J Cardiol 2004 Jul; 44（1）: 1 – 11

Influence of Paroxysmal Atrial
Fibrillation Attack on Brain
Natriuretic Peptide Secretion
Keizo

TSUCHIDA,MD

Kazuhiko

TANABE, MD＊

Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Objectives. Plasma brain natriuretic peptide（BNP）
concentration is higher during atrial fibrillation（Af）than sinus rhythm, based on studies of electrical defibrillation treatment of patients with chronic Af.
However, the change in paroxysmal atrial fibrillation（PAf）is not well known. This study investigated suchchanges and the relationship between BNP and Af.
Methods. BNP levels were successfully measured at three time points : before Af attack, during Af
attack, and after（spontaneous or pharmacological）termination of 68 consecutive Af attacks in 35 outpatients with PAf（23 men, 12 women, mean age 70.4 ± 9.6 years）. BNP was measured by immunoradiometric assay.
Results. BNP（median［quartiles］）during PAf was increased by 66［25, 120］pg/ml（2.4-fold）comparedto during sinus rhythm（p ＜ 0.0001）, and fell to the former level after return to sinus rhythm（before
attack ＝ 39
［18, 70］, during attack ＝ 102［52, 205］, after attack ＝ 35
［20, 67］）. BNP increased in 55（81%）
of 68 attacks, did not change（within ± 20 pg/ml）in 11（16%）, and decreased in （2 3%）. BNP was alreadyelevated immediately（within 4 hr）after onset of Af, and BNP elevation（Δ BNP）showed no significant
relationship with the time elapsed after onset. During the Af attack, 41% of PAf patients were asymptomatic although BNP increased significantly.
Conclusions. These results suggest that elevated amounts of BNP during Af are released from secretory
granules in the atrium, and BNP elevation of unknown cause may be attributed to the presence of asymptomatic Af. Cardiac function evaluation using BNP during Af requires special consideration, unlike duringsinus rhythm, even in patients with PAf or chronic Af, because BNP during Af is the sum of the BNP values from the ventricle（reflecting left ventricular function）and the atrium（due to Af）.
─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2004 Jul ; 44（1）
: 1−11

Key Words
Atrial fibrillation paroxysmal

INTRODUCTION
Brain natriuretic peptide（BNP）
is mainly secreted by the heart in man, especially in the（BNPventricle1−3）. The plasma BNP concentrationlevel）is also positively correlated with the left ventricular end-diastolic pressure and negatively correlated with the left ventricular ejection fraction4−7）,
so BNP level should be measured to evaluate left
ventricular function. Measurement of the BNP level
during atrial fibrillation（Af）was made in patientswith lone Af and patients with chronic heart failure

Natriuretic peptide, brain

and Af during Af rhythm and sinus rhythm after the
Af was terminated with direct current shocks,
showing that the BNP level was higher during Af
than sinus rhythm 8,9）. However, the time coursechange in BNP level and the significance in paroxysmal atrial fibrillation（PAf）
are unknown.
This study investigated the increase in BNP level
during PAf in outpatients, and examined the relationship between BNP and Af.

──────────────────────────────────────────────
土田内科循環器科クリニック : 〒 940−0033 新潟県長岡市今朝白 3−12−29 ; ＊田辺医院，新潟
Tsuchida Clinic of Internal and Cardiovascular Medicine, Niigata ; ＊ Tanabe Clinic, Niigata
Address for correspondence : TSUCHIDA K, MD, Tsuchida Clinic of Internal and Cardiovascular Medicine, Kesajiro 3−12−29,
Nagaoka, Niigata 940−0033
Manuscript received February 17, 2004 ; revised April 20, 2004 ; accepted April 20, 2004

