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Increase in heart rate after radiofrequency catheter ablation is mediated by parasympathetic nervous withdrawal and related to site of ablation
Journal of Electrocardiology Vol. 30 No. 3 1997
Increase in Heart Rate After R a d i o f r e q u e n c y Catheter A b l a t i o n Is M e d i a t e d by P a r a s y m p a t h e t i c N e r v o u s W i t h d r a w a l a n d R e l a t e d to Site of A b l a t i o n
Kyoko
Soejima, MD,* Makoto
Akaishi, MD,* Hideo Mitamura,
Satoshi Ogawa, MD,* Harumizu Hidetaka
Sakurada,
O k a z a k i MD,-]- T a k e s h i M o t o m i y a , and Masayasu
MD,*
MD,~MD,-]-
Hiraoka, MD,$
Abstract: To assess the mechanism for the increased sinus rate after radiofrequency catheter ablation performed for atrioventricular nodal reentrant tachycardia (AVNRT), we studied heart rate variability before and after radiofrequency catheter ablation in 17 patients with AVNRT and in 38 patients with an accessory pathway. The accessory pathway was located at the left ventricular free wall, the right ventricular free wall, or the posterior interventricular septum. An increased sinus rate was observed in patients with AVNRT or with the accessory pathway at the posterior septum or left free wall after radiofrequency ablation. In these groups, high-frequency power, root mean square of successive difference and percent of adjacent cycles that were more than 50 ms apart, all of which are indices reflecting parasympathetic nervous activity, were decreased. The ratio of low-frequency to high-frequency power reflecting sympathovagal balance, was increased in patients with AVNRT or with an accessory pathway at the posterior septum or left free wall Increases in sinus rate were correlated with decreases in high-frequency power, and percent of adjacent cycles more than 50 ms apart that the increase in heart rate was due to parasympathetic nervous withdrawal. K e y words: heart rate variability, radiofrequency ablation, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia.
Because of its high success rate and few serious complications, radiofrequency catheter ablation has b e c o m e the treatment of choice (1-5) for patients with atrioventricular nodal reentrant tachycardia (AVNRT) or atrioventricular reentrant tachycardia. I n f r e q u e n t but serious complications, such as cardiac perforation, myocardial infarction,
From the Division of Cardiology, Department of Medicine, Keio University, ~Division of Cardiology, Tokyo Metropolitan Hiroo Hospital, and ~:Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan.
Reprint requests: Kyoko Soejima, MD, Division of Cardiology, Department of Medicine, Keio University, 35 Shinanomachi Shinjuku-ku, Tokyo,Japan #160. © I997 Churchill Livingstone Inc.
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or aortic valve fenestration, have been reported. These hemodynamic complications can increase the sinus rate. Thus, the heart rate should be monitored carefully after RF ablation, since early detection of these complications is mandatory. An increased sinus rate after radiofrequency ablation, also referred to as inappropriate sinus tachycardia, has occurred. It is more common after ablation for AVNRT, but its mechanism is poorly understood (6,7). Our objective was to assess the mechanisms of the increased sinus rate after radiofrequency ablation for AVNRT. To accomplish this, we measured heart rate variability in various groups of patients before and after radiofrequency ablation.
Materials and Methods Patients The subjects were 55 Japanese patients who underwent radiofrequency ablation and 24-hour I-Iolter monitoring before and after the procedure at the Tokyo Metropolitan Hiroo Hospital between April 1993 and April 1994. The echocardiogram showed no abnormality before the procedure. No patients had diabetes mellitus, hypertension, congestive heart failure, or other pathophysiologic disorders. All procedures were performed after informed consent was obtained. Radiofrequency ablations and electrophysiologic studies before and after the ablation were carried out for AVNRT in 17 patients and for Wolff-Parkinson-White syndrome in 38 patients (Table 1). Of the 38 patients, 23 had the accessory pathway located at the left ventricular free wall, 8 at the right ventricular free wall, and 7 at the posterior half of the interventricular septum. The patients were divided into four groups consisting patients with AVNRT and patients with accessory pathways at the three locations. Radiofre-
Table 1. Characteristics of 55 Patients Undergoing Radiofrequency Ablation Group AVNRT PS LW RW Total
Age (Mean + SD) 35.8 42.1 44.8 37.3
_+ 19.5 _+22.0 _+ 13.2 ± 14.5
Patients (M/F) 17 7 23 8 55
(9/8) (3/4) (15/8) (5/3) (32123)
AVNRT, atrioventricular nodal reentrant tachycardia; LW, accessory pathway at the left free wall; PS, accessory p a t h w a y at the posterior interventricular septum; RW, accessory p a t h w a y at the right free wall.
quency ablation of the accessory pathway at the left ventricular free wall was performed below the mitral valve, radiofrequency ablation of the accessory pathway at the right ventricular free wall was performed above the tricuspid valve; ablation of the slow pathway of the AVNRT was performed near the ostium of the coronary sinus. No patients had diabetes mellitus, hypertension, congestive heart failure, or other pathophysiologic disorders. All medications were discontinued for at least five times the biologic half-lives of the drugs prior to initiating Holter monitoring before radiofrequency ablation. Each subject underwent 24-hour Holter monitoring within 3 days before and again 3 days after the radiofrequency ablation. In the morning of the day before and the day after the radiofrequency ablation procedure, the resting heart rate was counted manually for 1 minute by the nurse.
Data Analysis Heart Rate Variability Analysis. Holter monitoring was recorded with a Marquette Series 8500 recorder and analyzed with a Marquette 8000/% heart rate variability software, version 002A, being used to obtain heart rate variability. Premature beats were identified and corrected by linear interpolation with the previous and following beats. Each interval that was to be excluded owing to extrasystoles or artifacts was replaced by holding the previous coupling interval level throughout the time interval to the next valid coupling interval. Spectral Analysis. The power spectrum was calculated as the squared magnitude of the fast Fourier transform for each segment after an R-R interval signal was collected from a 2-minute segment of data and was then sampled to fill a 512point array to create 30 segments for 1 hour of data. The frequency domain measures of heart rate variability, the high-frequency power spectrum (range, 0.15-0.40 Hz), low-frequency power spectrum (range, 0.04-0.15 Hz), and the total power (range, 0.01-1.0 Hz) were obtained. All the values of the spectral power were expressed as the average of all the segments of the time of interest. T i m e - D o m a i n Analysis. The time domain measures of heart rate variability, including the standard deviation of all normal N-N intervals (SDNN), the 24-hour average of standard deviations of N-N in the 5-minute intervals, the rootmean-square of successive difference (rMSSD), the
Heart Rate and Radiofrequency Catheter Ablation
percent of adjacent cycles that are m o r e t h a n 50 ms apart, m e a s u r e d as percent of total beats (pNNs0) m e a n NN, and the standard deviation of the m e a n N-N of the 5 - m i n u t e intervals w e r e obtained by using all the continuous data t h r o u g h o u t 24 hours. The rMSSD, the pNNs0 of the r i m e - d o m a i n analysis, and the h i g h - f r e q u e n c y c o m p o n e n t of the freq u e n c y - d o m a i n analysis are k n o w n to reflect the activity of the p a r a s y m p a t h e t i c n e r v o u s system (8-10). All these p a r a m e t e r s w e r e c o m p a r e d before a n d after radiofrequency ablation. H e a r t R a t e A n a l y s i s . Because the h e a r t rate varies in response to the patients' activity, it should be carefully assessed by different measures. Thus, this study used five h e a r t rate m e a s u r e m e n t s obtained b y Holter m o n i t o r i n g : of (1) heart rate at 6 a.m., (2) the 2 4 - h o u r average h e a r t rate, (3) the 2 4 - h o u r m a x i m u m h e a r t rate, (4) the 2 4 - h o u r m i n i m u m h e a r t rate, a n d (5) the n i g h t t i m e - a v e r age h e a r t rate f r o m 1 to 6 a.m. The h e a r t rate at 6 a.m. in the supine position was m e a s u r e d o n the day before and again on the day following r a d i o f r e q u e n c y ablation. Other m e a s u r e s of h e a r t rate w e r e obtained f r o m 2 4 - h o u r Holter a m b u l a tory monitoring. Heart rate at 6 a.m., nighttimeaverage h e a r t rate, and 2 4 - h o u r m i n i m u m h e a r t rate b y Holter m o n i t o r i n g w e r e considered to reflect the activity of the p a r a s y m p a t h e t i c n e r v o u s system, while the 2 4 - h o u r m a x i m u m h e a r t rate was considered to reflect the activity of the s y m p a thetic n e r v o u s system. By c o m p a r i n g the changes in these values with h e a r t rate variability, w e inferred the causes of the increases in h e a r t rate. Changes in the h i g h - f r e q u e n c y c o m p o n e n t , rMSSD, pNNs0, and t h e y w e r e c o m p a r e d in each group, a n d the ratios of changes a m o n g the groups w e r e evaluated. Correlations b e t w e e n the m e a n h e a r t rate at 1 to 6 a.m. (night h e a r t rate) and the m e a n h i g h - f r e q u e n c y p o w e r s p e c t r u m during the same time periods w e r e evaluated. Because m o s t patients w e r e asleep f r o m 1 to 6 a.m., the high-treq u e n c y during this period was a s s u m e d to reflect mostly p a r a s y m p a t h e t i c n e r v e activity. S t a t i s t i c s . Data are p r e s e n t e d as m e a n s + SD. C o m p a r i s o n of c o n t i n u o u s data a m o n g the groups was m a d e by o n e - w a y analysis of variance with Bonferroni correction. A chi-square test was used to c o m p a r e d i c h o t o m o u s data a m o n g groups. Data within groups over time w e r e c o m p a r e d by the paired Student's t-test. Correlation coefficients b e t w e e n heart rate a n d h e a r t rate variability w e r e calculated. A P value of less t h a n .05 was required for statistical significance.
