Neuro-cardiac imaging has a proven value in patient management: Con

The sympathetic nervous system (SNS) is important in cardiac pathophysiology. By increasing heart rate and arterial blood pressure, the SNS plays a central role to adapt cardiac performance to conditions of increased external needs. Accordingly, a sympathetic surge instantaneously ameliorates left ventricular (LV) contractility and relaxation, abruptly increasing cardiac working capacities. However, while an elevated sympathetic tone may be beneficial in the short term, a chronic elevation of SNS activity, as in the case of congestive heart failure (CHF), has been clearly associated with a significantly higher rate of adverse events. Accordingly, an accurate evaluation of cardiac SNS activity has become a sine qua non in modern clinical cardiology. However, most of the techniques for the assessment of cardiac sympathetic tone (i.e., baroreflex sensitivity) offer an indirect estimation of its level of activation. Nuclear cardiac imaging has been considered the reference standard for the evaluation of cardiac innervation, allowing the evaluation of SNS activity in (semi)-quantitative terms. Therefore, in the last decades, both positron emission tomography (PET) and conventional nuclear imaging techniques [either planar scintigraphy or single-photon emission computed tomography (SPECT)] have been demonstrated to allow the characterization of cardiac sympathetic innervation. On one hand, PET imaging, with its higher image resolution, radiotracers’ versatility, and intrinsically quantitative nature, is widely considered the quality standard of cardiac SNS evaluation. On the other hand, conventional nuclear imaging, with its robustness, availability, and relatively limited operational costs, still represents the most frequently performed imaging test for cardiac innervation imaging. More specifically, despite the theoretical advantages of more refined techniques (i.e., PET and SPECT), planar scintigraphy with I-metaiodobenzylguanidine (I-MIBG) remains the workhorse of innervation imaging. Consequently, after almost 30 years from their introduction in the research arena, the two measures of cardiac sympathetic tone derived at planar scintigraphy, namely the heart-to-mediastinum (H/M) ratio and the washout rate of I-MIBG, still represent the most validated measures of LV innervation that are available, with the H/M ratio as reference standard. So, a depressed H/M ratio of I-MIBG has been shown to associate with a significantly worse prognosis, independently of LV ejection fraction. Moreover, in those years, a plethora of small-numbered studies have demonstrated the association between abnormal H/M values and various measures of LV structural and functional impairment, almost translating it as a universal marker of cardiac risk. Nevertheless, despite these apparently promising results, cardiac innervation imaging has a minimal, if any, clinical role in western countries, with currently no indications in major clinical guidelines, except for Japan. In order to understand this, some of the most evident limitations of cardiac I-MIBG imaging should be carefully considered.