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. 2025 Jan;35(1):232-243.
doi: 10.1007/s00330-024-10932-z. Epub 2024 Jul 17.

Temporal changes in CT-derived fractional flow reserve in patients after heart transplantation

Simran P Sharma  1   2 , Javier Sanz  3 , Alexander Hirsch  1   2 , Richa Patel  4 , Alina A Constantinescu  1   5 , Maya Barghash  3 , Donna M Mancini  3 , Jasper J Brugts  1   5 , Kadir Caliskan  1   5 , Yannick J H J Taverne  5   6 , Olivier C Manintveld #  1   5 , Ricardo P J Budde #  7   8
Affiliations

Temporal changes in CT-derived fractional flow reserve in patients after heart transplantation

Simran P Sharma et al. Eur Radiol. 2025 Jan.

Abstract

Background: Adding functional information by CT-derived fractional flow reserve (FFRct) to coronary CT angiography (CCTA) and assessing its temporal change may provide insight into the natural history and physiopathology of cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients. We assessed FFRct changes as well as CAV progression over a 2-year period in HTx patients undergoing serial CT imaging.

Methods: HTx patients from Erasmus MC and Mount Sinai Hospital, who had consecutive CCTAs 2 years apart were evaluated. FFRct analysis was performed for both scans. FFRct values at the most distal point in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) were measured after precisely matching the anatomical locations in both analyses. Also, the number of anatomical coronary stenoses of > 30% was scored.

Results: In total, 106 patients (median age 57 [interquartile range 47-67] years, 67% male) at 9 [6-13] years after HTx at the time of the baseline CCTA were included. Median distal FFRct values significantly decreased from baseline to follow-up for the LAD from 0.85 [0.79-0.90] to 0.84 [0.76-0.90] (p = 0.001), LCX from 0.92 [0.88-0.96] to 0.91 [0.85-0.95] (p = 0.009), and RCA from 0.92 [0.86-0.95] to 0.90 [0.86-0.94] (p = 0.004). The number of focal anatomical stenoses of > 30% increased from a median of 1 [0-2] at baseline to 2 [0-3] at follow-up (p = 0.009).

Conclusions: The distal coronary FFRct values in post-HTX patients in each of the three major coronary arteries decreased, and the number of focal coronary stenoses increased over a 2-year period. Temporal FFRct change rate may become an additional parameter in the follow-up of HTx patients, but more research is needed to elucidate its role.

Clinical relevance statement: CT-derived fractional flow reserve (FFRct) is important post-heart transplant because of additional information on coronary CT angiography for cardiac allograft vasculopathy (CAV) detection. The decrease and degree of reduction in distal FFRct value may indicate progression in anatomic CAV burden.

Key points: CT-derived fractional flow reserve (FFRct) is important for monitoring cardiac allograft vasculopathy (CAV) in heart transplant patients. Over time, transplant patients showed a decrease in distal FFRct and an increase in coronary stenoses. Temporal changes in FFRct could be crucial for transplant follow-up, aiding in CAV detection.

Keywords: Computed tomography angiography; Fractional flow reserve; Heart transplantation; Myocardial.

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Conflict of interest statement

Compliance with ethical standards. Guarantor: The scientific guarantors of this publication are Prof. R.P.J. Budde and Dr. O.C. Manintveld. Conflict of interest: S.P.S.: no conflict of interest. J.S.: no conflict of interest. A.H.: received a research grant and consultancy fees from GE Healthcare and speaker fees from GE Healthcare and Bayer. He is also a member of the medical advisory board of Medis Medical Imaging Systems and was the MRI corelab supervisor of Cardialysis BV until 2022. R.P.: no conflict of interest. A.A.C.: no conflict of interest. M.B.: no conflict of interest. D.M.M.: no conflict of interest. J.J.B.: Dr. Brugts received an independent research grant for ISS to the hospital. Dr. Brugts has had speaker engagements or advisory boards in the past 5 years with Astra Zeneca, Abbott, Bayer, Boehringer, Danchii Sankyo, Novartis and Vifor. K.C.: no conflict of interest. Y.J.H.J.T.: no conflict of interest. O.M.: reports personal fees from Astra Zeneca, Boehringer Ingelheim, Daiichi-Sanyo and Novartis. R.P.J.B.: Institutional support to Erasmus MC from Siemens Healthineers; lecture fee and travel reimbursement from Siemens Healthineers paid directly to Erasmus MC; lecture fee from Bayer; board member of the European Society of Cardiovascular Radiology and the Cardiovascular section of the Dutch Society of Radiology; editorial board member of Radiology: Cardiothoracic Imaging, European Heart Journal—Digital Health, and the European Journal of Hybrid Imaging; grant from HeartFlow to Erasmus MC. Statistics and biometry: Dr. A. Hirsch kindly provided statistical advice for this manuscript. One of the authors has significant statistical expertise. No complex statistical methods were necessary for this paper. Informed consent: Only if the study is on human subjects: 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: Some study subjects or cohorts have been previously reported in ref. [16]. Methodology: Retrospective Observational Multicenter study

Figures

Fig. 1
Fig. 1
Flowchart of patient inclusion. An overview of the included patients and the reasons why certain cases could not be analysed by HeartFlow Inc. CCTA, coronary computed tomography angiography; FFRct, CT-derived fractional flow reserve
Fig. 2
Fig. 2
Measurement of the number of focal stenoses and distal CT-derived fractional flow reserve values in a single patient at baseline and follow-up. The focal stenoses (indicated by HeartFlow, Inc.) and distal FFRct values were recorded from the FFRct analyses. A shows that the FFRctbase has no focal stenosis, whereas the same patient in B has one focal stenosis on the FFRctfollow-up with a value of 0.87 in the left circumflex artery. C displays the FFRctbase values at the most distal point of each of the three major coronary arteries, with the investigator placing the measurement pins. Since the length of the segmented coronary arteries varies between FFRctbase and FFRctfollow-up, the shortest segmentation available was used for the measurements. C The section distal to the 0.92 measurement point in the left anterior descending artery was disregarded. D shows the FFRctfollow-up values measured at the same location as in C, allowing for a direct comparison between the two analyses. Figure 1S illustrates the multiplanar and volume-rendered images of the distal left circumflex artery stenosis at baseline and follow-up, corresponding to the patient in Fig. 2. FFRct, CT-derived fractional flow reserve
Fig. 3
Fig. 3
Boxplots comparing FFRct values between baseline and follow-up. Box plot showing the distribution of the overall and per-vessel distal FFRct values for the baseline (blue) and follow-up (orange) measurements. The boxes represent the interquartile range (IQR), with the horizontal line inside indicating the median value. The whiskers extend to the minimum and maximum values within 1.5 times the IQR (interquartile range) below the first quartile and above the third quartile. FFRct, CT-derived fractional flow reserve; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery
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