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

Not Applicable

Terminated

• Conditions: Aortic Valve Stenosis
• Interventions: Other: strict clinical surveillance; Procedure: aortic valve replacement

• Registration Number: NCT03667365
• Lead Sponsor: Rennes University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-09-10
• Study First Submitted QC: 2018-09-10
• Study First Posted: 2018-09-12
• Study Start: 2019-03-19
• Primary Completion: 2021-11-16
• Study Completion: 2021-11-16
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-27
• Last Update Posted: 2023-03-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 52

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
strict clinical surveillance	strict clinical surveillance	-
aortic valve replacement	aortic valve replacement	-

Primary Outcome Measures

Name	Time	Method
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

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

Trial Locations

Locations (18)

CHU Liège; 🇧🇪 Liège, Belgium

CHU Brest - Hôpital La Cavale Blanche; 🇫🇷 Brest, France

APHM - Hôpital La Timone; 🇫🇷 Marseille, France

CH Bretagne Atlantique - Site de Vannes; 🇫🇷 Vannes, France

CHU Amiens - Picardie; 🇫🇷 Amiens, France

CHU Angers; 🇫🇷 Angers, France

APHP - CHU Henri Mondor; 🇫🇷 Créteil, France

CHU Lille; 🇫🇷 Lille, France

CHU Dijon - Hôpital François Mitterrand; 🇫🇷 Dijon, France

CH Bretagne Sud; 🇫🇷 Lorient, France

CHU Nantes; 🇫🇷 Nantes, France

Clinique du Millénaire; 🇫🇷 Montpellier, France

CHU Rennes; 🇫🇷 Rennes, France

CH Saint-Brieuc; 🇫🇷 Saint-Brieuc, France

Centre Cardiologique du Nord; 🇫🇷 Saint-Denis, France

CHU Tours - Hôpital Trousseau; 🇫🇷 Tours, France

CHU Nancy; 🇫🇷 Vandœuvre-lès-Nancy, France

CHU Toulouse - Hôpital Rangueil; 🇫🇷 Toulouse, France