Percutaneous Mitral Valve Repair and Replacement

Mitral Valve Anatomy

The mitral valve (MV) complex is composed of the mitral annulus, anterior and posterior leaflets, chordae tendineae, and papillary muscles. The mitral annulus is the elliptical area of attachment of the MV to the base of the LA ( Fig. 52.1 ). The posterior leaflet has three lobes or “scallops”: the lateral (P1), central (P2), and medial scallops (P3). The anterior leaflet scallops are named A1, A2, and A3, respectively, corresponding to the posterior scallops. The anatomic position of the valve is such that the two leaflets meet at the anterolateral and posteromedial commissures. Chordae connect both the leaflets and the anterolateral and posteromedial papillary muscles. The primary chordae connect to the free edge of the leaflet; the secondary chordae (“strut” chords) are thicker and connect to the rough zone of the leaflet; and the tertiary chordae are short and connect the basal zone of the leaflet to the ventricular free wall.

Etiology and Mechanism of Mitral Regurgitation

Anatomic or functional abnormalities of any of the structures in the MV apparatus may lead to MR. The disease process leading to MR may be primary MV disease, secondary regurgitation resulting from another cardiac disease, or MV involvement in a systemic inflammatory disease ( Table 52.1 ). Various terminologies are used to characterize the mechanisms of MR. The morphologic description, proposed by Carpentier, classifies the mechanism of regurgitation according to leaflet pathophysiology ( Fig. 52.2 ). Type I regurgitation occurs in the presence of normal leaflet motion and is usually caused by annular dilatation or leaflet perforation. Type II is caused by leaflet prolapse, which is commonly the result of degenerative (myxomatous) disease, chordal elongation or rupture, or papillary muscle elongation or rupture. Type III is caused by restricted leaflet motion, which may arise from posterior wall motion abnormality or papillary muscle dysfunction due to ischemic cardiac disease. The restricted leaflet motion may also be caused by commissural fusion, leaflet or chordal thickening from rheumatic heart disease, or both. This simplification has usefulness in terms of both the surgical approach and the percutaneous approach, because the goal of therapy is to restore normal leaflet function but not necessarily normal valve anatomy.

Another common method of categorizing MR is based on the etiology and mechanism of the MR. This classification is commonly used in the literature to study the clinical outcomes of patients ( Table 52.2 ). In this classification scheme, MR is loosely categorized on the basis of an abnormal or normal MV as degenerative or rheumatic disease (primary MR) and functional or ischemic disease (secondary MR) , respectively. However, the terms functional MR , ischemic MR , and secondary MR are often used interchangeably and may represent many different mechanisms and morphologic variants.

Degenerative disease includes Barlow disease (myxomatous degeneration) and fibroelastic deficiency, both of which can result in MV leaflet prolapse and degenerative MR (DMR). Fibroelastic deficiency is the most common etiology (approximately 70%) among patients undergoing surgical MVRe in the United States. MR in rheumatic disease is a result of leaflet deformity caused by severe thickening and calcification of the leaflets and subvalvular apparatus and apical leaflet doming resulting in malcoaptation. Although this is a common cause of mitral disease worldwide, it is less frequently encountered in the United States.

FMR occurs in the setting of LV dysfunction and is seen in patients with coronary artery disease (ischemic MR) or with dilated cardiomyopathy from other causes. Ischemic MR results from decreased closing force and increased tethering force on the leaflets. Various factors can lessen the closing force, including diminished left ventricular ejection fraction (LVEF), LV dyssynchrony, and decreased annular contraction; similarly, many factors can increase the tethering force, including papillary muscle displacement, LV remodeling, and annular dilatation. It is becoming increasingly clear that significant interaction among ventricular, valvular, and annular factors is involved in the generation, perpetuation, and progression of so-called functional MR ( Fig. 52.3 ). More recently, investigators have demonstrated the incidence of typical FMR due to annular dilation but with normal LVEF that results instead from progressive LA enlargement.

Natural History

The natural history of chronic MR depends on the degree of regurgitation, the cause of the underlying disorder, and the degree of LV dysfunction. Available data on the natural history of the disease are limited by small sample size, selection bias, inconsistent measures of MR severity, and the inclusion of disparate etiologies of regurgitation. However, it appears that many patients with chronic MR remain asymptomatic for many years. Among patients with mild MR, there is an inconsistent rate of progression to severe MR that appears to be independent of medical treatment. When chronic severe MR is present, approximately 5% to 10% of patients per year develop significant symptoms, clinical indication for surgery, death, or all of these.

