Author + information
- Received September 12, 2018
- Revision received November 21, 2018
- Accepted December 2, 2018
- Published online March 11, 2019.
- Timothy R.G. Cartlidge, MDa,
- Mhairi K. Doris, MDa,
- Stephanie L. Sellers, PhDb,
- Tania A. Pawade, MDa,
- Audrey C. Whitea,
- Renzo Pessotto, MDa,
- Jacek Kwiecinski, MDa,
- Alison Fletcher, PhDc,
- Carlos Alcaide, MSca,
- Christophe Lucatelli, PhDc,
- Cameron Densem, MDd,
- James H.F. Rudd, MDe,
- Edwin J.R. van Beek, MDc,
- Adriana Tavares, PhDa,
- Renu Virmani, MDf,
- Daniel Berman, MDg,
- Jonathon A. Leipsic, MDb,
- David E. Newby, DSca and
- Marc R. Dweck, PhDa,∗ (, )@marcdweck
- aBritish Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
- bEdinburgh Imaging Facility, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
- cDepartment of Radiology, St. Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
- dDepartment of Cardiology, Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom
- eDivision of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom
- fCVPath Institute, Gaithersburg, Maryland
- gCedars-Sinai Heart Institute, Los Angeles, California
- ↵∗Address for correspondence:
Dr. Marc R. Dweck, Centre for Cardiovascular Science, University of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom.
Background Bioprosthetic aortic valve degeneration is increasingly common, often unheralded, and can have catastrophic consequences.
Objectives The authors sought to assess whether 18F-fluoride positron emission tomography (PET)-computed tomography (CT) can detect bioprosthetic aortic valve degeneration and predict valve dysfunction.
Methods Explanted degenerate bioprosthetic valves were examined ex vivo. Patients with bioprosthetic aortic valves were recruited into 2 cohorts with and without prosthetic valve dysfunction and underwent in vivo contrast-enhanced CT angiography, 18F-fluoride PET, and serial echocardiography during 2 years of follow-up.
Results All ex vivo, degenerate bioprosthetic valves displayed 18F-fluoride PET uptake that colocalized with tissue degeneration on histology. In 71 patients without known bioprosthesis dysfunction, 14 had abnormal leaflet pathology on CT, and 24 demonstrated 18F-fluoride PET uptake (target-to-background ratio 1.55 [interquartile range (IQR): 1.44 to 1.88]). Patients with increased 18F-fluoride uptake exhibited more rapid deterioration in valve function compared with those without (annualized change in peak transvalvular velocity 0.30 [IQR: 0.13 to 0.61] vs. 0.01 [IQR: −0.05 to 0.16] ms−1/year; p < 0.001). Indeed 18F-fluoride uptake correlated with deterioration in all the conventional echocardiographic measures of valve function assessed (e.g., change in peak velocity, r = 0.72; p < 0.001). Each of the 10 patients who developed new overt bioprosthesis dysfunction during follow-up had evidence of 18F-fluoride uptake at baseline (target-to-background ratio 1.89 [IQR: 1.46 to 2.59]). On multivariable analysis, 18F-fluoride uptake was the only independent predictor of future bioprosthetic dysfunction.
Conclusions 18F-fluoride PET-CT identifies subclinical bioprosthetic valve degeneration, providing powerful prediction of subsequent valvular dysfunction and highlighting patients at risk of valve failure. This technique holds major promise in the diagnosis of valvular degeneration and the surveillance of patients with bioprosthetic valves. (18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome [18F-FAABULOUS]; NCT02304276)
- aortic valve replacement
- bioprosthetic valve degeneration
- positron emission tomography
This work was supported by the British Heart Foundation, London, United Kingdom (FS/13/77/30488). The Edinburgh Clinical Research Facility and Edinburgh Imaging Facility are supported by NHS Research Scotland. Dr. Rudd is supported in part by the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, HEFCE, the EPSRC and the Wellcome Trust. Dr. van Beek is supported by the Scottish Imaging Network–a Platform for Scientific Excellence Chair of Clinical Radiology. Dr. Newby is supported by the British Heart Foundation (CH/09/002, RE/13/3/30183, RM/13/2/30158); and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. Dweck is supported by the British Heart Foundation FS/14/78/31020; and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 JTA/15. Dr. van Beek has received research support from Seimens Healthineers; has been a consultant for Imbio, Aidence NV, InHealth, and Mentholatum; and owns QCTIS Ltd. Dr. Leipsic’s institution has served as an institutional core lab for Edwards Lifesciences, Abbott, and Medtronic; and has been a consultant for and holds stock options in Circle CVI and HeartFlow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received September 12, 2018.
- Revision received November 21, 2018.
- Accepted December 2, 2018.
- 2019 The Authors