The Role of Myocardial Fibrosis in Patients With Aortic Stenosis

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ClinicalTrials.gov Identifier: NCT01755936

Recruitment Status : Completed

First Posted : December 24, 2012

Last Update Posted : June 25, 2018

Sponsor:

Collaborator:

British Heart Foundation

Information provided by (Responsible Party):

University of Edinburgh

Study Description

Brief Summary:

Aortic stenosis is the most common adult valvular heart disease in the western world. Heart failure and sudden cardiac death are complications associated with aortic stenosis. In symptomatic individuals, valve replacement is often the only effective treatment. However, there are no good markers to identify patients who may benefit from early surgery before symptoms developed. The purpose of the study is to test the hypothesis that the presence heart muscle scarring on the cardiac magnetic resonance imaging may predict a worse outcome in patients with aortic stenosis, and thus may be helpful in identifying patients for early valve replacement.

Condition or disease	Intervention/treatment
Aortic Stenosis	Other: Cardiac Magnetic Resonance Imaging Other: Echocardiography Other: 72 hour Holter Monitor

Detailed Description:

Congestive heart failure and sudden cardiac death are associated complications of aortic stenosis. Currently, the indications for valvular replacement are based on the valvular severity evaluated by echocardiography and the presence of symptoms. There is some evidence to suggest the presence of myocardial fibrosis is associated with a poor outcome in patients with aortic stenosis. The aim of this prospective study is to investigate the prognostic implications of myocardial fibrosis in patients with aortic stenosis. The presence of myocardial fibrosis will be identified by delayed enhancement with the cardiac magnetic resonance imaging at 3T. We will also be evaluating the application of T1 mapping techniques to detect diffuse myocardial fibrosis.

Study Design

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Study Type :	Observational
Actual Enrollment :	203 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	The Role of Myocardial Fibrosis in Patients With Aortic Stenosis
Study Start Date :	January 2012
Actual Primary Completion Date :	January 2016
Actual Study Completion Date :	August 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Supravalvular aortic stenosis

Genetic and Rare Diseases Information Center resources: Aortic Valve Stenosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Controls Patients will undergo cardiac magnetic resonance imaging, echocardiography and 72 hour holter monitoring	Other: Cardiac Magnetic Resonance Imaging For the evaluation of left ventricular volumes, function and mass. Also for the assessment of myocardial fibrosis based on the presence of delayed enhancement. Novel application of T1 mapping techniques will be evaluated. Other: Echocardiography Assessment of aortic stenosis severity. Also evaluate diastolic and systolic function. Other: 72 hour Holter Monitor This will enable us to detect abnormal heart rhythms which may be associated with myocardial fibrosis
Aortic Stenosis patients All patients who agreed to study will undergo cardiac magnetic resonance imaging, echocardiography and 72 hour holter monitoring	Other: Cardiac Magnetic Resonance Imaging For the evaluation of left ventricular volumes, function and mass. Also for the assessment of myocardial fibrosis based on the presence of delayed enhancement. Novel application of T1 mapping techniques will be evaluated. Other: Echocardiography Assessment of aortic stenosis severity. Also evaluate diastolic and systolic function. Other: 72 hour Holter Monitor This will enable us to detect abnormal heart rhythms which may be associated with myocardial fibrosis

Group/Cohort

Intervention/treatment

Controls

Patients will undergo cardiac magnetic resonance imaging, echocardiography and 72 hour holter monitoring

Other: Cardiac Magnetic Resonance Imaging

For the evaluation of left ventricular volumes, function and mass. Also for the assessment of myocardial fibrosis based on the presence of delayed enhancement. Novel application of T1 mapping techniques will be evaluated.

Other: Echocardiography

Assessment of aortic stenosis severity. Also evaluate diastolic and systolic function.

Other: 72 hour Holter Monitor

This will enable us to detect abnormal heart rhythms which may be associated with myocardial fibrosis

Aortic Stenosis patients

All patients who agreed to study will undergo cardiac magnetic resonance imaging, echocardiography and 72 hour holter monitoring

Other: Cardiac Magnetic Resonance Imaging

Other: Echocardiography

Assessment of aortic stenosis severity. Also evaluate diastolic and systolic function.