Whether there is a small risk of sudden cardiac death in patients with severe asymptomatic MR remains controversial, and the data are not compelling enough to subject patients to intervention for this reason alone in the absence of other indications for MVRe. The importance of symptoms in regard to long-term prognosis is demonstrated by the high mortality rate reported for patients with New York Heart Association (NYHA) class III or IV symptoms, even in degenerative MV disease. LVEF is also an important independent predictor of outcome in patients with FMR.

Patients with degenerative MV disease have a favorable long-term prognosis whether they are treated conservatively or, when indicated, surgically. However, patients with degenerative MV disease and coronary disease are fundamentally different from those with degenerative disease alone; the former have a worse prognosis that is dominated by the contribution of coronary disease. Conversely, in the absence of degenerative disease, the presence and degree of MR after myocardial infarction is an independent predictor of mortality, emphasizing the need for accurate quantification; further studies are needed to investigate whether treatment of MR in these patients modifies outcomes.

Imaging: Echocardiography

Echocardiography is the dominant modality for imaging the MV and for the assessment of MR severity. Two-dimensional transthoracic echocardiography (TTE) is useful to evaluate the valvular anatomy, to determine the structure and function of the LV, and to assess the origin and degree of regurgitation. Therefore, TTE provides an understanding of MR severity as well as an insight into the primary or secondary nature of the disease. Furthermore, the anatomic assessment of the MV and the LV also allows determination of whether surgical or percutaneous MVRe may be feasible or whether valve replacement will be necessary. Longitudinal data collected by serial echocardiography may be used to determine the timing of intervention and to follow up the results. If transthoracic images are not adequate, transesophageal echocardiography (TEE) provides an excellent assessment of MV anatomy and severity of regurgitation. This can be particularly useful to determine whether valve repair is feasible.

Evaluation of the severity of valvular regurgitation with echocardiography relies heavily on Doppler methods, including color, pulsed-wave, and continuous-wave Doppler. The American Society of Echocardiography has determined the qualitative and quantitative echocardiographic parameters that are useful in grading MR ( Table 52.3 ). The assessment of severity should rely on the integration of both quantitative and qualitative measures obtained by Doppler techniques. In addition, structural findings such as a flail leaflet or an enlarged LA can add useful information with regard to regurgitation severity.

Color Doppler provides a number of qualitative and quantitative means to determine MR severity. A proximal flow convergence on color Doppler is present in severe regurgitation. The proximal isovelocity surface area (PISA) of this flow convergence can be used to accurately quantitate the effective regurgitant orifice area (EROA). The width of the regurgitant jet at or just downstream from the regurgitant orifice is known as the vena contracta and is slightly smaller than the anatomic regurgitant orifice. This distinction is particularly relevant in some patients with FMR, in which the regurgitant orifice has a slit-like rather than an oval shape. The area of the MR jet occupying the LA can provide a rapid semiquantitative assessment of regurgitation severity. However, this is influenced by instrument factors (e.g., gain) and by jet orientation (e.g., a central jet may appear more severe than an equally large jet that adheres to the atrial wall). In addition, the color jet area is influenced by the driving pressure across the valve and can be enhanced by elevated blood pressure. Color Doppler imaging is also important in the parasternal short-axis view to determine the origin of the MR jet because percutaneous approaches (especially the MitraClip) are more effective in centrally originating jets than in medial or lateral ones.

Regurgitant volume can be assessed with the use of continuous-wave Doppler data. Regurgitant volume is calculated by applying the continuity equation (conservation of mass), in which left-sided regurgitation volume is calculated as the difference between Doppler-derived flows across the aortic and mitral valves. The stroke volume equals the cross-sectional area of the valve annulus, multiplied by the velocity-time integral of flow across the annulus. The regurgitant volume at the MV is calculated as the difference between stroke volumes across the MV and the aortic valve. This can also be expressed as a regurgitant fraction.

Pulsed-wave Doppler is useful to assess the effect of regurgitation on the pulmonary venous flow. A pulmonary venous flow that is blunted or reversed in systole can indicate severe regurgitation. The contour and density of the regurgitant envelope on continuous-wave Doppler is also useful: a dense, early-peaking, or triangular envelope is most consistent with severe regurgitation. In addition, the mitral inflow pattern is typically E-wave dominant (>1.2 m/s) in severe regurgitation, reflecting increased flow across the valve.

