Atrial Fibrillation, thromboembolic risk, and the potential role of the natriuretic peptides, a focus on BNP and NT-proBNP - A narrative review

Abstract

Atrial fibrillation (AF) is one of the most commonly encountered arrythmia in clinical practice. AF itself can be driven by genetic predisposition, ectopic electrical activity, and abnormal atrial tissue substrates. Often there is no single etiological mechanism, but rather a combination of factors that feed back to remodel and worsen tissue substrate, "AF begets AF". The clinical consequences of AF can often include emboli, heart failure, and early mortality. The classical AF cardioembolic (CE) concept requires thrombus formation in the left atrial appendage, with subsequent embolization. The temporal dissociation between AF occurrence and CE events has thrown doubt on AF as the driver of this mechanism. Instead, there has been a resurgence of the "atrial cardiomyopathy" (ACM) concept. An ACM is proposed as a potential mechanism of embolic disease through promotion of prothrombotic mechanisms, with AF instead reflecting atrial disease severity. Regardless, AF has been implicated in 25% to 30% of cryptogenic strokes. Natriuretic peptide(NP)s have been shown to be elevated in AF, with higher levels of both NT-proBNP and BNP being predictive of incidental AF. NPs potentially reflect the atrial environment and could be used to identify an underlying ACM. Therefore, this narrative review examines this evidence and mechanisms that may underpin the role of NPs in identifying atrial dysfunction, with focus on both, BNP and NTproBNP. We explore their potential role in the prediction and screening for both, ACM and AF. Moreover, we compare both NPs directly to ascertain a superior biomarker.

Keywords: ACM, Atrial cardiomyopathy; AF, Atrial fibrillation; ARISTOTLE trial, Apixaban For Reduction In Stroke And Other Thromboembolic Events In Atrial Fibrillation Trial; ASSERT trial, Atrial Fibrillation Evaluation In Pacemaker Patient’s Trial; ASSERT-II trial, Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial; AUC, Area Under The Curve; Atrial cardiomyopathy; Atrial fibrillation; BNP; BNP, Brain natriuretic peptide; CE, Cardioembolic; CHA2DS2-Vasc, Congestive Heart Failure, Hypertension, Age ≥ 75, Diabetes, Stroke/TIA/Thromboembolism, Vascular Disease, Age 65–74; CHARGE, Cohorts For Heart And Aging Research In Genomic Epidemiology; CI, Confidence Intervals; CNP, C-type natriuretic peptide; EHRAS, EHRA/ HRS/APHRS/SOLAECE; ESUS, Embolic Stroke of Unknown Source; IMPACT Trial, Implementation of An RCT To Improve Treatment With Oral Anticoagulants In Patients With Atrial Fibrillation; MR-proANP, Mid Regional Pro-Atrial Natriuretic Peptide; NP, Natriuretic peptide; NT-proBNP; NT-proBNP, N-Terminal Pro Brain Natriuretic Peptide; Natriuretic peptides; RE-LY study, The Randomized Evaluation of Long-Term Anticoagulation Therapy study; SE, Standard Error; TE, Thromboembolic event; TIA, Transient ischemic attack; TRENDS trial, A Prospective Study of the Clinical Significance of Atrial Arrhythmias Detected by Implanted Device Diagnostics.

Fig. 1

Potential mechanism(s) of NP release in AF. Abbreviations: AF = Atrial fibrillation, NP = Natriuretic peptide.