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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Stenosis, Calcific
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 110

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Aalborg University Hospital
• Lithuania
  • Vilnius, Lithuania, 08416
    • Vilnius University Hospital Santaros Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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).

Description

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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
A composite of all-cause mortality and MACE (Acute myocardial infarction, stroke, heart failure requiring hospitalisation)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular mortality		2 years
Short term mortality	Intrahospital or 30 days mortality	30 days
Lengh of hospital stay		30 days
Time to the event ( deathe of MACE)		2 years

Collaborators and Investigators

• Sponsor: Vilnius University
• Investigators: Principal Investigator: Peter Sogaard, Prof., Aalborg University

Publications and helpful links

General Publications

• Balciunaite G, Palionis D, Zurauskas E, Skorniakov V, Janusauskas V, Zorinas A, Zaremba T, Valeviciene N, Aidietis A, Serpytis P, Rucinskas K, Sogaard P, Glaveckaite S. Prognostic value of myocardial fibrosis in severe aortic stenosis: study protocol for a prospective observational multi-center study (FIB-AS). BMC Cardiovasc Disord. 2020 Jun 8;20(1):275. doi: 10.1186/s12872-020-01552-8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 8, 2019
• Primary Completion (ANTICIPATED): August 1, 2024
• Study Completion (ANTICIPATED): August 1, 2024

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (ACTUAL): July 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 18, 2022
• Last Update Submitted That Met QC Criteria: October 16, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Cardiovascular magnetic resonance; Myocardial fibrosis; Scintigraphy; Severe aortic stenosis; SAVR/TAVI
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Fibrosis; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: 1014; 09.3.3-LMT-K-712 (OTHER_GRANT: European structural funds)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No