Yonago Acta medica 2005;48:17–25

Analysis of Heart Rate Variability before and after
Catheter Ablation for Atrial Flutter with Complicating
Atrial Fibrillation
Hisato Moritani, Junichi Hasegawa, Akira Marumoto, Akiko Sano and Norimasa
Miura
Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic
Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503 Japan
Efﬁcacy of radiofrequency (RF) catheter ablation in suppressing atrial ﬁbrillation (AF)was studied by analysis of heart rate variability (HRV) in 13 patients with atrial ﬂutter
complicated with AF. We treated these patients by RF ablation of the isthmus between
the tricuspid valve annulus and the inferior vena cava to create a bidirectional conduction block. To analyze the HRV, 24-h ambulatory electrocardiographic monitoring was
performed 1 day before, 1 day after and 1 month after the ablation. After the RF ablation of the isthmus, 7 patients continued to experience AF attacks, while the remaining
6 patients did not. We divided them into 2 groups, attacked by AF (AF group) and not
attacked by AF (non-AF group), and analyzed HRV parameters. The results obtained
were compared between the groups. One month after the ablation, the non-AF group
showed a signiﬁcantly higher average heart rate than the AF group. The HRV parameters indicating cardiac vagal nervous activities, such as the root-mean-square of differences, percentage of adjacent normal RR intervals and high frequency power, weresigniﬁcantly lower in the non-AF group 1 month after. Furthermore, the ratio of low
frequency power to high frequency power, which is a measure for cardiac sympathetic
nervous activity, was signiﬁcantly higher in the non-AF group 1 month after. From theseresults, we postulate that the suppression of postoperative AF may involve vagal nerve
suppression and sympathetic nerve activation.
Key words: atrial ﬁbrillation; atrial ﬂutter; catheter ablation; heart rate variability
problem. Though RF ablation of AF has spread
rapidly since Haissaguerre et al. (1998), pulmonaryvein stenosis (Saad et al., 2003) and atrio-esophageal ﬁstula (Pappone et al., 2004a) after ablation of
AF were reported as severe complications. Also,
pulmonary vein ablation of AF may predispose toproarrhythmias such as left atrial macroreentrant

Radiofrequency (RF) catheter ablation of the isthmus between the tricuspid valve annulus and theinferior vena cava (TVA-IVC isthmus) has become
an effective procedure for radical treatment ofcommon type atrial flutter (AFL). However, laterecurrence of atrial ﬁbrillation (AF) following successful ablation still remains an important clinicalAbbreviations: AF, atrial ﬁbrillation; AFL, atrial ﬂutter; AVNRT, atrioventricular nodal reentrant tachycardia; ECG,
electrocardiography; HF, high frequency power; HRV, heart rate variability; LF, low frequency power; LF/HF, theratio of LF/HF; pNN50, percentage of adjacent normal RR intervals; RF, radiofrequency; rMSSD, root-mean-squareof differences; SDNN, SD of RR intervals; TVA-IVC isthmus, isthmus between the tricuspid valve annulus and theinferior vena cava

17

H. Moritani et al.
Table 1. Patient characteristics
Group

Patient

Age (year)

Sex

Cardiovascular diagnosis

Antiarrhythmic drug

AF group

Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6

66
54
78
55
57
52
48
51
45
68
65
63
74

Male
Male
Male
Female
Male
Male
Male
Male
Male
Male
Male
FemaleMale

PAFL, PAF
PAFL, PAF
PAFL, PAF
PAFL, PAF, OMI
PAFL, PAF
PAFL, PAF
PAFL, PAF
PAFL, PAF
PAFL, PAF
PAFL, PAF, OMI
PAFL, PAF
PAFL, PAF
PAFL, PAF

Pilsicainide, Digitalis
Cibenzoline
None
Bepridil, Flecainide
Cibenzoline, Pilsicainide
Cibenzoline
None
None
Aprindine
Pilsicainide, Digitalis
Cibenzoline, Verapamil
Aprindine, Digitalis
Pilsicainide

Non-AF group

OMI, old myocardial infarction; PAF, paroxysmal atrial ﬁbrillation; PAFL, paroxysmal atrial ﬂutter.

present study, changes in autonomic nervous function before and after ablation in the postoperative
AF patients group were compared with the non-AF
group using HRV analysis.

tachycardias (Pappone et al., 2004b). It has beenreported that RF ablation for common type AFL of
the TVA-IVC isthmus is effective in reducing theincidence of AF attacks (Feld et al., 1992; Lesh et al.,
1994; Philippon et al., 1995; Saxon et al., 1996; Huang
et al., 1998; Paydak et al., 1998; Tai et al., 1998; Nabar et al., 1999; Kumagai et al., 2000). Huang et al.
(1998) reported that, in patients who experienced
conversion of AF to AFL during antiarrhythmic
drug treatment, ablation for AFL and continuationof pharmacologic therapy were effective means ofmaintaining sinus rhythm. As such, hybrid therapy
is well-known and effective not only in patients
experiencing a pharmacologic conversion of AF to
AFL, but also in patients with both AF and AFL(Feld et al., 1992; Lesh et al., 1994; Philippon et al.,
1995; Saxon et al., 1996; Paydak et al., 1998; Tai et al.,
1998; Nabar et al., 1999; Kumagai et al., 2000). We
wanted to characterize patients in which ablation
for AFL is also effective in suppression of concomitant AF. In this regard, a number of reports
have described the clinical features of such patients(Feld et al., 1992; Lesh et al., 1994; Philippon et al.,
1995; Saxon et al., 1996; Paydak et al., 1998; Tai etal., 1998; Nabar et al., 1999; Kumagai et al., 2000).
However, there is no report to characterize autonomic nervous function using heart rate variability(HRV) analysis in effective cases for suppressionof concomitant AF after ablation for AFL. In the

Subjects and Methods
Informed consent was obtained from all patientsprior to 24-h ambulatory electrocardiography(ECG) 1 day before ablation.
Patient population
A total of 13 patients (11 males and 2 females, age
59.5 ± 9.7 years, duration of observation 6.5 ± 4months) having had both AF and AFL before ablation, were selected by satisfying all the following
criteria: i) subjective attacks of paroxysmal tachycardia (AF or AFL), ii) paroxysmal AF, iii) no useof autonomic drugs (β blockers, etc.), iv) no thyroid
disease or valvular heart disease, v) the ablatedsite of the exact isthmus, excluding the posterior
septum, and vi) no switchover of medication during
the observation period. The observation period wasfrom the day of ablation to September 11, 2004.
These patients were divided into 2 groups:
7 patients (6 males and 1 female, age 58.3 ± 9.2
years, duration of observation 5.9 ± 3.4 months)

18

HRV changes after catheter ablation(pNN50). The frequency domain parameters were
low frequency power (LF) ranging from 0.04 to 0.15
Hz, high frequency power (HF) ranging from 0.15
to 0.40 Hz and the ratio of LF to HF (LF/HF). Of
these parameters, SDNN, rMSSD, pNN50 and HF
were reported to indicate cardiac vagal nervous activities, and LF/HF to indicate cardiac sympathetic
nervous activities (Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology, 1996).

with paroxysmal AF recorded with 12-lead ECGs
on paroxysmal attacks during the observation period after ablation (AF group) and 6 patients (5males and 1 female, age 61.0 ± 9.9 years, durationof observation 7.2 ± 5.6 months) without AF (nonAF group) (Table 1). There was no signiﬁcant difference in sex, age, observation period or clinicalfeatures between the 2 groups.
RF catheter ablation
After conﬁrming the involvement of the TVA-IVC
isthmus in the tachycardia circuit during AFL, abidirectional conduction block line was createdin the TVA-IVC isthmus by ablation. This ablation was performed in the portion of the isthmus
between the 6 and 7 oʼclock directions in the left
anterior oblique view, using a 6-mm deflectablelarge tip catheter. Subsequently, cardiac pacing
was performed from the low lateral right atrium
and the coronary sinus, and the bidirectional blockline in the TVA-IVC isthmus was conﬁrmed using
the 20-electrode halo catheter method (Poty et al.,1996) and the differential pacing method (Shah etal., 1999). One of the 7 patients in the AF groupand 1 of the 6 patients in the non-AF group had
been suffering from spontaneous AFL before ablation. For the other patients, ablation was performed
after inducing AFL by programmed stimulation.

