Autonomic nervous system dysfunction in advanced systolic heart failure Ignacio J. Sánchez-Lázaro a, ⁎, Óscar Cano-Pérez b , Cristina Ruiz-Llorca c , Luis Almenar-Bonet a , María José Sancho-Tello b , Luis Martínez-Dolz a , Antonio Navarro-Mateo c , Antonio Salvador Sanz a a Heart Failure and Transplantation Unit, Cardiology Department, Hospital Universitario La Fe, Valencia, Spain b Arrythmia's Unit, Cardiology Department, Hospital Universitario La Fe, Valencia, Spain c Nuclear Medicine Department, Hospital Universitario La Fe, Valencia, Spain abstract article info Article history: Received 12 January 2010 Received in revised form 14 May 2010 Accepted 2 July 2010 Available online 1 August 2010 Keywords: Heart failure Cardiac innervation Heart rate turbulence Background: An alteration of the autonomic nervous system has been described in heart failure (HF). The aim of this study was to assess, compare and relate the impairment of both arms of the autonomic nervous systems, the sympathetic and parasympathetic (SNS and PNS) in a same group of patients. Methods: We analyzed 23 patients with advanced HF (NYHA III–IV/IV and IV/IV) and EF b 35% who were on the waiting list for heart transplantation. We assessed the SNS by determining cardiac uptake of 123 I metaiodobenzylguanidine, and analyzed the heart mediastinum rate (HMR) and the myocardial washout rate (WR). The PNS was assessed by 24-hour Holter ECG recording and subsequent analyses of heart rate turbulence (HRT) in which turbulence onset (TO) and turbulence slope (TS) were determined. Results: In the study of the SNS, HMR values were1.32 ± 0.12, and WR 0.36 ± 0.1. Higher creatinine levels were associated with a lower WR (r =-0.604; p = 0.02). In the study of the SNP, TO was higher the lower the LVEF (r =-0.410; p = 0.052), and age was associated with a lower TS (r =-0.4; p = 0.059). In the study of the relationships between the SNS and PNS, HMR was correlated in a nearly significant manner with TO (r=-0.399; p=0.059) and WR with TS (r=-0.447; p = 0.033). Conclusions: In stable patients with advanced HF (NYHA III–IV and IV/IV), a significant and parallel impairment occurs in both arms of the autonomic nervous system. This could have prognostic implications and would help to prioritize patients on the waiting list for heart transplantation. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction It is currently thought that in heart failure (HF) there is a dysregulation and impairment of the autonomic nervous system. There are two arms of the nervous system that control the heart: the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS). Simultaneous assessment of dysregulation of both arms has not been yet analyzed, although this could have important implications in the prognosis of HF [1]. Norepinephrine is the primary neurotransmitter of the SNS, whose fibers arise from the cardiac plexus, which in turn originate from the cervical ganglia. Sympathetic innervation covers nearly all of the atria and ventricles. Acetylcholine is the primary main neurotransmitter of the PNS, which originates in the brain stem. From the brain stem, its fibers descend with the vagus nerve before separating and forming, together with the SNS, the cardiac plexus. Parasympathetic innerva- tion is centered above the sinus node and the AV node [2]. The interrelation between both systems is what determines the response of the myocardium to stimuli. In patients with congestive heart failure, activation of the adrenergic nerve system is one of the important physiologic responses elicited to compensate for depressed myocardial function. As heart failure progresses, circulating norepinephrine concentration is elevated and cardiac stores of norepinephrine are depleted and its uptake is decreased. A way to analyze the SNS is by studying the presynaptic nerve endings with false neurotransmitters such as metaiodobenzyl- guanidine labeled with 123iodine (123I-MIBG). MIBG is a physiologic norepinephrine analog that when labeled with Iodine 123 enables study of the distribution and density of the cardiac sympathetic nervous system. Decreased MIBG uptake is a consequence of chronic hyper- activation of the sympathetic system. A quite widespread method used to assess the SNP is heart rate turbulence (HRT), which analyzes the sensitivity of the reflex baroreceptors that form part of the PNS. Two parameters are normally used to quantify HRT: turbulence onset (TO) and turbulence slope (TS). Articles analyzing both arms of the autonomic nervous systems in HF patients have been published, but not the relationship between both arms in the same group of patients. International Journal of Cardiology 152 (2011) 83–87 ⁎ Corresponding author. Heart Failure and Transplantation Unit, Cardiology Department, 6-3th floor, Hospital Universitario La Fe, Avda, Campanar 21, 46009, Spain. Tel.: + 34 629821756; fax: +34961973314. E-mail address: ignaciosanchezlazaro@gmail.com (I.J. Sánchez-Lázaro). 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.07.010 Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard