Plasma natriuretic peptides during supraventricular tachycardia: A study in patients with atrioventricular nodal reentry tachycardia

doi:10.4236/wjcd.2013.37074

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World Journal of Cardiovascular Diseases, 2013, 3, 471-475 WJCD

http://dx.doi.org/10.4236/wjcd.2013.37074 Published Online October 2013 (http://www.scirp.org/journal/wjcd/)

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: *[email protected]

Received 16 August 2013; revised 15 September 2013; accepted 25 September 2013

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

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-

crease.

Keywords: Atrioventricular Nodal Reentry Tachycardia;

Atrial Natriuretic Peptide; Brain Natriuretic Peptide

1. INTRODUCTION

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

release.

*Corresponding autho

Published Online October 2013 in SciRes. http://www.scirp.org/journal/wjcd

R. Pecini et al. / World Journal of Cardiovascular Diseases 3 (2013) 471-475

472

2. METHODS

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-

mal.

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

procedure.

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-

lyzed.

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.

3. RESULTS

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

R. Pecini et al. / World Journal of Cardiovascular Diseases 3 (2013) 471-475

473

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.

4. DISCUSSION

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.

WJCD

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474

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].

5. LIMITATIONS

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.

6. CONCLUSION

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.

7. ACKNOWLEDGMENTS

Special thanks to Jens Peter Goetze MD, for his valuable comments on

the manuscript.

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