Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis

• ClinicalTrials.gov Identifier: NCT03422770
• Recruitment Status: Completed
• First Posted: February 6, 2018
• Last Update Posted: August 16, 2023
• Sponsor: Norwegian University of Science and Technology
• Collaborators: St. Olavs Hospital; Oslo University Hospital
• Information provided by (Responsible Party): Norwegian University of Science and Technology

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Aortic Valve Stenosis; Myocardial Fibrosis	Diagnostic Test: Echocardiography; Diagnostic Test: MRI; Diagnostic Test: Blood test; Diagnostic Test: ECG and Holter-ECG; Diagnostic Test: 6 min walking test	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 132 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: All participants will undergo 'echo', bloodtests and MRI. Participating patients will in addition undergo electrocardiogram (ECG/Holter ECG) and 6 min walking test.
• Masking: Single (Outcomes Assessor)
• Masking Description: Analysis will be blinded
• Primary Purpose: Diagnostic
• Official Title: Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis
• Actual Study Start Date: January 9, 2018
• Actual Primary Completion Date: June 30, 2020
• Actual Study Completion Date: June 30, 2020

Arms and Interventions

Arm	Intervention/treatment
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 Name: 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 Name: 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.
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 Name: 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 Name: 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.
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 Name: 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 Name: 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.
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 Name: 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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Cardiovascular morbidity and mortality [ Time Frame: 1 + 3 year ]
   Admission with heart failure or death caused by cardiac disease ('major adverse cardiac events' MACE)

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

Norway

Department of Circulation and Medical Imaging

Trondheim, Norway

Sponsors and Collaborators

Norwegian University of Science and Technology

St. Olavs Hospital

Oslo University 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Norwegian University of Science and Technology
• ClinicalTrials.gov Identifier: NCT03422770
• Other Study ID Numbers: 2017/1068
• First Posted: February 6, 2018
• Last Update Posted: August 16, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Norwegian University of Science and Technology:

Myocardium; Predictive Value of Tests; Prognosis; Clinical Decision-making; Heart Ventricles; Echocardiography

Additional relevant MeSH terms:

Aortic Valve Stenosis; Fibrosis; Constriction, Pathologic; Pathologic Processes; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction