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

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.

Study Overview

• Status: Terminated
• Conditions: Aortic Valve Stenosis
• Intervention / Treatment: Procedure: aortic valve replacement; Other: strict clinical surveillance

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicolas NM Mevel; Phone Number: 02 99 28 25 55; Email: drc@chu-rennes.fr
• Study Contact Backup: Name: Anne AG Ganivet; Phone Number: 02 99 28 25 55; Email: anne.ganivet@chu-rennes.fr

Study Locations

• Belgium
  • Liège, Belgium
    • CHU Liège
• France
  • Amiens, France
    • CHU Amiens - Picardie
  • Angers, France
    • CHU Angers
  • Brest, France
    • CHU Brest - Hôpital La Cavale Blanche
  • Créteil, France
    • APHP - CHU Henri Mondor
  • Dijon, France
    • Chu Dijon - Hôpital François Mitterrand
  • Lille, France
    • CHU Lille
  • Lorient, France
    • CH Bretagne Sud
  • Marseille, France
    • APHM - Hôpital la Timone
  • Montpellier, France
    • Clinique du Millenaire
  • Nantes, France
    • CHU Nantes
  • Rennes, France, 35000
    • CHU Rennes
  • Saint-Brieuc, France
    • CH Saint-Brieuc
  • Saint-Denis, France
    • Centre Cardiologique du Nord
  • Toulouse, France
    • CHU Toulouse - Hôpital Rangueil
  • Tours, France
    • CHU Tours - Hôpital Trousseau
  • Vandœuvre-lès-Nancy, France
    • CHU Nancy
  • Vannes, France
    • Ch Bretagne Atlantique - site de Vannes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Actual): November 16, 2021
• Study Completion (Actual): November 16, 2021

Study Registration Dates

• First Submitted: September 10, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 27, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: symptomatic patients; severe aortic valve stenosis; low gradient; preserved left ventricular ejection fraction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: 35RC17_8843_ROTAS; 2018-A02100-55 (Other Identifier: N°ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No