New Diagnostic and Therapeutic Strategies for Ischemic Mitral Regurgitation

Ischemic Mitral Regurgitation: Reversing the Cycle of Remodeling

Robert A. Levine

Massachusetts General Hospital
Boston, USA

Mitral regurgitation (MR) is a common complication of ischemic heart disease, resulting in a doubling of mortality after myocardial infarction (MI) over five years. MR contributes to and increases the left ventricle (LV) remodeling that occurs from ischemic heart disease, leading to increased MR, progressive remodeling and eventual heart failure. Dr. Robert A. Levine, Massachusetts General Hospital, reviewed advances in breaking the cycle of progressive MR and LV remodeling.

Understanding the mechanisms of disease is key to successful treatment of MR. Echocardiography shows that ischemic MR (functional MR) is characterized by normal leaflets but abnormal connections to the heart at the annulus, the chordae papillary muscles (PM), and the connecting ventricular wall, resulting in incomplete mitral leaflet closure. When evaluating individual patients, it is important to differentiate between dysfunction and dilation as the cause of restricted leaflet closure. The geometry of the tethering muscles in the valve has been characterized by 2D and 3D echocardiography. Otsuji and colleagues confirmed that ischemic MR is related to LV dysfunction with dilation, but not to LV dysfunction without changes in geometry. Increased tethering also is required for substantial regurgitation.

The initial therapeutic approach to ischemic MR was to reduce annular size by implanting a ring. However, 25% to 50% of patients treated with ring annuloplasty had persistent regurgitation due to continuing PM tethering. A newer approach that reduces tethering distance and decreases MR is to surgically reshape the ventricle. Another method is to replace the bulging ventricle wall with a balloon patch inflated until coaptation normalizes and regurgitation stops. This approach is particularly effective in patients with infarctions in the region. It allows targeted, individualized therapy and is adjustable by echocardiography guidance. The balloon treatment can be applied in the beating heart with use of echocardiograpic monitoring and avoids the mortality associated with ring insertion.

Cutting the chordae to improve coaptation has been studied as therapy for MR. In small clinical studies combining this method with ring implantation has been successful in relieving persistent regurgitation. Combinations of ventricular restoration, PM repositioning, chordal cutting, and annular reshaping also are being studied.

The ultimate aim of treatment approaches is to interrupt the cycle of ischemia leading to decreased contractile function, LV dilation, increased wall stress and resultant MR. A model has been developed of an apical infarction without MR with a surgical shunt between the LV and left atrium (LA), allowing independent variation of infarction and regurgitation. This model demonstrated that hearts with ischemia and MR have failed hypertrophy, diminished contractility, increased apoptosis, and extracellular matrix remodeling. These abnormalities contribute to decreased contractile function and LV dilation, and are driven by MR. When MR was eliminated by closing the shunt, end diastolic volume, end systolic volume, and the abnormal biological changes were reversed. These studies show that the biological changes can be reversed by curing the MR. Thus, the goal in new treatment approaches is to look at the variety of targets available—to have a versatile approach that depends on the mechanisms in each patient to produce a long-lasting repair and end the cycle of LV remodeling in patients.

Mechanism and Pathophysiology of Ischemic Mitral Valve Regurgitation

Yutaka Otsuji

Kagoshima University
Kagoshima, Japan

Ischemic mitral regurgitation (MR) develops in about 20% of patients with acute myocardial infarction (AMI). Even mild ischemic MR worsens patient survival. Dr. Yutaka Otsuji, Kagoshima University, discussed the physiological changes that lead to ischemic MR and the need for treatment interventions targeted to these mechanisms.

Otsuji studied the relationship of leaflet tethering, papillary muscle (PM) function, and MR in patients with inferior MI. A patient with significant MR and good PM function had systolic thickening. Tissue Doppler strain imaging showed good longitudinal shortening. The distance between the PM tip and anterior annulus was long and the leaflet tented. In contrast, a patient with minimal MR and poor PM function had a thin, long PM and no systolic thickening. Tissue Doppler showed dyskinetic PM motion. In this case the PM tip to the annulus distance was relatively short with only mild leaflet tenting and MR. These comparisons demonstrate that PM dysfunction attenuates leaflet tethering.

Otsuji evaluated the role of annular dilation in MR. A patient with a small annulus from ring annuloplasty had an enlarged ventricle with leaflet tenting and significant ischemic MR. A second patient with lone atrial fibrillation had a dilated annulus but good LV function and almost no MR. Thus, annular dilatation alone does not cause significant MR. Frequent discrepancies between annular dilatation and MR suggest annular dilatation may be a weak factor.

In patients with ischemic MR, anterior mitral leaflet (AML) and posterior mitral leaflet (PML) tethering increases symmetrically. Patients with recurrent MR after annuloplasty have asymmetrically increased AML and PML tethering, with most of the coaptation on the posterior side. As in the case shown, anteriorly directed jet is occasionally seen (Figure 1). Surgical annuloplasty reduces the anterior-posterior annulus diameter. It does not displace the anterior annulus, but does displace the posterior annulus anteriorly, causing no change in the anterior leaflet and augmented tethering of the posterior leaflet (Figure 2). The increased posterior leaflet tethering may be related to recurrent ischemic MR after surgical annuloplasty.

