Derivation and validation of the novel Functional FFRCT Score incorporating the burden of coronary atheroma and flow impairment to predict adverse cardiovascular events

Abstract

The current diagnostic pathways for patients with suspected coronary artery disease (CAD) exhibit considerable variation and often involve a stepwise approach, utilizing both anatomical and ischemia tests to assess risk and guide management decisions. Coronary computed tomography angiography (CCTA) has emerged as the preferred anatomical test for a broad spectrum of patients presenting with symptomatic CAD, with a consistent rise in utilization over the past decade. By adding fractional flow reserve derived from computed tomography (FFRCT) to the CCTA datasets for selected patients, it becomes possible to evaluate the functional implications of atheroma by estimating the reduction in coronary flow. Several parameters derived from CCTA, such as stenosis location and severity, as well as various levels of FFRCT reduction, have been shown to correlate with adverse prognosis. However, the relative roles of atheroma and ischemia in predicting downstream adverse events and guiding patient management remain unclear. While several risk prediction models based on CCTA data have been developed, the exclusively anatomical and simple CAD-RADS system is the most widely used in clinical practice. Models integrating both functional and anatomical severity of CAD have been proposed but are complex and have not been widely adopted clinically.
The main objectives of the analyses presented in this thesis are as follows. Firstly, to develop a risk prediction tool called the Functional FFRCT Score (FFS) that combines estimates of atheroma and ischemia burden from CCTA and FFRCT. Secondly, to validate the novel scoring model in two large cohorts of patients with symptomatic CAD by assessing its association with adverse cardiovascular events. Thirdly, to investigate sex-stratified differences between anatomical CAD severity on CCTA and estimated epicardial flow impairment via FFRCT. Lastly, to explore the role of FFS in stratifying management and predicting adverse events in female versus male patients.
Chapter 3 outlines the feasibility phase, where four candidate scoring systems were evaluated based on computation speed, reproducibility, and correlation with established models like CAD-RADS and CT-SYNTAX scores. The best-performing model, subsequently named the Functional FFRCT Score, was chosen for further validation.
Chapter 4 details the validation of the FFS in relation to revascularization and adverse cardiovascular events in two distinct cohorts of patients with symptomatic CAD.
Chapter 5 delves into analysing the sex-related differences in computed tomography coronary stenosis severity versus flow impairment and their impact on revascularization, clinical events, and healthcare costs.
Chapter 6 demonstrates that, despite disparities in atheroma and ischemia burden between men and women, the FFS remains an independent predictor of adverse clinical events in both sexes.
The results presented in this thesis suggest that the FFS is a promising risk stratification tool. Further validation in larger cohorts of symptomatic CAD patients, and potentially even in asymptomatic patients at risk of CAD, is warranted.

More information

Identifiers

ORCID for Michael Mahmoudi: orcid.org/0000-0003-1293-8461

ORCID for Nick Curzen: orcid.org/0000-0001-9651-7829

ORCID for Michael Mahmoudi: orcid.org/0000-0003-1293-8461

Catalogue record

Export record