Assessment of Myocardial Fibrosis in Aortic STenosis

Aortic Valve Stenosis Clinical Trial

— AMFAST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02316587
• Other study ID #: AMFAST
• Status: Completed
• Phase: N/A
• First received: December 10, 2014
• Last updated: April 3, 2017
• Start date: March 2014
• Est. completion date: December 2016

Study information

• Verified date: April 2017
• Source: Odense University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This observational cohort study studies the impact myocardial fibrosis has on patients with severe aortic stenosis undergoing aortic valve replacement.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: December 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic
• Endomyocardial Fibrosis
• Fibrosis

Locations

Country	Name	City	State
Denmark	Odense University Hospital	Odense C

Sponsors (1)

Lead Sponsor	Collaborator
Odense University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	NYHA change	New York Heart Association classification of dyspnea	1 year
Other	Functional capacity assessed by right heart catheterization and VO2-max test	Functional capacity assessed by right heart catheterization and VO2-max test	1 year
Other	Extracellular volume quantification Assessed by biopsy, CT and MRi	Assessed by biopsy, CT and MRi at baseline and after one year	1 year
Other	Duke Activity Score Index	Duke Activity Score Index Questionaire	1 year
Primary	MACE (Major Adverse Cardiac Event)	Major Adverse Cardiac Event defined as all-cause mortality or admission with heart failure	2 years
Secondary	Cardiovascular mortality		2 years