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Prognostic Value of Myocardial Fibrosis in Severe Aortic Valve Stenosis (FIB-AS)

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ClinicalTrials.gov Identifier: NCT03585933
Recruitment Status : Not yet recruiting
First Posted : July 13, 2018
Last Update Posted : July 20, 2018
Sponsor:
Collaborator:
Research Council of Lithuania
Information provided by (Responsible Party):
Peter Sogaard,MD DMSc, Aalborg University

Brief Summary:

Degenerative aortic valve stenosis (AS) is the most common valve heart disease in the developed Western countries. The hemodynamic progression of AS occurs over time and leads to LV hypertrophy (LVH) as a compensation mechanism of the heart. Morphological changes such as increasing muscle fibre thickness, collagen volume, and interstitial fibrosis occur in AS patients. These changes result in left ventricular (LV) diastolic and systolic dysfunction and, consequently, to with AS related symptoms. When symptoms associated with AS appear, patients' prognosis is poor if surgical aortic valve replacement (SAVR) or a trans-catheter aortic valve implantation (TAVI) is not performed.

Primary hypothesis of the research: fibrotic changes in the myocardium are related to immediate (in hospital) or long-term complications (MACE and all-cause mortality) in patients with severe AS.

The goal of the study is to determine the prognostic implications of focal as well as diffuse myocardial fibrosis in patients with severe aortic valve stenosis.


Condition or disease Intervention/treatment
Aortic Stenosis, Calcific Diagnostic Test: Cardiac magnetic resonance imaging

Detailed Description:

AS is the most common valvular heart condition in the Western world. In response to increased afterload imposed by AS adaptive left ventricular (LV) remodelling occurs which in a course of a disease transitions from LV hypertrophy to maladaptive changes in the myocardium leading to cardiac decompensation and symptoms development. This transition is predominantly driven by myocardial fibrosis and myocyte cell death. Increasing evidence have demonstrated that presence of myocardial fibrosis, detected by cardiovascular magnetic resonance (CMR), could serve as an early marker of LV decompensation and predict adverse outcomes in patients with aortic stenosis. Currently, the indications for valvular replacement are based on the stenosis severity evaluated by echocardiography and the presence of symptoms.

The objective of the project is to identify parameters of non-invasive imaging modalities (two-dimensional echocardiography with an extended myocardial deformation analysis, 1.5 T CMR with T1 parametric map and late gadolinium enhancement (LGE) predictive of cardiac decompensation and to evaluate the prognostic significance of myocardial fibrotic changes in patients with severe degenerative AS. In patients with suspicion of cardiac amyloidosis, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy will be performed.

Study design: a prospective, open, case-driven, multicentre study (Lithuania, Denmark).

Investigators will assess LV structural and functional alterations before and 12 months after aortic valve intervention. Cardiac imaging data will be aligned with histopathological data from myocardial tissue samples collected at the time of aortic valve replacement in SAVR group. In patients with suspicion of cardiac amyloidosis, DPD scintigraphy and further evaluation regarding amyloidosis will be performed.


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prognostic Value of Myocardial Fibrosis in Severe Aortic Valve Stenosis
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine



Intervention Details:
  • Diagnostic Test: Cardiac magnetic resonance imaging
    Echocardiography: assessment of aortic stenosis severity, evaluation of LV diastolic and systolic function; CMR: chambers quantification, LGE, T1 mapping; Intraoperative myocardial tissue biopsy for patients undergoing SAVR; DPD scintigraphy: assessment of cardiac transthyretin amyloidosis
    Other Names:
    • echocardiography
    • Intra-operative myocardial biopsy
    • DPD scintigraphy


Primary Outcome Measures :
  1. Cardiovascular mortality [ Time Frame: 2 years ]
    Cardiovascular death


Secondary Outcome Measures :
  1. Major adverse cardiovascular events [ Time Frame: 2 years ]
    Acute myocardial infarction, stroke, heart failure requiring hospitalisation

  2. Short term mortality [ Time Frame: 30 days ]
    Intrahospital or 30 days mortality


Biospecimen Retention:   Samples With DNA
Serum, myocardial tissue samples obtained intra-operatively


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with severe aortic stenosis without significant coronary artery disease (CAD), eligible for aortic valve intervention (SAVR or TAVI).
Criteria

Inclusion Criteria:

  • Severe aortic stenosis (aortic valve area ≤1.0cm2 or aortic valve area index ≤0.6 cm2/m2 and peak aortic velocity >4 m/s, or mean pressure gradient ≥40mmHg).
  • Age ≥18 years.
  • Signed informed patient consent form.

Exclusion Criteria:

  • Severe valvular disease other than AS.
  • Significant coronary heard disease requiring revascularisation.
  • History of myocardial infarction.
  • Previous cardiac surgery.
  • Severe renal impairment eGFR <30ml/min.
  • Any absolute contraindication to CMR.
  • Inherited or acquired cardiomyopathy.
  • Other medical conditions that limits life expectancy or precludes SAVR or TAVI.
  • Pregnant or nursing women
  • Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study or to follow the protocol
  • Patients in permanent atrial fibrillation.
  • Significant chronic obstructive pulmonary disease (FEV1 <70% of predicted value)
  • Patient with implanted devices (pacemaker, ICD)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03585933


Contacts
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Contact: Sigita Glaveckaite, PhD +37068240937 sigita.glaveckaite@santa.lt
Contact: Giedre Balciunaite, MD +37069823346 dr.giedre.balciunaite@gmail.com

Locations
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Denmark
Aalborg University Hospital Not yet recruiting
Aalborg, Denmark
Contact: Tomas Zaremba, PhD    +37068095463    tozaremba@gmail.com   
Lithuania
Vilnius University Hospital Santaros clinics Not yet recruiting
Vilnius, Lithuania, 08416
Contact: Sigita Glaveckaite, PhD    +37068240937    sigita.glaveckaite@santa.lt   
Contact: Giedre Balciunaite, MD    +37069823346    dr.giedre.balciunaite@gmail.com   
Sponsors and Collaborators
Vilnius University
Research Council of Lithuania
Investigators
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Principal Investigator: Peter Sogaard, Prof. Aalborg University

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Responsible Party: Peter Sogaard,MD DMSc, Peter Sogaard, Clinical Professor, Aalborg University
ClinicalTrials.gov Identifier: NCT03585933     History of Changes
Other Study ID Numbers: 1014
09.3.3-LMT-K-712 ( Other Grant/Funding Number: European structural funds )
First Posted: July 13, 2018    Key Record Dates
Last Update Posted: July 20, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peter Sogaard,MD DMSc, Aalborg University:
Myocardial fibrosis
Severe aortic stenosis
Cardiovascular magnetic resonance
Scintigraphy
SAVR/TAVI

Additional relevant MeSH terms:
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Aortic Valve Stenosis
Calcinosis
Fibrosis
Constriction, Pathologic
Pathologic Processes
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction
Calcium Metabolism Disorders
Metabolic Diseases