Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis

NCT01358513 | Completed DMC

• 1 other identifier: RING OF FIRE
• Study Type: observational
• Target: 121
• Locations: 1 country
• Sites: 1

Brief Summary

The aortic valve is the main outlet valve from the heart. This valve can become diseased and narrowed when it needs to be replaced with an artificial valve. Currently, this is the commonest reason for someone to undergo a heart valve operation in the UK. Unfortunately, there are no medical treatments that can prevent or delay the progression of this disease process. Here, the investigators propose to use new state-of-the-art imaging techniques to better understand the disease process so that the investigators can effectively design and assess potential new treatments. The ultimate aim is to stop this disease before patients need to have surgery. In addition the investigators believe this technique will allow us to predict the rate of progression of the disease

Conditions

Aortic Stenosis

Keywords

Positron Emission Tomography; Inflammation; Calcification

Outcome Measures

Primary Outcomes (1)

• Aortic Valve Peak Velocity

  We beleive NaF and FDG uptake in the valve will predict rate of progression of the disease. Disease severity will be measured by the aortic valve peak velocity

  2 years

Study Arms (5)

Control Patients

Patients with normal aortic valves

Aortic sclerosis

To undergo PET imaging and follow up with CT and echo for 2 years

Mild Aortic stenosis

To undergo PET imaging and follow up with CT and echo for 2 years

Moderate Aortic stenosis

To undergo PET imaging and follow up with CT and echo for 2 years

Severe aortic stenosis

To undergo PET imaging and follow up with CT and echo for 2 years

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The investigators will recruit 168 patients: 24 control patients, 24 mild, 48 moderate and 48 severe aortic stenosis

You may qualify if:

• Age \> 50 years

You may not qualify if:

• Age \< 50 years
• Life expectancy \< 2 years
• Insulin dependent diabetes mellitus
• Connective Tissue disorders

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• British Heart Foundation: collaborator

Study Sites (1)

Centre for Cardiovascular Sciences, University of Edinburgh

Edinburgh, Scotland, EH16 4SE, United Kingdom

Location

Related Publications (6)

• Fletcher AJ, Tew YY, Tzolos E, Joshi SS, Kaczynski J, Nash J, Debono S, Lembo M, Kwiecinski J, Bing R, Syed MBJ, Doris MK, van Beek EJR, Moss AJ, Jenkins WS, Walker NL, Joshi NV, Pawade TA, Adamson PD, Whiteley WN, Wardlaw JM, Slomka PJ, Williams MC, Newby DE, Dweck MR. Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease. JACC Cardiovasc Imaging. 2022 Jul;15(7):1274-1288. doi: 10.1016/j.jcmg.2021.12.013. Epub 2022 Feb 16.

  PMID: 35183477 DERIVED

• Pawade T, Clavel MA, Tribouilloy C, Dreyfus J, Mathieu T, Tastet L, Renard C, Gun M, Jenkins WSA, Macron L, Sechrist JW, Lacomis JM, Nguyen V, Galian Gay L, Cuellar Calabria H, Ntalas I, Cartlidge TRG, Prendergast B, Rajani R, Evangelista A, Cavalcante JL, Newby DE, Pibarot P, Messika Zeitoun D, Dweck MR. Computed Tomography Aortic Valve Calcium Scoring in Patients With Aortic Stenosis. Circ Cardiovasc Imaging. 2018 Mar;11(3):e007146. doi: 10.1161/CIRCIMAGING.117.007146.

  PMID: 29555836 DERIVED

• Dweck MR, Jenkins WS, Vesey AT, Pringle MA, Chin CW, Malley TS, Cowie WJ, Tsampasian V, Richardson H, Fletcher A, Wallace WA, Pessotto R, van Beek EJ, Boon NA, Rudd JH, Newby DE. 18F-sodium fluoride uptake is a marker of active calcification and disease progression in patients with aortic stenosis. Circ Cardiovasc Imaging. 2014 Mar;7(2):371-8. doi: 10.1161/CIRCIMAGING.113.001508. Epub 2014 Feb 7.

  PMID: 24508669 DERIVED

• Dweck MR, Khaw HJ, Sng GK, Luo EL, Baird A, Williams MC, Makiello P, Mirsadraee S, Joshi NV, van Beek EJ, Boon NA, Rudd JH, Newby DE. Aortic stenosis, atherosclerosis, and skeletal bone: is there a common link with calcification and inflammation? Eur Heart J. 2013 Jun;34(21):1567-74. doi: 10.1093/eurheartj/eht034. Epub 2013 Feb 7.

  PMID: 23391586 DERIVED

• Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, Richardson H, White A, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012 Apr 24;59(17):1539-48. doi: 10.1016/j.jacc.2011.12.037.

  PMID: 22516444 DERIVED

• Dweck MR, Jones C, Joshi NV, Fletcher AM, Richardson H, White A, Marsden M, Pessotto R, Clark JC, Wallace WA, Salter DM, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012 Jan 3;125(1):76-86. doi: 10.1161/CIRCULATIONAHA.111.051052. Epub 2011 Nov 16.

  PMID: 22090163 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

In patients undergoing aortic valve replacement during the course of the trial we will retain samples of their aortic valve for histological studies.

MeSH Terms

Conditions

Aortic Valve Stenosis; Inflammation; Calcinosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: May 23, 2011
• Study Start: July 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2015
• Last Updated: June 25, 2018

Record last verified: 2015-01

Locations

GB (1)