Mitral Valve Repair for Mitral Valve Regurgitation

(LAMBDA Trial)

Overseen By Kenza Rahmouni El Idrissi, Dr.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ottawa Heart Institute Research Corporation

Disqualifiers: Secondary MR, Endocarditis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Surgery and immediate recovery

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatments for mitral valve regurgitation (MR), a condition where the heart's mitral valve leaks, leading to shortness of breath, fatigue, and irregular heart rates. Researchers seek to determine if creating a small opening between the heart's chambers during mitral valve surgery (mitral valve repair with creation of an 8 mm inter-atrial shunt) can help prevent functional mitral stenosis (FMS), which causes high pressure and heart failure symptoms after surgery. Participants will be divided into two groups: one receiving only the mitral valve surgery and another receiving surgery plus the opening. Ideal candidates have severe symptoms due to primary MR and are planning to undergo mitral valve surgery. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance future treatment options for mitral valve regurgitation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that creating an inter-atrial shunt during mitral valve repair is safe?

Research has shown that using an interatrial shunt, a small opening between the heart's upper chambers, is generally safe for patients with heart failure. One study found that this method led to positive results without major safety concerns. Patients who underwent this procedure did well, regardless of their heart's pumping efficiency.

Another study tested an 8-mm interatrial shunt in heart failure patients and found it effective in managing symptoms. Most patients experienced improvements, and the procedure did not cause serious problems.

These findings suggest that creating a small opening between the heart's chambers during mitral valve surgery could be well-tolerated. However, it is important to consider individual health and consult healthcare professionals before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about mitral valve repair with the creation of an 8 mm inter-atrial shunt because it offers a potentially groundbreaking approach to treating mitral valve regurgitation. Unlike traditional surgical repairs that solely focus on fixing the valve itself, this technique involves creating an inter-atrial shunt, which may help to better manage the pressure in the heart chambers. This could reduce stress on the heart and improve patient outcomes by optimizing blood flow in a way that current options do not. By targeting the underlying hemodynamics, this method may offer a more comprehensive solution to mitral valve issues.

What evidence suggests that creating an inter-atrial shunt during mitral valve repair could be effective for preventing functional mitral stenosis?

This trial will compare two approaches to mitral valve repair for mitral valve regurgitation. One arm involves mitral valve repair with the creation of an 8 mm inter-atrial shunt, while the other arm involves mitral valve repair without a shunt. Research has shown that fixing the mitral valve and creating a small 8 mm opening between the heart's upper chambers can help lower heart pressure after surgery. Studies have found that these openings can safely improve heart function in people with heart failure symptoms. This method addresses functional mitral stenosis (FMS), a condition that causes high pressure in the left atrium after mitral valve surgery. The opening helps reduce this pressure, potentially easing heart failure symptoms like shortness of breath and tiredness. Overall, these findings suggest that adding this small opening during mitral valve repair could benefit patients with primary mitral regurgitation (MR). ^{3 4 6 7 8}

Who Is on the Research Team?

Vincent Chan, Dr.

Principal Investigator

Ottawa Heart Institute Research Corporation

Are You a Good Fit for This Trial?

This trial is for patients with primary mitral valve regurgitation, a heart condition causing symptoms like breathlessness and irregular heartbeat. Participants must need mitral valve surgery but cannot have other conditions that might complicate the procedure or recovery.

Inclusion Criteria

Right-to-left atrial pressure gradient ≥ 5 mmHg at baseline

Pulmonary vascular resistance ≤ 4 Wood units

I have severe valve leakage due to a degenerative condition.

Exclusion Criteria

My heart condition involves secondary causes of mitral regurgitation and mixed mitral valve disease.

I have not had infective endocarditis in the last 30 days.

Any prior mitral valve intervention

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo mitral valve surgery, with one group receiving an additional inter-atrial shunt procedure

Surgery and immediate recovery

Follow-up

Participants are monitored for heart failure symptoms and other outcomes after surgery

30 months

What Are the Treatments Tested in This Trial?

Interventions

• Mitral valve repair with creation of an 8 mm inter-atrial shunt

Trial Overview The study tests if creating an 8 mm hole between the left and right atria during standard mitral valve repair surgery can prevent high pressures in the heart and reduce post-surgery heart failure symptoms compared to surgery alone.

How Is the Trial Designed?

Group I: Mitral valve repair with creation of an 8m inter-atrial shunt Experimental Treatment 1 Intervention

Group II: Mitral valve repair without a shunt Active Control 1 Intervention

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Published Research Related to This Trial

In a study of 107 patients undergoing mitral valve repair with the MitraClip device, successful treatment led to a significant increase in cardiac output (CO) from 5.0 to 5.7 l/min and forward stroke volume (FSV) from 57 to 65 ml, indicating improved heart function immediately after the procedure.

The MitraClip procedure also resulted in reduced left ventricular (LV) pressure and volume, with no patients experiencing a low cardiac output state post-treatment, suggesting that this method may be safer than traditional surgical options for mitral regurgitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute hemodynamic effects of MitraClip therapy. Siegel, RJ., Biner, S., Rafique, AM., et al.[2022]

The MitraClip Transcatheter Mitral Valve Repair system has been shown to be safe and effective for treating symptomatic degenerative mitral regurgitation in high-risk patients, with over 4,000 patients treated in the U.S. and more than 35,000 worldwide since its approval in 2013.

Real-world data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry indicate that the MitraClip may be even safer and more effective than results from initial clinical trials, highlighting its potential for broader use in various patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Repair of Mitral Regurgitation. Barker, CM.[2019]

In a study of 86 patients undergoing mitral valve repair, intraoperative transoesophageal echocardiography (TOE) was found to be the most sensitive method for detecting residual mitral regurgitation, identifying successful repairs in 87% of cases.

Despite saline testing indicating successful repairs, TOE revealed significant residual regurgitation in 8.2% of patients, leading to necessary interventions such as valve replacement or revision, highlighting the importance of accurate intraoperative imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of mitral valve repair by intraoperative transoesophageal echocardiography. Kalman, JM., Jones, EF., Lubicz, S., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11308056/

Interatrial Shunt Devices—A Potential Therapy for Mitral ... The REDUCE-LAP HF II study assessed the effect of an 8-mm interatrial shunt device (ISD) on heart failure patients with ejection fraction of ≥40% and exercise- ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167527323013979

Mitral regurgitation outcomes after transcatheter atrial ... Deterioration of MR was observed in 12.2% of patients who underwent transcatheter ASD closure. · The clinical predictors of worsening MR were ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ejhf.3215

Interatrial shunt therapy in advanced heart failure ... Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF.

4. jacc.org jacc.org/doi/10.1016/j.jacc.2021.04.051

JACC State-of-the-Art Review Surgical mitral valve repair/replacement has been associated with excellent clinical outcomes in patients with severe MR. However, a high ...

5. eurointervention.pcronline.com eurointervention.pcronline.com/article/mitral-valve-transcatheter-edge-to-edge-repair

Mitral valve transcatheter edge-to-edge repair Predictors of outcomes after M-TEER in SMR​​ Chronic atrial fibrillation may entertain and worsen SMR and has a negative impact on outcomes60. ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11327884/

Clinical Outcomes of Mitral Valve Surgery in Atrial ... After MV repair, 8 of 61 patients (13.1%) had at least mild to moderate MR, and 1 of 41 patients (2.4%) experienced paravalvular leakage after ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2474870625000740

Outcomes of Iatrogenic Atrial Septal Defect Closure After ... Retrospective studies have suggested that persistent iASD following transcatheter edge-to-edge repair is associated with more residual mitral valve dysfunction, ...

8. jacc.org jacc.org/doi/10.1016/j.jcin.2023.09.003

The HighLife TSMVR Feasibility Study 30-day and 1-year outcomes ... At 30 days, 27 of 30 patients (90%) were alive. There were no additional deaths, strokes, myocardial infarctions, ...