Randomized Study for the Optimal Treatment of Symptomatic Patients With Low Gradient Severe Aortic Valve Stenosis and Preserved Left Ventricular Ejection Fraction

Study Overview
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Brief Summary
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According to current European Recommendations on valvular heart disease (VHD), classical severe aortic stenosis (AS) is defined by an aortic valve area (AVA) ≤1 cm2 and indexed AVA ≤0.6 cm2/m2, a mean aortic pressure gradient (MAG) >40 mmHg, and a maximal aortic velocity >4 m/sec. Aortic valve replacement (AVR) is recommended (class I indication) in patients with classical severe AS who have any symptoms related to aortic valve disease. In 2007, Hachicha et al. described a particular pattern of severe AS, characterized by an AVA ≤0.6 cm2/m2, low mean pressure aortic gradient (MAG <40 mmHg), despite the presence of a preserved left ventricular ejection fraction (LVEF ≥50%). This pattern of AS is encountered in nearly 15-25 % of patients who have severe AS. Typically, these patients are elderly subjects, with several comorbidities, a small left ventricular (LV) cavity with pronounced LV concentric remodeling and a restrictive physiology, leading to a decrease in LV stroke volume despite a preserved LVEF. The diagnosis and management of patients with low gradient severe AS and preserved LVEF are often challenging because: the presence of a true severe aortic stenosis should be carefully confirmed by a multi-modality imaging approach; the best therapeutic management (AVR versus conservative strategy) of symptomatic patients with low gradient severe AS and preserved LVEF is not clearly established. In very recently updated European guidelines on the management of VHD, symptomatic patients with low gradient and low flow severe AS and preserved LVEF have only a class IIa-level C indication for AVR. No specific indications are given for the management of symptomatic patients with low gradient and normal flow severe AS. This lack of indications is clearly attributed to a gap in knowledge which requires further investigations to be filled up.

Official Title
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Randomized Study for the Optimal Treatment of Symptomatic Patients With Low Gradient Severe Aortic Valve Stenosis and Preserved Left Ventricular Ejection Fraction

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Procedure: aortic valve replacement
* Other: strict clinical surveillance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Symptomatic and severe AS defined by an effective AVA ≤1 cm² and indexed AVA ≤0.6 cm2/m2 LVEF ≥50% MAG <40 mm Hg (measure confirmed by the multi-window continuous-wave Doppler interrogation and use of Pedoff probe) Confirmation of the presence of severe AS at DSE and MDCT aortic calcium score Feasibility of AVR by surgery or TAVR according to the heart team Signature of an informed consent Exclusion Criteria: Uncontrolled atrial of ventricular arrhythmias Patient having a life expectancy <1 year, independently from their aortic pathology Coronary artery disease necessitating a percutaneous or surgical revascularisation Presence of a concomitant valve disease needing surgical treatment Patient who are included in another research protocol Protected person (adults legally protected (under judicial protection, guardianship or supervision), person deprived of their liberty, pregnant woman, lactating woman and minor)

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aortic valve replacement<br> | Procedure: aortic valve replacement<br>* aortic valve replacement surgical or transcatheter aortic valve replacement (will be decided by the heart team before randomization)<br>|
| Active Comparator: strict clinical surveillance<br> | Other: strict clinical surveillance<br>* strict clinical surveillance strategy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time from randomization to first occurrence of any of the components of the composite outcome (adjudicated): all-cause mortality or cardiovascular related hospitalization |  | during 2 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of all-cause mortality |  | 2 years | 
| rate of cardiovascular mortality |  | 2 years | 
| rate of cardiovascular related hospitalization |  | 2 years | 
| rate of cerebrovascular events |  | 2 years | 
| walking distance | 6-minute walking test | 6, 12, 18 and 24 months | 
| NT-proBNP plasma levels |  | 6, 12, 18 and 24 months | 
| quality of life score | test EQ-5D | 6, 12, 18 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe aortic valve stenosis, low gradient, preserved left ventricular ejection fraction, symptomatic patients