Inspired by an anatomic variant in a patient, a double-orifice control device alleviates mitral regurgitation
Thomas Morrow, MD
The mitral valve, so named because of its resemblance to the mitre, a hat traditionally worn by Catholic bishops, comprises two leaflets that open to allow the left atrium of the heart to pump blood into the left ventricle. When the left ventricle contracts, these leaflets close and prevent backflow, thus allowing oxygenated blood to continue into the systemic circulation.
Mitral valve disease is common. There are two major manifestations: a relative blockage of blood flow, termed mitral stenosis, and backflow or regurgitation.
The estimates of incidence vary widely, partly because of a variety of diagnostic criteria. Older criteria relied on the sounds heard with a stethoscope, and incidence was estimated to be up to 38 percent of the population. Newer criteria rely on echocardiogram imaging and place the incidence at 2–3 percent.
Although there are a few conditions that appear to be associated with the development of mitral valve disease, such as thyroid disease and Marfan syndrome (from which Abraham Lincoln is thought to have suffered), most diseases of the mitral valve have no known cause.
Mitral regurgitation is the most common. This occurs when the two valve leaflets fail to stop and prolapse (flop backward), allowing blood under the relatively higher pressure of the ventricle to travel backward. Physicians use a +1 to +4 grading system to grade the extent of mitral valve regurgitation (MR).
When the valve fails to close properly, the decrease in blood pumped forward into the systemic circulation causes left ventricular hypertrophy, a compensatory increase in the strength and size of the ventricle. This hypertrophy increases the actual thickness of the muscle and increases the diameter of the heart chamber, which in turn stretches the electrical conduction system, leading to atrial fibrillation. The combined pressure and muscular changes also lead to symptoms such as palpitations, shortness of breath, and eventually heart failure.
Historically, open chest surgery has been used to repair or replace the defective valve. Recent advancements have led to the use of minimally invasive approaches as well as the use of a robot, which significantly reduces the trauma, but even these approaches require significant recovery time.
About 20 years ago, while operating on a patient with an unrelated problem, a cardiac surgeon saw an interesting anatomic variant where the two leaflets were actually connected in the middle — effectively producing a four-leaflet valve and a double orifice. The patient tolerated this variant for many decades with apparently no ill effects. This observation led to a novel approach of artificially creating the same effect by sewing the two leaflets together in the middle. This approach has been performed over 1,500 times worldwide and results in a strengthened valve mechanism and prevents prolapse.
Evalve, a company acquired in November 2009 by Abbott, is studying an investigational clip device delivered via a cardiac catheter to accomplish the same effect as suturing the leaflets together. Called the MitraClip, it can be attached to the two mitral valve leaflets without stopping the heart and without any chest incisions. It is attached while the catheter is guided by both echocardiographic and fluoroscopic imaging. The amount of regurgitation can be determined immediately and if it is not sufficiently corrected, the clip can be removed and reattached until the desired outcome is achieved.
In late summer a summary was published that detailed the results from two separate clinical trials: Endovascular Valve Edge-to-edge Repair Study I (EVEREST I) and EVEREST II.
In both trials, patients needed to meet class I guidelines of the 1998/2006 American College of Cardiology (ACC)/American Heart Association (AHA) Joint Task Force valvular heart disease intervention recommendation.
The patients had to be candidates for repair or replacement. Additional entrance criteria included moderate to severe (3 to 4) chronic mitral valve regurgitation and specific left ventricular ejection fraction limits as determined by echocardiogram. Finally the patient had to have symptoms, or if asymptomatic, needed to exhibit an increased pulmonary pressure or new onset atrial fibrillation.
The study looked at a composite safety endpoint at day 30 after the procedure. The composite was made up of mortality, heart attack, stroke, artificial ventilation, deep wound infection, adverse event or failed procedure requiring non-elective cardiac surgery, and new onset of atrial fibrillation.
The trials included 107 candidates, 96 of whom actually received a MitraClip placement. No patients died from the procedure; there was one death in a patient who did not have a clip implanted. There were 11 patients whose attempted placement was not completed. Of these, eight were unable to reach the desired MR goals and three had complications involving the cardiac septum.
There were 10 major adverse events (MAE) at 30 days. Of the 96 who received implants, 61 were discharged from the hospital with mitral regurgitation in the acceptable range. From the entire study group of 107 patients, 32 patients eventually had to have either mitral valve repair or replacement surgery after a clip attempt.
Benefits of this approach
The use of a catheter-based approach for valvular heart disease is rapidly progressing. The Evalve system was successful in treating mitral valve regurgitation in adults to an acceptable outcome range in 57 percent of patients who met the entrance criteria. Because it is considerably less invasive than open chest surgery, this technology has the potential capacity to treat patients who are not surgical candidates. Theoretically, implantation of the MitraClip may prevent further cardiac enlargement and all of the subsequent complications. Clinical trials comparing the use of the MitraClip with traditional surgical approaches are currently in progress — which will certainly be a topic of Tomorrow’s Medicine!
Thomas Morrow, MD, is the immediate past president of the National Association of Managed Care Physicians. He has 24 years of managed care experience at the payer or health plan level. Contact him at TMorrow@ManagedCareMag.com
The author is a director in the value-based health department at Genentech Inc. He has had no other industry affiliations in the past three years. The views expressed in Tomorrow’s Medicine are the author’s alone.
Two leaflets become four, and mitral regurgitation decreases.