Autonomic nervous system dysfunction in advanced systolic heart failure

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Abstract

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 < 35% who were on the waiting list for heart transplantation. We assessed the SNS by determining cardiac uptake of 123I 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.

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 innervation 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 metaiodobenzylguanidine 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 hyperactivation 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.

The aim of this study was to assess, compare and relate the impairment of both autonomic nervous systems in a group of stable patients with advanced HF.

Section snippets

Patients

From January 1st, 2008 to July 31st, 2009, 36 consecutive patients diagnosed with advanced HF due to systolic dysfunction (ejection fraction < 35%) and enrolled on the waiting list for heart transplantation were recruited. Functional status was NYHA class III–IV and IV.

All patients in stable condition underwent myocardial scintigraphy to determine 123I-MIBG uptake and a 24-hour Holter ECG recording to assess the SNS and PNS. The time interval between tests was less than 15 days in all cases. None

Results

The clinical profile of the patients analyzed is shown in Table 1. Etiological diagnosis of the cause leading to HF was confirmed histologically in all cases. We only found two significant differences between the groups according to etiology. Hypertension was more frequent among ischemic patients than in the group with idiopatic dilated myocardiopathy (IDMC) and the group with “other etiologies” (77.8% vs. 16.7% vs. 39.1%; p = 0.01). The body mass index (BMI) was significantly lower in the group

Discussion

Currently, there is evidence that the autonomic nervous system is altered in a large number of diseases, among which the most important are diabetes and Parkinson-type neurological disorders. Although this alteration is generally of minor importance within the context of these diseases, its demonstration can be of interest when performing early differential diagnosis with other disorders or as evidence of a systemic inflammatory state [7], [8].

In HF, an alteration occurs in both the sympathetic

Acknowledgement

The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology [28].

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