Extracellular volume fraction by cardiac computed tomography (ECV_CT): opportunities and challenges for clinical...

Cardiac computed tomography (CT)-derived extracellular volume (ECV_CT) estimates myocardial interstitial expansion by quantifying the distribution of iodinated contrast within the extracellular space, providing a CT marker of focal and diffuse fibrosis as well as amyloid infiltration. In single-energy CT, ECV_CT is calculated from the change in myocardial and blood-pool attenuation between non-contrast and delayed scans, adjusted for haematocrit. Spectral CT, including photon-counting CT (PCCT), can quantify ECV_CT from energy-resolved data and may reduce reliance on a separate true non-contrast scan. Across several disease cohorts, ECV_CT correlates well with cardiac magnetic resonance (CMR)-derived ECV and, in selected studies, with histological collagen volume fraction, supporting potential for global and regional assessment. ECV_CT can add myocardial tissue characterization to examinations already performed for coronary and structural heart disease, including opportunistic screening for concomitant transthyretin amyloidosis during transcatheter aortic valve implantation planning, risk stratification in aortic stenosis, and adjunct phenotyping after CT coronary angiography in troponin-positive acute chest pain or heart failure work-up. Furthermore, CT is more accessible, better tolerated, and potentially cheaper than CMR. However, clinical adoption is potentially limited by added workflow steps due to the delayed acquisition, additional radiation exposure, and heterogeneous approaches to acquisition, reconstruction, and analysis, which reduce reproducibility and complicate the definition of normalcy rates and diagnostic thresholds. Developments in PCCT, automation, and synthetic haematocrit may streamline protocols, but require further calibration and agreement-focused validation. Consensus guidance and prospective multicentre outcome studies are needed to standardize protocols, harmonize reporting, define reference ranges, and support clinically actionable thresholds.