Pathophysiological basis of myocardial innervation imaging in heart failure

Sympathetic nervous system dysfunction plays an acknowledged pathogenic role in several pathophysiological processes, including arrhythmias, dilated and hypertrophic cardiomyopathies, post-infarction remodeling, and congestive heart failure (HF). Selective cardiac adrenergic activation precedes the systemic adrenergic hyperactivity and predicts the progression of asymptomatic left ventricular dysfunction toward HF. The development of both pre- and postsynaptic radiotracers permitted the non-invasive assessment of sympathetic hyperactivity in HF, allowing to measure therapy effectiveness and clinical outcome. On the other hand, PET technology extended this evaluation to the characterization of the pathophysiological role of muscarinic receptor in the failing heart, becoming a potential tool to evaluate the risk of sudden cardiac death. The aim of the present narrative review is to update the reported evidence on the alterations of myocardial autonomic innervation underlying HF progression and its complications, focusing on their potential application on the development of new tracers for radionuclide imaging technologies.