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Results Holter m o n i t o r i n g was p e r f o r m e d 2.2 + 0.2 days before a n d 1.2 + 0.2 days after r a d i o f r e q u e n c y ablation. Radiofrequency ablation was successfully completed in all patients w i t h o u t complications. The e c h o c a r d i o g r a m obtained after the radiofreq u e n c y ablation s h o w e d n o h e m o d y n a m i c a l l y c o m p r o m i s i n g complications, such as a n e w l y developed aortic regurgitation, pericardial effusion, or asynergy of the left ventricular wall.
Resting Sinus Rate Figure l shows the difference b e t w e e n h e a r t rate at 6 a.m. values t a k e n before and after radiofreq u e n c y ablation. Each point represents an individual case. The change in h e a r t rate represents the difference in heart rate before a n d after RF ablation. The heart rate at 6 a.m. before radiofrequency ablation w e r e 60.0 + 7.0 b e a t s / m i n for the AVNRT, 72.0 + 8.6 b e a t s / m i n for the posterior septum, 69 + 7.9 b p m for the left wall, and 63.0 + 5.7 b e a t s / m i n for the right wall groups. After r a d i o f r e q u e n c y ablation, h e a r t rate significantly increased (P < .05) in the AVNRT (21.8 + 7.6 beats/min), the posterior s e p t u m (14.0 + 12.4 beats/min), a n d the left free wall (7.2 + 6.7 beats/rain) groups but n o t in the right free wall (2.8 + 8.5 beats/min) group. The 24h o u r h e a r t rate obtained by Holter a m b u l a t o r y m o n i t o r i n g was c o m p a r e d before and after radiof r e q u e n c y ablation (Table 2). A significant increase
5040" .o 30 "~ 20 ~- 10 .5
•
E
=~ 0 a= -10 AVNRT
PS
LW
RW
Fig. 1. Changes in heart rate measured at 6 a.m. after RF ablation. Each point represents an individual patient. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septum; LW, accessory pathway in the left free wail; RW, accessory pathway in the right free wall.
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Journal of Electrocardiology Vol. 30 No. 3 July 1997 Table 2. Heart Rate D e t e r m i n e d b y Itolter A m b u l a t o r y M o n i t o r i n g in A l l Patient Groups Before and After Radiofrequency A b l a t i o n
Group AVNRT PS LW RW
Mean HR (beats/min) Before After 67.8_+8.1 71.1+_7.8 72.4 _+9.4 67.6_+8.6
Maximum HR (beats/min) Before After
77.2_+9.7"]-:t; 80.4 -+9.9"J-$ 79.1 _+10.5" 70.4_+7.5
121.1-+16.5 120.4-+17.8 126.6 _+29.5 122.4_+17.8
Minimum HR (beats/min) Before After
125.1-+13.0 124.0-+11.0 131.2 + 15.7 126.1_+13.1
45.9-+5.6 50.4-+9.7 49.8 _+6.3 44.9+3.9
55.8-+8.1"-t-$ 57.3 -+9.9"]-~c 54.5 _+7.2* 46.4-+4.8
Heart rate is 24-hour heart rate. * P < .05 vs pre; J- P < .05 vs LW; $ P < .05 vs RW. HR, heart rate; AVNRT, atrioventricular nodal reentrant tachycardia; LW, accessory pathway at the left free wall; PS, accessory pathway at the posterior interventricular septum; RW, accessory pathway at the right free wall.
in a v e r a g e h e a r t r a t e a f t e r r a d i o f r e q u e n c y a b l a t i o n w a s s e e n in t h e AVNR% p o s t e r i o r s e p t u m , a n d left w a l l g r o u p s b u t n o t i n t h e r i g h t free w a l l g r o u p . T h e i n c r e a s e i n h e a r t r a t e in t h e left free w a l l g r o u p (6.7 + 7.6 b e a t s / m i n ) w a s less t h a n t h o s e i n c r e a s e s in t h e AVNRT (9.4 -1-_4.8 b e a t s / m i n ) o r p o s t e r i o r s e p t u m g r o u p s (9.3 + 6.4 b e a t s / m i n ) . While these three groups showed significant i n c r e a s e s in a v e r a g e h e a r t rate, t h e m a x i m u m h e a r t r a t e s h o w e d n o s i g n i f i c a n t c h a n g e after radiofrequency ablation. Conversely, the 24-hour m i n i m u m h e a r t r a t e s h o w e d t h e s a m e t e n d e n c y as t h e a v e r a g e h e a r t rate, t h a t is, t h e 2 4 - h o u r m i n i m u m h e a r t r a t e s h o w e d a s i g n i f i c a n t i n c r e a s e (P < .05) after r a d i o f r e q u e n c y a b l a t i o n i n t h e AVNRT, p o s t e r i o r s e p t u m , a n d left free w a l l g r o u p s b u t n o t in t h e r i g h t free w a l l g r o u p .
Changes in Heart Rate Variability After radiofrequency ablation, the rMSSD values d e c r e a s e d f r o m 39.7 _+ 17.8 to 22.6 + 10.3 m s i n t h e
AVNRT g r o u p (P < .05), f r o m 44.3 + 18.1 to 29.3 + 16.5 m s in t h e p o s t e r i o r s e p t u m g r o u p (P < .05), a n d f r o m 26.0 + 9.9 to 19.8 + 8.1 m s i n t h e left free w a l l g r o u p (P < .05) b u t n o t in t h e r i g h t free w a l l group. Figure 2 shows the changes in the rMSSD a n d pNNs0 v a l u e s a f t e r r a d i o f r e q u e n c y a b l a t i o n . P a t i e n t s w i t h AVNRT a n d t h e p o s t e r i o r s e p t u m accessory pathway showed significantly larger d e c r e a s e s in r M S S D as c o m p a r e d w i t h t h e left w a l l g r o u p . T h e AVNRT g r o u p s h o w e d a s i g n i f i c a n t d e c r e a s e i n r M S S D as c o m p a r e d w i t h t h e r i g h t w a l l g r o u p . The pNNso d e c r e a s e d f r o m 17.0 + 15.7 to 5.4 + 7 . 3 % i n t h e AVNRT g r o u p (P < .05), f r o m 26.0 + 7.9 to 12.2 +_ 9 . 3 % i n t h e p o s t e r i o r s e p t u m g r o u p (P < .05), a n d 6.7 +_ 6.9 to 3.3 + 4 . 5 % in t h e left free w a l l g r o u p (P < .05) b u t d i d n o t d e c r e a s e in t h e r i g h t free w a l l g r o u p . P a t i e n t s w i t h AVNRT and the posterior septum showed significant d e c r e a s e s in pNNs0 as c o m p a r e d w i t h t h e left free w a l l o r r i g h t free w a l l g r o u p s (P < .05). After radiofrequency ablation, the high-freq u e n c y p o w e r w a s d e c r e a s e d f r o m 5.65 + 0.96 to
Changes in rMSSD after RF ablation (ms)
Changes in pNN50 after RF ablation (%)
0-
N N~
-4-
d_
}!i!ii
#
-10
_L -20
-12-
#*
m
#*
#* ,
AVNRT PS
#
N~
-8-
,
,
LW
%
-16
RW
I
AVNRT~
PS
I
LW
RW
Fig. 2. Changes in the time domain of the heart rate variability after radiofrequency ablation. Left panel: rMSSD, root mean-square of the successive difference. Right panel: pNNs0, percent of adjacent cycles that are more than 50 ms apart, measured as percent of tatal beats. Data are expressed as m e a n _+ SEM. *P < ,05 vs. LW; #P < .05 vs. RW. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septum; LW, accessory pathway in the left free wall; RW, accessory p a t h w a y in the right free wall.
