18F-Fluoride Assessment of Aortic Bioprosthesis Durability and Outcome

NCT02304276 | Completed

• 1 other identifier: 147780
• Study Type: interventional
• Target: 105
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Heart; Complications, Valve, Prosthesis

Outcome Measures

Primary Outcomes (1)

• 18F-Fluoride uptake in aortic bioprostheses

  18F-Fluoride uptake expressed as tissue to background ratio (TBR) in aortic valve bioprostheses of different age and type as measured by PET/CT

  Baseline

Secondary Outcomes (4)

• CT calcium score of aortic valve

  Baseline and 2 years

• Echocardiographic evaluation of aortic valve function

  Baseline, 1 year and 2 years

• Frequency of major adverse cardiovascular events

  5 years

• Immunohistochemical staining of explanted aortic bioprostheses for marker of calcification

  intraoperative

Study Arms (3)

1 (Explanted valves)

ACTIVE COMPARATOR

10 subjects who are due to undergo repeat aortic valve replacement surgery Investigations: 1. Baseline 18F-Fluoride PET-CT scan 2. Retrieval of explanted bioprosthetic aortic valve at time of surgery for analysis

Radiation: 18F-Fluoride PET-CT

2 (AVR)

EXPERIMENTAL

70 subjects with surgical bioprosthetic AVR, to include 10 subjects who have had a valve replacement \< 1 month; 20 at 2 years; 20 at 5 years and 20 at \>10 years. Investigations: 1. Baseline 18F-Fluoride PET-CT scan 2. Repeat CT calcium score of aortic valve at 2 years 3. Annual clinical follow-up for 5 years (history, examination, blood tests, ECG and echocardiogram)

Radiation: 18F-Fluoride PET-CT; Radiation: CT calcium score of aortic valve

3 (TAVI)

EXPERIMENTAL

50 subjects who have undergone TAVI with the COREVALVE and 50 subjects with the SAPIEN valve. In each group this will include 10 subjects who have had TAVI \< 1 month; 20 at 2 years and 20 at 5 years. Investigations: 1. Baseline 18F-Fluoride PET-CT scan 2. Repeat CT calcium score of aortic valve at 2 years 3. Annual clinical follow-up for 5 years (history, examination, blood tests, ECG and echocardiogram)

Radiation: 18F-Fluoride PET-CT; Radiation: CT calcium score of aortic valve

Interventions

18F-Fluoride PET-CT RADIATION

Injection of 18F-Fluoride with target activity 125MBq giving an anticipated radiation exposure of 3mSv CT scanning protocol giving an anticipated radiation exposure of 13mSv

1 (Explanted valves); 2 (AVR); 3 (TAVI)

CT calcium score of aortic valve RADIATION

CT associated with an anticipated radiation exposure of 3mSv (Cohorts 2 and 3 only)

2 (AVR); 3 (TAVI)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• Cambridge University Hospitals NHS Foundation Trust: collaborator
• Papworth Hospital NHS Foundation Trust: collaborator
• Bichat Hospital: collaborator

Related Publications (2)

• 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.

  PMID: 30871693 RESULT

• 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.

  PMID: 34455857 DERIVED

Study Officials

• Marc Dweck, MBChB PhD

  University of Edinburgh, Scotland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: December 1, 2014
• Study Start: January 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: October 30, 2020
• Last Updated: May 21, 2024

Record last verified: 2024-05