A Closer Look at Mitral Valve Regurgitation

Mitral regurgitation is the most common disease of the mitral valve.

The mitral valve is located between the left atrium and ventricle. It opens during systole, when blood enters the left ventricle from the left atrium, and it closes during ventricular contraction, when blood exits the left ventricle to perfuse the rest of the body.

Unlike the aortic valve, a trileaflet structure that passively opens and closes during the cardiac cycle, the mitral valve is a bileaflet structure with a subvalvular apparatus consisting of cords that connect its leaflets to the papillary muscles. Papillary muscles are part of the left ventricle that help keep the mitral valve closed during ventricular contraction (Figure 1).

The Mitral Valve of the Heart

Figure 1 – The Mitral Valve

Mitral regurgitation is the leakage of blood back into the atrium during left ventricular contraction, resulting from inappropriate closure of the valve leaflets in systole. When regurgitation is mild it is well tolerated and no therapy is needed. However, patients can become symptomatic as the severity of the leakage increases.

Symptoms occur because the increased volume in the left atrium ultimately results in increased pressure in this chamber. This increase in pressure can cause congestion of the lungs resulting in shortness of breath, decrease in exercise tolerance and lower extremity swelling among other symptoms. The increase in volume in the left atrium also causes enlargement of this chamber and can result in cardiac arrhythmias such as atrial fibrillation, which manifest as palpitations – putting the patient at risk for stroke.

Diagnosis of mitral regurgitation starts with the physical exam. Patients usually have a harsh murmur present throughout systole, best heard at the apex. Ultimately, the diagnosis is made on echocardiography. The severity of mitral regurgitation is assessed based on color doppler flow with the use of quantitative measurements, as well as presence or absence of flow reversal in pulmonary veins (Figure2).

Diagnostics for Mitral Valve regurgitation

Figure 2 – Color doppler flow with quantitative measurements to determine severity of Mitral Valve Regurgitation

Generally, pathology of the mitral valve resulting in mitral regurgitation is classified into two separate categories; degenerative and functional.

In degenerative (primary) mitral regurgitation, the pathology involves the mitral valve itself causing malcoaptation of the leaflets. This could be the result of prolapse of one or both leaflets during systole, among other pathologies.

In functional mitral regurgitation, the mitral valve malcoaptation is due to the disease of the left ventricle. For example, patients with advanced congestive heart failure can have dilated left ventricles. This dilation can also stretch the mitral valve annulus and cause malcoaptation of the valve leaflets in systole (Figure3).

Types of Mitral Valve Regurgitation

Figure 3 – Examples of primary and functional mitral valve regurgitation.

Traditionally, surgical repair is shown to be superior to replacement in degenerative mitral regurgitation, while this distinction is not present in functional regurgitation. During repair, the surgeon uses multiple techniques to assure appropriate coaptation of the leaflets during ventricular contraction. Excision of part of the leaflet, suturing part of the leaflets together, and placing a ring along the valve annulus or rearranging the valvular chords are some of these techniques. Mitral valve replacement involves excising the native valve and replacing it with either a bio or mechanical prosthesis.

Over the past decade transcatheter techniques have been developed to mimic surgical ones. In the majority of these techniques, devices are advanced through the femoral vein from the patient’s leg to the mitral valve, avoiding any incisions.

Currently, the most studied and only commercially available transcatheter repair device is MitraClip. By using MitraClip (Figure4), the interventionalist tries to mimic the surgical technique of suturing part of the leaflets together by advancing a clip from the femoral vein and delivering it to the leaflets.


Figure 4 – MitraClip for transcatheter mitral valve therapy.

This delivery would require making a small hole in the intra-atrial septum, enabling the operator to deliver the device from the right side of the heart to the left. In the appropriate patient and in experienced hands, severe mitral regurgitation can be reduced to trace or mild, resulting in improvement of the patient’s symptoms as well as prognosis.  Multiple trials have shown that MitraClip is superior to medical therapy alone in patients with both functional as well as degenerative mitral regurgitation who are at high surgical risk.

While MitraClip is the only commercially available device currently in the US, many other devices are being investigated in different trials. Most of these devices try to duplicate other surgical techniques such as annuloplasty or chordal repair through transcatheter means.

Enthusiasm for transcatheter methods to treat mitral regurgitation is not limited to repair techniques. There is a lot of research focus on replacing the mitral valve without surgery. One area in which this is commercially available is in patients who have already had a mitral valve replacement with a bioprosthesis. Transcatheter methods can be used for therapy, should the initial bioprosthesis degenerate over time. In most cases a new valve can be delivered inside the degenerated one safely – the bioprosthetic valve functioning as the anchor for the new valve (Figure5).

Transcatheter Mitral Valve Repair

Figure 5 – Transcatheter therapy to address degenerative mitral valve bioprosthesis.

Unfortunately, the lack of appropriate anchoring is a major obstacle to replace a native mitral valve with severe regurgitation. The other obstacle is the potential obstruction of the blood flow path out of the heart by native leaflets that can be pushed into the left ventricular outflow track by the new valve. Different methods and devices are being developed and investigated to alleviate these obstacles.

In summary, while the MitraClip has matured into a valuable tool to treat mitral regurgitation in appropriate patients suffering from the condition, other modalities are actively being evaluated in trials for their safety and efficacy. Transcatheter techniques to treat mitral regurgitation are sure to expand as some of these techniques prove both safe and efficacious.

The Structural Heart Team at Carient Heart & Vascular has treated many patients with mitral regurgitation and is involved in a number of trials involving the mitral valve.

Dr. Shawn Yazdani has served as the primary investigator in many of the trials observing transcatheter therapy in patients at high or prohibitive risk for surgical valve replacement. To obtain more information or to schedule a consultation, please call 888-602-3339.

Mitral Regurgitation and Advancing Catheter Based Treatments – Results from Recent Landmark COAPT Trial

Mitral regurgitation (MR) is the most prevalent valvular heart disease in the United States and the world.

MR occurs due to malcoaptation of the mitral leaflets in systole (period of contraction of the ventricles). As a result, a portion of the left ventricular volume in systole is ejected back into the left atrium instead of the aorta. Patients become symptomatic when this regurgitant volume is severe. Additionally, the increase in volume and pressure in the heart causes remodeling of the left ventricle over time, ultimately ending in heart failure. Patients can also develop cardiac arrhythmias such as atrial fibrillation, which increases their risk for stroke.

There are two main etiologies for mitral regurgitation. The first is disease of the mitral valve apparatus itself. In some patients, leaflets are elongated, valvular cords are diseased, or one of the leaflets is flail. These conditions cause prolapse of the diseased leaflet in atria or leave a gap between the leaflets during systole. The second etiology causes regurgitation, not because the mitral valve is diseased itself but because the mitral valve is affected by the anatomy of the left ventricle. In this condition the left ventricle dilates because of either coronary artery disease (CAD) or other pathology resulting in malcoaptation of the mitral leaflets, which is either due to dilatation of the mitral valve annulus or through tethering of the leaflets in systole.

The first type of mitral valve regurgitation is called degenerative (DMR), the second is called functional (FMR). The natural history of the disease progression and patient prognosis is very different in each type and the effectiveness of the treatment options vary as well.

Surgical valve repair is the gold standard of treatment in DMR. During repair, an experienced mitral valve surgeon uses different techniques to ensure appropriate coaptation of the mitral leaflets in systole, effectively reducing the regurgitant volume to negligible. These patients do very well post repair and their long-term prognosis is excellent, barring any secondary disease of the heart such as left ventricular dysfunction. It is also well documented that these patients do much better with valve repair versus valve replacement.

Surgical valve repair does not have as good a result in patients with FMR. It has been shown that patients with FMR experience a recurrence of their regurgitation over the years, and in these patients mitral valve replacement – during which the mitral valve is excised and a prosthesis is placed – might be the better option.  Regardless, patients with FMR do not fair as well since their prognosis depends on the disease state of the left ventricle.

There has been tremendous interest generated over the past decade among cardiologists and cardiac surgeons regarding the ability to treat MR via catheter-based techniques. MitraClip® is a catheter-based device that clips the two leaflets of the mitral valve together at the site of the pathology. This device has shown to be effective in symptomatic relief among DMR patients at high risk for surgery and has been commercially available in the US for this indication since 2013. However, this represents a very small portion of patients with severe MR, therefore the utilization of MitraClip has been limited.

The results of the recent landmark trial COAPT, though, were recently published in the New England Journal of Medicine (NEJM). In this study investigators randomized patients with FMR to MitraClip versus medical therapy. These are patients who typically do not undergo surgery since their left ventricular function is poor, their risk higher and surgical results less robust than DMR patients.

The results of the COAPT trial were astounding.

Not only did patients do better with MitraClip in terms of hospitalization and symptomatic relief, but their mortality was also significantly improved. Physicians are optimistic that MitraClip will soon be approved for this indication in the US based on the trial.