Heart Rate and Radiofrequency Catheter Ablation
3.79 _+ 1.01 ln(ms 2) in the AVNRT group (P < .05), f r o m 5.64 _ 1.03 to 4.13 _+ 1.35 In (ms2) in the posterior s e p t u m group (P < .05), a n d f r o m 4.48 _+ 1.00 to 3.28 _+ 1.00 In (ms 2) in the left free wall group (P < .05) but was u n c h a n g e d in the right free wall group. Figure 3 shows the changes in high-frequency p o w e r and l o w - / h i g h f r e q u e n c y p o w e r ratio after radiofrequency ablation. Patients with AVNRT a n d those with a posterior s e p t u m accessory p a t h w a y s h o w e d significantly larger decreases in h i g h - f r e q u e n c y p o w e r t h a n those with a left wall anterior pathway. The decreases in high-frequency p o w e r in the AVNRT, posterior s e p t u m a n d left free wall groups w e r e larger t h a n in the right free wall group. The low-high frequency p o w e r ratio increased f r o m 2.56 + 2:13 to 4.59 + 1.72 in the AVNRT group, f r o m 1.56 + 0.76 to 2.5 + 1.34 in the posterior s e p t u m group and f r o m 4.73 + 2.54 to 6.02 + 3.38 in the left wall group, but not significant differences a m o n g these groups w e r e found.
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patient. Most arrows m o v e u p w a r d to the left, indicating that the h e a r t rate increased as high-freq u e n c y p o w e r decreased. The patient w i t h the largest increase in heart rate a n d the largest decrease in h i g h - f r e q u e n c y p o w e r shows the longest line. In the left u p p e r panel, almost all the patients w i t h AVNRT s h o w an increased h e a r t rate a n d a decreased h i g h - f r e q u e n c y power. In the right u p p e r panel, all the patients w i t h accessory pathw a y at the posterior s e p t u m s h o w a n increased h e a r t rate a n d decreased h i g h - f r e q u e n c y power. A similar, but weak, t e n d e n c y was seen in patients w i t h a left wall accessory p a t h w a y but not in patients w i t h an accessory p a t h w a y at the right wall. In addition, correlation coefficients b e t w e e n the increase in the resting sinus rate and h e a r t rate variability/heart rate, rMSSD, pNNs0, a n d lowh i g h - f r e q u e n c y ratio w e r e calculated (Table 3). The increases in resting sinus rate correlated with decreases in h i g h - f r e q u e n c y p o w e r a n d pNNs0 but not with the low- to h i g h - f r e q u e n c y ratio.
Relation Between Heart Rate and Heart Rate Variability Discussion B e t w e e n 1 a n d 6 a.m., the average heart rate and average h i g h - f r e q u e n c y p o w e r w e r e obtained f r o m the Holter a m b u l a t o r y m o n i t o r i n g data. Their relationship is plotted in Figure 4. All the patients w e r e asleep during this period, and p a r a s y m p a thetic n e r v o u s activity was considered to d o m i n a t e the a u t o n o m i c n e r v o u s system activity. Two points, w h i c h represent the values obtained before a n d after r a d i o f r e q u e n c y ablation for each patient, are c o n n e c t e d with arrows. Each a r r o w represents one
Changes in HF after RF ablation
Our results s h o w e d an increase in heart rate after the radiofrequency ablation of the slow p a t h w a y of patients w i t h AVNRT or w i t h the accessory p a t h w a y at the posterior s e p t u m or at the left v e n tricular free wall. Correlations w e r e observed b e t w e e n the indices of p a r a s y m p a t h e t i c n e r v o u s activity w i t h various m e a s u r e s of h e a r t rate (ie, the m o r n i n g supine h e a r t rate, the 2 4 - h o u r average h e a r t rate, the 2 4 - h o u r m i n i m u m h e a r t rate, a n d
Changes in LF/HF after RF ablation
0-
(In(ms) 2)
-1--
-1-
,# -2*#
-3 AVNRT I
PS
~ LW
RW
AVNRT
PS
LW
RW
Fig. 3. Changes in the frequency domain of the heart rate variability after radiofrequency ablation. Left panel: HE power spectrum for the high-frequency range. Right panel: LF/HE ratio of the power spectra for the low and high frequency ranges. Data are expressed as mean +_SEM. *P < .05 vs LW; #P < .05 vs. RW. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septum; LW, accessory pathway in the left free wall; RW, accessory pathway in the right free wall.
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Journal of Electrocardiology Vol. 30 No. 3 July 1997
100 90
100 AVNRT
PS
90
,o
8O 70
- - 5 x,,
70
g 60
60
40
50 40
3O
3O
20
20
10
l0
50
0
0 1
2
3
4
5
0
6
I
2
HF (ln(ms2))
IO0 90
LW
3
4
5
6
HF (In(ms2 D 100
~i
90
80
80
70
70
60
60
50
RW
50
40
40
30
3O 20
201 10 0
10 0 2
3 4 5 HF (In(ms 21)
6
I
2
3 4 5 HF (In(ms2))
6
Fig. 4. Changes in the right-time average high-frequency power spectrum and heart rate after radiofrequency ablation. Lines connect the values obtained before and after radiofrequency ablation for individual patients. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septurn; LW, accessory pathway in the left free wall; RW, accessory pathway in the right free wall.
the nighttime heart rate for 5 hours). Frey et al. observed a w e a k correlation b e t w e e n the parameters of heart rate variability and cumulative radiofrequency energy application in a group of patients w h o u n d e r w e n t ablation of a left lateral or posteroseptal accessory p a t h w a y or fast or slow atrioventricular nodal pathways (11). Other studies (6,7,11) have s h o w n that the prevalence of inappropriate sinus tachycardia following radiofre-
Table 3. Correlations Between Heart Rate and Heart
Rate Variability Obtained at Rest in the Morning Correlation Coefficient Group AVNRT PS LW RW
HF (In(ms2)) 0.45* 0.50* 0.76* 0.1
MSSD r (ms) 0.37 0.41 0.43 0.09
pNNso (%) 0.39 0.44 0.34 0.13
LF/HF 0.14 0.16 0.1 0.01
* Statistically significant correlation, P < .05. L o w - f r e q u e n c y power; HE h i g h - f r e q u e n c y power; rMSSD, r o o t - m e a n - s q u a r e of successive differences; pNNso, percent of adjacent cycles that are > 50 m s apart m e a s u r e d in percent in total beats; LF/HE ratio of LF to HF; AVNRT, atrioventricular nodal r e e n t r a n t tachycardia; LW, accessory p a t h w a y at t h e left free wall; PS, accessory p a t h w a y at t h e posterior interventricular septum; RW, accessory p a t h w a y at t h e right free wall.
