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

Sponsor

Vilnius University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03585933

Collaborator

(none)

110

Enrollment

Locations

37.8

Anticipated Duration (Months)

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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	Phase
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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

110 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prognostic Value of Myocardial Fibrosis in Severe Aortic Valve Stenosis

Actual Study Start Date :

May 8, 2019

Anticipated Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Jul 1, 2022

Outcome Measures

Primary Outcome Measures

A composite of all-cause mortality and MACE (Acute myocardial infarction, stroke, heart failure requiring hospitalisation) [2 years]

Secondary Outcome Measures

Cardiovascular mortality [2 years]
Short term mortality [30 days]
Intrahospital or 30 days mortality
Lengh of hospital stay [30 days]
Time to the event ( deathe of MACE) [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Severe aortic stenosis (aortic valve area <1.0cm2 or aortic valve area index <0.6 cm2/m2
Age ≥18 years.
Signed informed patient consent form.

Exclusion Criteria:

Severe valvular disease other than AS.
Significant coronary heart disease requiring revascularisation.
History of myocardial infarction.
Previous cardiac surgery.
Severe renal impairment eGFR <30ml/min/1.73m2.
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)