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Tsuchida, Tanabe

Table 1 Characteristics of the study population

SUBJECTS AND METHODS
Subjects
This study included 35 consecutive patients, 23
men and 12 women（mean age 70.4 ± 9.6 years）,
treated for PAf in Tsuchida Clinic, whose BNP levels were successfully measured three times at thefollowing times : 1）before Af attack（with documentation of sinus rhythm for at least 4 weeks prior
to the attack）, 2）during Af attack, and 3）duringsinus rhythm at least 2 weeks and no more than 4
weeks after the spontaneous or oral pharmacological termination of Af. The measurements weremade for 68 consecutive attacks in the 35 subjects.
The patient characteristics are summarized inTable 1. No underlying disease could be demonstrated in 6 patients, whereas underlying diseases
were found in 29 patients : valvular disease in 1 ;ischemic heart disease in 8 ; hypertrophic cardiomyopathy in 2 ; hypertension in 25, including 5
with hypertensive heart disease ; diabetes mellitus
in 8 ; chronic obstructive pulmonary disease in 3 ;hyperthyroidism in 1 ; cerebrovascular accident in
2 ; including some patients with more than one disease. Forty of the 68 attacks were symptomaticwith palpitations or anterior chest discomfort, and28 were asymptomatic.
BNP was measured in 91 patients, 56 men and35 women（mean age 71.3 ± 8.9 years）with chronic Af as the control with a mean follow-up period
in Af rhythm of 7.7 ± 4.8 years. Underlying disease was present in 78 patients, valvular disease in
27 and non-valvular disease in 51, and lone Af in
13 patients.
Methods
BNP level was measured by the Immunoradiometric Assay method using a Shionoria BNP
assay kit and blood samples taken in a sitting position. The change of BNP level（ΔBNP）was calculated as : Δ BNP ＝（BNP during attack）−（BNP
before attack）.
Statistical analysis
Values are shown as mean ± standard deviation（SD）or as median（ quartiles）. The BNP values
were transformed into natural logarithms to form anormal distribution for analysis（Fig. 1）. Multicomparison analyses were performed at the threetime points（ before attack, during attack, after
attack）
with Scheffe s analysis after one-way analy-

Number of patients35（68 attacks）

Age（yr, mean±SD）70.4±9.6

SexMen

23（65.7）

Women

12（34.3）

Underlying disease
Valvular disease

1（ 2.9）Other diseases

28（80.0）

Ischemic heart disease8（22.9）Congestive heart failure5（14.3）Hypertrophic cardiomyopathy2（ 5.7）Hypertension

25（71.4）

Diabetes mellitus

8（22.9）Chronic obstructive pulmonary disease3（ 8.6）Hyperthyroidism1（ 2.9）Cerebrovascular accidentNone2（ 5.7）6（17.1）

Symptoms
Present

40（59）

Absent28（41）

Medication（

Digitalis

33（94.3）

Beta-blocker

6（17.1）

Disopyramide3（ 8.6）

Aprindine

13（37.1）

Cibenzoline

8（22.9）Pilsicainide2（ 5.7）

Warfarin9（25.7））: %.

sis of variance. Analysis of factors affecting the
BNP level increase during Af attack was performed
using the unpaired t-test. Comparisons between
patients with persistent PAf and those with PAfchanged to chronic Af were analyzed with theunpaired t-test and chi-square analysis. p ＜ 0.05
was considered significant.
RESULTS
Changes in brain natriuretic peptide duringparoxysmal atrial fibrillation attacks
BNP level changes during the 68 PAf attacks areshown in Fig. 1. The mean（ ± SD）Δ BNP was
101 ± 132 pg/ml, calculated from the values before
attack of 61 ± 75, during attack of 162 ± 175, andafter attack of 57 ± 66. The median［quartile］
value
was 66［25, 120］pg/ml, before attack 39［18, 70］,
during attack 102［52, 205］, after attack 35［20,J Cardiol 2004 Jul; 44（1）: 1 – 11

Atrial Fibrillation and Brain Natriuretic Peptide

Fig. 1 Changes in levels of brain natriuretic peptide during an atrial fibrillation attack
A : Mean ± standard deviation（SD）.
B : Box plots spanning the 25th to 75th percentiles and errors from the 10th to the 90th percentile points.
Central lines represent distribution median.
C : Histogram of BNP levels during atrial fibrillation attack.
D : Natural logarithm of BNP levels during atrial fibrillation attack.
BNP ＝ brain natriuretic peptide ; Before ＝ before attack ; Attack ＝ during attack ; After ＝ after attack ;Δ BNP ＝ BNP during attack − BNP before attack.