q u e n c y ablation is relatively high for AVNRT and the posterior septum accessory pathway. In this study, sinus tachycardia occurred in only 2 of the 53 patients w h o u n d e r w e n t radiofrequency ablation, whereas an increase in heart rate was obseryed in most of the patients in the AVNRT, posterior septum and left wall groups. Heart rate variability is widely used as a noninvasive means for assessing autonomic nervous system activity, and is considered to reflect the effect of autonomic nervous system activity on the sinus node. The use of 24-hour ambulatory electrocardiographic monitoring allows the R wave to be detected more easily on the tape. The R-R interval can be used for heart rate variability analysis instead of the P-P interval. In patients with stable atrioventricular conduction, the R-R interval can be used to replace the P-P interval. Although autonomic nervous activity modulates atrioventricular conduction, the relative change in the P-Q interval is small compared with the change in the P-P interval. Thus, the R-R interval can be considered to reflect mainly a control of the autonomic nervous system on the sinus node. Of all the indices, frequency domain analysis of heart rate variability is the most useful for differentiating b e t w e e n the activity of the parasympathetic and sympathetic nerves. The high-frequency power spectrum reflects the activity of the parasympathetic input to the heart, as Pomeranz et al. (10) showed that high-frequency power was decreased by atropine administration and was increased in the supine position. Low-frequency p o w e r was decreased by propranolol administration and was increased on standing. Thus, while high-frequency power reflects only parasympathetic activity, low-frequency power reflects the activity of both the sympathetic and parasympathetic nervous system. The rMSSD and pNNso are parameters of time domain analysis and reflect parasympathetic nervous system activity. The ratio of low- to high-frequency p o w e r is considered to reflect the balance b e t w e e n sympathetic and parasympathetic nervous input to the heart ( 12). To assess the mechanism of increased heart rate after radiofrequency ablation, we used heart rate variability to evaluate w h e t h e r the increased in heart rate was caused by an increase in sympathetic nervous system activity or by a decrease in parasympathetic nervous system activity. In this study, heart rate increased after radiofrequency ablation of the slow p a t h w a y of the AVNRT and the accessory pathways at the posterior septum and the left wall. In these groups, the high-frequency power, rMSSD, and pNNso, all decreased after radiofrequency abla-
Heart Rate and Radiofrequency Catheter Ablation
tion. The increased heart rate correlated well with the decreased values of these parameters. Conversely, the low- high-frequency p o w e r ratio was increased in all the groups, but the increase was not correlated with the increased heart rate. This suggested that the increased heart rate after radiofreq u e n c y ablation was probably due not to the stimulation of the sympathetic nervous system but rather to the withdrawal of parasympathetic nervous system activity. The sites of energy delivered in the posterior septum group and AVNRT are very close to each other. The increase in heart rate was m o r e p r o m i n e n t after radiofrequency ablation performed in the AVNRT and posterior septum groups. Thus, it is possible that the posteroseptal portion is the site that specifically influences the parasympathetic postganglionic fibers. N u m e r o u s reports (13-17) have s h o w n the anatomic distribution of sympathetic and parasympathetic nerves in the canine heart. Surprisingly little is k n o w n about the a u t o n o m i c innervation of the h u m a n heart. Parasympathetic preganglionic fibers to the sinoatrial node emanate mainly from ganglia located in the p u l m o n a r y vein fat pad, and fibers to the atrioventricular node arise from ganglia located in the fat pad overlying the entry of the coronary sinus into the inferior interatrial septum at the junction of the inferior vena cava and inferior left atrium. Etferent sympathetic axons destined for the ventricle are located in the superficial subepicardium. Parasympathetic fibers are located at the ventricular surface within 10 m m of the right lateral atrioventricular groove. They penetrate intramurally and reach the medial sites of the anterior wall. Parasympathetic nerve fibers are relatively sparse in the left ventricular wall. The mechanisms of increased heart rate after radiofrequency ablation can be postulated. A direct effect of radiofrequency ablation on the sinoatrial node is less likely because the ablated site is distant f r o m the sinoatrial n o d e and the post-radiofreq u e n c y ablation electrophysiologic study s h o w e d no prolongation of the corrected sinoatrial nodal recovery time. The possibility that radiofrequency ablation causes sympathetic nerve stimulation cannot be excluded. However, because we observed no differences in low- high-frequency p o w e r ratio a m o n g the groups after radiofrequency ablation and since the sympathetic nerves are located at the epicardial surface, an effect of radiofrequency ablation on the sympathetic nerve activity appears less likely. Kocovic et al. (13) reported that the control patients w h o u n d e r w e n t only diagnostic electrophysiologic study did not show a significant increase in heart rate or in the p o w e r spectrum of
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heart rate variability. The changes in heart rate or in heart rate variability were probably caused by the radiofrequency catheter ablation, not by the electrophysiologic study. Taking these conditions into account, the radiofrequency ablation site for the slow pathways or the accessory pathways at the posterior septum are n e a r the ostium of the coronary sinus, w h e r e the ganglia of parasympathetic nerves destined for the atrioventricular node are located. RF ablation at this site m a y damage some of the postganglionic fibers destined for the sinoatrial node as well as the atrioventricular node. However, the exact mechanisms of the withdrawal of parasympathetic nerve activity after radiofreq u e n c y ablation of the left ventricular free wall remains to be determined.
Conclusions The sinus r h y t h m is sometimes increased in patients after radiofrequency ablation. This condition appeared to be more frequent after radiofreq u e n c y ablation of the slow p a t h w a y for AVNRT or the accessory p a t h w a y located in the posterior septum. The high-frequency ratio, rMSSD, and pNNs0 values were decreased and the low- to high-freq u e n c y p o w e r ratio increased in these latter cases concomitantly with an increase in sinus r h y t h m . As the heart rate increased, the parasympathetic nerve activity as m e a s u r e d by heart rate variability decreased. No correlation was observed b e t w e e n the increased heart rate and sympathetic nerve activity as m e a s u r e d by heart rate variability. We conclude that the increase in heart rate after radiofrequency ablation is mediated by parasympathetic withdrawal. W h e t h e r this withdrawal is due to a direct effect of radiofrequency ablation or is mediated by a reflex remains to be determined.
