Clinical trial NCT02304276: 18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome
Official title: 18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart; Complications, Valve, Prosthesis
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
name: Cambridge University Hospitals NHS Foundation Trust
name: Papworth Hospital NHS Foundation Trust
name: Bichat Hospital
First posted: 2014-12-01
Enrollment: 105
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: This study will evaluate the two main types of replacement tissue heart valve used in current practice, comparing outcomes from surgical aortic valve replacement (AVR) with that of the more recently introduced "key-hole" procedure called transcatheter aortic valve implantation (TAVI). Participants will be recruited at various time points ranging from 1 month to 10 years following valve replacement with either AVR or TAVI. It is thought that progressive calcium (chalk) formation is responsible for the failure of the majority of these valves. All participants will therefore have a PET-CT scan with a special type of "tracer" called 18F-fluoride in order to measure active calcium formation in the valve. They will then have annual clinical follow-up for 5 years and be invited back for a repeat CT scan at 2 years to measure change in calcium burden. This study aims to investigate, firstly, the effects of valve age and type on calcium formation as measured by PET-CT and, secondly, whether this measure of calcium formation can help to predict how long different types of valve will last. If successful, 18F-fluoride PET-CT could become a valuable tool for testing new treatments to improve valve longevity and new valve designs.

Detailed description: Aortic stenosis is the commonest form of valve disease in the western world and the leading indication for valve surgery. Bioprosthetic valves are known to degenerate via a process that is predominantly driven by calcification. Transcatheter aortic valve implantation (TAVI) has recently emerged as a less invasive alternative to conventional aortic valve replacement (AVR) surgery. Whilst this technique holds great promise, long-term follow up data are lacking and the longevity of these valves remains to be established.

In this longitudinal, cross-sectional study of 180 subjects with either surgical or transcatheter implanted bioprostheses, this study proposes to look for the earliest signs of active calcification using 18F-fluoride positron emission tomography (PET). During a 5 year follow-up period, this study hopes to demonstrate that 18F-fluoride PET will predict subsequent bioprosthetic valve degeneration and identify patients at risk of premature valve failure. The study also hopes that it will inform about the comparative durability of novel percutaneous valves. If successful, 18F-Fluoride could provide a useful method of assessing novel therapeutic strategies targeted at improving the longevity of bioprostheses and help to guide future valve design.

Eligibility criteria: Inclusion Criteria:

Cohort 1

* able to provide informed consent
* aged over 40 years
* patients with a bioprosthetic aortic valve who are due to undergo a redo-surgical aortic valve replacement

Cohort 2

* able to provide informed consent
* aged over 40 years
* patients at 1 month (n=10), 2 years (n=20), 5 years (n=20) and 10 years (n=20) following surgical bioprosthetic aortic valve replacement

Cohort 3

* able to provide informed consent
* aged over 40 years
* patients at 1 month (n=10), 2 years (n=20) and 5 years (n=20) following transcatheter aortic valve implantation (TAVI) with the Edward's SAPIEN and the COREVALVE.

Exclusion Criteria:

* Inability to give informed consent
* Pregnancy
* Breastfeeding
* Claustrophobia
* Allergy to iodinated contrast
* Liver failure
* Chronic kidney disease (with estimated glomerular filtration rate \<30 mL/min)
* Metastatic malignancy
* Paget's disease

Primary outcomes:
measure: 18F-Fluoride uptake in aortic bioprostheses
timeFrame: Baseline
Secondary outcomes:
measure: CT calcium score of aortic valve
timeFrame: Baseline and 2 years
measure: Echocardiographic evaluation of aortic valve function
timeFrame: Baseline, 1 year and 2 years
measure: Frequency of major adverse cardiovascular events
timeFrame: 5 years
measure: Immunohistochemical staining of explanted aortic bioprostheses for marker of calcification
timeFrame: intraoperative
Other outcomes:
Locations:
Study officials:
affiliation: University of Edinburgh, Scotland
name: Marc Dweck, MBChB PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cartlidge TRG, Doris MK, Sellers SL, Pawade TA, White AC, Pessotto R, Kwiecinski J, Fletcher A, Alcaide C, Lucatelli C, Densem C, Rudd JHF, van Beek EJR, Tavares A, Virmani R, Berman D, Leipsic JA, Newby DE, Dweck MR. Detection and Prediction of Bioprosthetic Aortic Valve Degeneration. J Am Coll Cardiol. 2019 Mar 19;73(10):1107-1119. doi: 10.1016/j.jacc.2018.12.056.
citation: Kwiecinski J, Tzolos E, Cartlidge TRG, Fletcher A, Doris MK, Bing R, Tarkin JM, Seidman MA, Gulsin GS, Cruden NL, Barton AK, Uren NG, Williams MC, van Beek EJR, Leipsic J, Dey D, Makkar RR, Slomka PJ, Rudd JHF, Newby DE, Sellers SL, Berman DS, Dweck MR. Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients With Transcatheter Aortic Valve Implantation. Circulation. 2021 Oct 26;144(17):1396-1408. doi: 10.1161/CIRCULATIONAHA.121.056891. Epub 2021 Aug 29.