Clinical trial NCT04853511: Comprehensive Assessment of Interconnection Between Brain Emotional Activity and Coronary Plaque Instability
Official title: Biological Interconnection Between Stress-associated Neurobiological Activity and Atherosclerotic Plaque Instability: A Prospective Cohort Study With OCT-FLIM Dual-modal Intravascular Imaging and Serial 18F-FDG-PET/CT Assessment
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Atherosclerosis, Coronary
Emotional Stress
Inflammation
Hematopoiesis
Atherosclerosis Coronary Artery With Angina Pectoris
Atheroma; Heart
Atherosclerosis
Acute Coronary Syndrome
Keywords: PET-CT
Fluorescence lifetime imaging
Optical coherence tomography
High-risk plaque
Amygdalar activity
Arterial Inflammation
Hematopoietic activity
Biochemical imaging
Lead sponsor: Korea University Guro Hospital
Sponsor class: OTHER
First posted: 2021-04-21
Enrollment: 200
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects are planned to undergo percutaneous coronary intervention with utilization of OCT-FLIM dual modal intravascular imaging for culprit plaque assessment and stent optimization. After PCI, subjects will undergo serial 18F-FDG-PET/CT molecular imaging at baseline and 6-month follow-up.

Brief summary: Emotional stress is associated with future cardiovascular events. However, the biological interconnection between brain emotional neural activity and acute plaque instability is not fully understood. Optical coherence tomography-Fluorescence Lifetime (OCT-FLIM) dual modal intravascular imaging is a novel technique that enables comprehensive assessment of structural and biochemical characteristics of coronary atheroma and estimates the level of plaque instability. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) enables simultaneous estimation of multi-system activities including emotional stress, arterial inflammation, and hematopoiesis. The present study aims to prospectively investigate mechanistic linkage between coronary plaque instability, stress-associated neurobiological activity, and macrophage hematopoiesis using OCT-FLIM and 18F-FDG PET/CT imaging assessment.

Detailed description: Thirty two patients with multivessel coronary artery disease (including both stable angina and acute coronary syndrome), who have at least one severe obstructive lesion (\>70% diameter stenosis) that is considered suitable for percutaneous coronary intervention (PCI), will be included in the study.

Structural/biochemical characteristics of coronary culprit plaque (with or without mild to moderate stenotic non-culprit plaque) will be assessed comprehensively using OCT-FLIM dual modal intravascular imaging.

After coronary revascularization with PCI, subjects will undergo serial 18F-FDG-PET/CT molecular imaging at baseline admission and 6-month follow-up to measure PET signal activities at target tissues including amygdala, carotid artery, aorta, bone marrow, and spleen.

Correlation between OCT-FLIM parameters and baseline PET signals will be assessed to provide insight into the mechanistic linkage between multi-system metabolic activities and coronary plaque instability. Serial PET/CT imaging after 6 month will enable estimation of natural course of multi-system PET signal activities according to different levels of coronary plaque instability.

Eligibility criteria: Inclusion Criteria:

* Age: greater than 20, less than 75
* Patients with severe coronary atherosclerosis (diameter stenosis \>70%) requiring coronary revascularization
* Reference vessel diameter: between 2.5 and 4.0 mm
* Obtained informed consent from voluntary participants before study enrollment

Exclusion Criteria:

* Complex coronary lesion (ostial lesion, unprotected left main lesion, chronic total occlusion, grafted vessels, etc)
* Reference vessel diameter: less than 2.5 mm, greater than 4.0 mm
* Coronary lesion with heavy calcification
* Hemodynamic instability during coronary intervention
* Contraindication to antithrombotic therapy
* Chronic renal insufficiency (Serum creatinine \>2.0mg/dL)
* Severe liver dysfunction (aspartate transaminase or alanine transferase \> 5 times of upper normal limit)
* Pregnancy or potential pregnancy
* Life expectancy less than 1 year
* Patient refused to sign the informed consent at enrollment

Primary outcomes:
measure: Baseline amygdalar activity (Stress-associated neurobiological activity)
timeFrame: Baseline (within index admission)
Secondary outcomes:
measure: Baseline carotid inflammation (arterial atherosclerotic inflammation)
timeFrame: Baseline (within index admission)
measure: Baseline aortic inflammation (arterial atherosclerotic inflammation)
timeFrame: Baseline (within index admission)
measure: Baseline bone marrow hematopoiesis (hematopoietic activity)
timeFrame: Baseline (within index admission)
measure: Baseline splenic hematopoiesis (hematopoietic activity)
timeFrame: Baseline (within index admission)
measure: Coronary plaque composition estimated by OCT-FLIM
timeFrame: Baseline (day 1)
Other outcomes:
measure: Follow-up amygdalar activity (Stress-associated neurobiological activity)
timeFrame: 6-month follow-up
measure: Follow-up carotid inflammation (arterial atherosclerotic inflammation)
timeFrame: 6-month follow-up
measure: Follow-up aortic inflammation (arterial atherosclerotic inflammation)
timeFrame: 6-month follow-up
measure: Follow-up bone marrow hematopoiesis (hematopoietic activity)
timeFrame: 6-month follow-up
measure: Follow-up splenic hematopoiesis (hematopoietic activity)
timeFrame: 6-month follow-up
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: Korea University Guro Hospital
name: Jin Won Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Guro Hospital
name: Dong Oh Kang, MD, PhD
role: STUDY_DIRECTOR
affiliation: Korea University
name: Sun Won Kim, MD, PhD
role: STUDY_DIRECTOR
affiliation: Korea Advanced Institute of Science and Technology
name: Hongki Yoo, PhD
role: STUDY_DIRECTOR
References:
citation: Tawakol A, Ishai A, Takx RA, Figueroa AL, Ali A, Kaiser Y, Truong QA, Solomon CJ, Calcagno C, Mani V, Tang CY, Mulder WJ, Murrough JW, Hoffmann U, Nahrendorf M, Shin LM, Fayad ZA, Pitman RK. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017 Feb 25;389(10071):834-845. doi: 10.1016/S0140-6736(16)31714-7. Epub 2017 Jan 12.
citation: Lee MW, Song JW, Kang WJ, Nam HS, Kim TS, Kim S, Oh WY, Kim JW, Yoo H. Comprehensive intravascular imaging of atherosclerotic plaque in vivo using optical coherence tomography and fluorescence lifetime imaging. Sci Rep. 2018 Sep 28;8(1):14561. doi: 10.1038/s41598-018-32951-9.
citation: Kim S, Yoo H, Kim JW. Long Journey of Intravascular Imaging: What and How to Look at the Atheroma in Coronary Artery. JACC Cardiovasc Imaging. 2021 Sep;14(9):1843-1845. doi: 10.1016/j.jcmg.2020.11.015. Epub 2020 Dec 16. No abstract available.