Statistical Analysis
Data were presented as the mean ± SD. Variablesof average heart rate and HRV analysis were compared using unpaired t-test. A P value < 0.05 wasconsidered statistically signiﬁcant.
Results
RF catheter ablation
A bidirectional block was successfully created in
all patients of both groups. Statistical difference
was examined for the number of RF application
times (AF group versus non-AF group; 6.2 ± 4.3
times versus 5.6 ± 4.0 times, not significant) andRF cumulative energy (AF group versus non-AF
group; 21,962 ± 3,160 W • s versus 19,330 ± 2,966
W • s, not signiﬁcant). There was no patient experiencing recurrent AFL during the observation period (Table 2).

Analysis of HRV
One day just before, 1 day just after and then 1
month later after ablation, 24-h ambulatory ECG
monitoring was performed using a 2-channel
Holter monitor (Fukuda Denshi, Tokyo, Japan),and HRV was analyzed and evaluated using the
ECG analytical software CHIRAM/MemCalc(GMS, Tokyo). The parameters determined wereaverage heart rate (recorded by 24-h ambulatory
ECG monitoring), time domain parameters andfrequency domain parameters of HRV. The time
domain parameters were SD of 5-min mean RR
intervals (SDNN), root-mean-square of differencesof adjacent RR intervals (rMSSD) and percentageof adjacent normal RR intervals > 50 ms different

Table 2. Results of RF catheter ablation
AF group[n = 7]

Non-AF group[n = 6]

Bidirectional block
7/7
6/6
RF application*
6.2 ± 4.3
5.6 ± 4.0
RF cumulative energy† 21,962 ± 3,160 19,330 ± 2,966
AFL recurrence
0/7
0/6
Values are mean ± SD.
AF, atrial ﬁbrillation; AFL, atrial ﬂutter; RF, radiofrequency.
* (times)† (W • s)

19

H. Moritani et al.
P < 0.05
NSNS(beats/min)(beats/min)160

Average heart rate

Average heart rate

160
140
120
100
80
60
40
20
0

Before

After

140
120
100
80
60
40
20
0

1 MonthBeforeAfter

1 MonthAfter

1 Month

AF group
Non-AF group
Fig. 1. The mean heart rate for the AF group and the non-AF group, just before, just after and 1 month after ablation. The non-AF group shows a signiﬁcantly higher value 1 month after ablation. NS, not signiﬁcant.
NS
NS
NS
(ms)
400

350

350

300

300

250

250

SDNN

SDNN

(ms)
400

200
150

200
150

100

100

50

50

0

BeforeAfter

AF group

0

1 MonthBeforeNon-AF group

Fig. 2. The SD of RR intervals (SDNN) for the AF group and the non-AF group: 196.9 ± 78.3 versus 112.1 ± 59.0
ms just before ablation; 123.6 ± 48.8 versus 99.4 ± 32.6 ms just after ablation; and 174.9 ± 47.7 versus 143.6 ± 58.5
ms 1 month after ablation. Differences between groups are not signiﬁcant (NS).

signiﬁcantly (P < 0.05) higher for the non-AF group,
61.3 ± 10.2 versus 74.8 ± 11.1 beats/min (Fig. 1).

24-h Ambulatory ECG monitoring and average heart rate
Compared between the AF and the non-AF groups,
the average heart rates just before ablation and justafter ablation, 85.2 ± 39.4 versus 67.8 ± 16.7 beats/min
and 67.3 ± 13.1 versus 71.8 ± 12.3 beats/min, respectively, showed no significant difference. The difference in average heart rate 1 month after ablation was

Time domain parameters of HRV
The SDNNs just before, just after and 1 month after
ablation compared between the AF and the non-AF
groups were not signiﬁcantly different, respectively(Fig. 2).