References 1. Jackmann WM, Wang X, Friday KJ et ah Catheter ablation of accessory atrioventricular pathways (Wolff-Parkinson-White syndrome) by radiofrequency current. N Engl J Med 324:1605, 1991 2. Jackmann WM, Beckman KJ, McClellan JH et at: Treatment of supraventricular tachycardia due to atrioventricular nodal reentry by radiofrequency catheter ablation of slow-pathway conduction. N Engl J Med 327:313, I992 3. Feld GK: Catheter ablation for the treatment of atrial tachycardia. Prog Cardiovasc Dis 37:205, I995 4. Langberg J J, Chin MC, Resenqvist M et al: Catheter ablation of the atrioventricular junction with radiofrequency energy. Circulation 80:1527, 1989
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5. Haissaguerre M, Gaita F, Fischer B e t al: Elimination of atrioventricular nodal reentrant tachycardia using discrete slow potentials to guide application of radiofrequency energy. Circulation 85:2162, 1992 6. Ehlert FA, Goldberger J J, Brooks R et al: Persistent inappropriate sinus tachycardia after radiolrequency current catheter modification of the atrioventricular node. Am J Cardiol 69:1092, 1992 7. Skeberis V, Simonis E Andries E, Brugada P: Inappropriate sinus tachycardia after radiofrequency ablation of AV nodal tachycardia: incidence and clinical significance (abstract) J Am Coll Cardiol 21: 358A, 1993 8. Akselrod S, Gordon D, Ubel FA et al: Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213:220, 1981 9. Hayano J, Sakakibara Y, Yamada A et al: Accuracy of assessment of cardiac vagal tone by heart rate variability in n o r m a l subjects. Am J Cardiol 67:199, 1991 10. Pomeranz B, Macaulay RJB, Caudill MA et al: Assessment of autonomic function in h u m a n s by heart rate spectral analysis. A m J Physiol 248:H151, 1985
11. Frey B, Heinz G, Kreiner G et al: Increased heart rate variability after radiofrequency ablation. Am J Cardiol 71:1460, 1993 12. Pagani M, Lombardi F, Guzzetti S et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in m a n and conscious dog. Circ Res 59:178, 1986 13. Kocovic DZ, Harada T, Shea J et al: Alteration of heart rate and of heart rate variability after radiofrequency catheter ablation of supraventricular tachycardia. Circulation 88:167I, 1993 14. Randall WC, Ardell JL: Nervous control of the heart: anatomy and pathophysiology, p. 291. In Zipes DP, Jalife J (eds): Cardiac electrophysiology, from cell to bedside. WB Saunders, Philadelphia, 1990 15. Ardell JL, Randall WC: Selective vagal innervation of sinoatrial and atrioventricular nodes in canine heart. A m J Physiol 20:H764, 1986 16. Ito M, Zipes DP: Efferent sympathetic and vagal irmervation of the canine right ventricle. Circulation 90:1459, 1994 17. Lazzara R, Scherlag BJ, Robinson MJ, Samet P: Selective in situ parasympathetic control of the canine sinoatrial and atrioventricular nodes. Circ Res 32:393, 1973
Increase in Heart Rate After R a d i o f r e q u e n c y Catheter A b l a t i o n Is M e d i a t e d by P a r a s y m p a t h e t i c N e r v o u s W i t h d r a w a l a n d R e l a t e d to Site of A b l a t i o n
Kyoko
Soejima, MD,* Makoto
Akaishi, MD,* Hideo Mitamura,
Satoshi Ogawa, MD,* Harumizu Hidetaka
Sakurada,
O k a z a k i MD,-]- T a k e s h i M o t o m i y a , and Masayasu
MD,*
MD,~MD,-]-
Hiraoka, MD,$
Abstract: To assess the mechanism for the increased sinus rate after radiofrequency catheter ablation performed for atrioventricular nodal reentrant tachycardia (AVNRT), we studied heart rate variability before and after radiofrequency catheter ablation in 17 patients with AVNRT and in 38 patients with an accessory pathway. The accessory pathway was located at the left ventricular free wall, the right ventricular free wall, or the posterior interventricular septum. An increased sinus rate was observed in patients with AVNRT or with the accessory pathway at the posterior septum or left free wall after radiofrequency ablation. In these groups, high-frequency power, root mean square of successive difference and percent of adjacent cycles that were more than 50 ms apart, all of which are indices reflecting parasympathetic nervous activity, were decreased. The ratio of low-frequency to high-frequency power reflecting sympathovagal balance, was increased in patients with AVNRT or with an accessory pathway at the posterior septum or left free wall Increases in sinus rate were correlated with decreases in high-frequency power, and percent of adjacent cycles more than 50 ms apart that the increase in heart rate was due to parasympathetic nervous withdrawal. K e y words: heart rate variability, radiofrequency ablation, atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia.
Because of its high success rate and few serious complications, radiofrequency catheter ablation has b e c o m e the treatment of choice (1-5) for patients with atrioventricular nodal reentrant tachycardia (AVNRT) or atrioventricular reentrant tachycardia. I n f r e q u e n t but serious complications, such as cardiac perforation, myocardial infarction,
From the Division of Cardiology, Department of Medicine, Keio University, ~Division of Cardiology, Tokyo Metropolitan Hiroo Hospital, and ~:Department of Cardiology, Tokyo Medical and Dental University, Tokyo, Japan.
Reprint requests: Kyoko Soejima, MD, Division of Cardiology, Department of Medicine, Keio University, 35 Shinanomachi Shinjuku-ku, Tokyo,Japan #160. © I997 Churchill Livingstone Inc.
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or aortic valve fenestration, have been reported. These hemodynamic complications can increase the sinus rate. Thus, the heart rate should be monitored carefully after RF ablation, since early detection of these complications is mandatory. An increased sinus rate after radiofrequency ablation, also referred to as inappropriate sinus tachycardia, has occurred. It is more common after ablation for AVNRT, but its mechanism is poorly understood (6,7). Our objective was to assess the mechanisms of the increased sinus rate after radiofrequency ablation for AVNRT. To accomplish this, we measured heart rate variability in various groups of patients before and after radiofrequency ablation.
Materials and Methods Patients The subjects were 55 Japanese patients who underwent radiofrequency ablation and 24-hour I-Iolter monitoring before and after the procedure at the Tokyo Metropolitan Hiroo Hospital between April 1993 and April 1994. The echocardiogram showed no abnormality before the procedure. No patients had diabetes mellitus, hypertension, congestive heart failure, or other pathophysiologic disorders. All procedures were performed after informed consent was obtained. Radiofrequency ablations and electrophysiologic studies before and after the ablation were carried out for AVNRT in 17 patients and for Wolff-Parkinson-White syndrome in 38 patients (Table 1). Of the 38 patients, 23 had the accessory pathway located at the left ventricular free wall, 8 at the right ventricular free wall, and 7 at the posterior half of the interventricular septum. The patients were divided into four groups consisting patients with AVNRT and patients with accessory pathways at the three locations. Radiofre-
Table 1. Characteristics of 55 Patients Undergoing Radiofrequency Ablation Group AVNRT PS LW RW Total
Age (Mean + SD) 35.8 42.1 44.8 37.3
_+ 19.5 _+22.0 _+ 13.2 ± 14.5
Patients (M/F) 17 7 23 8 55
(9/8) (3/4) (15/8) (5/3) (32123)
AVNRT, atrioventricular nodal reentrant tachycardia; LW, accessory pathway at the left free wall; PS, accessory p a t h w a y at the posterior interventricular septum; RW, accessory p a t h w a y at the right free wall.
quency ablation of the accessory pathway at the left ventricular free wall was performed below the mitral valve, radiofrequency ablation of the accessory pathway at the right ventricular free wall was performed above the tricuspid valve; ablation of the slow pathway of the AVNRT was performed near the ostium of the coronary sinus. No patients had diabetes mellitus, hypertension, congestive heart failure, or other pathophysiologic disorders. All medications were discontinued for at least five times the biologic half-lives of the drugs prior to initiating Holter monitoring before radiofrequency ablation. Each subject underwent 24-hour Holter monitoring within 3 days before and again 3 days after the radiofrequency ablation. In the morning of the day before and the day after the radiofrequency ablation procedure, the resting heart rate was counted manually for 1 minute by the nurse.
