World Journal of Cardiovascular Diseases, 2013, 3, 471-475 WJCD Published Online October 2013 (
Plasma natriuretic peptides during supraventricular
tachycardia: A study in patients with atrioventricular
nodal reentry tachycardia
Redi Pecini1*, Steen Pehrson1, Xu Chen1, Anna Margrethe Thøgersen2, Andreas Kjær3,
Jesper Hastrup Svendsen1,4,5
1Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
2Department of Cardiology, Center for Cardiovascular Research, Århus University Hospital, Aalborg Hospital, Aalborg, Denmark
3Department of Clinical Physiology, Nuclear Medicine and PET & Cluster for Molecular Imaging, Rigshospitalet, University of Co-
penhagen, Copenhagen, Denmark
4The Danish National Research Foundation Centre for Cardiac Arrhythmia, Copenhagen, Denmark
5Department of Surgery and Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
Email: *
Received 16 August 2013; revised 15 September 2013; accepted 25 September 2013
Copyright © 2013 Redi Pecini et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Aims: To characterize the plasma levels of the atrial
natriuretic peptide (ANP) and brain natriuretic pep-
tide (BNP) in patients with atrioventricular nodal
reentry tachycardia (AVNRT), we measured the plas-
ma levels of these peptides before and during ta-
chycardia. Methods: We included 10 consecutive pa-
tients scheduled for ablation of typical AVNRT with-
out structural heart disease. Catheters were inserted
in the femoral artery, femoral vein, and coronary
sinus (CS) prior to the ablation procedure. Blood
samples were drawn before and after 3 min of tachy-
cardia to measure plasma levels of ANP and BNP.
Right atrial pressure (RAP) was measured at base-
line. Results: Of the 10 patients, in three patients it
was not possible to induce tachycardia leaving a total
of 7 patients available for analysis. Mean age of the
seven included patients was 40 ± 12 years (mean ±
SD), five were female. ANP levels increased signifi-
cantly during tachycardia in the artery (p = 0.0009)
and vein (p = 0.003), but only borderline in CS (p =
0.09). BNP levels did not change during tachycardia
in any location. Conclusion: ANP levels measured in
the peripheral circulation increased acutely during
tachycardia due to AVNRT. BNP levels did not in-
Keywords: Atrioventricular Nodal Reentry Tachycardia;
Atrial Natriuretic Peptide; Brain Natriuretic Peptide
Brain natriuretic peptide (BNP) and to a lesser extent
atrial natriuretic peptide (ANP) have shown to be of
value in the diagnosis of heart failure [1,2]. Furthermore,
increased levels of BNP have been shown to predict ad-
verse events in patients with heart failure [3,4], coronary
heart disease [5,6] and mitral regurgitation [7].
The importance of ANP and BNP in patients with
tachycardias is less well known. In patients with atrial
fibrillation, levels of BNP are increased [8], and the lev-
els are higher in patients with persistent and permanent
AF than those with paroxysmal AF [9]. In addition, one
study of patients with AF found higher levels of BNP in
the coronary sinus than in the peripheral circulation. The
studies of BNP in patients with supraventricular tachy-
cardias are of limited number [10,11]. The measurement
of BNP levels in these studies was only done from pe-
ripheral blood.
As such, the levels of ANP and BNP in patients with
supraventricular arrhythmias have not been well charac-
terized. For this reason, we undertook the present study
in patients with atrioventricular nodal reentry tachycardia
(AVNRT) without concomitant structural heart disease
and without the influence of pre-study medication. We
measured ANP and BNP levels directly at the coronary
sinus, as well as from arterial and venous peripheral
blood with the purpose of evaluating the possible cardiac
*Corresponding autho
Published Online October 2013 in SciRes.
R. Pecini et al. / World Journal of Cardiovascular Diseases 3 (2013) 471-475
2.1. Study Population
We included consecutive patients referred to our center
for ablation of suspected AVNRT. The patients did not
have any other concurrent diseases and did not take any
medications. They had not had symptoms of arrhythmia
for at least one week prior to the ablation procedure. We
performed an echocardiography in each patient the day
before the ablation procedure. All patients had normal
left ventricular ejection fraction (LVEF) and no signs of
structural heart disease. Creatinine levels were also nor-
The study was carried out in accordance to the decla-
ration of Helsinki and was approved by the local ethical
committee for Copenhagen, study number KF01-046/04.
All patients gave written informed consent.
2.2. Ablation Procedure
All antiarrhythmic drugs were withdrawn at least five
plasma half-lives prior to the procedure. Two 7 French
sheaths were inserted; one in each femoral vein, and a 5
French sheath was positioned in the femoral artery. An
additional sheath was also inserted in the coronary sinus.
The femoral vein sheaths were used for catheter insertion
and for the blood samples. The femoral artery and the
coronary sinus sheaths were only used for the purpose of
blood sampling.
