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Assessment of Myocardial Fibrosis in Aortic STenosis

Assessment of Myocardial Fibrosis - Impact on Postoperative Outcome i Patients With Severe Aortic STenosis Undergoing Aortic Valve Replacement

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT02316587
Acronym
AMFAST
Enrollment
112
Registered
2014-12-15
Start date
2014-03-31
Completion date
2016-12-31
Last updated
2017-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Aortic Valve Stenosis, Endomyocardial Fibrosis

Keywords

Computerized Tomography, Magnetic Resonance Imaging, Echocardiography, Right Heart Catheterization

Brief summary

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.

Interventions

None listed

Sponsors

Odense University Hospital
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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).

Design outcomes

Primary

MeasureTime frameDescription
MACE (Major Adverse Cardiac Event)2 yearsMajor Adverse Cardiac Event defined as all-cause mortality or admission with heart failure

Secondary

MeasureTime frame
Cardiovascular mortality2 years

Other

MeasureTime frameDescription
NYHA change1 yearNew York Heart Association classification of dyspnea
Functional capacity assessed by right heart catheterization and VO2-max test1 yearFunctional capacity assessed by right heart catheterization and VO2-max test
Extracellular volume quantification Assessed by biopsy, CT and MRi1 yearAssessed by biopsy, CT and MRi at baseline and after one year
Duke Activity Score Index1 yearDuke Activity Score Index Questionaire

Countries

Denmark

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 25, 2026