Quantification of Myocardial Fibrosis in Aortis Stenosis (SAS-F-5)

Myocardial Fibrosis With High Frame Rate Echocardiography in Patients With Aortic Stenosis - A Follow-up Study

This study is a long term follow-up of patients that were included as part of a previous study (NCT03422770), where patients with aortic stenosis and healthy controls went through echocardiography, cardiac MRI, long-term ECG-recording, blood tests and quality of life assessment. Echocardiography included high frame ultrasound for detection of natural mechanical waves, and the measured speed of these waves were used as a marker of the extent of myocardial fibrosis.

Up to five years have now passed since inclusion at baseline, and a proportion of the patients in the cohort have undergone aortic valve replacement at some point. In this study, the investigators will repeat the cardiac imaging (echocardiography and cardiac MRI), ECG and blood test, to assess long-term changes in myocardial fibrosis in aortic stenosis patients.

Study Overview

• Status: Enrolling by invitation
• Conditions: Myocardial Fibrosis; Aortic Valve Stenosis
• Intervention / Treatment: Diagnostic test: ECG and Holter-ECG; Diagnostic test: High frame rate echocardiography; Diagnostic test: MRI; Diagnostic test: Blood test; Diagnostic test: 6 min walking test

Detailed Description

High frame rate ultrasound with quantification of myocardial mechanical wave velocities provides a new approach to evaluation of myocardial stiffness.

Principle: An elastic medium (the left ventricle) is incited by a force (naturally occuring mechanical wave generated by atrial contraction and/or closure of mitral and aortic valve), and the resulting oscillation wave propagates through the medium with a speed that depends only on the density and stiffness of the medium. If the density of the medium is known, measuring the propagation velocity of the wave is the same as measuring the stiffness of the medium.

There is a lack of longitudinal data in this research area. A follow-up study of the described cohort, will add valuable insight into high frame rate ultrasound as a potential tool to quantify myocardial fibrosis in heart failure patient, and to monitor any changes from baseline.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

Study Locations

• Norway
  • Trøndelag
    • Trondheim, Trøndelag, Norway, 7030
      • St. Olavs Hosptial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients: Mild, moderate, or severe aortic valve stenosis. A subset of the patients will have undergone aortic valve replacement since inclusion.

Controls: Healthy with no valve disease, or other cardiac disease known to cause myocardial fibrosis

Description

Inclusion Criteria:

• Part of the initial cohort that were included in the baseline study
• Still able to undergo protocolled investigations
• Patients: Mild, moderate or severe AS

Exclusion Criteria:

• Renal insufficiency
• Previously myocardial infarction (ECG, echocardiogram or hospital record)
• Severe valvular heart disease (except patients)
• Other cardiac disease known to cause myocardial fibrosis
• Severe hypertension
• Other medical conditions deterring protocolled investigation and follow-up
• Other medical conditions affecting 5-years prognosis (cancer, pulmonary disease)
• Severely reduced image-quality (echocardiography and MRI)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Aortic stenosis; Mild aortic stenosis:25 patients were included at baseline, and those that still avoid exclusion criteria, will be invited to undergo repeat echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. Moderate aortic stenosis: 25 patients were included at baseline, and those that still avoid exclusion criteria, will be invited to undergo repeat echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. Severe aortic stenosis: 50 patients were included at baseline, and those that still avoid exclusion criteria, will be invited to undergo repeat echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG.	Diagnostic test: ECG and Holter-ECG; ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.; Diagnostic test: High frame rate echocardiography; Conventional transthoracic echocardiography will be performed, with added 3D-imaging and acquisitions with high frame rate. The data from these patients will be anonymized and transferred for post-hoc analysis in dedicated computer software (GE Vingmed, EchoPac 2.6) and in validated machine learning algorithms.; Other Names: GE Vingmed ultrasound scanner E95, 2017; Diagnostic test: MRI; Cardiac MRI will be performed. In all patients without contraindications, a gadolinium-based contrast agent will be given.; Other Names: Cardiac magnetic resonance imaging (CMRI); Diagnostic test: Blood test; Conventional brachial venous blood samples will be drawn. Hematocrit value {in %} will be used to calculate CMR-derived exttracellular volume (ECV); Diagnostic test: 6 min walking test; 6 MWT will be performed, and the findings will be related to findings from CMRI/echocardiography.
Controls; The controls from baseline inclusion will be invited to undergo repeat echocardiography, blood test and CMRI	Diagnostic test: High frame rate echocardiography; Conventional transthoracic echocardiography will be performed, with added 3D-imaging and acquisitions with high frame rate. The data from these patients will be anonymized and transferred for post-hoc analysis in dedicated computer software (GE Vingmed, EchoPac 2.6) and in validated machine learning algorithms.; Other Names: GE Vingmed ultrasound scanner E95, 2017; Diagnostic test: MRI; Cardiac MRI will be performed. In all patients without contraindications, a gadolinium-based contrast agent will be given.; Other Names: Cardiac magnetic resonance imaging (CMRI); Diagnostic test: Blood test; Conventional brachial venous blood samples will be drawn. Hematocrit value {in %} will be used to calculate CMR-derived exttracellular volume (ECV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular morbidity	Admissions with heart failure	5 year
Cardiovascular mortality	Death caused by cardiac disease	5 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Mortality in general	5 years
Time of first re-hospitalization	Time of first re-hospitalization after inclusion	5 years
Cardiac systolic function	Systolic function based on left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Unit of measure for LVEF and for GLS is % for both (a positive number for LVEF, and a negative number for GLS)	5 years
Cardiac diastolic function (1 of 5)	Echocardiographic diastolic function based on i) left atrial volume index {ml/m^2).	5 years
Cardiac diastolic function (2 of 5)	Echocardiographic diastolic function based on ii) mitral annular velocities {cm/sec}	5 years
Cardiac diastolic function (3 of 5)	Echocardiographic diastolic function based on iii) mitral inflow velocities {cm/sec}	5 years
Cardiac diastolic function (4 of 5)	Echocardiographic diastolic function based on iv) ricuspid regurgitation velocity {cm/sec}	5 years
Cardiac diastolic function (5 of 5)	Echocardiographic diastolic function based on v) E/è-ratio	5 years
Velocity of natural mechanical waves propagating through the myocardium	Investigate for prognotisc value and if it can be a marker of diastolic dysfunction. Unit of velocity measurement is m/sec.	5 years

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: Oslo University Hospital; St. Olavs Hospital
• Investigators: Principal Investigator: Brage H: Amundsen, MD, PhD, Norwegian University of Science and Technology (NTNU)

Publications and helpful links

General Publications

• M. Mohajery, S. Salles, T. Espeland, S. Fadnes and L. Lovstakken,
• Salles S, Espeland T, Molares A, Aase SA, Hammer TA, Stoylen A, Aakhus S, Lovstakken L, Torp H. 3D Myocardial Mechanical Wave Measurements: Toward In Vivo 3D Myocardial Elasticity Mapping. JACC Cardiovasc Imaging. 2021 Aug;14(8):1495-1505. doi: 10.1016/j.jcmg.2020.05.037. Epub 2020 Aug 26.
• Espeland T, Wigen MS, Dalen H, Berg EAR, Hammer TA, Salles S, Lovstakken L, Amundsen BH, Aakhus S. Mechanical Wave Velocities in Left Ventricular Walls in Healthy Subjects and Patients With Aortic Stenosis. JACC Cardiovasc Imaging. 2024 Feb;17(2):111-124. doi: 10.1016/j.jcmg.2023.07.009. Epub 2023 Sep 6.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): April 15, 2026

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: August 23, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Prognosis; Heart failure; Cardiac MRI; Aortic stenosis; High frame rate echocardiography; Quantification of severity
• Additional Relevant MeSH Terms: Aortic Valve Disease; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Anatomical; Heart Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic; Fibrosis
• Other Study ID Numbers: 527717

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