Data Analysis Heart Rate Variability Analysis. Holter monitoring was recorded with a Marquette Series 8500 recorder and analyzed with a Marquette 8000/% heart rate variability software, version 002A, being used to obtain heart rate variability. Premature beats were identified and corrected by linear interpolation with the previous and following beats. Each interval that was to be excluded owing to extrasystoles or artifacts was replaced by holding the previous coupling interval level throughout the time interval to the next valid coupling interval. Spectral Analysis. The power spectrum was calculated as the squared magnitude of the fast Fourier transform for each segment after an R-R interval signal was collected from a 2-minute segment of data and was then sampled to fill a 512point array to create 30 segments for 1 hour of data. The frequency domain measures of heart rate variability, the high-frequency power spectrum (range, 0.15-0.40 Hz), low-frequency power spectrum (range, 0.04-0.15 Hz), and the total power (range, 0.01-1.0 Hz) were obtained. All the values of the spectral power were expressed as the average of all the segments of the time of interest. T i m e - D o m a i n Analysis. The time domain measures of heart rate variability, including the standard deviation of all normal N-N intervals (SDNN), the 24-hour average of standard deviations of N-N in the 5-minute intervals, the rootmean-square of successive difference (rMSSD), the
Heart Rate and Radiofrequency Catheter Ablation
percent of adjacent cycles that are m o r e t h a n 50 ms apart, m e a s u r e d as percent of total beats (pNNs0) m e a n NN, and the standard deviation of the m e a n N-N of the 5 - m i n u t e intervals w e r e obtained by using all the continuous data t h r o u g h o u t 24 hours. The rMSSD, the pNNs0 of the r i m e - d o m a i n analysis, and the h i g h - f r e q u e n c y c o m p o n e n t of the freq u e n c y - d o m a i n analysis are k n o w n to reflect the activity of the p a r a s y m p a t h e t i c n e r v o u s system (8-10). All these p a r a m e t e r s w e r e c o m p a r e d before a n d after radiofrequency ablation. H e a r t R a t e A n a l y s i s . Because the h e a r t rate varies in response to the patients' activity, it should be carefully assessed by different measures. Thus, this study used five h e a r t rate m e a s u r e m e n t s obtained b y Holter m o n i t o r i n g : of (1) heart rate at 6 a.m., (2) the 2 4 - h o u r average h e a r t rate, (3) the 2 4 - h o u r m a x i m u m h e a r t rate, (4) the 2 4 - h o u r m i n i m u m h e a r t rate, a n d (5) the n i g h t t i m e - a v e r age h e a r t rate f r o m 1 to 6 a.m. The h e a r t rate at 6 a.m. in the supine position was m e a s u r e d o n the day before and again on the day following r a d i o f r e q u e n c y ablation. Other m e a s u r e s of h e a r t rate w e r e obtained f r o m 2 4 - h o u r Holter a m b u l a tory monitoring. Heart rate at 6 a.m., nighttimeaverage h e a r t rate, and 2 4 - h o u r m i n i m u m h e a r t rate b y Holter m o n i t o r i n g w e r e considered to reflect the activity of the p a r a s y m p a t h e t i c n e r v o u s system, while the 2 4 - h o u r m a x i m u m h e a r t rate was considered to reflect the activity of the s y m p a thetic n e r v o u s system. By c o m p a r i n g the changes in these values with h e a r t rate variability, w e inferred the causes of the increases in h e a r t rate. Changes in the h i g h - f r e q u e n c y c o m p o n e n t , rMSSD, pNNs0, and t h e y w e r e c o m p a r e d in each group, a n d the ratios of changes a m o n g the groups w e r e evaluated. Correlations b e t w e e n the m e a n h e a r t rate at 1 to 6 a.m. (night h e a r t rate) and the m e a n h i g h - f r e q u e n c y p o w e r s p e c t r u m during the same time periods w e r e evaluated. Because m o s t patients w e r e asleep f r o m 1 to 6 a.m., the high-treq u e n c y during this period was a s s u m e d to reflect mostly p a r a s y m p a t h e t i c n e r v e activity. S t a t i s t i c s . Data are p r e s e n t e d as m e a n s + SD. C o m p a r i s o n of c o n t i n u o u s data a m o n g the groups was m a d e by o n e - w a y analysis of variance with Bonferroni correction. A chi-square test was used to c o m p a r e d i c h o t o m o u s data a m o n g groups. Data within groups over time w e r e c o m p a r e d by the paired Student's t-test. Correlation coefficients b e t w e e n heart rate a n d h e a r t rate variability w e r e calculated. A P value of less t h a n .05 was required for statistical significance.
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Results Holter m o n i t o r i n g was p e r f o r m e d 2.2 + 0.2 days before a n d 1.2 + 0.2 days after r a d i o f r e q u e n c y ablation. Radiofrequency ablation was successfully completed in all patients w i t h o u t complications. The e c h o c a r d i o g r a m obtained after the radiofreq u e n c y ablation s h o w e d n o h e m o d y n a m i c a l l y c o m p r o m i s i n g complications, such as a n e w l y developed aortic regurgitation, pericardial effusion, or asynergy of the left ventricular wall.
Resting Sinus Rate Figure l shows the difference b e t w e e n h e a r t rate at 6 a.m. values t a k e n before and after radiofreq u e n c y ablation. Each point represents an individual case. The change in h e a r t rate represents the difference in heart rate before a n d after RF ablation. The heart rate at 6 a.m. before radiofrequency ablation w e r e 60.0 + 7.0 b e a t s / m i n for the AVNRT, 72.0 + 8.6 b e a t s / m i n for the posterior septum, 69 + 7.9 b p m for the left wall, and 63.0 + 5.7 b e a t s / m i n for the right wall groups. After r a d i o f r e q u e n c y ablation, h e a r t rate significantly increased (P < .05) in the AVNRT (21.8 + 7.6 beats/min), the posterior s e p t u m (14.0 + 12.4 beats/min), a n d the left free wall (7.2 + 6.7 beats/rain) groups but n o t in the right free wall (2.8 + 8.5 beats/min) group. The 24h o u r h e a r t rate obtained by Holter a m b u l a t o r y m o n i t o r i n g was c o m p a r e d before and after radiof r e q u e n c y ablation (Table 2). A significant increase
5040" .o 30 "~ 20 ~- 10 .5
•
E
=~ 0 a= -10 AVNRT
PS
LW
RW
Fig. 1. Changes in heart rate measured at 6 a.m. after RF ablation. Each point represents an individual patient. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septum; LW, accessory pathway in the left free wail; RW, accessory pathway in the right free wall.
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Journal of Electrocardiology Vol. 30 No. 3 July 1997 Table 2. Heart Rate D e t e r m i n e d b y Itolter A m b u l a t o r y M o n i t o r i n g in A l l Patient Groups Before and After Radiofrequency A b l a t i o n
Group AVNRT PS LW RW
Mean HR (beats/min) Before After 67.8_+8.1 71.1+_7.8 72.4 _+9.4 67.6_+8.6
Maximum HR (beats/min) Before After
77.2_+9.7"]-:t; 80.4 -+9.9"J-$ 79.1 _+10.5" 70.4_+7.5
121.1-+16.5 120.4-+17.8 126.6 _+29.5 122.4_+17.8
Minimum HR (beats/min) Before After
125.1-+13.0 124.0-+11.0 131.2 + 15.7 126.1_+13.1
45.9-+5.6 50.4-+9.7 49.8 _+6.3 44.9+3.9
55.8-+8.1"-t-$ 57.3 -+9.9"]-~c 54.5 _+7.2* 46.4-+4.8
Heart rate is 24-hour heart rate. * P < .05 vs pre; J- P < .05 vs LW; $ P < .05 vs RW. HR, heart rate; AVNRT, atrioventricular nodal reentrant tachycardia; LW, accessory pathway at the left free wall; PS, accessory pathway at the posterior interventricular septum; RW, accessory pathway at the right free wall.
in a v e r a g e h e a r t r a t e a f t e r r a d i o f r e q u e n c y a b l a t i o n w a s s e e n in t h e AVNR% p o s t e r i o r s e p t u m , a n d left w a l l g r o u p s b u t n o t i n t h e r i g h t free w a l l g r o u p . T h e i n c r e a s e i n h e a r t r a t e in t h e left free w a l l g r o u p (6.7 + 7.6 b e a t s / m i n ) w a s less t h a n t h o s e i n c r e a s e s in t h e AVNRT (9.4 -1-_4.8 b e a t s / m i n ) o r p o s t e r i o r s e p t u m g r o u p s (9.3 + 6.4 b e a t s / m i n ) . While these three groups showed significant i n c r e a s e s in a v e r a g e h e a r t rate, t h e m a x i m u m h e a r t r a t e s h o w e d n o s i g n i f i c a n t c h a n g e after radiofrequency ablation. Conversely, the 24-hour m i n i m u m h e a r t r a t e s h o w e d t h e s a m e t e n d e n c y as t h e a v e r a g e h e a r t rate, t h a t is, t h e 2 4 - h o u r m i n i m u m h e a r t r a t e s h o w e d a s i g n i f i c a n t i n c r e a s e (P < .05) after r a d i o f r e q u e n c y a b l a t i o n i n t h e AVNRT, p o s t e r i o r s e p t u m , a n d left free w a l l g r o u p s b u t n o t in t h e r i g h t free w a l l g r o u p .
