Emerging cardiac CT biomarkers: a systematic review of diagnostic and prognostic utility in cardiovascular disease

Mubariz Ahmed Hassan; Mohammed Mhanna; Ashraf Alzahrani; Muhammad Adil Afzal; Ola Abdelkarim; Rodrigo Bello; Paulo Savoia; Promporn Suksaranjit; Joao A. C. Lima; Kimberly Delcour

doi:10.37349/ec.2025.101278

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Emerging cardiac CT biomarkers: a systematic review of diagnostic and prognostic utility in cardiovascular disease

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Emerging cardiac CT biomarkers: a systematic review of diagnostic and prognostic utility in cardiovascular disease

Mubariz Ahmed Hassan, Mohammed Mhanna, Ashraf Alzahrani, Muhammad Adil Afzal, Ola Abdelkarim, Rodrigo Bello, Paulo Savoia, Promporn Suksaranjit, Joao A. C. Lima and Kimberly Delcour

Exploration of Cardiology, Vol.3, 101278

10/23/2025

DOI: 10.37349/ec.2025.101278

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Abstract

Background: Cardiac computed tomography (CT) has evolved from an anatomic test to a platform that quantifies functional, inflammatory, and tissue-characterization biomarkers. We synthesized evidence on the diagnostic and prognostic value of CT-based biomarkers. Methods: Systematic review of 29 human studies (2015–2025) appraising low-attenuation plaque (LAP), perivascular fat attenuation index (FAI/PCAT), total/non-calcified plaque burden, epicardial adipose tissue, CT-derived fractional flow reserve (FFR-CT), and CT myocardial perfusion. Study quality was assessed with risk of bias (RoB) 2.0, Newcastle-Ottawa Scale (NOS), and AMSTAR 2. Results: CT biomarkers extended risk assessment beyond stenosis severity. LAP burden > 4% predicted myocardial infarction (MI) [hazard ratio (HR) 4.65; 95% CI 2.06–10.5] and per-doubling LAP predicted MI (HR 1.60; 95% CI 1.10–2.34). Perivascular FAI/PCAT showed independent prognostic value: high FAI was associated with ~2-fold higher cardiac mortality (derivation HR 2.15, validation HR 2.06), and RCA PCAT ≥ −70.5 Hounsfield unit (HU) predicted MI (HR 2.45) with additive risk when combined with high-risk plaque (HRP) features (reported up to ~6-fold vs. reference). FFR-CT achieved up to 81% diagnostic accuracy (sensitivity ~86%, specificity ~79%) vs. invasive FFR, improving specificity over CTA alone. Emerging metrics (e.g., total plaque volume, CT perfusion) demonstrated incremental discrimination in selected cohorts, though standardization remains variable. Discussion: CT-based biomarkers provide measurable diagnostic and prognostic information on coronary anatomy, function, inflammation, and tissue health. Priorities include standardized acquisition/analysis, multicenter validation, and integration into decision pathways to optimize individualized risk stratification and therapy.

Details

Title: Subtitle: Emerging cardiac CT biomarkers: a systematic review of diagnostic and prognostic utility in cardiovascular disease
Creators: Mubariz Ahmed Hassan - University of Iowa Hospitals and Clinics
Mohammed Mhanna - University of Iowa
Ashraf Alzahrani - University of Iowa
Muhammad Adil Afzal - St. Joseph’s University Medical Center
Ola Abdelkarim - University of Iowa
Rodrigo Bello - University of Iowa Hospitals and Clinics
Paulo Savoia
Promporn Suksaranjit - University of Iowa Hospitals and Clinics
Joao A. C. Lima - Johns Hopkins Hospital
Kimberly Delcour - University of Iowa Hospitals and Clinics
Resource Type: Journal article
Publication Details: Exploration of Cardiology, Vol.3, 101278
DOI: 10.37349/ec.2025.101278
ISSN: 2994-5526
eISSN: 2994-5526
Language: English
Date published: 10/23/2025
Academic Unit: Radiology; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9985017451202771

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