sinus node
function as a result of application of radiofrequency energy may result
from destruction of pacemaker tissue, of sympathetic inputs, or of
both. Evidence from our study suggests that both effects are likely to
have occurred. First, modification in sympathetic responsiveness was
demonstrated in response to both direct and reflex-mediated
sympathetic activation. Second, lesions produced by radiofrequency
application via a 10-mm electrode tip involved the full thickness of
the atrial wall, and no residual pacemaker tissue was demonstrated in
any animal. Finally, histological examination using
special staining techniques to highlight sympathetic nerve terminals
failed to demonstrate any sympathetic innervation in the lesion
area.
Use of Intracardiac
Echocardiography
In a previous study of total sinus node ablation using
radiofrequency energy, anatomic localization was performed with
fluoroscopic guidance alone.27 Successful ablation was
achieved in 8 of 10 animals and required a mean of >16 applications.
Pathological evaluation demonstrated that radiofrequency energy was not
well targeted, with some noncontiguous lesions being located in the
right atrial appendage, the superior vena cava, and the right atrial
free wall. We previously demonstrated that intracardiac
echocardiography can be used to accurately localize
the ablation electrode tip within the right atrium and can guide
radiofrequency lesion placement to within a mean of 1.9 mm of the
designated site.7 The anatomic location of the sinus
pacemaker is clearly defined by the crista terminalis, and in all
cases, pathological examination confirmed that intracardiac
echocardiography provided accurate anatomic
localization. In addition, the area of ablation at pathological
examination in both group 1 and group 2 animals was very similar to
that previously demonstrated in surgical studies.9 25 This
suggests that unnecessary radiofrequency lesion application was
limited. In no case was it necessary to apply radiofrequency energy
away from this anatomically defined ridge to achieve the result of
modification of sinus pacemaker function.
It is also worth noting that inadvertent conversion of a successful sinus pacemaker modification to a total sinus pacemaker ablation with an unstable escape rhythm (necessitating permanent pacemaker implantation) may require only several poorly targeted lesions. Fluoroscopy does not allow accurate visualization of the crista terminalis.
Limitations
Since our primary aim was to demonstrate the feasibility of sinus
pacemaker modification by use of radiofrequency energy, we did not
compare intracardiac imaging with standard fluoroscopy for anatomic
localization. Therefore, the notion that intracardiac imaging provides
better anatomic localization of the sinus pacemaker than fluoroscopy,
thereby allowing a reduction in procedure time, fluoroscopy time, and
number of energy applications, must still be considered
speculative.
Extensive lesion creation in the atrium could potentially increase the risk of development of atrial arrhythmias in the long term. Indeed, this may potentially occur with any ablative procedure in the atrium. However, if the lesion is extended to the junction of the superior vena cava and if care is taken, by use of intracardiac echocardiography, to make a continuous lesion, the risk of reentry occurring around the lesion is in theory reduced.
We used the decapolar catheter to evaluate changes in pacemaker location and supplemented this with endocardial activation mapping using the ablation catheter. A more accurate evaluation of the earliest activation site might have been facilitated by use of a multipolar basket catheter.28 In addition, we did not perform mapping of the left atrium.
Potential Clinical Implications
If the results of our animal study can be duplicated in patients,
the potential clinical implications of modification of sinus pacemaker
function with radiofrequency energy might include (1) control of heart
rate in patients with the syndrome of inappropriate sinus
tachycardia29 and (2) nonpharmacological heart
rate control in patients with intractable angina intolerant to
medications. If average heart rate is reduced and rate response to
exertion is blunted, myocardial oxygen requirement would be expected to
decrease. This may also be applicable in selected patients with heart
failure in whom excessive sinus tachycardia appears to be
detrimental to hemodynamics and ß-adrenergic
blockade is not tolerated.30
Conclusions
This study demonstrates the feasibility of modification of sinus
pacemaker function for sinus rate control using catheter-based
radiofrequency ablation guided by intracardiac
echocardiography. This can be done while pacemaker
stability and responsiveness to autonomic influences are preserved. If
these results can be duplicated in patients, this may represent
a useful nonpharmacological method of achieving sinus rate control in a
spectrum of conditions in which the sinus rate is inappropriately
rapid.
Intracardiac echocardiography accurately defined the crista terminalis and provided a reliable means to anatomically localize catheter position in relation to the sinus node.
|
Acknowledgments |
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Dr Kalman was funded as the Ralph Reader Overseas Research Fellow of the National Heart Foundation of Australia and was the recipient of a Telectronics traveling grant of the Royal Australasian College of Physicians. Dr Fisher was funded by the US Navy. We gratefully acknowledge Margret Mayes for excellent technical assistance and Zaida Rizzo for expert help with Holter analysis.
Received June 7, 1994; revision received June 5, 1995; accepted June 23, 1995.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. James TN. Anatomy of the sinus node of the dog. Anat Rec. 1962;143:251-265. [Medline] [Order article via Infotrieve]
2.
James TN, Sherf L, Fine G, Morales AR.
Comparative ultrastructure of the sinus node in man and
dog. Circulation. 1966;34:139-163.
3.
Anderson KR, Ho SY, Anderson RH. Location and
vascular supply of sinus node in human heart. Br Heart
J. 1979;41:28-32.
4. Boineau JP, Schuessler RB, Cain ME, Corr PB, Cox JL. Activation mapping during normal atrial rhythms and atrial flutter. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia, Pa: WB Saunders Co; 1990:537-547.
5. Boineau JP, Schuessler RB, Hackel DB, Miller CB, Brockus CW, Wylds AC. Widespread distribution and rate differentiation of the atrial pacemaker complex. Am J Physiol. 1980;239:H406-H415.
