- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02316587
Assessment of Myocardial Fibrosis in Aortic STenosis (AMFAST)
Assessment of Myocardial Fibrosis - Impact on Postoperative Outcome i Patients With Severe Aortic STenosis Undergoing Aortic Valve Replacement
Study Overview
Status
Conditions
Detailed Description
Aortic stenosis is the most common valvular disease in the Western World. It is a slow evolving degenerative disease caused by gradual accumulation of calcium in the valve. Untreated it is fatal. Reduced opening area of the valve increases afterload on the left ventricle (LV), which leads to raised end-diastolic pressure in the LV. Increased wall stress leads to LV hypertrophy and expansion of the extracellular matrix. An abnormally high extracellular volume fraction is called myocardial fibrosis (MF), which causes increased LV stiffness, diastolic dysfunction, dilatation of the left atrium and in the end heart failure.
The standard of treatment for aortic stenosis is an operation, aortic valve repair (AVR), where a mechanical or biological valve replaces the old one. The operation involves a substantial risk of postoperative mortality, and is therefore delayed until the patient develops symptoms such as shortness of breath, chest pains or syncope. For most patients AVR causes significant symptom reduction and reduced mortality. Recent studies have indicated that patient with severe MF, which may account for up to one third of the patients treated, have little or no symptom improvement and an increased mortality after AVR. This raises concern that their LV is so severely fibrotic that it is beyond repair. These patients may not benefit from an operation, or should possibly have had AVR performed at an earlier stage of the disease.
Today, cardiac fibrosis can be detected by a biopsy which is invasive. Late Gadolinium and T1-mapping cardiac Magnetic Resonance imaging (MRi) has recently been evaluated as a new method to detect MF, but this method is costly and contraindicated for some patients. Cardiac Computerized Tomography (CT) has been proposed as a method to evaluate MF, but has not been properly validated yet.
In this study we compare different methods (biopsy, MRi, CT, echocardiography and different biomarkers) to evaluate the extent of MF in 130 patients with severe aortic stenosis undergoing AVR. We will focus on their symptom improvement and survival rate one year after the operation. Our main thesis is that patients with severe fibrosis before the operation have little or no symptom improvement and reduced survival after the operation. If this thesis is correct, it will question which patients to offer AVR. Some patients we operate today may have no benefit from the operation because the left ventricle is damaged from severe fibrosis, and some patients from who we withhold the operation today because they are asymptomatic may benefit from AVR before they develop severe fibrosis.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Odense C, Denmark, 5000
- Odense University Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Severe aortic valve stenosis (AVA ≤1cm2).
- Scheduled for aortic valve replacement.
- Signed consent
Exclusion Criteria:
- At least moderate mitral regurgitation or stenosis.
- Primary aortic insufficiency.
- Persistent or permanent atrial fibrillation/flutter.
- CKD with e-GFR < 40 ml/kg/min.
- Pacemaker or Implantable Cardioverter Defibrillator (ICD).
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MACE (Major Adverse Cardiac Event)
Time Frame: 2 years
|
Major Adverse Cardiac Event defined as all-cause mortality or admission with heart failure
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Cardiovascular mortality
Time Frame: 2 years
|
2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
NYHA change
Time Frame: 1 year
|
New York Heart Association classification of dyspnea
|
1 year
|
Functional capacity assessed by right heart catheterization and VO2-max test
Time Frame: 1 year
|
Functional capacity assessed by right heart catheterization and VO2-max test
|
1 year
|
Extracellular volume quantification Assessed by biopsy, CT and MRi
Time Frame: 1 year
|
Assessed by biopsy, CT and MRi at baseline and after one year
|
1 year
|
Duke Activity Score Index
Time Frame: 1 year
|
Duke Activity Score Index Questionaire
|
1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Jacob E Møller, MD PhD DMsc, Odense University Hospital
- Study Chair: Jordi S Dahl, MD, Ph.D., Odense University Hospital
- Study Chair: Kristian A Øvrehus, MD, Ph.D., Odense University Hospital
- Study Chair: Lars M Rasmussen, MD PhD DMsc, Odense University Hospital
Publications and helpful links
General Publications
- Carter-Storch R, Mortensen NSB, Christensen NL, Ali M, Laursen KB, Pellikka PA, Moller JE, Dahl JS. First-phase ejection fraction: association with remodelling and outcome in aortic valve stenosis. Open Heart. 2021 Feb;8(1):e001543. doi: 10.1136/openhrt-2020-001543. Erratum In: Open Heart. 2021 Mar;8(1):
- Carter-Storch R, Dahl JS, Christensen NL, Pecini R, Sondergard EV, Ovrehus KA, Moller JE. Postoperative atrial fibrillation after aortic valve replacement is a risk factor for long-term atrial fibrillation. Interact Cardiovasc Thorac Surg. 2019 Sep 1;29(3):378-385. doi: 10.1093/icvts/ivz094.
- Carter-Storch R, Moller JE, Christensen NL, Irmukhadenov A, Rasmussen LM, Pecini R, Ovrehus KA, Sondergard EV, Marcussen N, Dahl JS. Postoperative Reverse Remodeling and Symptomatic Improvement in Normal-Flow Low-Gradient Aortic Stenosis After Aortic Valve Replacement. Circ Cardiovasc Imaging. 2017 Dec;10(12):e006580. doi: 10.1161/CIRCIMAGING.117.006580.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AMFAST
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Aortic Valve Stenosis
-
Anteris Technologies Ltd.Active, not recruitingAortic Stenosis | Aortic Valve Calcification | Severe Aortic Valve Stenosis | Symptomatic Aortic StenosisUnited States
-
The Medicines CompanyCompletedTranscatheter Aortic Valve Replacement | Aortic Valve Replacement | Severe Aortic StenosisNetherlands, Germany, United Kingdom, Canada, France, Italy, Switzerland
-
Anteris Technologies Ltd.Active, not recruitingAortic Valve Calcification | Severe Aortic Valve Stenosis | Symptomatic Aortic StenosisGeorgia
-
Ningbo Jenscare Biotechnology Co., Ltd.UnknownAortic Regurgitation | Severe Aortic Stenosis
-
Edwards LifesciencesCompletedAortic Valve Stenosis | Aortic Valve Stenosis With Insufficiency | Regurgitation, Aortic Valve | Aortic Valve IncompetenceUnited States
-
Sorin Group USA, Inc.TerminatedAortic Valve Stenosis | Aortic Valve Stenosis With Insufficiency | Regurgitation, Aortic Valve | Aortic Valve IncompetenceUnited States
-
Edwards LifesciencesActive, not recruitingAortic Stenosis | Aortic Regurgitation | Symptomatic Aortic StenosisChina
-
BC Centre for Improved Cardiovascular HealthEdwards LifesciencesUnknownTranscatheter Aortic Valve Implantation | Severe Aortic StenosisCanada
-
Genesis Medtech CorporationRecruitingDiseases of Aortic Valve | Aortic Stenosis DiseaseChina
-
Hospices Civils de LyonRecruiting