After insertion of the sheaths and positioning of
catheters, the right atrial pressure (RAP) measured and
then the first series of blood samples was performed.
Blood was drawn sequentially in the same order in each
patient, first from the coronary sinus (CS), then from the
femoral artery and then from the femoral vein. Sampling
from each location took approximately 30 seconds. After
the first blood sampling (baseline), programmed electri-
cal stimulation was used to induce the arrhythmia. If the
first electrical programmed stimulation was unsuccessful,
a second programmed stimulation was tried after infu-
sion of isoprotenerol to achieve an increase in heart rate
to about 100 beats per minute. Once the tachycardia oc-
curred, it was allowed to continue for at least three min-
utes and then the blood sampling was repeated. Thereaf-
ter, the arrhythmia was stopped and the ablation of the
slow pathway at the atrioventricular node was performed.
The right atrial pressure (RAP) was only measured at the
baseline. No complications occurred during or after the
2.3. ANP and BNP Analysis
Ten ml of blood was drawn from each sheath, before and
during tachycardia (a total of 60 ml) into tubes contain-
ing EDTA and 500 μl aprotinin (Trasylol® 500 KIU/ml;
Bayer, Leverkusen, Germany) and centrifuged at 2000 ×
g for 15 min. Then plasma was transferred to glass tubes
and immediately frozen and kept at 80˚C until ana-
BNP was measured by an automated two-site sand-
wich immunoassay technique using chemiluminescence
(ADVIA Centaur; Siemens Healthcare Diagnostics). The
physiologically active C-terminal peptide of BNP was
measured (77 - 108). The sensitivity of the assay was 2
pg/ml, and the intra-assay and interassay coefficients of
variation were 1.2% and 2.3%, respectively.
ANP was measured by an enzyme immunoassay ac-
cording to the instructions of the manufacturer (Bio-
medica Medicinprodukte GmbH, Vienna, Austria). The
lower detection limit for NT-pro-ANP (1-98) was 0.05
nmol/l, and the intra-assay and interassay coefficients of
variation were 2% and 4%, respectively.
The plasma values of ANP and BNP at the baseline
were compared with the values during tachycardia in
each patient.
2.4. Statistical Analysis
Continuous variables are presented median values and
inter-quartile range, and discrete variables are presented
as percent. We tested the ANP and BNP values for nor-
mal distribution visually with histogram graphs and with
the use of Kolmogorov-Smirnov test for normal distribu-
tion. Not all the data showed normal distribution. There-
fore, we performed logarithmic transformation of the
values, after which all values showed normal distribution
using the same statistical tests. We used paired t-test for
the comparison of ANP and BNP logarithmic values be-
fore and during tachycardia. For the correlation analyses,
we used the general linear model. A p-value less than
0.05 was considered to indicate statistical significance.
We initially included 10 patients in the study. They all
had episodes with palpitations and 12-lead ECGs per-
formed during the episodes had shown short RP tachy-
cardia. The arrhythmia could not be induced in three
patients. These patients were excluded from the study. In
all the inducible patients the induced arrhythmia was the
clinically relevant tachycardia. There was no evidence of
an accessory pathway between the atria and the ventri-
cles. The ablation of the slow pathway for AVNRT at the
atrioventricular node was successful in all the patients
and the arrhythmia could not be induced thereafter.
The baseline data of the seven included patients are
presented in Ta b l e 1. Baseline values of ANP and BNP
were slightly higher in the coronary sinus, but they were
not significantly different from the values in the femoral
artery or vein. ANP levels increased significantly during
Copyright © 2013 SciRes. WJCD
R. Pecini et al. / World Journal of Cardiovascular Diseases 3 (2013) 471-475
Copyright © 2013 SciRes.
arrhythmia in the peripheral circulation (femoral artery
and vein) compared to the baseline values (Figure 1 and
Table 2), but not in the coronary sinus (Table 2). BNP
levels did not change significantly during arrhythmia
compared to the baseline values (Table 2).
mones are released into the circulation in response to
volume overload and stretch mechanisms [14,15]. In
experimental studies, which simulate ventricular over-
loading conditions, BNP production and release is sti-
mulated more quickly than that of ANP [16]. Our results
show the contrary. Two factors may have contributed to
our results. First, we did not apply volume-overloading
conditions in our patients. It is possible that the stretch
stimulus during tachycardia was higher in the thin-walled
atria than in the thick-walled ventricles. Second, our pa-
tients had no evidence of structural heart disease. BNP
baseline levels rise in different pathological conditions of
the heart and this increase has prognostic value [3-7].
The failure of BNP to rise during tachycardia in our pa-
tients may in part explain the good prognosis in patients
with AVNRT and no structural heart disease.
There was no correlation between the patients’ age and
the baseline levels of ANP and BNP, or the levels of
these hormones during tachycardia. Similarly, there was
no correlation between the patients’ age and the changes
of the hormones during tachycardia. Neither did we find
a correlation between the ANP and BNP levels at base-
line, during tachycardia, or their changes, and RAP.
We measured changes of ANP and BNP during tachycar-
dia in a small group of patients with AVNRT. Our data
show that, in the peripheral circulation, ANP levels rose
significantly in response to tachycardia. In constrast,
BNP levels did not change significantly. ANP is pre-
dominately found in the atrial tissue [12,13], while BNP
is predominantly found in the ventricles [13]. Both hor-
Another finding of our study was that the ANP levels
increased in the peripheral sites (femoral artery and vein)
but not in the coronary sinus. This finding is somehow
surprising. The particular anatomy of the left atrium
could be an explanation for this finding. The veins,
which drain the posterosuperior part of left atrium, empty
directly into the left atrium itself, and not into the coro-
Table 1. Baseline data of the patients.
Variable Value
Age (years) 40 ± 12 (mean ± SD)
Female sex, number (percentage) 5 (71)
Tachycardia cyclus (ms) 336 ± 28 (mean ± SD)
RAP (mmHg) 7 ± 2 (mean ± SD)
log_ANP, femoral artery 0.25 ± 0.16 (mean ± SD)
log_ANP, femoral vein 0.25 ± 0.19 (mean ± SD)
log_ANP, coronary sinus 0.34 ± 0.21 (mean ± SD)
log_BNP, femoral artery 1.49 ± 0.43 (mean ± SD)
log_BNP, femoral vein 1.34 ± 0.43 (mean ± SD)
log_BNP, coronary sinus 1.67 ± 0.39 (mean ± SD)
(a) (b)
Figure 1. Changes of ANP levels during tachycardia measured
in the femoral artery (a) and changes of ANP levels during
tachycardia measured in the femoral vein (b).
RAP: right atrial pressure.
Table 2. ANP and BNP changes during tachycardia.
Variable Baseline During tachycardia Change p-value
log_ANP femoral artery 0.25 ± 0.16 (mean ± SD) 0.42 ± 0.21 (mean ± SD) 0.17 ± 0.04 0.0009
log_ANP femoral vein 0.25 ± 0.19 (mean ± SD) 0.34 ± 0.18 (mean ± SD) 0.10 ± 0.05 (mean ± SD) 0.003
log_ANP coronary sinus 0.34 ± 0.21 (mean ± SD) 0.50 ± 0.22 (mean ± SD) 0.16 ± 0.20 (mean ± SD) 0.1
log_BNP femoral artery 1.49 ± 0.43 (mean ± SD) 1.60 ± 0.37 (mean ± SD) 0.12 ± 0.15 (mean ± SD) 0.1
log_BNP femoral vein 1.34 ± 0.43 (mean ± SD) 1.43 ± 0.36 (mean ± SD) 0.09 ± 0.13 (mean ± SD) 0.1
log_BNP coronary sinus 1.67 ± 0.39 (mean ± SD) 1.64 ± 0.41 (mean ± SD) 0.03 ± 0.11 (mean ± SD) 0.6
NP: atrial natriuretic peptide. BNP: B-type natriuretic peptide.
R. Pecini et al. / World Journal of Cardiovascular Diseases 3 (2013) 471-475
nary sinus. This amount of blood empties then in the left
ventricle. Thus, the majority of this amount of blood cir-
culates directly into the periphery, and only a minor
amount into the coronary artery system. One other ex-
planation could be our sequential method of blood sam-
pling, starting in the coronary sinus. In any case, there is
little doubt that the increased levels of ANP are directly
related to the tachycardia episode.
Even in patients with lone atrial fibrillation, baseline
BNP levels are increased [8], and these levels are even
higher in patients with persistent and permanent atrial
fibrillation [9,17,18]. On the other hand, atrial fibrillation
is an arrhythmia, which is associated with considerable
morbidity and mortality [19]. On the contrary, AVNRT is
not associated with increased mortality and the treatment
is usually guided by the burden of symptoms. Further-
more, recent data have shown that the BNP levels in pa-
tients with atrial fibrillation are especially increased in
the coronary sinus [20]. We did not detect any increase of
BNP in blood samples from coronary sinus. This is an-
other fundamental difference between these two arrhy-
thmias. Whether this difference in BNP levels can ex-
plain the difference in the morbidity between atrial fib-
rillation and AVNRT is unsure. However, we know that
in other cardiac pathologies, morbidity and mortality risk
is closely related to the levels of BNP [4-7].
Our number of patients was limited. For this reason, we
may have overlooked changes in BNP levels due to in-
adequate power. It is also possible that if we had repeated
the measurements of BNP later on we might have been
able to detect a change in the BNP levels.
Peripheral plasma levels of ANP but not BNP rose
acutely in response to tachycardia in patients with AVNRT.
This finding is in contrast to patients with chronic atrial
fibrillation indicating the different pathophysiology in-
volved in the two conditions.
Special thanks to Jens Peter Goetze MD, for his valuable comments on
the manuscript.
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