Variation of computed tomography-derived extracellular volume fraction and the impact of protocol parameters: A systematic review and meta-analysis

Abstract

Background

Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation.

Methods

We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity.

Results

Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%–29.4%) with significant heterogeneity (I² ​= ​93%) compared to 50.2% (95%CI 46.2%–54.2%) in amyloidosis, 31.2% (28.5%–33.8%) in severe aortic stenosis and 36.9% (31.6%–42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates.

Conclusion

CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis.