In coronary artery disease (CAD), the decision on revascularization is based on the hemodynamic significance of stenoses. However, this cannot directly be determined from the first-line anatomical imaging methods coronary computed tomography angiography (CCTA) in chronic coronary syndrome (CCS) or invasive coronary angiography (ICA) in acute coronary syndrome (ACS). The aim of this thesis was to investigate the prognostic value of two novel approaches to determine functionally significant CAD according to impaired invasive fractional flow reserve (FFR) directly from CCTA in CCS and ICA in ACS.

Quantitative flow ratio (QFR) is a novel computational fluid dynamic-based technique to estimate the presence of impaired FFR from biplane ICA. In this study, QFR from untreated non-culprit lesions showed incremental 5-year prognostic value for major adverse cardiac events among ST-elevation myocardial infarction patients undergoing angiography-guided complete revascularization. However, non-culprit QFR did not independently predict non-target-vessel related events prior to planned staged percutaneous coronary intervention (PCI) in ACS patients, and the study does not provide conceptual evidence that QFR could be useful to refine the timing of staged PCI on top of clinical judgement.

AI-QCTischemia is an artificial intelligence-based method to predict the probability of an impaired invasive FFR using 37 morphological features from CCTA. Among symptomatic patients with suspected CAD undergoing CCTA, AI-QCTischemia showed incremental prognostic value for the composite of death, myocardial infarction, or unstable angina pectoris throughout a median of 7 years follow-up. This risk stratification pertained especially to patients with no/non-obstructive disease. Patients with obstructive disease on CCTA were referred for downstream myocardial perfusion imaging with positron emission tomography (PET), and among those, AI-QCTischemia showed incremental risk stratification among patients with normal PET perfusion, but not among those with abnormal PET perfusion.