Prognostic value of N-terminal Brain Natriuretic Peptide (NT-proBNP) in Risk Assessment of Adverse Cardiovascular Events in Patients with Atrial Fibrillation and Heart Failure with Reduced Left Ventricular Systolic Function

Abstract

According to Russian epidemiological studies, the incidence of chronic heart failure (HF) in the general population is approximately 7%, increasing from 0.3% in the group aged 2029 years to 70% in patients aged 90 years [1]. In the general population, the incidence of atrial fibrillation (AF) ranges from 1% to 2%, which increases with age, that is, from 0.5% at the age of 4050 years to 5%15% at the age of 80 years [2]. HF and AF aggravate significantly each others course and mutually increase the risk of adverse outcomes [3, 4]. Moreover, the incidence of AF in patients with HF increases with increasing New York Heart Association (NYHA) grade; that is, among patients with HF of NYHA grade I, the incidence of AF is 5%, whereas among patients with HF NYHA grade IV, the AF incidence in 50% [5].
 Chronic HF is a syndrome with complex pathophysiology, which is characterized by the activation of neurohumoral systems, namely, the reninangiotensinaldosterone system (RAAS), sympathetic nervous system (SNS), and insufficient activity of the natriuretic peptide (NUP) system. In the early stage of HF, i.e. asymptomatic dysfunction of the left ventricle, the activation of the SNS and RAAS plays a compensatory role aimed at maintaining cardiac output and circulatory homeostasis [6]. Moreover, the NUP system has a counter-regulatory function in relation to the RAAS and SNS, and with prolonged and excessive activation of the SNS and RAAS or with insufficient NUP system activity, imbalance occurs and HF progresses [7].
 The brain natriuretic peptide (BNP) and biologically inactive N-terminal fragment of BNP (NT-proBNP) are the most studied and significant in clinical practice representatives of the NUP system. BNP and NT-proBNP are secreted by cardiomyocytes of the left ventricular (LV) myocardium in response to an increase in the mechanical load and stress of the LV myocardium. NT-proBNP is widely used as a test to rule out HF in patients with dyspnea. The NUP level also correlates with the severity and prognosis in patients with an established diagnosis of HF, and studies have reported that the NUP level acts as a criterion for treatment efficiency in patients with HF [8]. NT-proBNP is a biomarker not only for HF but also for several other conditions, such as acute coronary syndrome and myocardial infarction (MI), because it is associated with an increased risk of death from all causes, regardless of age, stable effort angina grade, myocardial infarction history, and LV ejection fraction (LVEF) [9].
 NT-proBNP levels can be influenced by several additional factors such as age, obesity, or glomerular filtration rate. The prognostic value of NT-proBNP is relevant in comorbid patients with AF associated HF because AF can increase NT-proBNP levels independently [10]. Given that NUP secretion depends on intracardiac hemodynamics, the NT-proBNP levels may also depend on the approach to managing AF. Tachycardia is associated with high NT-proBNP levels [11].
 The rhythm control approach has advantages over the heart rate control approach in patients with HF and LVEF 50% to reduce mortality and the number of unplanned hospitalizations due to HF progression [12].
 To date, the prognostic significance of NT-proBNP levels in relation to the risk of adverse events in patients with HF and reduced LV systolic function associated with AF, depending on the approach of AF management, remains unresolved.
 This study aimed to assess the predictive value of NT-proBNP in relation to the development of adverse cardiovascular events in patients with permanent or persistent AF associated with HF and LVEF 50%.