Novel F-18-labeled Tracers of Sympathetic Function for Improved Risk Stratification and Clinical Outcomes

This review summarizes the role of the novel ¹⁸F-labeled positron emission tomography (PET) sympathetic radiotracers for risk stratification in patients with ischemic heart disease. PET tracers have demonstrated prognostic value by characterizing myocardial sympathetic nerve density and by extension the extent of myocardial sympathetic denervation. The unique features of these PET radiotracers are discussed in relation to clinical application.

Absolute quantification of sympathetic denervation has been possible with ¹⁸F-labeled PET tracers which outperform low ejection fraction (<35%) in predicting sudden cardiac death (SCD) and allow for more optimal risk stratification in patients with heart failure. This underscores their utility in selecting patients for preventable strategies with implantable cardioverter defibrillators (ICD). Appropriate candidate selection for ICD placement is a major priority as at present 80% of patients that die from SCD do not receive an ICD (potentially preventable mortality) while only 1 in 8 patients with an ICD receive a life-saving shock. Furthermore, 1 in 3 patients with ICDs receive inappropriate shocks. Thus, there is a pressing need to more appropriately select and exclude patients who will and will not benefit from ICD placement, respectively, as both suffer poor outcomes. Despite the clear prognostic benefit offered by prior PET sympathetic radiotracers in imaging myocardial sympathetic denervation, their short half-lives necessitated costly onsite cyclotron synthesis obviating their pragmatic clinical use. ¹⁸F-labeled radiotracers have a longer half-life allowing centralized synthesis and transport to their point of use. As such, ¹⁸F-labeled sympathetic radiotracers define an innovation and may offer a more affordable and clinically practical approach for evaluation of risk in patients with cardiovascular disease. ¹⁸F-labeled sympathetic radiotracers are currently available for evaluation and risk stratification of patients with ischemic heart disease and heart failure. These radiotracers may offer a more practical approach for selection of ICD placement and consequent prevention of SCD; a major, yet unmet need, in heart failure patients and those that suffer SCD at large. However, further development and clinical testing of these ¹⁸F-labeled sympathetic radiotracers is required.