Natriuretic peptides and right atrial fibrosis in patients with paroxysmal versus persistent atrial fibrillation

Natriuretic peptides (NPs) are excellent diagnostic and prognostic markers of heart failure, but their roles in atrial fibrillation (AF), particularly of isolated cardiac valvular origin, are unclear. We assessed the mRNA and protein content of pro-atrial natriuretic peptide (pro-ANP) and pro-brain natriuretic peptide (pro-BNP) in right atrial appendages (RAAs) and their N-terminal fragments (nt-proANP and nt-proBNP) in the plasma of 30 patients with paroxysmal AF (PaAF) and 40 patients with persistent AF (PeAF) matched with 34 patients in sinus rhythm (SR) undergoing isolated valvular replacement. To explore the underlying mechanism, fibrosis related examinations were simultaneously carried out in RAAs. Unexpectedly, atrial expression of pro-NPs mRNA was notably augmented in the PaAF subgroup, but not so pronounced in the PeAF subgroup. Atrial content of pro-NPs proteins and plasma nt-proNPs, between which surprisingly strong positive correlations were found (pro-ANP and nt-proANP: r = 0.918, p < 0.001; pro-BNP and nt-proBNP: r = 0.913, p < 0.001), were increased analogously in PaAF and PeAF subgroups. We identified significantly increasing gradients of atrial collagen volume fraction (CVF), levels of collagen I and III in the SR, PaAF and PeAF groups, and convincing negative linear correlations between CVF, levels of collagen I and III, and atrial transcripts of pro-NPs. These findings suggest that the discordance between transcripts and protein contents of pro-NPs was possibly due to the more outstanding atrial fibrosis in PeAF, and that circulating nt-proNPs levels could reflect the corresponding atrial pro-NPs contents in this report.