20

HRV changes after catheter ablation

P < 0.05
NS

(ms)

(ms)

120

120

100

100

80

80

rMSSD

rMSSD

P < 0.05

60
40
20
0

60
40
20

BeforeAfter

AF group

0

1 MonthBeforeAfter

Non-AF group

1 MonthFig. 3. The root-mean-square of differences (rMSSD) for the AF group and the non-AF group, just before, just afterand 1 month after ablation. The non-AF group shows signiﬁcantly lower values just before and 1 month after ablation. NS, not signiﬁcant.

P < 0.05
NS

(%)

(%)

40

40

35

35

30

30

pNN50

pNN50

P < 0.05

25
20
15

25
20
15

10

10

5

5

0

BeforeAfter

AF group

0

1 MonthBeforeAfter

Non-AF group

1 MonthFig. 4. The percentage of adjacent normal RR intervals (pNN50) for the AF group and the non-AF group, justbefore, just after and 1 month after ablation. The non-AF group shows signiﬁcantly lower values just before and 1
month after ablation. NS, not signiﬁcant.

The pNN50s just before ablation and 1 monthafter ablation were 16.5 ± 11.9 versus 2.7 ± 3.0%
and 20.0 ± 12.1 versus 1.4 ± 1.3%, respectively,
showing signiﬁcantly (P < 0.05 both) lower levels
for the non-AF group. The levels just after ablation, 10.3 ± 8.4 versus 3.8 ± 6.7%, were not signiﬁcantly different (Fig. 4).

The rMSSDs compared between the 2 groups
just before ablation, 60.9 ± 25.6 versus 23.2 ± 9.6
ms, were signiﬁcantly (P < 0.05) lower for the nonAF group, as well as levels 1 month after ablation,
59.1 ± 23.7 versus 18.0 ± 5.7 ms (P < 0.05). The
difference in levels just after ablation, 44.4 ± 23.7
versus 24.7 ± 18.2 ms, was not signiﬁcant (Fig. 3).

21

H. Moritani et al.
P < 0.05
NS
NS

1200

1200

1000

1000

800

800

HF

(ms2)
1400

HF

(ms2)
1400

600

600

400

400

200

200

0

BeforeAfter

AF group

0

1 MonthBeforeAfter

Non-AF group

1 MonthFig. 5. The high frequency power (HF) for the AF group and the non-AF group, just before, just after and 1 monthafter ablation. The non-AF group shows a signiﬁcantly lower value 1 month after ablation. NS, not signiﬁcant.

P < 0.05
NS

6

6

5

5

4

4

LF/HF

LF/HF

NS

3
2
1
0

3
2
1

BeforeAfter

AF group

0

1 MonthBeforeAfter

Non-AF group

1 MonthFig. 6. The ratio of low frequency power/high frequency power (LF/HF) for the AF group and the non-AF group,
just before, just after and 1 month after ablation. The non-AF group shows a signiﬁcantly higher value 1 month after
ablation. NS, not signiﬁcant.

Frequency domain parameters of HRV
The compared LF/HF levels were 1.8 ± 0.8
versus 1.8 ± 1.1 just before ablation and 1.6 ± 0.7
versus 2.1 ± 0.7 just after ablation, showing no signiﬁcant differences between the groups. The levels
1 month after ablation, 1.7 ± 0.7 versus 2.9 ± 0.9,
were signiﬁcantly (P < 0.05) higher for the non-AF
group (Fig. 6).

The HF levels compared between the groups were462.3 ± 386.8 versus 115.8 ± 109.7 ms2 just before
ablation, 221.1 ± 150.7 versus 108.4 ± 137 ms2
just after ablation and 460.4 ± 358.7 versus 62.2 ±55.6 ms2 1 month after ablation. The difference 1
month after ablation was signiﬁcantly lower for the
non-AF group (Fig. 5).

