Early Valve Replacement Guided by Biomarkers of LV Decompensation in Asymptomatic Patients With Severe AS

Not Applicable

Active, not recruiting

• Conditions: Hypertrophy, Left Ventricular; Aortic Valve Stenosis
• Interventions: Procedure: Aortic valve intervention

• Registration Number: NCT03094143
• Lead Sponsor: University of Edinburgh

Brief Summary

Aortic stenosis is the most common valvular disease in the Western world. It is caused by progressive narrowing of the aortic valve leading to increased strain on the heart muscle which has to work increasingly hard to pump blood through the narrowed valve. Over time the heart muscle thickens to generate more force, but eventually the heart fails leading to death if the valve is not replaced with an operation. No medical treatments exist to stop or reverse the heart valve narrowing. Current clinical guidelines suggest that an operation should be performed only when symptoms develop or the heart muscle is visibly weak on cardiac ultrasound scanning. However, symptoms can be difficult to interpret and in many patients the heart muscle has become irreversibly damaged and the heart fails to recover following surgery.

Using MRI scans of the heart, the investigators have identified heart scarring which seems to develop as the heart muscle thickens. Several studies now show that people who have developed this scarring are more likely to suffer poor outcomes including death. The investigators have also identified clinical risks that predict the presence of scarring.

The investigators propose a study where patients with severe aortic stenosis but no indications for valve replacement as per current guidelines are assessed for those clinical risks. If a participant's risk of having scarring is higher they will undergo a cardiac MRI scan. If scarring is present participants will be randomised to routine clinical care, or referral for valve replacement surgery. Participants with no evidence of scarring will be randomised routine care with study follow or not. The investigators of this study hypothesize that early surgery will lead to fewer complications and reduced risk of death compared to standard care.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-03-10
• Study First Submitted QC: 2017-03-22
• Study First Posted: 2017-03-29
• Study Start: 2017-07-21
• Status Verified: 2024-05
• Last Update Submitted: 2024-06-27
• Primary Completion: 2024-07-01
• Last Update Posted: 2024-07-01
• Study Completion: 2032-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

1. Severe aortic stenosis (aortic valve jet velocity ≥4.0 m/s, or aortic valve area indexed to body surface area <0.6cm2/m2 with aortic jet velocity ≥3.5m/s)
2. Age over 18 years
3. No symptoms attributable to aortic stenosis that require aortic valve replacement

Exclusion Criteria

1. Deemed lower risk for mid-wall fibrosis on screening
2. Planned cardiac surgery
3. Previous valve replacement
4. Severe hypertension (systolic >180 or diastolic >110 mmHg)
5. Acute pulmonary oedema or cardiogenic shock
6. Left ventricular ejection fraction <50% on cardiac MRI
7. Significant abnormalities on cardiac MRI that would prevent enrolment
8. Coexistent severe aortic regurgitation or mitral regurgitation
9. Coexistent mitral stenosis greater than mild in severity
10. Coexistent hypertrophic cardiomyopathy or cardiac amyloidosis
11. Any contraindication to MRI scanning (such as permanent pacemaker)
12. Advanced renal impairment (glomerular filtration rate <30 mL/min/1.73 m2)
13. Pregnancy or breast feeding
14. Patient judged to be unfit to be considered for aortic valve replacement or transcatheter aortic valve implantation
15. Patient declines to consider undergoing valve replacement surgery or transcatheter aortic valve implantation
16. Inability to give informed consent
17. Previous randomisation into this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: Early intervention	Aortic valve intervention	Patients will be referred immediately for aortic valve intervention.

Primary Outcome Measures

Name	Time	Method
Composite of all-cause mortality or unplanned aortic stenosis-related hospitalisation	Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years)	The first event of all-cause mortality or unplanned aortic stenosis-related hospitalisation; Unplanned aortic stenosis-related hospitalisation is defined as an unplanned admission with syncope, heart failure, chest pain or arrhythmia (ventricular arrhythmia or second or third degree heart block) attributed to aortic stenosis. This endpoint will be adjudicated by two independent investigators blinded to the details of randomisation following review of the case notes and hospital records.

Secondary Outcome Measures

Name	Time	Method
LV systolic function	Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years)	The development of LV systolic dysfunction (EF \<50% quantitatively or at least mild LV dysfunction qualitatively)
AS-related death	Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years)	AS-related death is a death where aortic stenosis has been listed as a contributory cause by the clinical care team on the patient's official death certificate.
Cardiovascular death	Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years)
Sudden cardiac death	Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years)
WHODAS 2.0 (12 item)	At study completion (mean follow up is expected to be an average of 2.75 years)	The World Health Organization Disability Assessment Schedule (WHODAS 2.0) is a generic assessment instrument developed by WHO to provide a standardized method for measuring health and disability across cultures.
All-cause mortality	Randomisation through to study completion, an average of 2.75 years
NYHA status	At study completion (mean follow up is expected to be an average of 2.75 years)	Self reported patient symptoms on a scale of I-IV (I = No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, IV = Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.)
Unplanned aortic-stenosis related hospitalisation	Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years)	Unplanned aortic stenosis-related hospitalisation is defined as an unplanned admission with syncope, heart failure, chest pain or arrhythmia (ventricular arrhythmia or second or third degree heart block) attributed to aortic stenosis.
Permanent pacemaker insertion, cardiac resynchronisation therapy or automated implantable cardioverter defibrillator	Randomisation to through to study completion (mean follow up is expected to be an average of 2.75 years)	To compare between study arms the number of participants who have had a permanent pacemaker insertion, cardiac resynchronisation therapy or automated implantable cardioverter defibrillator
Stroke	Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years)
Endocarditis	Randomisation to through to study completion (mean follow up is expected to be an average of 2.75 years)	To compare between study arms the number of participants who have endocarditis
Post-operative complications following aortic valve intervention	30 days post aortic valve intervention

Trial Locations

Locations (1)

NHS Lothian; 🇬🇧 Edinburgh, United Kingdom