Quantification of Myocardial Fibrosis in Aortis Stenosis

Not yet recruiting

• Conditions: Aortic Valve Stenosis; Myocardial Fibrosis
• Interventions: Diagnostic Test: High frame rate echocardiography; Diagnostic Test: MRI; Diagnostic Test: Blood test; Diagnostic Test: ECG and Holter-ECG; Diagnostic Test: 6 min walking test

• Registration Number: NCT06571175
• Lead Sponsor: Norwegian University of Science and Technology

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-07-10
• Status Verified: 2024-08
• Study Start: 2024-08
• Study First Submitted QC: 2024-08-23
• Last Update Submitted: 2024-08-23
• Study First Posted: 2024-08-26
• Last Update Posted: 2024-08-26
• Primary Completion: 2025-06
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Aortic stenosis	Blood test	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.
Controls	Blood test	The controls from baseline inclusion will be invited to undergo repeat echocardiography, blood test and CMRI
Aortic stenosis	6 min walking test	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.
Controls	High frame rate echocardiography	The controls from baseline inclusion will be invited to undergo repeat echocardiography, blood test and CMRI
Aortic stenosis	High frame rate echocardiography	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.
Aortic stenosis	MRI	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.
Aortic stenosis	ECG and Holter-ECG	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.
Controls	MRI	The controls from baseline inclusion will be invited to undergo repeat echocardiography, blood test and CMRI

Primary Outcome Measures

Name	Time	Method
Cardiovascular morbidity	5 year	Admissions with heart failure
Cardiovascular mortality	5 year	Death caused by cardiac disease

Secondary Outcome Measures

Name	Time	Method
Cardiac diastolic function (5 of 5)	5 years	Echocardiographic diastolic function based on v) E/è-ratio
Cardiac diastolic function (1 of 5)	5 years	Echocardiographic diastolic function based on i) left atrial volume index {ml/m\^2).
All cause mortality	5 years	Mortality in general
Cardiac diastolic function (2 of 5)	5 years	Echocardiographic diastolic function based on ii) mitral annular velocities {cm/sec}
Cardiac diastolic function (3 of 5)	5 years	Echocardiographic diastolic function based on iii) mitral inflow velocities {cm/sec}
Cardiac systolic function	5 years	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)
Velocity of natural mechanical waves propagating through the myocardium	5 years	Investigate for prognotisc value and if it can be a marker of diastolic dysfunction. Unit of velocity measurement is m/sec.
Time of first re-hospitalization	5 years	Time of first re-hospitalization after inclusion
Cardiac diastolic function (4 of 5)	5 years	Echocardiographic diastolic function based on iv) ricuspid regurgitation velocity {cm/sec}

Trial Locations

Locations (1)

St. Olavs Hosptial; 🇳🇴 Trondheim, Trøndelag, Norway