Cardiac Imaging in Adults With Congenital Aortic Stenosis

Study Overview
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Brief Summary
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The CAS study is a prospective observational cohort study investigating the effects of congenital aortic stenosis (ConAoS) on the left ventricular function and the prevalence, pattern and expanse of left ventricular hypertrophy (LVH), myocardial stiffness and myocardial fibrosis.

Detailed Description
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Congenital aortic stenosis (ConAoS) accounts for 4-8% of all congenital cardiac diagnoses. It is often caused by a bicuspid aortic valve (BAV), which has an estimated prevalence of 0.5-2% in the general population. Patients with ConAoS may remain asymptomatic, but gradual deterioration of the stenosis and the strong association of BAV with aortic dilatation contributes to important morbidity and mortality. The prevalent nature of this heart defect implies an important health problem resulting in hospitalization and (re-) interventions. As it is still largely unknown which markers predict adverse outcome, the aim of this study is to evaluate trends in imaging and biomarkers in this patient population and their relation with clinical outcome. It is increasingly acknowledged that aortic stenosis is not only a disease of the valve, but also of the left ventricle (LV) and the aorta. In the course of disease progression, pressure overload and ventricular wall stress lead to remodeling of the LV, which eventually leads to left ventricular hypertrophy (LVH) and myocardial fibrosis. Although these processes have been described in patients with aortic stenosis, little is known about the prevalence and prognostic relevance of LVH and myocardial fibrosis in patients with ConAoS, who are often relatively young. Applying upcoming innovative imaging modalities such as high frame rate echocardiography and T1-mapping in patients with ConAoS will increase our knowledge on tissue characterization, which in turn will facilitate identifying patients at high risk for complications and rapid disease progression. The CAS study is a clinical observational study investigating the effects of ConAoS on the left ventricular function and the prevalence, pattern and expanse of LVH, myocardial stiffness and myocardial fibrosis. Moreover, the prognostic capacity of the presence of these pathological processes will be assessed, correlating findings at baseline to clinical outcome by assessing the occurrence of cardiovascular events and all-cause mortality during 3-year clinical follow-up. The investigators will unravel biomarker and imaging predictors for myocardial dysfunction (systolic and diastolic) with specific attention for male-female differences. This newly gained knowledge will enable the investigators to improve and individualize current treatment protocols and derive novel therapeutic strategies for adult patients with ConAoS.

Official Title
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Cardiac Imaging in Congenital Aortic Stenosis - Unravelling Risk Factors and Predicting Clinical Outcome

Conditions
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Congenital Aortic Stenosis

Participation Criteria
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Eligibility Criteria
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In order to be eligible to participate in this study, a subject must meet the following criteria: Aged ≥ 18 years Capable of understanding and signing informed consent. Inclusion criteria for the CAS study are patients diagnosed with a valvular congenital aortic stenosis. Two groups of patients will be included: Patients with a prior aortic valve replacement (AVR) Patients without a prior AVR and with an aortic jet velocity ≥ 2.5 m/s. Exclusion Criteria: Patients with severe aortic regurgitation Presence of any of the following contra-indications for MRI Contra-indication to gadolinium based contrast media (eGFR <30 ml/min or contrast allergy) Other contra-indications such as presence of pacemaker/implantable cardioverter defibrillator, severe claustrophobia or pregnancy Patients known with or previously treated because of aortic coarctation. Patients known with genetic syndromes or connective tissue disorders

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adults with congenital aortic stenosis<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of myocardial fibrosis | Assessed at baseline using cardiovascular magnetic resonance imaging (late gadolinium enhancement (LGE) and T1 mapping pre- and post-contrast) | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular function | This outcome is measured by strain measurements using echocardiography and cardiovascular magnetic resonance imaging (CMR) | Baseline | 
| Shear wave velocity | Shear wave velocity is measured using high frame rate echocardiography | Baseline | 
| Physical activity in daily life | This outcome is measured by the following questionnaire: Short Questionnaire to Assess Health-enhancing physical activity (SQUASH) | Baseline | 
| Quality of life (SF-36) | This outcome is assessed by using the SF-36 questionnaire | Baseline | 
| Occurence of ventricular arrhythmias | This outcome is assessed by the occurence of ventricular ectopies and non-sustained ventricular tachycardia (VT) on Holter ECG for 48 hours. | Baseline | 
| Conduction abnormalities on ECG | For this outcome the conduction times on ECG will be measured | Baseline | 
| All-cause mortality |  | 3 years | 
| Cardiovascular events | Incidents of heart failure, arrhythmias, endocarditis, aortopathy (aortic dissection and/or aortic aneurysm), (re-) interventions and (re-) operations of the aortic valve and/or ascending aorta and hospitalizations for other cardiac reasons | 3 years | 
| Aortic flow patterns | This outcome is measured using 4D flow CMR | Baseline | 
| Blood biomarkers |  | Baseline | 
| Fear of movement | This outcome is measured using the following questionnaire: Tampa Scale for Kinesiophobia (TSK-NL Heart) | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Congenital Aortic Stenosis, Bicuspid Aortic Valve, Left ventricular function, Cardiac imaging, Myocardial tissue characterization