Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis

This study is part of a research project in which new ultrasound-based techniques will be examined to improve clinical decision making for patients with aortic stenosis. These patients could develop increased amounts of myocardial fibrosis. This fibrosis is associated with the patients' prognosis. Fibrosis can be evaluated with magnetic resonance imaging (MRI), which unfortunately is quite expensive and not easily available. Ultrasound-based parameters will be developed for the assessment of the amounts of myocardial fibrosis, especially in the left ventricle. Then it will be examined whether these parameters can predict the patients magnitude of fibrosis and check for association with the patients prognosis. MRI will serve as a gold standard for quantification of myocardial fibrosis. The new echocardiographic techniques and parameters are expected to provide new insights in the interplay between aortic stenosis and left ventricular function, and to ultimately improve the care for patients with aortic stenosis.

The present study's objectives are:

• Quantify the level of myocardial fibrosis in mild, moderate, and severe aortic stenosis compared with a healthy population.
• Evaluate the patients outcome after one and three year of follow-up

Study Overview

• Status: Completed
• Conditions: Myocardial Fibrosis; Aortic Valve Stenosis
• Intervention / Treatment: Diagnostic test: Echocardiography; Diagnostic test: MRI; Diagnostic test: Blood test; Diagnostic test: ECG and Holter-ECG; Diagnostic test: 6 min walking test

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Svend Aakhus, MD PhD; Phone Number: +47 72828072; Email: svend.aakhus@ntnu.no
• Study Contact Backup: Name: Torvald Espeland, MD; Phone Number: +47 99703156; Email: torvald.espeland@ntnu.no

Study Locations

• Norway
  • Trondheim, Norway
    • Department of Circulation and Medical Imaging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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-yrs prognosis (cancer, pulmonary disease)
• Severely reduced image-quality (echocardiography and MRI)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Mild aortic stenosis; 25 patients, all undergoing echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. All undergoing 1 year control.	Diagnostic test: Echocardiography; Conventional transthoracic echocardiography will be performed, in addition 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 2.0) 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: Magnetic resonance imaging; Diagnostic test: Blood test; Conventional brachial venous blood samples will be drawn. Blood samples will be analyzed for markers of myocardial fibrosis at Oslo University Hospital.The findings will be related to imaging findings.; Diagnostic test: ECG and Holter-ECG; ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.; Diagnostic test: 6 min walking test; 6 MWT will be performed, and the findings will be related to findings from MRI/echocardiography.
Other: Moderate aortic stenosis; 25 patients, all undergoing echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. All undergoing 1 year control.	Diagnostic test: Echocardiography; Conventional transthoracic echocardiography will be performed, in addition 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 2.0) 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: Magnetic resonance imaging; Diagnostic test: Blood test; Conventional brachial venous blood samples will be drawn. Blood samples will be analyzed for markers of myocardial fibrosis at Oslo University Hospital.The findings will be related to imaging findings.; Diagnostic test: ECG and Holter-ECG; ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.; Diagnostic test: 6 min walking test; 6 MWT will be performed, and the findings will be related to findings from MRI/echocardiography.
Other: Severe aortic stenosis; 50 patients, all undergoing echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. All undergoing 1 year control.	Diagnostic test: Echocardiography; Conventional transthoracic echocardiography will be performed, in addition 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 2.0) 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: Magnetic resonance imaging; Diagnostic test: Blood test; Conventional brachial venous blood samples will be drawn. Blood samples will be analyzed for markers of myocardial fibrosis at Oslo University Hospital.The findings will be related to imaging findings.; Diagnostic test: ECG and Holter-ECG; ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.; Diagnostic test: 6 min walking test; 6 MWT will be performed, and the findings will be related to findings from MRI/echocardiography.
Other: Controls; 31 subjects, all undergoing echocardiography and blood test and MRI.	Diagnostic test: Echocardiography; Conventional transthoracic echocardiography will be performed, in addition 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 2.0) 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: Magnetic resonance imaging; Diagnostic test: Blood test; Conventional brachial venous blood samples will be drawn. Blood samples will be analyzed for markers of myocardial fibrosis at Oslo University Hospital.The findings will be related to imaging findings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular morbidity and mortality	Admission with heart failure or death caused by cardiac disease ('major adverse cardiac events' MACE)	1 + 3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Mortality in general	3 years
Time of first re-hospitalisation	Time of first re-hospitalisation after inclusion	3 years
Cardiac systolic function	Echocardiographic systolic function based on left ventricular ejection fraction, global longitudinal strain, mitral annular plane systolic excursion (MAPSE)	1 year.
Cardiac diastolic function	Echocardiographic diastolic function based on the volume of the left atrium, the tricuspidal regurgitation, mitral annular velocities and mitral flow	1 year.

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: Oslo University Hospital; St. Olavs Hospital
• Investigators: Study Director: Svend Aakhus, MD PhD, Norwegian University of Science and Technology; Study Director: Brage Høyem Amundsen, MD PhD, Norwegian University of Science and Technology

Publications and helpful links

General Publications

• 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. Erratum In: JACC Cardiovasc Imaging. 2023 Feb;16(2):268.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2018
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Prognosis; Echocardiography; Predictive Value of Tests; Myocardium; Clinical Decision-making; Heart Ventricles
• 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: 2017/1068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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