Natriuretic Peptide System in AF. Introduction: Circulating cardiac natriuretic peptides play an important role in maintaining volume homeostasis, especially during conditions affecting hemodynamics. During atrial fibrillation (AF), levels of plasma atrial natriuretic peptide (ANP) becomes elevated. The aim of this study was to gather information about gene expression of the natriuretic peptide system on the atrial level in patients with AF.Methods and Results: Right atrial appendages of 36 patients with either paroxysmal or persistent AF were compared with 36 case matched controls in sinus rhythm for mRNA expression of pro- atrial natriuretic peptide (pro-ANP), pro-brain natriuretic peptide (pro-BNP), and their natriuretic peptide receptor type-A (NPR-A). We investigated patients without (n = 36) and with (n = 36) valvular disease. Persistent AF was associated with higher mRNA expression of pro-BNP (+66%, P = 0.04, in patients without valvular disease, and +69%, P Conclusion: This study demonstrates that persistent, but not paroxysmal, AF induces alterations in gene expression of pro-BNP and NPR-A on the atrial level. Although AF generally is associated with an increase of plasma ANP level, a change in mRNA content of pro-ANP is only observed in the presence of concomitant valvular disease and is of minor magnitude.