Cardiac Imaging in Adults With Congenital Aortic Stenosis (CAS)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Congenital Aortic Stenosis

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 75

Contacts and Locations

• Study Contact: Name: Annemien E van den Bosch, MD, PHD; Phone Number: +31107034079; Email: a.e.vandenbosch@erasmusmc.nl
• Study Contact Backup: Name: Zoë A Keuning, MD; Phone Number: +31107033989; Email: z.keuning@erasmusmc.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Erasmus Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population consists of adult ConAoS patients, who are visiting the outpatient clinic of the Erasmus MC.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Adults with congenital aortic stenosis

What is the study measuring?

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
All-cause mortality		3 years
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
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

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Dutch Heart Foundation
• Investigators: Principal Investigator: Annemien E van den Bosch, MD, PHD, Erasmus Medical Center; Principal Investigator: Alexander Hirsch, MD, PHD, Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: January 17, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Left ventricular function; Cardiac imaging; Congenital Aortic Stenosis; Bicuspid Aortic Valve; Myocardial tissue characterization
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: CAS study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No