Microvascular Dysfunction in Aortic Stenosis

NCT01658345 | Completed DMC

• 1 other identifier: 87768
• Study Type: observational
• Target: 175
• Locations: 1 country
• Sites: 3

Brief Summary

Aortic stenosis (AS), or narrowing of the aortic valve, is the commonest condition requiring valve surgery in the developed world. It is currently not known what determines who will go on to develop symptoms. Exercise testing may be able to identify these patients better than the severity of the narrowing itself, but with some limitations. The purpose of this study is to compare whether MRI scanning or exercise testing can better identify patients with AS who are likely to benefit from surgery. Design: The investigators will measure blood flow to the heart muscle with MRI scanning and perform exercise testing in 170 patients with AS and follow them for up to up to 2 years. Expected outcomes: MRI scanning will more accurately identify those patients with AS who will need surgery during this period. Anticipated Health Benefits: improved selection of patients with AS who are likely to benefit from early surgery. This is likely to reduce deaths in such patients.

Conditions

Aortic Stenosis

Keywords

aortic stenosis; asymptomatic; microvascular dysfunction; Cardiac MRI

Outcome Measures

Primary Outcomes (3)

• Typical AS Symptoms necessitating AVR.

  12 months

• Cardiovascular death.

  12 months

• Major adverse cardiovascular events (MACE)

  MACE: hospitalisation with heart failure, chest pain, syncope, arrhythmia or stroke

  12 months

Secondary Outcomes (2)

• Individual components of primary composite outcome measures.

  Upto 2 years.

• Development of typical symptoms, AVR, death from any cause or MACE during the entire study period.

  2 years

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cardiology outpatients department and echocardiography department.

You may qualify if:

• Moderate-severe aortic stenosis (2 or more of: AVA \< 1.5cm2, peak PG \>36mmHg or mean PG \> 25mmHg).
• Asymptomatic.
• Age \> 18 years and \< 85 years.
• Prepared to consider AVR if symptoms develop.
• Ability to perform bicycle exercise test

You may not qualify if:

• History of CABG or MI within previous 6 months.
• Severe valvular disease other than AS.
• Previous Valve surgery
• Persistent Atrial Fibrillation or Flutter
• History of Heart Failure
• Severe Asthma.
• Severe renal impairment eGFR \< 30ml/min.
• Planned aortic valve replacement.
• Significant LV systolic dysfunction (EF \< 40%)
• Any absolute contraindication to CMR
• Any absolute contraindication to Adenosine
• Other medical condition that limits life expectancy or precludes AVR.
• Pregnancy

Sponsors & Collaborators

• University Hospitals, Leicester: lead

Study Sites (3)

Glenfield Hospital

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Leeds General Infirmary

Leeds, West Yorkshire, LS1 3EX, United Kingdom

Location

University of Glasgow

Glasgow, G12 8QQ, United Kingdom

Location

Related Publications (8)

• Steadman CD, Jerosch-Herold M, Grundy B, Rafelt S, Ng LL, Squire IB, Samani NJ, McCann GP. Determinants and functional significance of myocardial perfusion reserve in severe aortic stenosis. JACC Cardiovasc Imaging. 2012 Feb;5(2):182-9. doi: 10.1016/j.jcmg.2011.09.022.

  PMID: 22340825 BACKGROUND

• McCann GP, Steadman CD, Ray SG, Newby DE; British Heart Valve Society. Managing the asymptomatic patient with severe aortic stenosis: randomised controlled trials of early surgery are overdue. Heart. 2011 Jul;97(14):1119-21. doi: 10.1136/hrt.2011.223800. Epub 2011 Mar 12. No abstract available.

  PMID: 21398695 BACKGROUND

• Steadman CD, Ray S, Ng LL, McCann GP. Natriuretic peptides in common valvular heart disease. J Am Coll Cardiol. 2010 May 11;55(19):2034-48. doi: 10.1016/j.jacc.2010.02.021.

  PMID: 20447526 BACKGROUND

• Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J. 2005 Jul;26(13):1309-13. doi: 10.1093/eurheartj/ehi250. Epub 2005 Apr 8.

  PMID: 15820999 BACKGROUND

• Chan DCS, Singh A, Greenwood JP, Dawson DK, Lang CC, Berry C, Pakkal M, Everett RJ, Dweck MR, Ng LL, McCann GP. Effect of the 2017 European Guidelines on Reclassification of Severe Aortic Stenosis and Its Influence on Management Decisions for Initially Asymptomatic Aortic Stenosis. Circ Cardiovasc Imaging. 2020 Dec;13(12):e011763. doi: 10.1161/CIRCIMAGING.120.011763. Epub 2020 Dec 8.

  PMID: 33287584 DERIVED

• Graham-Brown MP, Singh AS, Gulsin GS, Levelt E, Arnold JA, Stensel DJ, Burton JO, McCann GP. Defining myocardial fibrosis in haemodialysis patients with non-contrast cardiac magnetic resonance. BMC Cardiovasc Disord. 2018 Jul 13;18(1):145. doi: 10.1186/s12872-018-0885-2.

  PMID: 30005636 DERIVED

• Singh A, Greenwood JP, Berry C, Dawson DK, Hogrefe K, Kelly DJ, Dhakshinamurthy V, Lang CC, Khoo JP, Sprigings D, Steeds RP, Jerosch-Herold M, Neubauer S, Prendergast B, Williams B, Zhang R, Hudson I, Squire IB, Ford I, Samani NJ, McCann GP. Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study. Eur Heart J. 2017 Apr 21;38(16):1222-1229. doi: 10.1093/eurheartj/ehx001.

  PMID: 28204448 DERIVED

• Singh A, Ford I, Greenwood JP, Khan JN, Uddin A, Berry C, Neubauer S, Prendergast B, Jerosch-Herold M, Williams B, Samani NJ, McCann GP. Rationale and design of the PRognostic Importance of MIcrovascular Dysfunction in asymptomatic patients with Aortic Stenosis (PRIMID-AS): a multicentre observational study with blinded investigations. BMJ Open. 2013 Dec 18;3(12):e004348. doi: 10.1136/bmjopen-2013-004348.

  PMID: 24353258 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

With consent, a blood sample (up to 50ml) will be drawn and banked for prospective research studies. All research projects will be related to cardiovascular disease and approved by the Trial Steering Committee (TSC) or a committee delegated this responsibility by the TSC. All tissue will be collected, stored and disposed of in accordance with the Codes of Practice as laid out by the Human Tissue Authority.

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Officials

• Gerry P McCann, MBChB, MD

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 6, 2012
• First Posted: August 7, 2012
• Study Start: April 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: October 1, 2014
• Last Updated: February 23, 2015

Record last verified: 2015-02

Locations

GB (3)