Atrial fibrillation is associated with increased neurohumoral activation and reduced exercise tolerance in patients with non-ischemic dilated cardiomyopathy

Objectives To assess atrial fibrillation (AF) associated differences in proinflammatory cytokines, natriuretic peptide levels and exercise capacity in patients with heart failure (HF) secondary to non-ischemic dilated cardiomyopathy (NIDC). Methods We studied 147 NIDC patients, mean age 58.3 ± 12.5 years, left ventricular (LV) ejection fraction 27.8 ± 10.9% and NYHA class II–III. Neurohumoral activation was assessed by measurement of interleukin IL-1, IL-6, tumor necrosis factor-a (TNF-a), its soluble receptors sTNFR I and II, N-terminal atrial (NT-ANP) and -brain (NT-BNP) natriuretic peptide levels, and functional class was assessed by cardiopulmonary exercise test. Results Forty patients (27.5%) had chronic AF and they did not differ in age, LV ejection fraction or HF duration compared to patients in sinus rhythm (SR). AF was associated with increased levels of IL-6 (p = 0.001), TNF-a (p = 0.002), sTNFRI (p = 0.023), NT-ANP (p < 0.001) and NT-BNP (p = 0.003), decreased exercise duration (p < 0.001) and slightly reduced maximal oxygen consumption at peak exercise (p = 0.07) compared to SR patients. No significant differences in cytokine and natriuretic peptide levels or exercise tolerance were noted when patients in AF were compared to the subgroup of SR with restrictive LV filling pattern. Multivariate analysis showed that NT-ANP (p = 0.003) and IL-6 (p = 0.006) plasma levels were independently associated with the presence of AF in our patient population. Conclusion AF is associated with increased inflammatory state, natriuretic peptide levels and reduced exercise capacity in patients with HF secondary to NIDC. These findings suggest that the presence of AF in HF represents a more advanced stage of the syndrome.