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Detecting Early Bioprosthetic Valve Degeneration with 18F-Fluoride PET-CT
Timothy RG Cartlidge1, Mhairi K. Doris1, Tania A. Pawade1, Audrey C. White1, Renzo Pessotto1, James HF Rudd2, Edwin van Beek1, David E. Newby1, Marc R. Dweck1.
1University of Edinburgh, Edinburgh, United Kingdom, 2University of Cambridge, Cambridge, United Kingdom.

OBJECTIVE:
There is no recognised method to detect early bioprosthetic valve degeneration. We investigated the hypothesis that 18F-fluoride positron emission tomography (PET) computed tomography (CT) could detect valve degeneration before functional deterioration was apparent.
METHODS:
Volunteers with surgically-implanted bioprosthetic aortic valves were prospectively recruited. Patients with established bioprosthetic valve failure (cohort 1) were compared to participants without known bioprosthesis dysfunction (cohort 2). Subjects underwent clinical assessment, echocardiography, contrast-enhanced CT and 18F-fluoride PET (to detect microcalcification, target-to-background ratio (TBRmean) >1.3). Cohort 2 underwent repeat clinical assessment and echocardiography at 12 months.
RESULTS:
Seventy-seven participants (757 years, 54% male) completed baseline assessment. Cohort 1 (n=6) all exhibited valve leaflet abnormalities on CT and PET, and the highest TBRmean values in the study. In cohort 2 (1 month (n=9), 2 years (n=22), 5 years (n=20) and 10 years (n=20) post-valve implantation), 4.2% had abnormal baseline echocardiography, 18.3% had abnormal leaflet morphology on CT (8.5% calcification, 5.6% non-calcific leaflet thickening, 9.9% pannus) and 38% had abnormal 18F-fluoride leaflet uptake on PET. Within cohort 2, patients with abnormal 18F-fluoride leaflet uptake demonstrated more rapid deterioration in valve performance over 12 months (change in mean gradient: 2.3 [0.0-4.0] versus -0.3 [-2.0-1.5] mmHg/year, p<0.001). The 2 patients with the highest 18F-fluoride uptake values developed new bioprosthetic valve failure within 12 months of baseline assessment. In multivariable analysis, 18F-Fluoride was the only independent predictor of change in valve function, demonstrating a significant correlation with all echocardiographic parameters of valve function (e.g. TBRmean versus peak velocity: r=0.64, p<0.001).
CONCLUSIONS:
18F-Fluoride PET offers greatly improved sensitivity for detection of early bioprosthesis degeneration over echocardiography and CT, and independently predicts functional valve deterioration. This suggests exciting potential as a clinical investigation to identify patients at risk of impending valve failure and as a research tool to compare new treatments and valve technologies.


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