22

HRV changes after catheter ablationof autonomic nervous function due to ablation has
been postulated (Ehlert et al., 1992). Kocovic etal. (1993) investigated autonomic nervous function from the viewpoint of HRV after ablation forsupraventricular tachycardia, and reported that the
HF of HRV decreased only in AVNRT and septal
ablation of the posterior septum accessory pathway.
With regard to ablation for AFL, Li et al. (2002)
reported that ordinary ablation of the TVA-IVC
isthmus did not affect autonomic nervous functionin terms of HRV. Kawamura et al. (2002) investigated differences related to AFL ablation sites, andreported that the HF of HRV decreased only in thesite of the posterior septum, rather than in the ordinary TVA-IVC isthmus.
In the present study, we investigated HRV justbefore ablation, just after ablation and 1 month after ablation in order to characterize cases in which
ablation for AFL was also effective in suppressing
AF. As a result, signiﬁcantly lower values of rMSSD and pNN50 were obtained from the non-AF
group just before ablation. However, 1 month after
ablation, a higher value of average heart rate, lower
values of rMSSD and pNN50, a lower value of HF
and a higher value of LF/HF were obtained for the
non-AF group than for the AF group. These results
demonstrate suppression of vagal nervous function
and accentuation of sympathetic nervous functionin the non-AF group 1 month after ablation. These
effects were not attributable to ablation because thecases in which RF application was delivered to theatrial septum were excluded from the analysis to
avoid the possible inﬂuence of ablation on the autonomic nervous system. As for why a signiﬁcantdifference became clear 1 month after ablation, we
postulated i) changes in autonomic nervous function due to the disappearance of AFL and ii) a
latent abnormality of autonomic nervous function
becoming symptomatic. Although the mechanism
remains unclear, these results suggested that analysis of HRV 1 month after ablation might enable
selection of cases in which ablation of the TVAIVC isthmus is also effective in the suppression therecurrence of AF. For appropriate follow-up, thecase to require anticoagulant and antiarrthythmic
drugs should be clariﬁed. And we suppose that for

Discussion
It has been reported that ablation for common type
AFL, which circles between the tricuspid valve annulus and the inferior vena cava, is effective in reducing the incidence of AF attacks, and the percent
incidence of AF after ablation of the TVA-IVC
isthmus is reportedly variable, from 8% to 86%(Feld et al., 1992; Lesh et al., 1994; Philippon et al.,
1995; Saxon et al., 1996; Paydak et al., 1998; Tai etal., 1998; Nabar et al., 1999; Kumagai et al., 2000).
Regarding the identity of cases in which ablationof the TVA-IVC isthmus is effective in suppressing
AF, Philippon et al. (1995) reported that the risk of
postoperative AF was especially high for patientsin whom sustained AF remained inducible after ablation of AFL, while Paydak et al. (1998) reported
the same ﬁnding in the presence of both a past history of AF and a left ventricular ejection fractionof 50% or less. Nabor et al. (1999) reported low
AF suppressing effects in patients frequently experiencing AF episodes before ablation. They also
reported that there were 3 mechanisms for the coexistence of AF and AFL: i) a difference between
the 2 atria, the right atrium showing AFL and theleft atrium showing AF; ii) AFL in the right atrium
becoming unstable or irregular and hence leading
to AF; and iii) a time lag between AFL and AF.
They concluded that in cases i) and ii) ablation for
AFL was also effective against AF (Nabar et al.,1999).
Regarding the distribution of vagal nervous ﬁbers to the cardiac sinoatrial node and atrioventricular node, relatively extensive investigations havebeen conducted. Randall and Ardell (1990) pointed out the importance of the atrial septum as theanatomical route for this distribution as the courseof vagal nervous postganglionic fibers from theright pulmonary venous adipose tissue to the sinoatrial node passing between the 2 atria. Since theearly days of the spread of ablation as a therapeutictechnique, it has been known that some patients experience sinus tachycardia mainly after ablation of
the fast pathway in atrioventricular nodal reentrant
tachycardia (AVNRT), and possible disturbance23

