Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis

Study Overview
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Brief Summary
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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

Official Title
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Ultrasonic Markers for Myocardial Fibrosis and Prognosis in Aortic Stenosis

Conditions
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Aortic Valve Stenosis, Myocardial Fibrosis

Intervention / Treatment
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* Diagnostic Test: Echocardiography
* Diagnostic Test: MRI
* Diagnostic Test: Blood test
* Diagnostic Test: ECG and Holter-ECG
* Diagnostic Test: 6 min walking test


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Mild aortic stenosis<br>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<br>* 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.<br>* Other names: GE Vingmed ultrasound scanner e95, 2017;Diagnostic Test: MRI<br>* Cardiac MRI will be performed. In all patients without contraindications a gadolinium-based contrast agent will be given.<br>* Other names: Magnetic resonance imaging;Diagnostic Test: Blood test<br>* 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.<br>Diagnostic Test: ECG and Holter-ECG<br>* ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.<br>Diagnostic Test: 6 min walking test<br>* 6 MWT will be performed, and the findings will be related to findings from MRI/echocardiography.<br>|
| Other: Moderate aortic stenosis<br>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<br>* 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.<br>* Other names: GE Vingmed ultrasound scanner e95, 2017;Diagnostic Test: MRI<br>* Cardiac MRI will be performed. In all patients without contraindications a gadolinium-based contrast agent will be given.<br>* Other names: Magnetic resonance imaging;Diagnostic Test: Blood test<br>* 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.<br>Diagnostic Test: ECG and Holter-ECG<br>* ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.<br>Diagnostic Test: 6 min walking test<br>* 6 MWT will be performed, and the findings will be related to findings from MRI/echocardiography.<br>|
| Other: Severe aortic stenosis<br>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<br>* 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.<br>* Other names: GE Vingmed ultrasound scanner e95, 2017;Diagnostic Test: MRI<br>* Cardiac MRI will be performed. In all patients without contraindications a gadolinium-based contrast agent will be given.<br>* Other names: Magnetic resonance imaging;Diagnostic Test: Blood test<br>* 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.<br>Diagnostic Test: ECG and Holter-ECG<br>* ECG/Holter-ECG will be performed, and the findings will be related to the imaging findings.<br>Diagnostic Test: 6 min walking test<br>* 6 MWT will be performed, and the findings will be related to findings from MRI/echocardiography.<br>|
| Other: Controls<br>31 subjects, all undergoing echocardiography and blood test and MRI. | Diagnostic Test: Echocardiography<br>* 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.<br>* Other names: GE Vingmed ultrasound scanner e95, 2017;Diagnostic Test: MRI<br>* Cardiac MRI will be performed. In all patients without contraindications a gadolinium-based contrast agent will be given.<br>* Other names: Magnetic resonance imaging;Diagnostic Test: Blood test<br>* 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.<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardium, Predictive Value of Tests, Prognosis, Clinical Decision-making, Heart Ventricles, Echocardiography