Clinical trial NCT03667365: Randomized Study for the Optimal Treatment of Symptomatic Patients With Low Gradient Severe Aortic Valve Stenosis and Preserved Left Ventricular Ejection Fraction
Official title: Randomized Study for the Optimal Treatment of Symptomatic Patients With Low Gradient Severe Aortic Valve Stenosis and Preserved Left Ventricular Ejection Fraction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Aortic Valve Stenosis
Keywords: severe aortic valve stenosis
low gradient
preserved left ventricular ejection fraction
symptomatic patients
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2018-09-12
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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:

1. the presence of a "true" severe aortic stenosis should be carefully confirmed by a multi-modality imaging approach;
2. 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.


Eligibility criteria: Inclusion Criteria:

1. Age \>18 years
2. Symptomatic and severe AS defined by an effective AVA ≤1 cm² and indexed AVA ≤0.6 cm2/m2
3. LVEF ≥50%
4. MAG \<40 mm Hg (measure confirmed by the multi-window continuous-wave Doppler interrogation and use of Pedoff probe)
5. Confirmation of the presence of severe AS at DSE and MDCT aortic calcium score
6. Feasibility of AVR by surgery or TAVR according to the "heart team"
7. Signature of an informed consent

Exclusion Criteria:

1. Uncontrolled atrial of ventricular arrhythmias
2. Patient having a life expectancy \<1 year, independently from their aortic pathology
3. Coronary artery disease necessitating a percutaneous or surgical revascularisation
4. Presence of a concomitant valve disease needing surgical treatment
5. Patient who are included in another research protocol
6. Protected person (adults legally protected (under judicial protection, guardianship or supervision), person deprived of their liberty, pregnant woman, lactating woman and minor)

Primary outcomes:
measure: time from randomization to first occurrence of any of the components of the composite outcome (adjudicated): all-cause mortality or cardiovascular related hospitalization
timeFrame: during 2 years follow-up
Secondary outcomes:
measure: rate of all-cause mortality
timeFrame: 2 years
measure: rate of cardiovascular mortality
timeFrame: 2 years
measure: rate of cardiovascular related hospitalization
timeFrame: 2 years
measure: rate of cerebrovascular events
timeFrame: 2 years
measure: walking distance
timeFrame: 6, 12, 18 and 24 months
measure: NT-proBNP plasma levels
timeFrame: 6, 12, 18 and 24 months
measure: quality of life score
timeFrame: 6, 12, 18 and 24 months
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: CHU Liège
city: Amiens
country: France
facility: CHU Amiens - Picardie
city: Angers
country: France
facility: CHU Angers
city: Brest
country: France
facility: CHU Brest - Hôpital La Cavale Blanche
city: Créteil
country: France
facility: APHP - CHU Henri Mondor
city: Dijon
country: France
facility: CHU Dijon - Hôpital François Mitterrand
city: Lille
country: France
facility: CHU Lille
city: Lorient
country: France
facility: CH Bretagne Sud
city: Marseille
country: France
facility: APHM - Hôpital La Timone
city: Montpellier
country: France
facility: Clinique du Millénaire
city: Nantes
country: France
facility: CHU Nantes
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Brieuc
country: France
facility: CH Saint-Brieuc
city: Saint-Denis
country: France
facility: Centre Cardiologique du Nord
city: Toulouse
country: France
facility: CHU Toulouse - Hôpital Rangueil
city: Tours
country: France
facility: CHU Tours - Hôpital Trousseau
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Nancy
city: Vannes
country: France
facility: CH Bretagne Atlantique - Site de Vannes
Study officials:
affiliation: CHU Rennes
name: Elena EG Galli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Rennes
name: Erwan ED Donal, PhD
role: PRINCIPAL_INVESTIGATOR
References: