Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) have been used as markers for diagnosis or risk stratification in patients with heart failure (HF), stable coronary artery disease, and acute coronary syndrome [1]. BNP secretion is mainly triggered by myocardial wall stretch [2]. Tachycardia-induced cardiomyopathy is a well-known cause of arrhythmia-induced elevation in natriuretic peptide levels [3–5]. Therefore, we decided to investigate whether bradyarrhythmia causes an increase in plasma NT-pro-BNP levels.

We retrospectively enrolled 125 patients who received a temporary pacemaker because they were found to have sinus node dysfunction (SND) or atrioventricular blocks (AVBs) at the emergency department of Daegu Catholic University Medical Center from March 2006 to February 2012. The SND cases included symptomatic marked sinus bradycardia (<40 bpm) or long sinus pause (>3.0 s). AVB cases included high degree AVBs or complete AVBs. Patients with renal dysfunction, hyperkalemia, reduced left ventricular systolic function (left ventricular ejection fraction [LVEF] <40%), and atrial fibrillation were excluded. Heart failure (HF) was defined as a NT-pro-BNP level of >300 pg/mL, as described in the 2012 European Society of Cardiology (ESC) Guidelines [6]. We evaluated history of hypertension, diabetes mellitus, ischemic heart disease, plasma NT-pro-BNP levels, body mass index (BMI), LVEF, left atrial diameter (LAD), and ventricular rate. Blood samples were drawn from patients within 1 hour after arrival at the emergency department, and specimens were placed in 5-mL ethylenediaminetetraacetic acid tubes and immediately centrifuged. Plasma NT-pro-BNP levels were measured by using an automated system (Elecsys 2010™, Roche Diagnostics, Indianapolis, IN, USA). The current study was conducted in accordance with the Declaration of Helsinki, and the Institutional Review Board of Daegu Catholic University Medical Center approved the study protocol.

The present study demonstrated that bradyarrhythmia can cause an increase in plasma NT-pro-BNP levels. Furthermore, NT-pro-BNP levels were higher in patients with AVBs as compared to those with SND.

Kovats et al. [7] reported that in elderly women with beta-blocker therapy-induced sinus arrest with a 40 bpm junctional escape rhythm and elevated NT-pro-BNP serum levels, the stroke volume increased at the lower heart rate in order to keep up the cardiac output. Increased stroke volume results in increased wall tension, which in turn triggers natriuretic peptide secretion [8]. Further, Meiracker et al. [9] demonstrated that in hypertensive patients, decreased heart rate due to beta-blocker therapy increased plasma atrial natriuretic peptide and BNP concentrations.

Pan et al. [10] reported that patients with SND, AVB, and atrial fibrillation had increased plasma NT-pro-BNP levels as compared to the controls, and NT-pro-BNP levels were lower in patients with SND than in patients with AVB; this finding is consistent with our result. They also demonstrated that the severity of atrioventricular asynchrony was an independent determinant of NT-pro-BNP levels. Atrioventricular asynchrony leads to stretching of the atrial wall and increased ventricular end-diastolic pressure, resulting in increased secretion of NT-pro-BNP from the atrium and ventricle [11–12]. Koch et al. [13] reported that patients with dual-chamber pacing had significantly lower BNP values as compared to those with single-chamber ventricular pacing due to the loss of atrioventricular synchrony.

Taken together, bradyarrhythmia due to beta-blocker therapy, AVBs, or SND can lead to elevated plasma NT-pro-BNP levels by increasing cardiac wall stretch through an increase in stroke volume or loss of atrioventricular synchrony (Figure 2).

As in the case of patients with tachyarrhythmia, bradyarrhythmia, especially that caused by AVBs, may cause an increase in plasma NT-pro-BNP levels, leading to HF. Therefore, the possibility of HF should be considered in patients with bradyarrhythmia.