Dutch-AMR: Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Mitral Regurgitation

Sponsor

UMC Utrecht (Other)

Overall Status

Recruiting

CT.gov ID

NCT03975998

Collaborator

Netherlands Heart Institute (Other), Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), Amphia Hospital (Other), Maastricht University Medical Center (Other), Medisch Spectrum Twente (Other), Leiden University Medical Center (Other)

500

Enrollment

Locations

180

Duration (Months)

83.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rationale:

Severe asymptomatic organic Mitral Valve (MV) regurgitation with preserved left ventricular (LV) function is a challenging clinical entity as data on the recommended treatment strategy for these patients are scarce and conflicting, which is reflected in current guidelines. European guidelines advocate a more conservative strategy i.e. watchful waiting, with yearly echocardiography, whilst American guidelines are more in favour of early surgery to reconstruct the MV, i.e. MV repair (in contrast to MV replacement) in order to prevent future LV dysfunction and complaints.

A number of non-randomised trials show a favourable outcome of early surgery: in the study of Enriquez-Sarano et al. for instance, the early surgery strategy has shown to be associated with improved long-term survival, decreased cardiac mortality, and decreased morbidity compared with the conservative management [1]. On the other hand, non-randomised trials describe also that a conservative strategy (i.e. watchful waiting) can be safely accomplished. If facilitated surgery is performed in this population (50% at 10 years follow-up according to Rosenhek et al [2]), it has proven to be eventually associated with good perioperative and postoperative outcome when careful follow-up is being carried out [2].

Objective:

To compare early MV repair versus watchful waiting in asymptomatic patients with severe organic mitral valve regurgitation and preserved left ventricular function.

Study design:

Multicenter, registry trial.

Study population:

250 Asymptomatic patients (18-75 years old) with severe organic MV regurgitation and preserved left ventricular function. The current European Society of Cardiology (ESC) guidelines on Valvular Heart Disease will be applied [3]. These guidelines are also used in the Netherlands. Accordingly, patients with an indication for MV surgery will not be included.

Intervention:

Intervention will be early MV repair compared to a watchful waiting strategy.

Condition or Disease	Intervention/Treatment	Phase
Mitral Regurgitation	Procedure: Mitral valve repair

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

500 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Dutch-AMR Study: Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Organic Mitral Regurgitation and Preserved Ejection Fraction: a Multicenter Registry Trial

Study Start Date :

Oct 1, 2016

Anticipated Primary Completion Date :

Oct 1, 2026

Anticipated Study Completion Date :

Oct 1, 2031

Arms and Interventions

Arm	Intervention/Treatment
Aymptomatic patients with severe mitral regurgitation Watchful waiting Early Surgery	Procedure: Mitral valve repair Minimally invasive repair of severe organic mitral regurgiation

Arm

Intervention/Treatment

Aymptomatic patients with severe mitral regurgitation

Watchful waiting Early Surgery

Procedure: Mitral valve repair

Minimally invasive repair of severe organic mitral regurgiation

Outcome Measures

Primary Outcome Measures

Time to event: cardiovascular mortality, congestive heart failure, hospitalization, class I or class IIa indication for MV surgery [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18-75 years.
Asymptomatic patients. "Asymptomatic" is defined as absence of subjective limitations of exercise capacity or complaints expressed by the patient and confirmed by the treating cardiologist.
Severe organic mitral valve regurgitation. "Severe organic mitral valve regurgitation" is defined as non-ischemic mitral valve regurgitation with an organic cause (intrinsic valve lesion) as determined by echocardiographic core-lab reading based on the criteria for definition of severe MR as issued by the ESC guidelines [4]. For practical reasons, referring cardiologists can use an ESC guidelines based index that was validated in the investigator's core-lab (Jansen et al, Practical echocardiographic semi-quantitative scoring system to determine severity of mitral regurgitation. Abstract presentation at ESC EUROECHO Congress 2011 and annual spring congress 2012 Netherlands Society of Cardiology).
Preserved left ventricular function, "Preserved left ventricular function" is defined as left ventricular ejection fraction >60% and left ventricular end-systolic dimension <45 mm (no indexed value, measured by echocardiography).
The likelihood of MV repair should be more than 90% determined by the local heart team with a cardiologist and cardiothoracic surgeon.

Exclusion Criteria:

Pulmonary hypertension (>50 mmHg at rest).
Atrial fibrillation, either on 12-lead ECG or holter-monitoring.
Physical inability as determined by the heart team to undergo surgery.
Other life-threatening morbidity.
Higher expected surgical risks in advance, according to the dedicated heart team.
Patients with moderate to severe kidney disease (estimated glomerular filtration rate (eGFR) less than 30 mL/min).
Flail leaflet together with a left ventricular end systolic diameter (LVESD) ≥40 mm (no indexed value)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Amsterdam Medical Center (AMC)	Amsterdam	Netherlands
2	Amphia Breda	Breda	Netherlands
3	Medisch Spectrum Twente (MST)	Enschede	Netherlands
4	Leiden University Medical Center (LUMC)	Leiden	Netherlands
5	Maastricht UMC	Maastricht	Netherlands
6	University Medical Center Utrecht (UMC Utrecht)	Utrecht	Netherlands	3584 CX