67］, showing a significant increase（p ＜ 0.0001）
during attacks and resumption of the former levels
after the attacks.
Distribution of Δ BNP for the 68 Af attacks isshown in Fig. 2. BNP increased during 55 attacks（81%）（Δ BNP ＞− 20 pg/ml）, did not change during 11（16%）（20 pg/ml ＞Δ BNP ＞−− 20 pg/ml）＜− 20 pg/ml）
and decreased in 2（3%）（Δ BNP −.
The increase in BNP was moderate in 18 attacks,
mostly ranging from 50−100 pg/ml, and marked in
10 of more than 200 pg/ml. Decreased BNP
occured during PAf attacks in patients with symptoms of heart failure during sinus rhythm before theattacks. Administration of diuretics in one patient
and the discontinuance of β-blocker in anotherimproved the symptoms of heart failure at the next
visit, coincidentally with the PAf attack, and BNPlevels decreased after termination of Af.
J Cardiol 2004 Jul; 44（1）: 1 – 11

Fig. 2 Distribution of Δ BNP
Abbreviation as in Fig. 1.

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Tsuchida, Tanabe

Fig. 4 Comparison of brain natriuretic peptide inpatients with chronic atrial fibrillation andparoxysmal atrial fibrillation（during attack）
PAf ＝ paroxysmal atrial fibrillation. Other abbreviations as in Figs. 1, 3.

Fig. 3 Correlation of brain natriuretic peptide during
atrial fibrillation and sinus rhythm
Af ＝ atrial fibrillation ; SR ＝ sinus rhythm. Other
abbreviation as in Fig. 1.

Correlation of BNP levels during the PAf attacks
and during sinus rhythm. These correlations werevery good（r ＝ 0.87 ; Fig. 3）, increasing by about
2.4 times during Af over the sinus rhythm level
before attack（95% confidence interval, 2.1−2.7）.
Furthermore, comparison of the BNP levels during
Af attacks with chronic Af（Fig. 4）showed an elevation during PAf（PAf ＝ 102［52, 205］pg/ml）tothe same level as in chronic Af（chronic Af ＝ 110［56, 190］pg/ml）in all patients.（Patients without
underlying diseases had 40［18, 71］during PAf and66［38, 84］in chronic Af, whereas patients with
underlying diseases had 128［70, 216］during PAf,and 130［67, 200］in chronic Af）.
Relationship between time elapsed after onset ofparoxysmal atrial fibrillation attack and Δ BNP
BNP was measured in nine patients who visitedthe clinic within 4 hr after the onset of PAf attack
as shown in Fig. 5−A. The BNP levels werealready elevated at this early point of the PAf
attack, with a Δ BNP of 44［25, 93］pg/ml（before
attack ＝ 58［23, 76］, during attack ＝ 100［61,160］, after attack ＝ 56［29, 85］, p ＜ 0.0001）. In
addition, 17 attacks with exactly known onset time
were analyzed to investigate the relationshipbetween time elapsed after the onset and Δ BNP,
but no significant correlation was seen（r ＝ 0.42,

p ＝ 0.09 ; Fig. 5−B）. These results suggested thatthe BNP level was immediately elevated at theonset of the PAf attack, and Af had no further effecton BNP levels during the time course.
Change in brain natriuretic peptide level after
return to sinus rhythm
Five patients were followed up for 1 week after
return to sinus rhythm. BNP had significantly
returned to the former levels after 1 week
（beforeattack ＝ 14［11, 23］, during attack ＝ 87［57, 189］,
1 week after attack ＝ 14
［13, 37］, p ＝ 0.012）.
Symptoms during paroxysmal atrial fibrillation
attack and Δ BNP
Seventeen（25%）
of 68 PAf attacks manifested as
obvious symptoms（palpitations or anterior chest
discomfort）
noted by the patients, and in 23 attacks（34%）caused vague symptoms noted by thepatients only after PAf was pointed out by a physician, totalling 40 symptomatic attacks（59% ; Fig.
6−A）. Twenty eight attacks（ 41%）remained
asymptomatic even after PAf was pointed out.
Symptomatic attacks were associated with marked
elevation of BNP of 91［44,184］pg/ml（before
attack ＝ 45［19, 78］, during attack ＝ 135［80,236］, after attack ＝ 45［23, 76］, p ＜ 0.0001）, but
asymptomatic attacks also showed substantial elevation of BNP of 48［1, 65］pg/ml（before attack ＝
31［ 16, 45］, during attack ＝ 71［ 38, 119］, after
attack ＝ 24［18, 44］, p ＜ 0.0001）.

