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. 2024 May 13;45(18):1613-1630.
doi: 10.1093/eurheartj/ehae162.

Imaging of the brain-heart axis: prognostic value in a European setting

Nidaa Mikail  1   2 , Dominik F Sager  1   2 , Pimrapat Gebert  1   2   3 , Achi Haider  1   2   4 , Atanas Todorov  1   2 , Susan Bengs  1   2 , Noemi Sablonier  1   2 , Isabelle Glarner  1   2 , Adriana Vinzens  1   2 , Nastaran Sang Bastian  1   2 , Gioia Epprecht  1   2 , Claudia Sütsch  1   2 , Alessia Delcò  1   2 , Michael Fiechter  1   2   5 , Angela Portmann  1   2 , Valerie Treyer  1 , Susanne Wegener  6 , Christoph Gräni  7 , Aju Pazhenkottil  1 , Caroline E Gebhard  8 , Vera Regitz-Zagrosek  9   10 , Felix C Tanner  11 , Philipp A Kaufmann  1 , Ronny R Buechel  1 , Alexia Rossi  1   2 , Catherine Gebhard  1   2   7
Affiliations

Imaging of the brain-heart axis: prognostic value in a European setting

Nidaa Mikail et al. Eur Heart J. .

Abstract

Background and aims: Increasing data suggest that stress-related neural activity (SNA) is associated with subsequent major adverse cardiovascular events (MACE) and may represent a therapeutic target. Current evidence is exclusively based on populations from the U.S. and Asia where limited information about cardiovascular disease risk was available. This study sought to investigate whether SNA imaging has clinical value in a well-characterized cohort of cardiovascular patients in Europe.

Methods: In this single-centre study, a total of 963 patients (mean age 58.4 ± 16.1 years, 40.7% female) with known cardiovascular status, ranging from 'at-risk' to manifest disease, and without active cancer underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography between 1 January 2005 and 31 August 2019. Stress-related neural activity was assessed with validated methods and relations between SNA and MACE (non-fatal stroke, non-fatal myocardial infarction, coronary revascularization, and cardiovascular death) or all-cause mortality by time-to-event analysis.

Results: Over a maximum follow-up of 17 years, 118 individuals (12.3%) experienced MACE, and 270 (28.0%) died. In univariate analyses, SNA significantly correlated with an increased risk of MACE (sub-distribution hazard ratio 1.52, 95% CI 1.05-2.19; P = .026) or death (hazard ratio 2.49, 95% CI 1.96-3.17; P < .001). In multivariable analyses, the association between SNA imaging and MACE was lost when details of the cardiovascular status were added to the models. Conversely, the relationship between SNA imaging and all-cause mortality persisted after multivariable adjustments.

Conclusions: In a European patient cohort where cardiovascular status is known, SNA imaging is a robust and independent predictor of all-cause mortality, but its prognostic value for MACE is less evident. Further studies should define specific patient populations that might profit from SNA imaging.

Keywords: 18F-FDG-PET/CT; Amygdala; Haematopoietic tissue activity; MACE; Mortality; Psychological stress; Stress-related neural activity; Ventromedial prefrontal cortex.

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Figures

Structured Graphical Abstract
Structured Graphical Abstract
In a well-characterized European population (Switzerland) including patients with known comorbidities, SNA imaging is a predictor of MACE and all-cause mortality. However, after adjusting for baseline characteristics, the association between SNA imaging and MACE is lost, and SNA only remains a strong and independent predictor of all-cause mortality. 18F-FDG-PET, 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography; BMI, body mass index; CVRF, cardiovascular risk factor; HR, hazard ratio; lAmygA, left amygdala activity; MACE, major adverse cardiovascular events; SHR, sub-distribution hazard ratio; SNA, stress-related neural activity; vmPFC, ventromedial prefrontal cortex.
Figure 1
Figure 1
Flowchart depicting patient recruitment and exclusion. 18F-FDG-PET, 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography; MACE, major adverse cardiovascular events
Figure 2
Figure 2
Analysis of SNA (AmygA/vmPFC) vs. study outcomes based on bilateral, right, and left amygdala activities, for (A) MACE, and (B) all-cause mortality. MACE, major adverse cardiovascular events; SNA, stress-related neural activity; vmPFC, ventromedial prefrontal cortex
Figure 3
Figure 3
Unadjusted cumulative incidences of (A) MACE, and cumulative hazard of (B) all-cause mortality. 18F-FDG-PET, 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography; HR, hazard ratio; lAmygA, left amygdala activity; MACE, major adverse cardiovascular events; SHR, sub-distribution hazard ratio; SNA, stress-related neural activity; vmPFC, ventromedial prefrontal cortex
Figure 4
Figure 4
Multivariate analysis adjusted for baseline clinical characteristics, laboratory measures, and cardiac imaging findings, for (A) MACE, and (B) all-cause mortality. BMI, body mass index; CVRF, cardiovascular risk factor; HR, hazard ratio; MACE, major adverse cardiovascular events; SHR, sub-distribution hazard ratio
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