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Impact of machine-learning CT-derived fractional flow reserve for the diagnosis and management of coronary artery disease in the randomized CRESCENT trials



To determine the potential impact of on-site CT-derived fractional flow reserve (CT-FFR) on the diagnostic efficiency and effectiveness of coronary CT angiography (CCTA) in patients with obstructive coronary artery disease (CAD) on CCTA.


This observational cohort study included patients with suspected CAD who had been randomized to cardiac CT in the CRESCENT I and II trials. On-site CT-FFR was blindly performed in all patients with at least one ≥ 50% stenosis on CCTA and no exclusion criteria for CT-FFR. We retrospectively assessed the effect of adding CT-FFR to the CT protocol in patients with a stenosis ≥ 50% on CCTA in terms of diagnostic effectiveness, i.e., the number of additional tests required to determine the final diagnosis, reclassification of the initial management strategy, and invasive coronary angiography (ICA) efficiency, i.e., ICA rate without ≥ 50% CAD.


Fifty-three patients out of the 372 patients (14%) had at least one ≥ 50% stenosis on CCTA of whom 42/53 patients (79%) had no exclusion criteria for CT-FFR. CT-FFR showed a hemodynamically significant stenosis (≤ 0.80) in 27/53 patients (51%). The availability of CT-FFR would have reduced the number of patients requiring additional testing by 57%-points compared with CCTA alone (37/53 vs. 7/53, p < 0.001). The initial management strategy would have changed for 30 patients (57%, p < 0.001). Reserving ICA for patients with a CT-FFR ≤ 0.80 would have reduced the number of ICA following CCTA by 13%-points (p = 0.016).


Implementation of on-site CT-FFR may change management and improve diagnostic efficiency and effectiveness in patients with obstructive CAD on CCTA.

Key Points

• The availability of on-site CT-FFR in the diagnostic evaluation of patients with obstructive CAD on CCTA would have significantly reduced the number of patients requiring additional testing compared with CCTA alone.

• The implementation of on-site CT-FFR would have changed the initial management strategy significantly in the patients with obstructive CAD on CCTA.

• Restricting ICA to patients with a positive CT-FFR would have significantly reduced the ICA rate in patients with obstructive CAD on CCTA.

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Coronary artery disease


Coronary computed tomography angiography


Computed Tomography vs. Exercise Testing in Suspected Coronary Artery Disease


Computed tomography–derived fractional flow reserve


Fractional flow reserve


Invasive coronary angiography


Major adverse cardiovascular events


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We owe gratitude to all participating patients of the CRESCENT trials, as well as the medical teams, in particular Paul Musters, who made this study and the CRESCENT trials possible.


This study has received funding by grants from the Dutch Heart Foundation (NHS 2014T061 and NHS 2013T071).

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Corresponding author

Correspondence to Koen Nieman.

Ethics declarations


The scientific guarantor of this publication is Koen Nieman.

Conflict of interest

The authors of this manuscript declare relationships with the following companies: Siemens Healthineers, HeartFlow, GE Healthcare, Bayer Healthcare.

Statistics and biometry

Isabella Kardys kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

All subjects have been previously reported in the CRESCENT I and CRESCENT II trials. The prior studies evaluated the clinical effectiveness of a tiered cardiac CT approach against standard functional testing. The current study expands on these studies by combing the subjects of the CT arm of both studies and implement CT-FFR analyses into the protocol. The previous studies were published in European Heart Journal (CRESCENT I trial) and JACC Cardiovascular Imaging (CRESCENT II trial).


• Retrospective

• Observational

• Multicenter study

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Nous, F.M.A., Budde, R.P.J., Lubbers, M.M. et al. Impact of machine-learning CT-derived fractional flow reserve for the diagnosis and management of coronary artery disease in the randomized CRESCENT trials. Eur Radiol 30, 3692–3701 (2020).

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  • Coronary artery disease
  • Computed tomography angiography
  • Myocardial fractional flow reserve
  • Myocardial ischemia
  • Myocardial perfusion imaging