Autonomic dysfunction is associated with brief episodes of atrial fibrillation in type 2 diabetes Maria Rosaria Rizzo a , Ferdinando Carlo Sasso b , Raffaele Marfella a, ⁎, Mario Siniscalchi c , Pasquale Paolisso a , Ornella Carbonara b , Maria Carmela Capoluongo a , Nadia Lascar d , Caterina Pace e , Celestino Sardu a , Beatrice Passavanti e , Michelangela Barbieri a , Ciro Mauro b , Giuseppe Paolisso a a Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Italy b Department of Internal and Experimental Medicine Center of Cardiovascular Excellence Second University of Naples, Italy c Department of Cardiology, Hospital Cardarelli, Naples, Italy d University of Birmingham, Institute of Biomedical Research, Second University of Naples, Italy e Department of Anaesthesiology Sciences, Second University of Naples, Italy abstract article info Article history: Received 26 June 2014 received in revised form 2 September 2014 accepted 3 September 2014 Available online xxxx Keywords: Type 2 diabetes Atrial fibrillation Autonomic nervous system Heart rate variability ECG Holter Background and Aims: This study aimed to investigate the relationship between asymptomatic episodes of atrial fibrillation (AF) and abnormalities of the autonomic nervous system in type 2 diabetic patients who did not have evidence of atrial fibrillation at baseline. Methods and Results: In a multicentric cross-sectional controlled study, 1992 patients with type 2 diabetes were screened. All underwent ambulatory ECG recording for 48-hour at 3, 6, 9, and 12 months. Heart rate variability (HRV) was used as indicator of autonomic activity. One hundred seventy-six diabetics with silent atrial fibrillation episodes (SAFE group) and 288 without silent atrial fibrillation (non-SAFE group) were enrolled. These selected diabetics were matched on clinical and anthropometric data to 120 control subjects without diabetes of the control group. HRV analysis evidenced that LF/HF ratio was significantly higher in the SAFE group than in the non-SAFE group (P b 0.05) in the whole period of HM analysis. AF absolute burdens were positively correlated with LF/HF ratio (r = 0.31, P b 0.001). Multiple regression analysis showed that LF/HF ratio was an independent determinant of AF episodes. Conclusions: This study originally showed a strong relationship between autonomic dysfunction and silent atrial fibrillation in type 2 diabetes. © 2014 Elsevier Inc. All rights reserved. The risk of atrial fibrillation is increased by 40% in diabetic people (Kannel et al., 1998). Notably, for men and women, respectively, diabetes mellitus (DM) conferred a 1.4- and 1.6-fold AF risk after adjusting for other associated conditions (Kannel et al., 1998). The role of the autonomic nervous system in the genesis and/or in the maintenance of atrial fibrillation (AF) has been clinically recognized for many years (Coumel, 1990). In this context, previous studies pointed out on abnormalities of the autonomic nervous system as an important mechanism in initiation and maintenance of atrial fibrillation (Bettoni & Zimmermann, 2002; Gami, Hodge, Herges, et al., 2007). Careful attention should be paid to the changes of heart rate that occur in the minutes prior to the paroxysmal attacks of AF, and the trend of acceleration or slowing of cardiac frequency observed in ECG Holter tracings provides reliable indications of the state of the vago-sympathetic balance in these patients (Coumel, 1990). The diabetic autonomic neuropathy (DAN) is a frequent complication in DM with a reported prevalence of 46% in DM diagnosed less than 5 years ago and up to 70% with N 20 years of diabetes (Bissinger et al., 2011). DAN has a significant negative impact on the cardiovascular system. Typical findings in DAN include cardiac arrhythmias, cardiovascular instability, exercise intolerance and also higher mortality among diabetic patients (Nichols, Reinier, Chugh, et al., 2009). Unfortunately, there are few data about the occurrence of paroxysmal atrial fibrillation (PAF) in the population with DAN. Recently, a study showed that the occurrence of DAN caused a significant increase in P-wave duration and dispersion, which might be responsible for more frequent development of AF (Vinik et al., 2003). These findings were strongly limited because the analysis was performed only on ECG-proven episodes of AF; therefore, the number of AF episodes could certainly be underestimated, especially as PAF episodes were mainly asymptomatic. Actually, diabetic patients frequently have asymptomatic (e.g., silent) AF (Chen et al., 2001), Journal of Diabetes and Its Complications xxx (2014) xxx–xxx Conflict of interest: All authors do not have any financial associations that might pose a conflict of interest in connection with the submitted article. ⁎ Corresponding author at: Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Italy, Piazza Miraglia, 2, 80138 Naples, Italy. Tel.: +39 081 5665110; fax: +39 081 5665303. E-mail address: raffaele.marfella@unina2.it (R. Marfella). http://dx.doi.org/10.1016/j.jdiacomp.2014.09.002 1056-8727/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Journal of Diabetes and Its Complications journal homepage: WWW.JDCJOURNAL.COM Please cite this article as: Rizzo, M.R., et al., Autonomic dysfunction is associated with brief episodes of atrial fibrillation in type 2 diabetes, Journal of Diabetes and Its Complications (2014), http://dx.doi.org/10.1016/j.jdiacomp.2014.09.002