Alternative Imaging Modalities

Although historically echocardiography has been the dominant imaging modality in the assessment of MR, cardiac computed tomography (CT), cardiac magnetic resonance imaging (MRI), and three-dimensional (3-D) echocardiography are beginning to play more important roles. Coronary sinus devices that indirectly alter annular geometry are under development, so the relationship of the coronary sinus to the mitral annulus is becoming increasingly important ( Fig. 52.4 ). In addition, the coronary sinus and left circumflex arteries are close to each other and overlap in more than 90% of patients, creating the potential for cinching devices to hinder coronary blood flow. Cardiac CT has the potential to provide significant anatomic details in the screening of patients and procedural planning.

With cardiac MRI, it is possible to obtain significant structural information regarding the geometry of the LV, mitral annulus, and leaflets, as well as quantitative regurgitant volumes. It is likely that regurgitant volumes calculated with the use of cardiac MRI are more accurate and more operator or reader independent compared with those derived from TTE. However, limited experience with this modality currently limits its usefulness for research purposes.

3-D echocardiography provides a more in-depth understanding of the anatomy of the MV apparatus and the changes of MR. Because the position of the MV apparatus in the LV can be disrupted in all directions, 3-D echocardiography is more likely to define the exact mechanism of MR in ischemic disease and to detect multiple jets of MR that may affect the treatment approach. Furthermore, the ability to acquire real-time 3-D images with color flow allows the team to gauge safety and efficacy during both percutaneous and traditional surgical repairs.

Surgical Approach

MV surgery can be performed via median sternotomy, a minimally invasive approach that uses partial upper sternotomy or small right thoracotomy, or it can be performed robotically through multiple “ports.” Median sternotomy is required if concomitant coronary artery bypass is undertaken. Cardioplegic arrest and cardiopulmonary bypass are necessary regardless of the type of chest wall incision, although typically less than 1 hour is required for a valve repair. Techniques of repair address the annulus (annuloplasty with or without a rigid or flexible ring, decalcification, débridement), the leaflets (triangular or quadrangular resection, sliding annuloplasty, patch enlargement, decalcification, E2E repair), the chordae (resection or elongation of chords), the myocardium itself (e.g., remodeling through the Dor procedure, plication of scar, pericardial cushions, transventricular slings), the papillary muscles (realignment), or some combination of all these.

Isolated Annuloplasty

Isolated mitral annuloplasty is usually reserved for patients with FMR. Available annuloplasty techniques include suture alone, suture with buttressing material, and prosthetic annuloplasty devices. The choice of annuloplasty technique is surgeon and patient specific. A prosthetic annuloplasty band or ring is placed to correct annular dilatation, increase leaflet coaptation by reducing the anteroposterior dimension of the annulus, and prevent future annular dilatation.

Annuloplasty for FMR results in significant improvement in NYHA class, decreased hospital admissions for heart failure, and modest survival rates of 71% to 82% at 2 years and 58% at 5 years. Although favorable changes in LV size, shape, and function have been demonstrated after successful MVRe, a propensity analysis failed to demonstrate any mortality benefit compared with matched patients not undergoing valve surgery. The recurrence rate of FMR after isolated annuloplasty is disappointing (28% at 1 year) and, along with the usually comorbid conditions of this patient population, remains a limitation to widespread use of the procedure.

Annuloplasty With Leaflet Repair

The combination of annuloplasty and leaflet repair, referred to as Carpentier’s techniques , is most frequently performed for degenerative MV disease. Among the surgical methods of mitral leaflet repair, correction of posterior leaflet or bileaflet prolapse is the most common. Posterior leaflet prolapse occurs in most cases of degenerative MV disease and is the primary cause of regurgitation in approximately 50% of patients. Prolapse results from chordal elongation or rupture and affects the central P2 segment most frequently. This type of problem is most often corrected by posterior leaflet quadrangular resection and plication of the valve annulus, usually accompanied by the placement of a prosthetic annuloplasty ring except in cases of severe calcification of the annulus.

Anterior leaflet prolapse, although less common than posterior leaflet prolapse, is a more challenging problem and has been commonly treated with initial valve replacement due to poor results of repair in this group and greater parity with replacement outcomes. However, when appropriate, several methods have been developed to treat anterior leaflet prolapse with leaflet repair. The most common are chordal transfer, artificial chordae creation, and the Alfieri E2E repair. Chordal transfer is performed by resection of a segment of the posterior leaflet, which is then transferred and sewn to the prolapsing segment of the anterior leaflet. A quadrangular repair of the anterior leaflet completes this procedure. Another method of anterior leaflet repair involves the creation of artificial chordae from Gore-Tex sutures. These artificial chordae are attached to the prolapsing leaflet and the papillary muscle by pledgeted sutures.