H. Moritani et al.
patients with postoperative recurrent AF, drugs thatsuppress vagal nervous function and accentuate
sympathetic nervous function might be more effective than other drugs.
In the present study, HRV was analyzed toevaluate autonomic nervous function in AFL patients with paroxysmal AF, whereas other means ofevaluation for cardiac autonomic nervous function
such as baroreceptor reﬂex and 123I-metaiodobenzylguanidine scintigraphy were not used. Becauseof the many requirements for studying a population, the sample size of this study was not enoughto ensure data reliability. Additionally, the study
was conducted in a relatively short period, fromjust before and just after ablation to 1 month after
ablation. Further investigation ranging over an extended period will be necessary.

pulmonary veins. N Engl J Med 1998;339:659–666.
4 Huang DT, Monahan KM, Zimetbaum P, Papageorgiou
P, Epstein LM, Josephson ME. Hybrid pharmacologic
and ablative therapy: a novel and effective approachfor the management of atrial ﬁbrillation. J Cardiovasc Electrophysiol 1998;9:462–469.
5 Kawamura Y, Yokoyama A, Kakuchi H, Sato N, Kikuchi K. Effect of radiofrequency catheter ablation
on autonomic tone in patients with common atrial
ﬂutter: difference depending on the site of ablation.
J Cardiol 2000;36:103–111 (in Japanese with English abstract).
6 Kocovic DZ, Harada T, Shea JB, Soroff D, Friedman PL. Alterations of heart rate and of heart ratevariability after radiofrequency catheter ablation of
supraventricular tachycardia. Delineation of parasympathetic pathways in the human heart. Circulation 1993;88(4 Pt 1):1671–1681.
7 Kumagai K, Tojo H, Yasuda T, Noguchi H, Matsumoto N, Nakashima H, et al. Treatment of mixedatrial fibrillation and typical atrial flutter by hybrid catheter ablation. Pacing Clin Electrophysiol
2000;23(11 Pt 2):1839–1842.
8 Lesh MD, Van Hare GF, Epstein LM, Fitzpatrick
AP, Scheinman MM, Lee RJ, et al. Radiofrequency
catheter ablation of atrial arrhythmias. Results andmechanisms. Circulation 1994;89:1074–1089.
9 Li A, Kuga K, Suzuki A, Endo M, Niho B, Enomoto
M, et al. Effects of linear ablation at the isthmus between the tricuspid annulus and inferior vena cava for
atrial ﬂutter on autonomic nervous activity: analysisof heart rate variability. Circ J 2002;66:53–57.
10 Nabar A, Rodriguez LM, Timmermans C, van den
Dool A, Smeets JL, Wellens HJ. Effect of rightatrial isthmus ablation on the occurrence of atrial ﬁbrillation: observations in four patient groups having
type I atrial ﬂutter with or without associated atrial
ﬁbrillation. Circulation 1999;99:1441–1445.
11 Pappone C, Oral H, Santinelli V, Vicedomini G,
Lang CC, Manguso F, et al. Atrio-esophageal fistula as a complication of percutaneous transcatheter
ablation of atrial ﬁbrillation. Circulation 2004a;109:2724–2726.
12 Pappone C, Manguso F, Vicedomini G, Gugliotta F,
Santinelli O, Ferro A, et al. Prevention of iatrogenic
atrial tachycardia after ablation of atrial ﬁbrillation:a prospective randomized study comparing circumferential pulmonary vein ablation with a modified
approach. Circulation 2004b;110:3036–3042.
13 Paydak H, Kall JG, Burke MC, Rubenstein D,
Kopp DE, Verdino RJ, et al. Atrial ﬁbrillation afterradiofrequency ablation of type I atrial ﬂutter: time toonset, determinants, and clinical course. Circulation
1998;98:315–322.

Conclusion
To characterize the autonomic nervous function
profiles in cases in which ablation for AFL is effective in suppressing concomitant AF, HRV wasanalyzed in patients with both AF and AFL. In
the group with suppressed AF after ablation, asignificantly higher value of average heart rate,
significantly lower values of rMSSD, pNN50 and
HF, and a signiﬁcantly higher value of LF/HF wereobtained 1 month after ablation, showing characteristic changes in autonomic nervous function.

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Received December 9, 2004; accepted December 27, 2004
Correspoding author: Junichi Hasegawa, MD

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