J Cardiol 2004 Jul; 44（1）: 1 – 11

Atrial Fibrillation and Brain Natriuretic Peptide

5

Fig. 5 Brain natriuretic peptide level changes in nine patients within 4 hr of the onset of paroxysmal
atrial fibrillation attack（A）and correlation between time elapsed after paroxysmal atrial fibrillation attack onset and Δ BNP（B）
Abbreviations as in Figs. 1, 4.

Underlying diseases and Δ BNP
Patients with underlying diseases had marked
elevation of BNP of 74［ 31, 148］pg/ml（before
attack ＝ 43［22, 75］, during attack ＝ 128［70,216］, after attack ＝ 42［22, 73］, p ＜ 0.0001）, butpatients without underlying diseases（lone Af）also
had significant elevation of BNP, of 31［ 8, 49］
pg/ml（before attack ＝ 11［7, 29］, during attack ＝40［18, 71］, after attack ＝ 12［8, 31］, p ＝ 0.0106 ;Fig. 6−B）.
Factors affecting Δ BNP
Continuous values were divided using the median for analyzing the factors that affected Δ BNP（Table 2）. Factors demonstrating significant correlations were the presence of symptoms（ p ＝0.0379）, underlying diseases（p ＝ 0.0018）, BNP
level over 40 pg/ml before Af attack（p ＜ 0.0001）,
and age over 70 years（ p ＝ 0.0030）. Left atrial
dimension（LAD）
greater than 41 mm also tended to
be associated greater Δ BNP（p ＝ 0.0832）. On theother hand, Af heart rate, left ventricular fractional
shortening（FS）, and left ventricular diastolicdimension（LVDd）
were not significant.
In addition, patients with and without symptoms
showed no significant differences in Af heart rate,age, BNP levels before attack, FS, LVDd, and
LAD. Patients with and without underlying diseases showed significant differences in Af heartrate（p ＝ 0.001）, age（p ＝ 0.037）and BNP levels
J Cardiol 2004 Jul; 44（1）: 1 – 11

before attack（p ＝ 0.008）, but not in FS, LVDd, and
LAD.
Factors influencing the change from paroxysmal
atrial fibrillation to chronic atrial fibrillation
rhythm Table 3
Prediction of change from PAf to chronic Af wasstudied by analyzing the 7 patients who later developed chronic Af and the 28 patients with persistent
PAf. The mean follow-up period in all cases was
17.1 ± 10.5 months, and the mean duration ofchange from PAf to chronic Af was 9.4 ± 7.8
months. Analysis of the BNP data revealed no significant difference between these two groups in
BNP level before attack, during attack, or after
attack, or in Δ BNP. Other factors were also analyzed, and Af fixation was found to be significantly
greater in older patients（p ＝ 0.004）, in those withlarger LAD（p ＝ 0.044）and in asymptomaticpatients（p ＜ 0.001）, but no significant difference
was seen in Af heart rate, FS, or LVDd.
Fig. 7 presents the data of monthly BNP measurements during changes from PAf to chronic Af
in four representative cases. Patterns of BNP levelchanges during the course of change from PAf tochronic Af varied and no significant pattern was
found.

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Tsuchida, Tanabe

Fig. 6 Comparison between changes of brain natriuretic peptide in symptomatic and asymptomaticpatients（A）
and comparison between changes of brain natriuretic peptide in patients withand without underlying diseases（B）
Abbreviations as in Fig. 1.

DISCUSSION
Changes in brain natriuretic peptide levels withatrial fibrillation attacks
BNP measurement has recently become an
essential method for the evaluation of heart function（left ventricular function）. Studies of electricaldefibrillation treatment with chronic Af have shownthat BNP is significantly elevated in Af as compared with sinus rhythm 8,9）. Factors such as
decreased cardiac function, atrial function andremodeling with a sustained period of Af rhythm
can affect the BNP level in chronic Af, but theeffect of an PAf attack that replaces sinus rhythm
may simply be reflected in the BNP levels. The pre-sent study performed BNP measurements threetimes（before, during and after PAf attack）, andshowed that the values rose during attacks andreturned to the former levels afterwards. This study
may also have identified the only effect of Af,
namely the atrial load, on BNP levels.
This study showed that BNP rose to 66［25, 120］pg/ml during Af attack, an increase of about 2.4fold（ 95% confidence interval, 2.1−2.7）, which
was the same as found in 91 patients with chronic
Af used as the controls. A study on electrical defibrillation in patients with chronic lone Af showed anincrease of about three times during Af（mean ±SD ; 137 ± 104 pg/ml）than in sinus rhythm（mean ± SD ; 46 ± 44 pg/ml）8）, which was slightly
J Cardiol 2004 Jul; 44（1）: 1 – 11

