Endomyocardial FibrosisAMFASTNCT02316587
Assessment of Myocardial Fibrosis in Aortic STenosis
An observational study of Endomyocardial Fibrosis and Aortic Valve Stenosis, run by Odense University Hospital at 1 site in Denmark.
Trial summary
This observational cohort study studies the impact myocardial fibrosis has on patients with severe aortic stenosis undergoing aortic valve replacement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endomyocardial Fibrosis, Aortic Valve Stenosis
- How many people
- 112 participants
- Where
- 1 siteDenmark
- Study dates
- Mar 2014to Dec 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients with severe aortic valve stenosis.
Who may be able to join
- Severe aortic valve stenosis (AVA ≤1cm2).
- Scheduled for aortic valve replacement.
- Signed consent
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of Myocardial Fibrosis - Impact on Postoperative Outcome i Patients With Severe Aortic STenosis Undergoing Aortic Valve Replacement
This observational cohort study studies the impact myocardial fibrosis has on patients with severe aortic stenosis undergoing aortic valve replacement.
Read the 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.
- Conditions
- Endomyocardial Fibrosis, Aortic Valve Stenosis
- Keywords
- Computerized Tomography, Magnetic Resonance Imaging, Echocardiography, Right Heart Catheterization
- Medical subject headings
- Endomyocardial Fibrosis, Aortic Valve Stenosis
What is being measured
The primary outcome is the main question the study is designed to answer.
MACE (Major Adverse Cardiac Event)
Major Adverse Cardiac Event defined as all-cause mortality or admission with heart failure
Measured: 2 years
Secondary outcomes (1)
Cardiovascular mortality
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2014 (estimated)
- Study startMar 2014
- Primary completionJan 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Endomyocardial FibrosisStudies of the same condition, open and under way.
- More trials run by Odense University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rasmus Carter-Storch, Odense University Hospital
- Investigators
- Jacob E Møller, MD PhD DMsc, Study director, Odense University HospitalJordi S Dahl, MD, Ph.D., Study chair, Odense University HospitalKristian A Øvrehus, MD, Ph.D., Study chair, Odense University HospitalLars M Rasmussen, MD PhD DMsc, Study chair, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02316587
- Sponsor's protocol ID
- AMFAST
- Acronym
- AMFAST
- Status last verified
- Apr 2017
- First submitted
- 10 Dec 2014
- Last updated
- 4 Apr 2017
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 33574022Carter-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.
PubMed 30977792Carter-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.
PubMed 29222121
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Myocardial Fibrosis - Impact on Postoperative Outcome i Patients With Severe Aortic STenosis Undergoing Aortic Valve Replacement
- ClinicalTrials.gov ID
- NCT02316587
- Acronym / sponsor ID
- AMFAST / AMFAST
- Conditions
- Endomyocardial Fibrosis, Aortic Valve Stenosis
- Keywords
- Computerized Tomography, Magnetic Resonance Imaging, Echocardiography, Right Heart Catheterization
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 15 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This observational cohort study studies the impact myocardial fibrosis has on patients with severe aortic stenosis undergoing aortic valve replacement.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients with severe aortic valve stenosis.
Key inclusion criteria (3 listed)
- Severe aortic valve stenosis (AVA ≤1cm2).
- Scheduled for aortic valve replacement.
- Signed consent
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
MACE (Major Adverse Cardiac Event)
Time frame: 2 years
Major Adverse Cardiac Event defined as all-cause mortality or admission with heart failure
1 secondary outcome
Cardiovascular mortality
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2017.
- Derived from this study: PubMed 33574022Carter-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.
- Derived from this study: PubMed 30977792Carter-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.
- Derived from this study: PubMed 29222121Carter-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacob E Møller, MD PhD DMsc study director
Odense University Hospital
Jordi S Dahl, MD, Ph.D. study chair
Odense University Hospital
Kristian A Øvrehus, MD, Ph.D. study chair
Odense University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Endomyocardial Fibrosis and Aortic Valve Stenosis, run by Odense University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MACE (Major Adverse Cardiac Event) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02316587, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2017.