Whole Blood Transcriptomic Signal According to Coronary Atherosclerotic Plaque Burden Assessed by CT Angiography

• Conditions: Calcific Coronary Arteriosclerosis; Coronary Stenosis; Coronary Plaque; Aortic Calcification; Atherosclerotic Plaque

• Registration Number: NCT06194526
• Lead Sponsor: MultiplAI Health Limited

Brief Summary

The present clinical study aims to identify transcriptomic patterns derived from whole blood samples related to coronary atherotic burden. Additionally, as a secondary analysis, the research team will explore the algorithm's ability to detect the presence of aortic disease and pro-inflammatory cardiometabolic alterations, such as hepatic steatosis and surrogate markers of coronary inflammation.

Detailed Description

This will be a prospective observational study. A convenience sample will be carried out to include 200 patients who attend the ENERI Medical Institute, La Sagrada Familia Clinic and Sanatorio Mendez with a clinical indication to be evaluated by a CCTA due to suspected CAD or known CAD. The study will have a baseline stage in which a clinical evaluation will be performed, blood samples will be drawn for transcriptome analysis and laboratory analysis. Then, a DNA sample obtained by swabbing the buccal mucose will be taken. Subsequently, the images obtained from the clinically indicated CCTA will be assessed to explore the outcomes of interest. At the end of patient enrollment, biological samples will be sequenced for in silico evaluation of the results. Finally, a 5-year follow-up will be carried out via telephone or email contact to collect data on the incidence of fatal and non-fatal cardiovascular events.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2023-09-19
• Study First Submitted: 2023-10-31
• Status Verified: 2024-01
• Study First Submitted QC: 2024-01-04
• Last Update Submitted: 2024-01-04
• Study First Posted: 2024-01-08
• Last Update Posted: 2024-01-08
• Primary Completion: 2024-08
• Study Completion: 2028-09

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Men and women between 18 and 75 years, with a clinical indication to be evaluated by a CCTA due to suspected or known CAD.
• Signature of informed consent.

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Exclusion Criteria

• Previously known chronic renal or hepatic insufficiency.
• Active chronic lung disease, defined as: exacerbated asthma, exacerbated COPD, or pulmonary fibrosis.
• Myocardial infarction, unstable angina, cerebrovascular accident, or vascular interventions (any territory) in the past 6 months.
• Implantation of drug-eluting stents in the last 12 months.
• Revascularization surgery (By-pass)
• Indication of Angio-CT for congenital heart disease or Transcatheter Aortic Valve Replacement (TAVI)
• Presence/ diagnosis of heart failure symptoms or signs (ie. dyspnea, asthenia, edema) with objective evidence of pulmonary or systemic congestion at rest or with exercise in the last 6 months.
• Left ventricular ejection fraction <50% confirmed by objective diagnostic methods (eg doppler echocardiogram).
• Severe valvulopathies, confirmed by objective diagnostic methods (eg doppler echocardiogram).
• Uncontrolled hyper or hypothyroidism.
• Suprarenal insufficiency.
• Previous surgeries in the last 3 months.
• Severe trauma in the last 6 months, defined as one that involved bone fractures and/or surgical interventions.
• Known active cancer disease or under treatment (acute or preventive), or history of cancer disease without criteria for cure.
• Diagnosis of active autoimmune disease or any pathology under immunosuppressive treatment.
• Ongoing pregnancy, postpartum period of less than 12 months or breastfeeding.
• Other serious diseases with an estimated life expectancy of less than 12 months (according to the investigator's opinion).
• Temperature greater than 37.5°C recorded by a thermometer or any acute infection caused by viruses or bacteria confirmed by a health professional in the previous 30 days.
• Pacemaker/Cardio-Defibrillator Implantation.
• Prior to the study: heart rate > 70 l/m or atrial fibrillation or frequent extrasystoles that in the opinion of the specialist physician will affect the quality of the cardiovascular imaging.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Coronary calcium score	At baseline (cross-sectional assessment)	Coronary artery calcium (CAC) score (Agatston units) stratified with increasing risk according to the Society of Cardiovascular Computed Tomography Guidelines as CAC=0; CAC 1-99; CAC 100-299; and CAC≥300.
Degree of coronary stenosis	At baseline (cross-sectional assesment)	Each coronary segment will be graded based on the degree of coronary stenosis as 0% (no visible stenosis), 1-24% (minimal stenosis); 25-49% (mild stenosis); 50-69% (moderate stenosis); 70-99% (severe stenosis); 100% (occluded).
Coronary high-risk plaques (low-attenuation, positive remodeling; spotty calcification, or napkin-ring sign)	At baseline (cross-sectional assesment)	Presence of any of the following features: low-attenuation (average density equal or lower than 30 Hounsfield units), positive remodeling (remodeling index equal or higher than 1.1; spotty calcification (average density \>130 HU, diameter \<3 mm in any direction with the length of the calcium \<1.5 times the vessel diameter and width of the calcification less than two-thirds of the vessel diameter), or napkin-ring sign (ring-like attenuation pattern with peripheral high attenuation tissue that surrounds a central lower attenuation portion).
Total coronary plaque burden	At baseline (cross-sectional assesment)	The extension of atherosclerotic disease burden will be assessed using the Modified Duke prognostic CAD index as follows: 1) ,50% stenosis; (2) ≥2 non-obstructive stenoses (including one artery with proximal disease or one artery with 50-69% stenosis); (3) two vessels with stenoses 50-69% or one vessel with ≥70% stenosis; (4) three-vessel disease with stenoses 50-69%, or two vessels ≥70%, or proximal LAD stenosis ≥70%; (5) three-vessel disease with stenoses ≥70% or two-vessel disease ≥70% with proximal LAD; (6) left main stenosis ≥50%.

Secondary Outcome Measures

Name	Time	Method
Coronary artery inflammation (perivascular fat attenuation index)	At baseline (cross-sectional assessment)	This secondary analysis will be performed using using specific software.
Presence and extent of aortic calcification	At baseline (cross-sectional assessment)	Aortic valve calcification score (Agatston units) as a continuous variable with increasing risk and without preestablished thresholds (ranging from 0 to 5.000 Agatston units).
Hepatic steatosis	At baseline (cross-sectional assessment)	Defined as liver attenuation level lower than 48 Hounsfield units (HU), and lower than than the spleen attenuation.
Death	Up to 5 years of Follow-up	Death

Trial Locations

Locations (2)

Sanatorio Julio Mendez; 🇦🇷 Ciudad Autónoma de Buenos Aire, Ciudad Autónoma De Buenos Aires, Argentina

Clinica Sagrada Familia; 🇦🇷 Ciudad Autónoma de Buenos Aire, Ciudad Autónoma De Buenos Aires, Argentina