6.
Littmann L, Svenson RH, Gallagher JJ, Bharati S, Lev
M, Linder KD, Tatsis GP, Nichelson C. Modification of sinus node
function by epicardial laser irradiation in dogs.
Circulation. 1990;81:350-359.
7.
Chu E, Fitzpatrick AP, Chin MC, Sudhir K, Yock PG,
Lesh MD. Radiofrequency catheter ablation guided by intracardiac
echocardiography.
Circulation. 1994;89:1301-1305.
8. Fisher WG, Swartz JF. Three-dimensional electrogram mapping improves ablation of left-sided accessory pathways. PACE Pacing Clin Electrophysiol. 1992;15:2344-2356. [Medline] [Order article via Infotrieve]
9. Randall WC, Rinkema LE, Jones SB, Moran JF, Brynjolfsson G. Functional characterization of atrial pacemaker activity. Am J Physiol. 1982;242:H98-H106.
10.
Langberg JJ, Gallagher M, Strickberger SA, Amirana O.
Temperature-guided radiofrequency catheter ablation with
very large distal electrodes. Circulation. 1993;88:245-249.
11. Ursell PC, Ren CL, Danilo P Jr. Autonomic neural tissue in the developing dog heart, I: adrenergic innervation. Anat Rec. 1990;226:71-80. [Medline] [Order article via Infotrieve]
12. Lewis T, Oppenheimer BS, Oppenheimer A. The site of origin of the mammalian heart beat: the pacemaker in the dog. Heart. 1911;2:147-169.
13. Meek WJ, Eyster JAE. Experiments on the origin and propagation of the impulse in the heart, IV: the effect of vagal stimulation and of cooling on the location of the pacemaker within the sino-auricular node. Am J Physiol. 1914;34:368-383.
14. Bouman LN, Gerlings ED, Biersteker PA, Bonke FIM. Pacemaker shift in the sinoatrial node during vagal stimulation. Pflugers Arch. 1968;302:255-267. [Medline] [Order article via Infotrieve]
15. Geesbreght JM, Randall WC. Area localization of shifting cardiac pacemakers during sympathetic stimulation. Am J Physiol. 1971;220:1522-1527.
16. Goldberg JM. Intra SA nodal pacemaker shifts induced by autonomic stimulation in the dog. Am J Physiol. 1975;229:1116-1123.
17. Goldberg JM, Lynn-Johnson MH, Neely B. Use of P wave morphology for inferring pacemaker localization along the sulcus terminalis in the dog. J Electrocardiol. 1981;14:115-124. [Medline] [Order article via Infotrieve]
18.
Boineau JP, Schuessler RB, Mooney CR, Wylds AC, Miller
CB, Hudson RD, Borremans JM, Brockus CW. Multicentric origin of
the atrial depolarization wave: the pacemaker complex: relation to
dynamics of atrial conduction, P-wave changes and heart rate
control. Circulation. 1978;58:1036-1048.
19. Boineau JP, Schuessler RB, Roeske WR, Autry LJ, Miller CB, Wylds AC. Quantitative relation between sites of atrial impulse origin and cycle length. Am J Physiol. 1983;245:H781-H789.
20.
Boineau JP, Canavan TE, Schuessler RB, Cain ME, Corr
PB, Cox JL. Demonstration of a widely distributed atrial
pacemaker complex in the human heart.
Circulation. 1988;77:1221-1237.
21. James TN. The sinus node. Am J Cardiol. 1977;40:965-986. [Medline] [Order article via Infotrieve]
22. Sealy WC, Bache RJ, Seaber AV, Bhattacharga SK. The atrial pacemaking site after surgical exclusion of the sinoatrial node. J Thorac Cardiovasc Surg. 1973;65:841-850. [Medline] [Order article via Infotrieve]
23. Randall WC, Wehrmacher WH, Jones SB. Hierarchy of supraventricular pacemakers. J Thorac Cardiovasc Surg. 1981;82:797-800. [Abstract]
24. Randall WC, Talano J, Kaye MP, Euler D, Jones S, Brynjolfsson G. Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade. Am J Physiol. 1978;234:H465-H470.
25.
Euler DE, Jones SB, Gunnar WP, Loeb JM, Murdock DK,
Randall WC. Cardiac arrhythmias in the conscious dog
after excision of the sinoatrial node and crista terminalis.
Circulation. 1979;59:468-475.
26.
Kocovic DZ, Harada T, Shea JB, Soroff D, Friedman PL.
Alterations of heart rate and of heart rate variability after
radiofrequency catheter ablation of supraventricular
tachycardia: delineation of parasympathetic pathways in the
human heart. Circulation. 1993;88:1671-1681.
27. Sanchis J, Chorro FJ, Lopez-Merino V, Such L, Cerda M, Valentin V. Closed chest radiofrequency ablation of the sinoatrial node in dogs. PACE Pacing Clin Electrophysiol. 1990;13:745-756. [Medline] [Order article via Infotrieve]
28. Jenkins KJ, Walsh EP, Colan SD, Bergau DM, Saul P, Lock JE. Multipolar endocardial mapping of the right atrium during cardiac catheterization: description of a new technique. J Am Coll Cardiol. 1993;22:1105-1110. [Abstract]
29. Bauernfeind RA, Amat-y-Leon F, Dhingra RC, Kehoe R, Wyndham C, Rosen KM. Chronic nonparoxysmal sinus tachycardia in otherwise healthy persons. Ann Intern Med. 1979;91:702-710.
30. Bristow MR. Pathophysiologic and pharmacologic rationales for clinical management of chronic heart failure with beta-blocking agents. Am J Cardiol. 1993;71:12C-22C.[Medline] [Order article via Infotrieve]
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