Atrial Fibrillation and Brain Natriuretic Peptide

Table 2 Factors affectingΔ BNP
Δ BNP

p value

Present

91［44, 184］

0.0379Absent48［1, 65］

higher than that in our study.
The effect of Af on cardiac function or atrial
contraction has been studied by analyzing therecovery processes of cardiac function in patientswith chronic Af after electrical defibrillation. The
atrial contribution to left ventricular filling recovered within 1 week, and the left ventricular ejection
fraction and maximum oxygen consumption continued to increase for 1 month after the defibrillation10）. On the other hand, atrial function recovery
takes much longer, from several weeks up to several months11）. Study of BNP change after electricaldefibrillation in patients with chronic Af found thatthe elevated BNP rapidly decreased in the first
week, and a gradual decrease followed for up to 1
month after the defibrillation 9）. This gradualdecrease was inversely well correlated with the A
wave height of the left ventricular inward blood
flow, and indicated cardiac function recovery due toatrial contraction recovery.
The present study showed that elevated BNP
associated with PAf attack returned to former levels
1 week after termination of Af. This suggests that
BNP elevation caused by PAf attack resulted fromatrial overload（elevation of atrial pressure, stretchof atrial wall, etc.）
and lack of atrial contribution toleft ventricular filling, and that no impairment ofcardiac function or atrial contraction occurred during PAf attacks, although such impairment occurs
in chronic Af.

Symptoms

History
Underlying diseases

74［31, 148］

None

31［8, 49］0.0018

BNP levels at sinus rhythm＞40 pg/ml−＜40 pg/ml

102［53, 189］

＞70 years

74［48, 129］＜0.0001

48［22, 74］Age−＜70 years

0.003048［19, 102］

Heart rate at attack＞90 beats/min−＜90 beats/min

74［25, 146］NS
（0.6226）

55［27, 100］LAD
＞41 mm−＜41 mm74［30, 129］＜0.34

70［25, 145］

＞0.34

55［26, 107］＞48 mm74［25, 132］NS
（0.0832）

51［23, 100］

FS
−
LVDd

−
＜48 mmNS（0.9324）NS（0.4761）

55［25, 86］

Each continuous value is expressed as the median［quartiles］.
LAD＝left atrial dimension ; FS＝fractional shortening ; LVDd
＝left ventricular diastolic dimension. Other abbreviations as inFig. 1.

Table 3 Comparison of parameters between patients who developed chronic atrial fibrillation andpatients with persistent paroxysmal atrial fibrillation
PAf-to-chronic Af（n＝7）

Persistent PAf（n＝28）

p value

BNP before attack（pg/ml）

41［25, 79］

39［15, 60］

NS（0.916）

BNP during attack（pg/ml）

93［47, 177］

123［55, 217］

NS
（0.414）

BNP after attack（pg/ml）
Δ BNP（pg/ml）
Heart rate during attack（beats/min）Age（yr）
LAD
（mm）
FS
LVDd
（mm）
No symptoms at attack

36［21, 78］

34［19, 70］

NS（0.956）60［15, 69］

67［36, 143］NS
（0.253）

93±36

94±21

NS
（0.878）

76±8

67±10

0.004

45±7

40±6

0.044

30±8

33±5

NS
（0.259）

47±40

48±25

NS
（0.636）

5/7

16/28

＜0.001Each continuous value is expressed as the median［quartiles］
or mean±SD.
Abbreviations as in Figs. 1, 3, 4, Table 2.

J Cardiol 2004 Jul; 44（1）: 1 – 117

8Tsuchida, Tanabe

Fig. 7 Patterns of brain natriuretic peptide level with the fixation from paroxysmal atrial fibrillation to chronic atrial fibrillation
Attack ＝ atrial fibrillation attack ; Chronic ＝ chronic atrial fibrillation. Other abbreviation as in Fig. 1.

