Heart; Disease, Mitral(Valve), Diseases of Mitral Valve, Mitral Valve Insufficiency
Conditions
Keywords
Mitral Valve Insufficiency, Mitral Valve Regurgitation, Asymptomatic Mitral Valve Regurgitation, Asymptomatic Mitral Valve Insufficiency, Mitral Valve Repair, Watchful Waiting
Brief summary
The purpose of this study is to compare early mitral valve repair versus a watchful waiting strategy in asymptomatic patients with severe organic mitral valve regurgitation and preserved left ventricular function.
Detailed description
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 and 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 \[citations 1-3\]. 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 it has proven to be eventually associated with good perioperative and postoperative outcome in 50% of the patients at 10 years when careful follow-up is being carried out \[citation 4\]. Non-randomised trials inherently have a number of drawbacks. A randomised trial comparing both strategies and objectivising the best treatment strategy has never been performed. The Dutch AMR (Asymptomatic Mitral Regurgitation) trial is a multicenter, prospective, randomised trial comparing early MV repair versus watchful waiting in asymptomatic patients with severe organic MV regurgitation and preserved LV function \[citation 5, 6\].
Interventions
OTHERWatchful waiting
In case of watchful waiting a conservative treatment is performed, based on close monitoring of the patient for clear signs of deterioration that triggers facilitated surgery before left ventricular dysfunction is present.
PROCEDUREEarly mitral valve repair
Patients in the group of early mitral valve repair will be operated by way of routine mitral valve repair procedures in specialized centres.
Sponsors
Leiden University Medical Center
The Interuniversity Cardiology Institute of the Netherlands
WCN, Dutch Network for Cardiovascular Research
UMC Utrecht
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Asymptomatic * Severe organic mitral valve regurgitation. * Preserved left ventricular function (left ventricular ejection fraction \>60% and left ventricular end-systolic dimension ≤45 mm) * 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 * 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 * Moderate to severe kidney disease (eGFR less than 30 mL/min) * Flail leaflet together with a left ventricular end systolic diameter (LVESD) \>40 mm
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite endpoint: cardiovascular mortality, congestive heart failure and hospitalization for nonfatal cardiovascular events | Min. 5 years | The primary outcome is defined as 'time to first event'. It concerns time to first event of the composite endpoint of cardiovascular mortality, congestive heart failure, non-fatal cardiovascular events requiring hospitalization, defined as: stroke/cerebrovascular accident (CVA), atrial fibrillation (permanent or requiring hospitalization) and/or reoperation after elective MV surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular mortality | Min. 5 years | Secondary outcome measures are the separate components of the composite primary endpoint: cardiovascular mortality, congestive heart failure, hospitalization for nonfatal cardiovascular events (stroke/cerebrovascular accident (CVA), AF (permanent or requiring hospitalization) and reoperation after elective MV surgery). |
| Congestive heart failure | Min. 5 years | Secondary outcome measures are the separate components of the composite primary endpoint: cardiovascular mortality, congestive heart failure, hospitalization for nonfatal cardiovascular events (stroke/cerebrovascular accident (CVA), AF (permanent or requiring hospitalization) and reoperation after elective MV surgery). |
| Hospitalization for nonfatal cardiovascular events | Min. 5 years | Secondary outcome measures are the separate components of the composite primary endpoint: cardiovascular mortality, congestive heart failure, hospitalization for nonfatal cardiovascular events (stroke/cerebrovascular accident (CVA), AF (permanent or requiring hospitalization) and reoperation after elective MV surgery). |
| All-cause mortality | Min. 5 years | Secondary outcome measures the incidence of all-cause mortality at a minimum of 5 years. |
| Costs and effectiveness | Min. 5 years | Secondary outcome measures total direct and indirect costs and cost-effectiveness at a minimum of 5 years. |
| Health-related quality of life | Min. 5 years | Secondary outcome measures health-related quality of life at a minimum of 5 years. |
| Echocardiographic parameters | Min. 5 years | Secondary outcome measures echocardiographic parameters at a minimum of 5 years. |
| CMR parameters | Min. 5 years. | Secondary outcome measures Cardiovascular Magnetic Resonance imaging (CMR) parameters at a minimum of 5 years. |
| Transient ischemic attack | Min. 5 years | Secondary outcome measures the incidence of transient ischemic attack (TIA) at a minimum of 5 years. |
| Pulmonary embolism | Min. 5 years | Secondary outcome measures the incidence of pulmonary embolism at a minimum of 5 years. |
| Paroxysmal atrial fibrillation | Min. 5 years | Secondary outcome measures the incidence of paroxysmal atrial fibrillation at a minimum of 5 years. |
| Exercise test parameters | Min. 5 years. | Secondary outcome measures exercise test parameters at a minimum of 5 years. |
| BNP | Min. 5 years | Secondary outcome measures brain natriuretic peptide (BNP) plasma levels at a minimum of 5 years. |
| Myocardial infarction | Min. 5 years | Secondary outcome measures the incidence of myocardial infarction at a minimum of 5 years. |
| Pacemaker implantation | Min. 5 years | Secondary outcome measures the incidence of pacemaker implantation at a minimum of 5 years. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Surgery complication rate | Min. 5 years | The complication rate in the mitral valve surgery group (e.g. re-operation for bleeding, pneumonia, residual or recurrent mitral valve regurgitation) will be determined at a minimum of 5 years. |
| Rate for the need of facilitated surgery | Min. 5 years | Rate for the need of facilitated surgery in the watchful waiting group will be determined at a minimum of 5 years. |
Countries
Netherlands
Outcome results
None listed