Assessment of Myocardial Fibrosis in Aortic STenosis

NCT ID: NCT02316587

Last Updated: 2017-04-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 112 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2016-12-31

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.

Conditions

Endomyocardial Fibrosis; Aortic Valve Stenosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Rasmus Carter-Storch

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jacob E Møller, MD PhD DMsc

Role: STUDY_DIRECTOR

Odense University Hospital

Jordi S Dahl, MD, Ph.D.

Role: STUDY_CHAIR

Odense University Hospital

Kristian A Øvrehus, MD, Ph.D.

Role: STUDY_CHAIR

Odense University Hospital

Lars M Rasmussen, MD PhD DMsc

Role: STUDY_CHAIR

Odense University Hospital

Locations

Odense University Hospital

Odense C, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 33574022 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30977792 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29222121 (View on PubMed)

Other Identifiers

AMFAST

Identifier Type: -

Identifier Source: org_study_id