Brain natriuretic peptide secretion during atrial
fibrillation
Atrial natriuretic peptide（ANP）is released fromsecretory granules in the atrium under control of aregulated pathway, whereas BNP is released fromthe ventricle via a constitutive pathway after thedetection of the stimulation.
However during Af, the BNP level in the coronary sinus is higher than in the anterior inter-ventricular vein in the patients with chronic lone Af,
which indicates that BNP is released from the atrium12）. The BNP level begins to decrease significantly 15 min after electrical defibrillation of Af inpatients with chronic heart failure, suggesting that
BNP is released from the atrium granules13）. We
previously studied the benefits of BNP measurement in cardiac disease screening, and found that
BNP is not always elevated during a non-attack
period of tachycardia or ischemic heart disease, aslong as no depression of heart function is present,
and also that the Af attack caused BNP elevationeven immediately after the onset, but not in patientswith acute myocardial infarction14）.

The present study demonstrated that the BNPlevel was already significantly elevated immediately（within 4 hr）after the Af attack onset, and thiselevated BNP level was not significantly correlatedwith the time elapsed after Af onset. These facts
seem to suggest that BNP is released from granules
in the atrium during Af attack, unlike BNP released
from the ventricle during myocardial infarction.
These findings indicate that we must be awarethat the BNP level seen in Af is a combined value
resulting from release from both the atrium andventricle, which means that the evaluation of cardiac function using BNP in patients with PAf or
chronic Af requires special consideration, unlike
the situation in sinus rhythm.
Elevation of brain natriuretic peptide in asymptomatic cases
The substantial and significant BNP elevation inasymptomatic cases may indicate that patients with
BNP elevation of unknown origin may be attributed to the occurrence of asymptomatic Af attack.

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Atrial Fibrillation and Brain Natriuretic Peptide

9

Δ BNP had no significant relationship with fractional shortening, left ventricular diastolicdimension
In this study, significant factors related to BNP
increase included the presence of symptoms, underlying diseases, BNP level before attack, and age.
On the other hand, FS and LVDd were not significant. In addition, analyses of the presence of symptoms and of underlying diseases revealed no significant correlation between the Δ BNP and the FS or
LVDd, as indices of left ventricular function（particularly systolic function）. These facts indicatethat Δ BNP had no significant relationship with left
ventricular systolic function. However, since
ΔBNP is significantly related to BNP level duringsinus rhythm before attack, the possibility cannot
be excluded that Δ BNP may be related to othercardiac functions, such as atrial function or left
ventricular diastolic function.

ventricular systolic function, but had a significant
relationship to BNP levels during sinus rhythm
before Af. Further studies are needed to evaluate
many other factors, such as atrial function or left
ventricular diastolic function.
Examination of the prediction of change from
PAf to chronic Af included a small number ofpatients, and the mean follow-up period was relatively short and not the same in all patients. Further
studies in many more patients and longer follow-up
periods are needed.
The present study was done during treatment
with oral medications（digitalis, anti-arrhythmic
drugs, etc.）in the outpatient clinic. Therefore, thepossibility cannot be excluded that medicationinfluenced the BNP levels, Af heart rate, symptoms, and so on. This is a limit of clinical researchin the outpatient clinic.

Atrial fibrillation fixation from paroxysmal atrial fibrillation to chronic atrial fibrillation
Low ANP and high BNP before electrical defibrillation in patients with chronic Af and congestive
heart failure were independent predictive factors
for Af recurrence13）. The reason for the Af relapse
in patients with low ANP and high BNP may bethat the progression of fibrosis in the atrial tissue
reflects a decrease in ANP production, and atrial
and ventricular dysfunction reflects BNP elevation.
The present study analyzed BNP data to ascertain whether Af fixation from PAf to chronic Af
could be predicted, but concluded that this is difficult with only BNP, because the BNP levels during
an Af attack and during sinus rhythm, as well as
ΔBNP, all showed non-significant differences. The
reason for this lack of significance may be that thepatterns of BNP levels varied during the course ofchanges from PAf to chronic Af（Fig. 7）, which
may be caused by the presence of asymptomatic Af
attacks. Therefore, BNP was not very useful for
prediction of Af fixation, but advancing age, large
LAD, and asymptomatic Af attacks seemed to be
useful.

