Brain-heart Interaction in Coronary Plaque Stability and Cardiovascular Events (Blueprint)

Biological Interconnection of Brain Neurobiological Activity With Atherosclerotic Plaque Vulnerability and the Prognostic Value

The effect of brain-heart interaction remains unclear. The study aims to investigate the biological interconnection between brain neural activity and coronary plaque morphological and inflammatory features, as well as their connection with clinical outcomes.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Diagnostic test: CCTA and 18F-FDG-PET/CT

Detailed Description

Brain neural activity assessed by resting amygdalar activity (AmygA) can predict cardiovascular events. However, its biological interconnection with plaque vulnerability i is not fully understood. Coronary computed tomographic angiography (CCTA) is a non-invasive technique that enables comprehensive assessment of morphological characteristics of coronary atheroma and estimates the level of plaque instability. Recently, perivascular fat attenuation index (FAI) enables assessment of coronary inflammation by analyzing changes of perivascular adipose tissue attenuation in CCTA.

18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) enables simultaneous estimation of multi-system activities including brain neural activity and hematopoiesis.

The present study aims to use ¹⁸F-FDG PET/CT to assess the AmygA, and to investigate its association with CCTA assessed plaque morphological and inflammatory features as well as their ability in predicting future cardiovascular disease events.

• Study Type: Observational
• Enrollment (Anticipated): 300

Contacts and Locations

Study Locations

• China
  • Beijing, China, 200000
    • Recruiting
    • Fuwai Hospital
    • Contact: LEI WANG
  • Shanghai, China, 200032
    • Recruiting
    • Shanghai Zhongshan Hospital
  • Shanghai, China
    • Recruiting
    • Shanghai Tenth People's Hospital
    • Contact: Haidong Cai
  • Shanghai, China
    • Recruiting
    • Universal Medical Imaging Diagnostic
    • Contact: Lu Sun

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who underwent clinically indicated 18F-FDG PET/CT and with CCTA performed within 90 days of 18F-FDG PET/CT scan will be included.

Description

Inclusion Criteria:

• 1) Age: greater than 20
• 2) Patients either absence of prior cancer or remission from cancer for at least 1 year prior to imaging and throughout the follow-up period;
• 3) Patients absence of acute or chronic inflammatory or autoimmune disease at the time of imaging;
• 4) Patients with CCTA performed within 90 days of 18F-FDG PET/CT scan as part of routine clinical practice
• 5) Patients with diameter stenosis >30% by CCTA but without coronary revascularization

Exclusion Criteria:

• 1) Complex coronary lesion (ostial lesion, unprotected left main lesion, chronic total occlusion, grafted vessels, etc)
• 2) Coronary lesion with heavy calcification
• 3) Chronic renal insufficiency (Serum creatinine >2.0mg/dL)
• 4) Severe liver dysfunction (aspartate transaminase or alanine transferase > 5 times of upper normal limit)
• 5) Pregnancy or potential pregnancy
• 6) Life expectancy less than 5 year

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CCTA imaging with 18F-FDG-PET/CT assessment; Group of patients with 18F-FDG-PET/CT imaging and Coronary Computed Tomographic Angiography within 90 days	Diagnostic test: CCTA and 18F-FDG-PET/CT; 18F-FDG-PET/CT imaging and comprehensive assessment of coronary plaque with CCTA within 90 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between amygdalar activity (neurobiological activity) and bone marrow hematopoiesis (hematopoietic activity)	Amygdalar target-to-background ratio (TBR) = Amygdalar standardized uptake value (SUV) / Temporal lobe SUV Bone marrow TBR = Bone marrow SUV / Jugular vein SUV Correlation between amygdalar activity (neurobiological activity) and bone marrow hematopoiesis (hematopoietic activity) will be assessed	at the index imaging
Correlation Between amygdalar activity (neurobiological activity) and high-risk plaque	High-risk plaque features will be assessed by CCTA including positive remodeling (PR, defined as lesion diameter/reference diameter ≥1.1), low attenuation plaque (LAP, defined as a focal central area of plaque with an attenuation density of <30 Hounsfield Units), spotty calcification (SC, defined as focal calcification within the coronary artery wall <3mm in maximum diameter), and the "napkin ring" sign (defined as a central area of low attenuation plaque that had a peripheral rim of high attenuation). Correlation Between amygdalar activity and number of high-risk plaque features will be assessed.	at the index imaging
Correlation Between amygdalar activity (neurobiological activity) and coronary inflammation	Coronary inflammation will be assessed by FAI. Correlation Between amygdalar activity and FAI will be assessed	at the index imaging
Major adverse cardiac events	Death from coronary heart disease, nonfatal myocardial infarction or hospitalization for unstable angina.	5 years after index imaging

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular death, or nonfatal myocardial infarction	Cardiovascular death, or nonfatal myocardial infarction	5 years after index imaging

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Publications and helpful links

General Publications

• 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. Erratum In: Lancet. 2017 Feb 25;389(10071):804. Lancet. 2017 Feb 25;389(10071):804.
• Tawakol A, Osborne MT, Wang Y, Hammed B, Tung B, Patrich T, Oberfeld B, Ishai A, Shin LM, Nahrendorf M, Warner ET, Wasfy J, Fayad ZA, Koenen K, Ridker PM, Pitman RK, Armstrong KA. Stress-Associated Neurobiological Pathway Linking Socioeconomic Disparities to Cardiovascular Disease. J Am Coll Cardiol. 2019 Jul 2;73(25):3243-3255. doi: 10.1016/j.jacc.2019.04.042.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2015
• Primary Completion (ANTICIPATED): October 30, 2022
• Study Completion (ANTICIPATED): December 30, 2022

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 15, 2022
• First Posted (ACTUAL): September 19, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 19, 2022
• Last Update Submitted That Met QC Criteria: September 15, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: ZS-2022-9-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No