Complementary Role of Combined Indirect and Direct Cardiac Sympathetic (Hyper)Activity Assessment in Patients with Heart Failure by Spectral Analysis of Heart Rate Variability and Nuclear Imaging: Possible Application in the Evaluation of Exercise Training Effects

Abstract

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training.

Keywords: MIBG; cardiac autonomic regulation; exercise training; heart failure; heart rate variability.

Figure 1

Dose–response relationship between weekly TRIMPi and autonomic cardiovascular parameters during aerobic continuous training (left panel) and aerobic interval training (right panel). * p < 0.05 versus pretraining baseline values. ACT: aerobic continuous training. AIT: aerobic interval training. HRV: heart rate variability. BRS: baroreflex sensitivity. Reproduced with permission from Iellamo et al. [35].

Figure 2

123I-metaiodobenzylguanidine (123I-MIBG) cardiac scintigraphy (planar images at 4 h) in a patient with heart failure ((a), absent myocardial uptake of the radiopharmaceutical) and in a healthy patient ((b), normal myocardial uptake of the tracer).

Figure 3

123I-meta-iodobenzylguanidine (123I-MIBG) single-photon emission computed tomography (SPECT) in a patient with previous myocardial infarction of the apex, with involvement of the anterior and the posterior wall (absent uptake of the radiopharmaceutical in these sites).