Changes in Heart Rate Variability After radiofrequency ablation, the rMSSD values d e c r e a s e d f r o m 39.7 _+ 17.8 to 22.6 + 10.3 m s i n t h e
AVNRT g r o u p (P < .05), f r o m 44.3 + 18.1 to 29.3 + 16.5 m s in t h e p o s t e r i o r s e p t u m g r o u p (P < .05), a n d f r o m 26.0 + 9.9 to 19.8 + 8.1 m s i n t h e left free w a l l g r o u p (P < .05) b u t n o t in t h e r i g h t free w a l l group. Figure 2 shows the changes in the rMSSD a n d pNNs0 v a l u e s a f t e r r a d i o f r e q u e n c y a b l a t i o n . P a t i e n t s w i t h AVNRT a n d t h e p o s t e r i o r s e p t u m accessory pathway showed significantly larger d e c r e a s e s in r M S S D as c o m p a r e d w i t h t h e left w a l l g r o u p . T h e AVNRT g r o u p s h o w e d a s i g n i f i c a n t d e c r e a s e i n r M S S D as c o m p a r e d w i t h t h e r i g h t w a l l g r o u p . The pNNso d e c r e a s e d f r o m 17.0 + 15.7 to 5.4 + 7 . 3 % i n t h e AVNRT g r o u p (P < .05), f r o m 26.0 + 7.9 to 12.2 +_ 9 . 3 % i n t h e p o s t e r i o r s e p t u m g r o u p (P < .05), a n d 6.7 +_ 6.9 to 3.3 + 4 . 5 % in t h e left free w a l l g r o u p (P < .05) b u t d i d n o t d e c r e a s e in t h e r i g h t free w a l l g r o u p . P a t i e n t s w i t h AVNRT and the posterior septum showed significant d e c r e a s e s in pNNs0 as c o m p a r e d w i t h t h e left free w a l l o r r i g h t free w a l l g r o u p s (P < .05). After radiofrequency ablation, the high-freq u e n c y p o w e r w a s d e c r e a s e d f r o m 5.65 + 0.96 to
Changes in rMSSD after RF ablation (ms)
Changes in pNN50 after RF ablation (%)
0-
N N~
-4-
d_
}!i!ii
#
-10
_L -20
-12-
#*
m
#*
#* ,
AVNRT PS
#
N~
-8-
,
,
LW
%
-16
RW
I
AVNRT~
PS
I
LW
RW
Fig. 2. Changes in the time domain of the heart rate variability after radiofrequency ablation. Left panel: rMSSD, root mean-square of the successive difference. Right panel: pNNs0, percent of adjacent cycles that are more than 50 ms apart, measured as percent of tatal beats. Data are expressed as m e a n _+ SEM. *P < ,05 vs. LW; #P < .05 vs. RW. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septum; LW, accessory pathway in the left free wall; RW, accessory p a t h w a y in the right free wall.
Heart Rate and Radiofrequency Catheter Ablation
3.79 _+ 1.01 ln(ms 2) in the AVNRT group (P < .05), f r o m 5.64 _ 1.03 to 4.13 _+ 1.35 In (ms2) in the posterior s e p t u m group (P < .05), a n d f r o m 4.48 _+ 1.00 to 3.28 _+ 1.00 In (ms 2) in the left free wall group (P < .05) but was u n c h a n g e d in the right free wall group. Figure 3 shows the changes in high-frequency p o w e r and l o w - / h i g h f r e q u e n c y p o w e r ratio after radiofrequency ablation. Patients with AVNRT a n d those with a posterior s e p t u m accessory p a t h w a y s h o w e d significantly larger decreases in h i g h - f r e q u e n c y p o w e r t h a n those with a left wall anterior pathway. The decreases in high-frequency p o w e r in the AVNRT, posterior s e p t u m a n d left free wall groups w e r e larger t h a n in the right free wall group. The low-high frequency p o w e r ratio increased f r o m 2.56 + 2:13 to 4.59 + 1.72 in the AVNRT group, f r o m 1.56 + 0.76 to 2.5 + 1.34 in the posterior s e p t u m group and f r o m 4.73 + 2.54 to 6.02 + 3.38 in the left wall group, but not significant differences a m o n g these groups w e r e found.
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patient. Most arrows m o v e u p w a r d to the left, indicating that the h e a r t rate increased as high-freq u e n c y p o w e r decreased. The patient w i t h the largest increase in heart rate a n d the largest decrease in h i g h - f r e q u e n c y p o w e r shows the longest line. In the left u p p e r panel, almost all the patients w i t h AVNRT s h o w an increased h e a r t rate a n d a decreased h i g h - f r e q u e n c y power. In the right u p p e r panel, all the patients w i t h accessory pathw a y at the posterior s e p t u m s h o w a n increased h e a r t rate a n d decreased h i g h - f r e q u e n c y power. A similar, but weak, t e n d e n c y was seen in patients w i t h a left wall accessory p a t h w a y but not in patients w i t h an accessory p a t h w a y at the right wall. In addition, correlation coefficients b e t w e e n the increase in the resting sinus rate and h e a r t rate variability/heart rate, rMSSD, pNNs0, a n d lowh i g h - f r e q u e n c y ratio w e r e calculated (Table 3). The increases in resting sinus rate correlated with decreases in h i g h - f r e q u e n c y p o w e r a n d pNNs0 but not with the low- to h i g h - f r e q u e n c y ratio.
Relation Between Heart Rate and Heart Rate Variability Discussion B e t w e e n 1 a n d 6 a.m., the average heart rate and average h i g h - f r e q u e n c y p o w e r w e r e obtained f r o m the Holter a m b u l a t o r y m o n i t o r i n g data. Their relationship is plotted in Figure 4. All the patients w e r e asleep during this period, and p a r a s y m p a thetic n e r v o u s activity was considered to d o m i n a t e the a u t o n o m i c n e r v o u s system activity. Two points, w h i c h represent the values obtained before a n d after r a d i o f r e q u e n c y ablation for each patient, are c o n n e c t e d with arrows. Each a r r o w represents one
Changes in HF after RF ablation
Our results s h o w e d an increase in heart rate after the radiofrequency ablation of the slow p a t h w a y of patients w i t h AVNRT or w i t h the accessory p a t h w a y at the posterior s e p t u m or at the left v e n tricular free wall. Correlations w e r e observed b e t w e e n the indices of p a r a s y m p a t h e t i c n e r v o u s activity w i t h various m e a s u r e s of h e a r t rate (ie, the m o r n i n g supine h e a r t rate, the 2 4 - h o u r average h e a r t rate, the 2 4 - h o u r m i n i m u m h e a r t rate, a n d
Changes in LF/HF after RF ablation
0-
(In(ms) 2)
-1--
-1-
,# -2*#
-3 AVNRT I
PS
~ LW
RW
AVNRT
PS
LW
RW
Fig. 3. Changes in the frequency domain of the heart rate variability after radiofrequency ablation. Left panel: HE power spectrum for the high-frequency range. Right panel: LF/HE ratio of the power spectra for the low and high frequency ranges. Data are expressed as mean +_SEM. *P < .05 vs LW; #P < .05 vs. RW. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septum; LW, accessory pathway in the left free wall; RW, accessory pathway in the right free wall.
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100 90
100 AVNRT
PS
90
,o
8O 70
- - 5 x,,
70
g 60
60
40
50 40
3O
3O
20
20
10
l0
50
0
0 1
2
3
4
5
0
6
I
2
HF (ln(ms2))
IO0 90
LW
3
4
5
6
HF (In(ms2 D 100
~i
90
80
80
70
70
60
60
50
RW
50
40
40
30
3O 20
201 10 0
10 0 2
3 4 5 HF (In(ms 21)
6
I
2
3 4 5 HF (In(ms2))
6
Fig. 4. Changes in the right-time average high-frequency power spectrum and heart rate after radiofrequency ablation. Lines connect the values obtained before and after radiofrequency ablation for individual patients. AVNRT, atrioventricular nodal reciprocating tachycardia; PS, accessory pathway in the posterior septurn; LW, accessory pathway in the left free wall; RW, accessory pathway in the right free wall.
the nighttime heart rate for 5 hours). Frey et al. observed a w e a k correlation b e t w e e n the parameters of heart rate variability and cumulative radiofrequency energy application in a group of patients w h o u n d e r w e n t ablation of a left lateral or posteroseptal accessory p a t h w a y or fast or slow atrioventricular nodal pathways (11). Other studies (6,7,11) have s h o w n that the prevalence of inappropriate sinus tachycardia following radiofre-
Table 3. Correlations Between Heart Rate and Heart
Rate Variability Obtained at Rest in the Morning Correlation Coefficient Group AVNRT PS LW RW
HF (In(ms2)) 0.45* 0.50* 0.76* 0.1
MSSD r (ms) 0.37 0.41 0.43 0.09
pNNso (%) 0.39 0.44 0.34 0.13
LF/HF 0.14 0.16 0.1 0.01
* Statistically significant correlation, P < .05. L o w - f r e q u e n c y power; HE h i g h - f r e q u e n c y power; rMSSD, r o o t - m e a n - s q u a r e of successive differences; pNNso, percent of adjacent cycles that are > 50 m s apart m e a s u r e d in percent in total beats; LF/HE ratio of LF to HF; AVNRT, atrioventricular nodal r e e n t r a n t tachycardia; LW, accessory p a t h w a y at t h e left free wall; PS, accessory p a t h w a y at t h e posterior interventricular septum; RW, accessory p a t h w a y at t h e right free wall.
q u e n c y ablation is relatively high for AVNRT and the posterior septum accessory pathway. In this study, sinus tachycardia occurred in only 2 of the 53 patients w h o u n d e r w e n t radiofrequency ablation, whereas an increase in heart rate was obseryed in most of the patients in the AVNRT, posterior septum and left wall groups. Heart rate variability is widely used as a noninvasive means for assessing autonomic nervous system activity, and is considered to reflect the effect of autonomic nervous system activity on the sinus node. The use of 24-hour ambulatory electrocardiographic monitoring allows the R wave to be detected more easily on the tape. The R-R interval can be used for heart rate variability analysis instead of the P-P interval. In patients with stable atrioventricular conduction, the R-R interval can be used to replace the P-P interval. Although autonomic nervous activity modulates atrioventricular conduction, the relative change in the P-Q interval is small compared with the change in the P-P interval. Thus, the R-R interval can be considered to reflect mainly a control of the autonomic nervous system on the sinus node. Of all the indices, frequency domain analysis of heart rate variability is the most useful for differentiating b e t w e e n the activity of the parasympathetic and sympathetic nerves. The high-frequency power spectrum reflects the activity of the parasympathetic input to the heart, as Pomeranz et al. (10) showed that high-frequency power was decreased by atropine administration and was increased in the supine position. Low-frequency p o w e r was decreased by propranolol administration and was increased on standing. Thus, while high-frequency power reflects only parasympathetic activity, low-frequency power reflects the activity of both the sympathetic and parasympathetic nervous system. The rMSSD and pNNso are parameters of time domain analysis and reflect parasympathetic nervous system activity. The ratio of low- to high-frequency p o w e r is considered to reflect the balance b e t w e e n sympathetic and parasympathetic nervous input to the heart ( 12). To assess the mechanism of increased heart rate after radiofrequency ablation, we used heart rate variability to evaluate w h e t h e r the increased in heart rate was caused by an increase in sympathetic nervous system activity or by a decrease in parasympathetic nervous system activity. In this study, heart rate increased after radiofrequency ablation of the slow p a t h w a y of the AVNRT and the accessory pathways at the posterior septum and the left wall. In these groups, the high-frequency power, rMSSD, and pNNso, all decreased after radiofrequency abla-
Heart Rate and Radiofrequency Catheter Ablation
tion. The increased heart rate correlated well with the decreased values of these parameters. Conversely, the low- high-frequency p o w e r ratio was increased in all the groups, but the increase was not correlated with the increased heart rate. This suggested that the increased heart rate after radiofreq u e n c y ablation was probably due not to the stimulation of the sympathetic nervous system but rather to the withdrawal of parasympathetic nervous system activity. The sites of energy delivered in the posterior septum group and AVNRT are very close to each other. The increase in heart rate was m o r e p r o m i n e n t after radiofrequency ablation performed in the AVNRT and posterior septum groups. Thus, it is possible that the posteroseptal portion is the site that specifically influences the parasympathetic postganglionic fibers. N u m e r o u s reports (13-17) have s h o w n the anatomic distribution of sympathetic and parasympathetic nerves in the canine heart. Surprisingly little is k n o w n about the a u t o n o m i c innervation of the h u m a n heart. Parasympathetic preganglionic fibers to the sinoatrial node emanate mainly from ganglia located in the p u l m o n a r y vein fat pad, and fibers to the atrioventricular node arise from ganglia located in the fat pad overlying the entry of the coronary sinus into the inferior interatrial septum at the junction of the inferior vena cava and inferior left atrium. Etferent sympathetic axons destined for the ventricle are located in the superficial subepicardium. Parasympathetic fibers are located at the ventricular surface within 10 m m of the right lateral atrioventricular groove. They penetrate intramurally and reach the medial sites of the anterior wall. Parasympathetic nerve fibers are relatively sparse in the left ventricular wall. The mechanisms of increased heart rate after radiofrequency ablation can be postulated. A direct effect of radiofrequency ablation on the sinoatrial node is less likely because the ablated site is distant f r o m the sinoatrial n o d e and the post-radiofreq u e n c y ablation electrophysiologic study s h o w e d no prolongation of the corrected sinoatrial nodal recovery time. The possibility that radiofrequency ablation causes sympathetic nerve stimulation cannot be excluded. However, because we observed no differences in low- high-frequency p o w e r ratio a m o n g the groups after radiofrequency ablation and since the sympathetic nerves are located at the epicardial surface, an effect of radiofrequency ablation on the sympathetic nerve activity appears less likely. Kocovic et al. (13) reported that the control patients w h o u n d e r w e n t only diagnostic electrophysiologic study did not show a significant increase in heart rate or in the p o w e r spectrum of
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heart rate variability. The changes in heart rate or in heart rate variability were probably caused by the radiofrequency catheter ablation, not by the electrophysiologic study. Taking these conditions into account, the radiofrequency ablation site for the slow pathways or the accessory pathways at the posterior septum are n e a r the ostium of the coronary sinus, w h e r e the ganglia of parasympathetic nerves destined for the atrioventricular node are located. RF ablation at this site m a y damage some of the postganglionic fibers destined for the sinoatrial node as well as the atrioventricular node. However, the exact mechanisms of the withdrawal of parasympathetic nerve activity after radiofreq u e n c y ablation of the left ventricular free wall remains to be determined.
Conclusions The sinus r h y t h m is sometimes increased in patients after radiofrequency ablation. This condition appeared to be more frequent after radiofreq u e n c y ablation of the slow p a t h w a y for AVNRT or the accessory p a t h w a y located in the posterior septum. The high-frequency ratio, rMSSD, and pNNs0 values were decreased and the low- to high-freq u e n c y p o w e r ratio increased in these latter cases concomitantly with an increase in sinus r h y t h m . As the heart rate increased, the parasympathetic nerve activity as m e a s u r e d by heart rate variability decreased. No correlation was observed b e t w e e n the increased heart rate and sympathetic nerve activity as m e a s u r e d by heart rate variability. We conclude that the increase in heart rate after radiofrequency ablation is mediated by parasympathetic withdrawal. W h e t h e r this withdrawal is due to a direct effect of radiofrequency ablation or is mediated by a reflex remains to be determined.
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5. Haissaguerre M, Gaita F, Fischer B e t al: Elimination of atrioventricular nodal reentrant tachycardia using discrete slow potentials to guide application of radiofrequency energy. Circulation 85:2162, 1992 6. Ehlert FA, Goldberger J J, Brooks R et al: Persistent inappropriate sinus tachycardia after radiolrequency current catheter modification of the atrioventricular node. Am J Cardiol 69:1092, 1992 7. Skeberis V, Simonis E Andries E, Brugada P: Inappropriate sinus tachycardia after radiofrequency ablation of AV nodal tachycardia: incidence and clinical significance (abstract) J Am Coll Cardiol 21: 358A, 1993 8. Akselrod S, Gordon D, Ubel FA et al: Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control. Science 213:220, 1981 9. Hayano J, Sakakibara Y, Yamada A et al: Accuracy of assessment of cardiac vagal tone by heart rate variability in n o r m a l subjects. Am J Cardiol 67:199, 1991 10. Pomeranz B, Macaulay RJB, Caudill MA et al: Assessment of autonomic function in h u m a n s by heart rate spectral analysis. A m J Physiol 248:H151, 1985
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