BNP levels during Af attacks in patients with
PAf showed an increase of 66［25, 120］pg/ml（＝2.4-fold）elevation compared to that in sinus
rhythm, and the BNP level returned to normal aftertermination of Af. BNP levels were already elevated at the hospital visit, and occurred immediately（within 4 hr）after the onset of Af attack. ΔBNP
showed no significant relationship with the time
elapsed after the onset, which suggests that BNP
was released from secretory granules in the atrium
during Af attack. Forty-one percent of Af attacks
were asymptomatic, and also demonstrated significant BNP increases, which suggests that somecases of BNP elevation of unknown cause may be
attributed to the occurrence of asymptomatic Af
attack. Finally, cardiac function evaluation using
BNP in patients with Af, regardless of any PAf or
chronic Af, requires special consideration, unlike insinus rhythm, because BNP in Af is the sum of thereleases from the ventricle（reflecting left ventricular function）and the atrium（due to Af）.

Study limitations
This study showed that Δ BNP had no significant relationship to FS or LVDd, as indices of left

J Cardiol 2004 Jul; 44（1）: 1 – 11

CONCLUSIONS

Acknowledgements
We would like to thank Nobuo Shirahashi（Novartis Pharma K.K.）
for statistical support, and Dr Naoki Matsumoto（ St. Marianna
University School of Medicine）for clinical suggestions, and Dr
Joukichi Suzuki（Suzuki Clinic）and Dr Takashi Tomidokoro（Nagaoka Chuo General Hospital）for important advice.

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Tsuchida, Tanabe

要約

発作性心房細動による脳性ナトリウム利尿ペプチド分泌への影響
土田
目

桂蔵

田辺

一彦

的 : 脳性 Na 利尿ペプチド（BNP）は主に心室から分泌され左室機能を反映するが，慢性心房細動では洞調律時に比べて BNP 値が高値を示すとされている．本研究では，発作性心房細動における発作時の BNP 値の変動について検討し，さらに心房細動と BNP 値の関係について検討した．
方

法 : 発作性心房細動患者で，心房細動発作時，発作前（4 週間以上）および発作後（自然停止あるいは内服による除細動後 2−4 週間）の洞調律時の計 3 回の BNP 値を測定できた，35 例（男性 23 例，
女性 12 例，平均年齢 70.4 ± 9.6 歳）の連続 68 発作を対象とした．BNP 値は，外来受診時に座位で随時採血してイムノラジオメトリックアッセイ法で測定した．BNP 値の代表値は中央値で表した．
結

果 : 1）全 68 発作の発作時の BNP 値の変化（Δ BNP）は，66 pg/ml（発作前 39 →発作時 102 →発作後 35 pg/ml）と有意の上昇が認められ，心房細動発作時 BNP 値は洞調律時 BNP 値の約 2.4 倍であった．そして発作後にまた発作前値に復した．2）発作時 BNP 値上昇例は 55 発作（81%）で，不変例（Δ BNP が± 20 pg/ml 以内）は 11 発作（16%），低下例は 2 発作（3%）であった．3）発作出現直後（4 時間以内）受診の 9 例全例において，すでにΔ BNP は 44 pg/ml（58 → 100 → 56）と有意の上昇が認められた．また，心房細動発作経過時間とΔ BNP の間に有意な相関は認められなかった．4）発作時の症状（動悸・前胸部不快など）の有無でみると，有症状 40 発作（59%）ではΔ BNP は 91 pg/ml（45 →
135 → 45）と有意の上昇が認められ，無症状 28 発作（41%）でもΔ BNP は 48 pg/ml（31 → 71 → 24）と有意の上昇が認められた．
結論 : 心房細動発作時の BNP 値は洞調律時の BNP 値の約 2.4 倍であった．発作出現直後の受診でもすでに BNP 値の上昇があり，心房細動時には BNP が心房から顆粒分泌されている可能性が示唆された．また原因不明の BNP 値の変動の中に，無症状の心房細動発作が関与している可能性も示唆された．最後に，心房細動時の BNP 値による心機能評価においては，心房細動時の BNP 値が，心室由来の（左室機能を反映する）BNP に心房由来の（心房細動による心房負荷で分泌された）BNPが加わった値であることを考慮する必要がある．

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