The potential for PET-guided revascularization of coronary artery disease

Abstract

Over the past two decades, positron emission tomography (PET) has been very useful for the diagnosis and staging of various cancers and successful for guiding therapy [1]. A striking illustration is the use of F-fluorodeoxyglucose (FDG) PET to guide chemotherapy in patients with lymphoma. For example, in patients with limited-stage Hodgkin’s lymphoma, FDG PET can be performed after two cycles of chemotherapy to establish disease activity. Persistent disease on PET will trigger a change in chemotherapeutic agents and higher radiation therapy doses, while a negative PET study will result in shorter therapy and lower radiation therapy doses with better patient outcomes [2, 3]. This is one of many effective PET-guided interventions in oncology. In contrast, demonstration of the effectiveness of PET-guided therapy for cardiovascular applications has been more challenging. For example, the PARR-2 trial [4] was a randomized controlled trial designed to evaluate the role of myocardial viability assessment with FDG PET to guide revascularization in patients with severe left ventricular dysfunction. Although the study concept was supported by much clinical evidence and rooted in strong physiology, it failed to demonstrate a significant benefit for the PET-guided management versus standard care. Interestingly, a single-site post hoc analysis showed that the adverse outcome rate was significantly lower when revascularization was concordant with the PET recommendation, compared to revascularization discordant with the PET recommendation [5]. These better outcomes with concordant PET and revascularization may reflect optimal patient management in centers with integrated imaging, heart failure and surgical teams and clinical management teams, a factor which was not accounted for in the original trial. Similarly, other clinical factors may influence the decision for a specific therapy more than the PET result and lead to discordant PET revascularization decisions. Thus, implementation of a robust prospective clinical trial to determine the efficacy of cardiac PET-guided therapy may be particularly difficult. PET myocardial perfusion imaging (MPI) has been repeatedly shown to be accurate for the detection and risk stratification of obstructive coronary artery disease (CAD) [6]. In addition, PET MPI allows accurate quantification of global and regional myocardial blood flow (MBF) [7] and has improved risk stratification in ischemic and non-ischemic cardiomyopathy [8–14], facilitated assessment of the coronary response to various interventions [15, 16], and improved detection of balanced ischemia [17]. Decision making for revascularization in stable CAD has been guided for many years by the presence of ischemia shown by reversible perfusion defects on MPI. The concept that patients with large areas of ischemia (>10% to 15% of the left ventricle) have better outcomes with revascularization than with medical therapy is well accepted and is based on large observational SPECT studies [18, 19]. However, more recent large randomized controlled trials, such as COURAGE and STICH, failed to show a benefit of revascularization over medical therapy [20, 21]. On the other hand, the FAME and FAME-II trials demonstrated that revascularization guided by fractional flow reserve (FFR) significantly improves patient outcomes [22, 23]. Thus, revascularization based solely on anatomic angiographic stenosis and not physiologic flow impairment may have suboptimal outcomes and explain in part the disappointing results of the COURAGE and STICH trials. Since PET can quantify regional MBF, PET may be useful for guiding the selection of patients for revascularization and specific vessels for grafting. In this issue of the European Journal of Nuclear Medicine and Molecular Imaging, Bober et al. [24] report a study of the * Terrence D. Ruddy [email protected]