Edwards Cardioband System

Medtronic Intrepid Valve

The field of transcatheter mitral valve therapies is evolving fast. There are ongoing trials with flexible and semi-rigid devices to mimic surgical annuloplasty via transcatheter techniques. Millipede (Boston Scientific), Cardioband (Edwards), and Carillon (Cardiac Dimensions) are just a few. There is also much activity involving transcatheter mitral valve replacement. Early feasibility trials are ongoing with Intrepid (Medtronic) and Tendyne (Abbott), both of which are delivered by puncturing the tip of the heart. Also, CardiaQ (Edwards) and M3 (Edwards) are two which are delivered via the leg vessels.

The challenge with transcatheter mitral replacement remains how to deliver the valve safely via the leg vessels and through the heart with good anchoring while avoiding obstruction to other areas of the heart such as left ventricular outflow tract.

One thing is certain – we are in the early stages of a big revolution in the treatment of severe mitral regurgitation. There is nothing more satisfying for an interventional cardiologist than to be part of this journey.

 Shawn Yazdani, MD, FACC, FSCAI, is an interventional cardiologist specializing in structural heart care – leading the way in innovative new approaches and advanced cardiovascular treatments. For more information, 888.602.3339 / www.shawnyazdanimd.com.

A Tale of Two Valves: Why Is Surgery Still the Preferred Treatment for Mitral Valve Disease?

Transcatheter aortic valve replacement (TAVR) has become a mainstream treatment for aortic valve stenosis, a disease that affects the heart’s aortic valve.

As the technique has grown in popularity, many patients are wondering whether similar minimally invasive approaches can be used to treat disease in other heart valves. However, each of the heart’s valves has its own unique anatomy and presents its own unique challenges.

TAVR Takes Over

TAVR was initially approved for patients at high risk of experiencing complications from surgical valve replacement. By 2015, a third of patients being treated for aortic valve stenosis underwent TAVR. And in late 2016, the Food and Drug Administration (FDA) approved TAVR for treating patients at moderate surgical risk after clinical trials showed it was safe and effective for them.

Experts predict the number of patients undergoing TAVR will grow significantly in the next five years, overtaking surgical valve replacement as the most common treatment for aortic valve stenosis.

How We Treat Mitral Valve Disease Today

Now patients and healthcare professionals are wondering: Could the same concept be used to repair other heart valves?

There’s great interest in doing so, especially for treating mitral valve disease – a condition that affects far more patients than aortic valve disease. In fact, experts estimate that several billion dollars have already been spent on research and development of transcatheter therapies for mitral valve disease.

Despite all that activity, though, the only device approved for mitral valve disease so far is the MitraClip. This device has been shown to be somewhat effective in treating mitral regurgitation (backward fow of blood into the heart) in patients with severe disease, who aren’t good surgical candidates.

MitraClip has so far been approved only for treatment of degenerative mitral valve disease, a condition that is the result of pathology of mitral valve itself. Only a mi purity of patients with mitral valve disease have degenarative disease. However, the results of Coapt trial recently presented showed that this device could be as effective in functioitral regurgitation a condition that caused malfunctioning of the mitral valve as a result of dilitation of left ventricule.By far the majority of patients with severe mitral regurgitation have functional disease.

The Mitral Valve’s Tricky Anatomy

While Mitraclip has certainly shown promise in treatment of mitral regurgitation, transcatheter mitral therapies are yet to show similar effectiveness in treatment of mitral valve disease as surgery in all comers. Why is it, then, that transcatheter techniques have been so effective for aortic valves but not for mitral valves? The answer lies in the anatomy and location of these two valves:

  • Shape: The aortic valve is a circular apparatus sitting at the end of a tube. The mitral valve, on the other hand, is noncircular saddle shape and sits in the middle of the heart. As a result, it’s influenced by the many different forces that act on the heart.
  • Location: In addition, the mitral valve is located close to the left ventricle outflow tract, an area in which blood flows out of the heart and into the major arteries. Those factors make mitral valve replacement much more challenging.

Unanswered Questions

While there continues to be a lot of enthusiasm for transcatheter mitral valve therapies, we have a long road ahead before these techniques become mainstream. There are many repair or replacement devices that are being studied. We also don’t know yet whether minimally invasive techniques might be more effective for repairing or for replacing the mitral valve. So far, it seems that mitral valve repair techniques are safer but less effective than mitral valve replacements using these catheter-based approaches.

It took a while before TAVR reached prime time – and it only got there after years of development and proof that the technique was as good or better than surgery. New mitral valve therapies must also pass that test before they become established as an alternative to surgery in patients healthy enough for operations.