Early Valve Replacement Guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients With Severe Aortic Stenosis
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Aortic Valve Stenosis
- Sponsor
- University of Edinburgh
- Enrollment
- 1000
- Locations
- 1
- Primary Endpoint
- Composite of all-cause mortality or unplanned aortic stenosis-related hospitalisation
- Status
- Active, Not Recruiting
- Last Updated
- 7 months ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
- •Age over 18 years
- •No symptoms attributable to aortic stenosis that require aortic valve replacement
Exclusion Criteria
- •Deemed lower risk for mid-wall fibrosis on screening
- •Planned cardiac surgery
- •Previous valve replacement
- •Severe hypertension (systolic \>180 or diastolic \>110 mmHg)
- •Acute pulmonary oedema or cardiogenic shock
- •Left ventricular ejection fraction \<50% on cardiac MRI
- •Significant abnormalities on cardiac MRI that would prevent enrolment
- •Coexistent severe aortic regurgitation or mitral regurgitation
- •Coexistent mitral stenosis greater than mild in severity
- •Coexistent hypertrophic cardiomyopathy or cardiac amyloidosis
Outcomes
Primary Outcomes
Composite of all-cause mortality or unplanned aortic stenosis-related hospitalisation
Time Frame: 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 Outcomes
- LV systolic function(Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years))
- AS-related death(Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years))
- 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))
- 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))
- Unplanned aortic-stenosis related hospitalisation(Randomisation through to study completion (mean follow up is expected to be an average of 2.75 years))
- 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))
- 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))
- Post-operative complications following aortic valve intervention(30 days post aortic valve intervention)