Other: 72 hour Holter Monitor

This will enable us to detect abnormal heart rhythms which may be associated with myocardial fibrosis

Outcome Measures

Primary Outcome Measures :

Cardiovascular events [ Time Frame: 1 year ]
Cardiovascular events defined as cardiovascular deaths, development of heart failure symptoms, and the need for aortic valve replacement.

Biospecimen Retention: Samples Without DNA

Full blood count and renal panel will be measured.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

Study Population

A total of 240 individuals will be recruited. This includes 48 individuals who do not have aortic stenosis. A total of 192 individuals with aortic stenosis will be recruited:

Mild aortic stenosis, n=48
Moderate aortic stenosis, n=48
Severe aortic stenosis, n=48
Symptomatic aortic stenosis with planned valve replacement, n=48

Criteria

Inclusion Criteria:

Patients with aortic stenosis
Willing to undergo all investigations

Exclusion Criteria:

Coexisting mitral valvular heart disease and aortic regurgitation (more than moderate severity)
Active medical conditions: ongoing heart failure, infection
Significant comorbidities: advanced malignancy with limited life expectancy
Unable to give informed consent
Contraindication for cardiac magnetic resonance imaging: impaired renal function, pacemaker, claustrophobia

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01755936

Locations

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United Kingdom
University of Edinburgh
Edinburgh, Midlothian, United Kingdom, EH16 4SB

Sponsors and Collaborators

University of Edinburgh

British Heart Foundation

Investigators

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Principal Investigator:	David E Newby, MD PhD	University of Edinburgh

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Everett RJ, Tastet L, Clavel MA, Chin CWL, Capoulade R, Vassiliou VS, Kwiecinski J, Gomez M, van Beek EJR, White AC, Prasad SK, Larose E, Tuck C, Semple S, Newby DE, Pibarot P, Dweck MR. Progression of Hypertrophy and Myocardial Fibrosis in Aortic Stenosis: A Multicenter Cardiac Magnetic Resonance Study. Circ Cardiovasc Imaging. 2018 Jun;11(6):e007451. doi: 10.1161/CIRCIMAGING.117.007451.

Anand A, Chin C, Shah ASV, Kwiecinski J, Vesey A, Cowell J, Weber E, Kaier T, Newby DE, Dweck M, Marber MS, Mills NL. Cardiac myosin-binding protein C is a novel marker of myocardial injury and fibrosis in aortic stenosis. Heart. 2018 Jul;104(13):1101-1108. doi: 10.1136/heartjnl-2017-312257. Epub 2017 Dec 1.

Kwiecinski J, Chin CWL, Everett RJ, White AC, Semple S, Yeung E, Jenkins WJ, Shah ASV, Koo M, Mirsadraee S, Lang CC, Mills N, Prasad SK, Jansen MA, Japp AG, Newby DE, Dweck MR. Adverse prognosis associated with asymmetric myocardial thickening in aortic stenosis. Eur Heart J Cardiovasc Imaging. 2018 Mar 1;19(3):347-356. doi: 10.1093/ehjci/jex052.

Chin CWL, Everett RJ, Kwiecinski J, Vesey AT, Yeung E, Esson G, Jenkins W, Koo M, Mirsadraee S, White AC, Japp AG, Prasad SK, Semple S, Newby DE, Dweck MR. Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis. JACC Cardiovasc Imaging. 2017 Nov;10(11):1320-1333. doi: 10.1016/j.jcmg.2016.10.007. Epub 2016 Dec 21.

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Responsible Party:	University of Edinburgh
ClinicalTrials.gov Identifier:	NCT01755936
Other Study ID Numbers:	2010/R/CAR/05
First Posted:	December 24, 2012 Key Record Dates
Last Update Posted:	June 25, 2018
Last Verified:	July 2016

Keywords provided by University of Edinburgh:


Aortic Stenosis Cardiac magnetic resonance imaging Late Gadolinium enhancement	T1 mapping techniques Replacement fibrosis Diffuse interstitial fibrosis

Additional relevant MeSH terms:

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Aortic Valve Stenosis Fibrosis Constriction, Pathologic Pathologic Processes Pathological Conditions, Anatomical	Heart Valve Diseases Heart Diseases Cardiovascular Diseases Ventricular Outflow Obstruction

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