https://orcid.org/0000-0001-9847-5917
This editorial refers to ‘Stress-associated neurobiological activity is linked with acute plaque instability via enhanced macrophage activity: a prospective serial 18F-FDG-PET/CT imaging assessment’†, by J.W. Kim et al., on page .
In a single scan, multisystem 18F-FDG-PET imaging allows simultaneous interrogation of vascular inflammation, psychological stress, and bone marrow activation following myocardial infarction. Moderate associations are observed between 18F-FDG activity in these disparate organ systems; however, further work is now required to assess the causality and directionality or these associations. Several potential pathways that might exist in isolation or in combination to explain these associations are outlined
Molecular cardiovascular positron emission tomography (PET) imaging is a rapidly developing and exciting field. Modern scanners and image processing techniques now allow the non-invasive assessment of disease activity in the cardiovascular system, providing complementary information to the anatomic and functional information provided by computed tomography (CT), cardiovascular magnetic resonance (CMR), and echocardiography. In principle, the activity of any biological process can be targeted. Indeed, a wide range of tracers have recently become available in humans, allowing assessment of inflammation, calcification, fibrosis, and platelet activity.1 , 2 This has major potential to improve our pathological understanding of disease but also to impact clinical care: molecular PET imaging now plays a central role in the clinical assessment of patients with cardiac sarcoidosis, prosthetic valve endocarditis, and cardiac device infection.
For many years [18F]fluorodeoxyglucose (18F-FDG) was the predominant, indeed the only, molecular tracer in this field. A glucose analogue, 18F-FDG accumulates in cells and tissues according to their glycolytic requirements. Uptake in cancer cells is high, underlying its widespread use in oncology imaging. In the cardiovascular system 18F-FDG has been used as a marker of inflammation, on the basis that inflammatory cells use more glucose than surrounding cells. However, glucose is also the preferred energy source for the myocardium, which frequently obscures pathological 18F-FDG uptake in the heart, leading many investigators to seek more specific inflammatory tracers.
In the manuscript by Kim et al. published in this issue of the European Heart Journal, the authors have elegantly harnessed 18F-FDG’s low specificity to their advantage, turning this apparent weakness into a strength.3 Indeed, on a single scan and with a single tracer, the authors were able to simultaneously assess carotid artery inflammation, amygdala activity in the brain (as a marker of emotional stress), and haemopoietic activity in the bone marrow, providing key insights into the concordant activity of these disparate organ systems following acute myocardial infarction (MI). This builds on the pioneering work by Ahmed Tawakol’s lab that first used this multisystem PET imaging approach in patients with stable coronary artery disease and proposed a pathway of emotional stress causing increased haemopoietic activity, the release of macrophages, and increased plaque inflammation.4
Kim et al. performed 18F-FDG-PET/CT imaging in 45 patients within 45 days of their myocardial infarct, alongside 17 control patients of similar age. 18F-FDG activity was higher in acute MI patients than controls in the amygdala, bone marrow, and carotid artery, and these correlated moderately with each other (r values between 0.35 and 0.47). Ten MI patients were rescanned after 6 months when 18F-FDG levels in each organ system had returned to baseline and the levels observed in controls. The study therefore demonstrates the concordant up-regulation of glucose utilization across these organ systems following MI and their concurrent return to baseline with time. It therefore adds to our growing appreciation of the complex interdependence of the cardiovascular system with the rest of the body and the growing need to investigate cardiac disorders in that wider context. The authors conclude that their results suggest psychological stress is linked to plaque instability via macrophage activation and that this pathway could be the targeted to prevent MI. This is possible; however, this observational study cannot inform us as to the direction of the associations observed nor establish causality. Indeed, it would seem equally plausible that myocardial inflammation induces psychological stress, and haemopoeitic activity leading to the observation of increased plaque inflammation (Graphical abstract). A similar pathway has been established in mouse models5 and fits better with the delayed time points at which the initial 18F-FDG-PET scans were performed following MI. This classic chicken and egg conundrum is in truth difficult to disentangle. Ideally it would require 18F-FDG-PET scans performed both before and after MI, a highly challenging task given the unpredictable nature of plaque rupture events.6 One potential method would be to image patients before and after the predictable iatrogenic MI induced by alcohol septal ablation performed in patients with hypertrophic cardiomyopathy. Studies to this effect are currently underway.
The study by Kim et al. has other limitations including the small sample size and relatively long delay between infarction and imaging, during which the anti-inflammatory effects of drugs such as statins may have had an effect. Moreover, the study did not investigate cardiac inflammation at the site of infarction, which may have provided additional insights as to the direction of the observed associations. Nevertheless, this study underlines the potential value of multisystem 18F-FDG-PET imaging as a method for interrogating the association of atherosclerotic inflammation with activity in other organ systems. Future studies should aim to elucidate the directionality of these associations and test the hypothesis that reductions in psychological stress may aid in the recovery from MI and in the prevention of future and recurrent cardiac events.
Conflict of interest: none declared.
The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
Footnotes
† doi:10.1093/eurheartj/ehaa1095.
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