Cardiac innervation imaging: implications for risk stratification and therapeutic decision-making

Abstract

Neurocardiology, the specialty that deals with the interaction between brain, heart, and autonomic nervous system, is a vivid area of research. It is well known that a lifethreatening stressor may induce a generalized autonomic storm, with both sympathetic and parasympathetic effects and the apparent predominance of one over the other depends on the variables considered, the timing of the observations and, probably, the type of the stressor. Moreover, remodeling of the cardiac nervous system influences the course of several cardiac diseases. As an example, cholinergic transdifferentiation of cardiac adrenergic neurons into cholinergic neurons, induced by leukemia inhibitory factor via a gp130 signaling pathway, supports the existence of potential plasticity of sympathetic neurons in heart failure (HF). The translational relevance of cardiac and extracardiac neural remodeling is under investigation and at this time many studies have demonstrated the value of autonomic indices to identify patients at risk for sudden death [1]. Relevant aspects of cardiac innervations, including preand postsynaptic receptors of the autonomic nervous system, are now investigated either by single-photon emission computed tomography (SPECT) and positron emission tomography (PET). In the setting of HF, the prognostic relevance of cardiac neuronal imaging is under active evaluation. Several studies have indicated worse prognosis and higher risk of sudden death in patients with HF and reduced I-metaiodobenzylguanidine (MIBG) myocardial uptake or higher washout rate. Although dichotomizing the late H/M ratio may be useful for stratifying patients into high-and low-risk categories, the patient survival rate decreases linearly accordingly to the impairment in cardiac MIBG activity. Moreover, the endpoint selection may influence the results observed in the setting of HF prognostication [2]. These challenges have slowed the wider clinical use of cardiac MIBG imaging, and the great potential of adrenergic system imaging still needs to be investigated in larger prospective studies before this technique can be implemented in clinical guidelines [3]. As an example, the importance of non-sudden cardiac death risk in predicting benefit from implantable cardioverter defibrillators (ICD) therapy must be considered. Due to the high cost of widespread ICD use, it is mandatory to identify a high-risk population who will benefit most from these devices. A number of non-left ventricular ejection fraction risk stratification tests for predicting a variety of outcomes (overall mortality, arrhythmic events/mortality, ICD shocks, and mortality benefit from ICD) are under evaluation. These tests include signal-averaged electrocardiogram, microvolt T wave alternans, electrophysiological testing, serum markers (including brain natriuretic peptide), and autonomic function evaluation (including heart rate variability, baroreflex sensitivity, heart rate turbulence, and deceleration capacity of heart rate). However, these tests have not demonstrated sufficiently high predictive value for arrhythmic death or arrhythmic events. Thus, it has been hypothesized that cardiac radionuclide imaging may be useful for identifying patients at risk for sudden cardiac death, therefore potentially offering a way to better select patients for ICD therapy. In patients with previous myocardial infarction, assessing the presence of an innervation/perfusion mismatch, i.e., a peri-infarction zone of sympathetic denervation that extends beyond the area of myocardial scar, as well as the presence of regional & M. Petretta petretta@unina.it