A case study of surgery to reduce tethering was presented by Otsuji. A patient with dilated cardiomyopathy and end-stage CHF presented with a tethered mitral leaflet with completely restricted motion. Mitral annuloplasty and surgery to realign the PM were performed. Post-operative echocardiography demonstrated marked reduction in tethering with significantly improved mitral leaflet motion, elimination of MR, and clinical improvement from NYHA IV to II.

In conclusion, mitral valve tethering due to PM displacement by LV remodeling is the major cause of ischemic MR (Figure 3). Procedures that reduce tethering attenuate ischemic MR with clinical improvement.

Quantitative Assessment of Tethering by 3D Echocardiography

Nozomi Watanabe

Kawasaki Medical School
Kurashiki, Japan

Ischemic mitral regurgitation (MR) is commonly treated with annuloplasty, even though MR often persists after surgery. New surgical procedures have been developed to correct abnormal changes in leaflet geometry. However, current assessment with 2D echocardiography may not adequately measure leaflet tethering. Dr. Nozomi Watanabe, Kawasaki Medical School, described a new method for quantitative assessment of tethering by 3D echocardiography.

The mitral valve has a unique morphology with a saddle-shaped, curved annulus and curved mitral leaflets. Because of this geometry, 2D echocardiography for measuring tenting length or area may miss the maximum tethering site. Ten years ago, Watanabe’s group created 3D images of the mitral annulus using extracted images from multiple planes but this procedure was too time consuming and could not be used for 3D quantitation. With the advent of transthoracic real-time 3d echocardiography, a three-dimensional volumetric image of the heart and its structures could be visualized. However, this method could not be used for 3D quantitation.

Watanabe and colleagues developed a software system for use with real-time 3D echocardiographic images, which provides quantifiable 3D images of the mitral leaflets and annulus. A real-time 3D echocardiographic study using this quantitative method showed that the mitral annulus flattens in ischemic MR. From these measurements, three-dimensional images of leaflets from normal mitral valves and mitral valves with ischemic MR were produced (Figure 1). The image from ischemic MR clearly shows the mitral valve tethering toward the left ventricle (LV) from the level of the annulus.

Watanabe’s quantitative method can be used to:

• measure the degree of tenting.
• tenting volume.
• tenting length.
• curve of the annulus.

From these data, a quantitative map of mitral valve tenting can be made (Figure 2). Using this method to visualize and measure geometric differences in mitral valve tenting in different situations, they found that the tenting site is larger in patients with anterior infarction compared to those with inferior infarction. Images taken in a patient before and after annuloplasty showed that after surgery the annulus shrank in size and tenting volume was reduced but tenting height remained the same (Figure 3).

Watanabe concluded that the software can be expanded in the future to measure the entire mitral valve complex and analyze dynamics during the cardiac cycle. Using this technique, mechanisms of ischemic MR and individual variations can be evaluated. Importantly, surgeons can evaluate current surgical procedures and choose the best type of repair for individual patients.

New Therapeutic Strategy for Ischemic Mitral Regurgitation: Repairing and Protecting LV

Masashi Komeda

Kyoto University School of Medicine
Kyoto, Japan

Repair surgery for ischemic mitral regurgitation (IMR) is a challenge because it is a disease of the ventricle rather than of the valve. Dr. Masashi Komeda, Kyoto University School of Medicine, stressed that ventricular solutions are needed to effectively repair the defects that cause IMR. Surgical solutions used by Komeda include mitral annuloplasty (MAP) for annular dilatation; left ventricle restoration (LVR) for papillary dislocation; chordal cutting and translocation for leaflet tethering; and revascularization and resynchronization therapy when necessary.

MAP alone improves LV geometry and function. In an animal model of acute heart failure, MAP improved the LV short axis dimension (LVDd), wall motion in the direction of the short axis, and sphericity (LV became less spherical). Depending on the method used, LVR may distort LV shape. MAP with the SAVE procedure maintains the LV pear shape.

Strategies for IMR used at Kyoto University are complete revascularization, undersized MAP, LVR when indicated, and chordal cutting and translocation when necessary. In the past five years, 61 patients underwent procedures for IMR. Of these, 30 patients had MAP and coronary artery bypass graft (CABG) (MV repair group), and 31 had LV restoration, MAP, and CABG (LVR group). Mitral ring size used averaged 25 mm. LV repair methods were SAVE 12, Dor 20, and m-Batista 4.

Preoperatively, patients in the LVR group had larger ventricle diameter (p <0.01) and lower ejection fraction (EF) (p <0.01) (Figure 1). Hospital mortality was 11% (7/61), with 6% (2/29) in the MV repair group and 16% (5/30) in the LVR group. After surgery, results of all patients showed that MR almost disappeared (p <0.001) and tenting significantly decreased (p <0.001) from baseline (Figure 2). The LVR group had greater improvement in LVDd and EF (Figure 3). Both groups had significant improvement in symptoms (p <0.001) and MR ((p <0.001).

A case study patient (46 year-old male) with a history of AMI developed MR with CHF. The ventricle was repaired with the Dor procedure, MAP was performed, and the secondary chordae were cut from the LV. Chordal translocation was done, connecting the papillary tips with the anterior mitral annulus using a new technique of chordal replacement. After surgery, the LV was much smaller with improved wall motion, leaflet tethering was decreased, and MR disappeared.

Komeda concluded that IMR should be treated as a ventricular disease. MAP and LVR can provide significant benefit for patients with poor LV function. Additionally, chordal reconstruction surgery may help improve the results