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

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

All participants will undergo 'echo', bloodtests and MRI. Participating patients will in addition undergo electrocardiogram (ECG/Holter ECG) and 6 min walking test.

25 patients, all undergoing echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. All undergoing 1 year control.

25 patients, all undergoing echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. All undergoing 1 year control.

50 patients, all undergoing echocardiography, MRI, blood test, questionnaires, 6 min walking test, ECG and Holter-ECG. All undergoing 1 year control.

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.

Cardiac MRI will be performed. In all patients without contraindications a gadolinium-based contrast agent will be given.

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.

Admission with heart failure or death caused by cardiac disease ('major adverse cardiac events' MACE)

Echocardiographic systolic function based on left ventricular ejection fraction, global longitudinal strain, mitral annular plane systolic excursion (MAPSE)

Echocardiographic diastolic function based on the volume of the left atrium, the tricuspidal regurgitation, mitral annular velocities and mitral flow

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)

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.