The long-term results for mortality, recurrent MR, and reoperation with MVRe in experienced centers are outstanding, are far superior than those for MV replacement, and the mortality rate is similar to that of the general population (86% to 93% survival at 5 years). At clinical centers of excellence, such as The Cleveland Clinic, MVRe provides durable results with a 10-year freedom-from-reoperation rate of 93% ( Fig. 52.5A ) and contemporary rates of in-hospital mortality of well under 0.1% (see Fig. 52.5B ).

Isolated Leaflet Repair with Edge-to-Edge Technique

Dr. Ottavio Alfieri (Milan, Italy) pioneered a creative repair known as the double-orifice, or E2E, technique. This procedure was initially developed for anterior leaflet prolapse: the free edges of the anterior and the posterior leaflets are sewn together in an attempt to increase leaflet contact and coaptation and reduce regurgitation. This technique also works for repair of posterior leaflet and bileaflet prolapse. The resulting double-orifice MV usually does not cause stenosis, even when combined with an annuloplasty ring.

The first report of this technique was published in 1998. A larger series, published in 2001, consisted of 260 patients who underwent E2E repair, 81% of whom had DMR, and 80% of whom also had an annuloplasty ring placed. There was a low rate of in-hospital mortality (0.7%), and overall survival was good (94% at 5 years), with 95% freedom from reoperation ( Fig. 52.6 ). Most patients (>80%) were NYHA class I or II. A subsequent report comparing patients who did with patients who did not receive concomitant annuloplasty demonstrated worse freedom from significant MR and a higher rate of reoperation in those with isolated E2E repair.

Following Dr. Alfieri’s lead, the technique was adopted into practice at many prominent institutions performing MVRe, although usually as a specialized technique and not as a primary method. The introduction of percutaneous E2E repair has fueled interest in the surgical outcomes of this procedure, leading to the publication of a number of single-center case series. The procedure has been applied to both DMR and ischemic MR with favorable results. Although the surgical double-orifice MVRe has been shown to be effective as a treatment for structural or functional MV disease, the surgical literature is limited by a lack of data on isolated E2E repair.

A series of patients with up to 18 years (mean 9.2 years) of follow-up after surgical E2E repair was recently published by Dr. Alfieri’s group. Of the 61 patients, 36 did not have concomitant annuloplasty due to heavy annular calcification or limited annular dilatation. The average age was 64 years, the average LVEF was 60%, and the indications for surgery were bileaflet prolapse/flail (46%), anterior prolapse/flail (18%), and posterior prolapse/flail (36%). Survival at 12 years was 51%, and freedom from reoperation was only 58%. Of these 36 patients, 55% had 3+ or greater MR, and residual MR greater than 1+ at hospital discharge was a significant predictor of severe MR at follow-up (hazard ratio 3.8; 95% confidence interval 1.7 to 8.2; P = .001). Although this was a small series, these results question the long-term benefit of isolated E2E repair in a group of relatively young patients with DMR and may be relevant to the discussion of percutaneous E2E repair in young and otherwise healthy patients.

Percutaneous Mitral Valve Repair

The aim of percutaneous strategies for MVRe is to provide relief from severe MR in patients who would otherwise not be candidates for surgical correction or in those who prefer a less invasive approach without the need for cardiopulmonary bypass. The latter is a more difficult proposition, especially in patients with primary (degenerative) MR, given the historical success and safety of surgical MVRe in treating this problem as detailed previously.

There are currently five major approaches to percutaneous repair. The best-studied approach is the E2E repair, based loosely on the surgical repair championed by Dr. Alfieri. The second approach uses the proximity of the coronary sinus to the mitral annulus to accomplish favorable changes in annular geometry, bringing the posterior leaflet toward the anterior leaflet and thereby improving coaptation. In the third approach, LV reshaping, which accomplishes a reduction in septal-to-lateral diameter and improves leaflet coaptation, can reduce MR. In the fourth approach, called the transventricular (direct) approach, mitral annuloplasty is performed by various methods. Another novel approach involves the implantation of artificial chordae. Finally, recent preclinical and clinical work in transcatheter MV replacement has produced interesting results ( Table 52.4 ).