To compare effects of levosimendan on brain natriuretic factor (BNP) and other myocardial injury indicators in heart failure (HF) patients with chronic atrial fibrillation (AF) versus sinus rhythm (SR). This study was prospective, double blinded and included a total of 62 chronic HF patients in NYHA III-IV classes. Left ventricular ejection fraction <= 35%, and with either SR (n=38) or AF (n=24) received a 12 mu g/kg dose of levosimendan. Then they were followed up by IV infusions, as tolerated. BNP, cardiac troponin I, creatinine kinase-myocardial band levels were measured. Age mean (67.5 +/- 16.5 years), demographic features and medical history were not significantly different between groups. Diastolic blood pressure was lower (p=0.008), whereas blood urea nitrogen was higher (p=0.03) in the AF group. The frequently used concomitant medication in the AF group was amiodarone (p=0.02). Both systolic and diastolic blood pressures were decreased in the SR Group (p=0.009 and 0.006, respectively). Despite the reduction in systolic blood pressure (p=0.04), diastolic blood pressure remained unchanged in the AF group. Levosimendan significantly decreased BNP levels in the SR group (p=0.002). There was symptomatic improvement and decrease in the NYHA classification among patients in both groups, but no significant difference between groups. Levosimendan did not reduce BNP levels in patients with AF patients, which might be considered as an indicator of a limited efficacy of levosimendan on decompensated, acute HF patients with AF, compared to patients with SR.