The Mitral Valve Apparatus

SECTION 1 CLASSIFICATION OF MITRAL VALVE DISORDERS

The mitral valve apparatus has several amazing functions. The leaflets act as a one-way door in diastole allowing blood to enter from the left atrium to the left ventricle with very little resistance to flow. The leaflets also direct blood to the lateral and apical regions of the left ventricle allowing it to course around the apex and line up in the direction of the left ventricular outflow tract (LVOT) then being ready for ejection. As part of the doorlike function, the leaflets close at the beginning of systole under the influence of changing pressures. Coaptation regions are sealed to the degree of not letting any blood back into the atrium during systolic contraction of the heart. During systole, the anterior mitral leaflet acts a baffle and directs blood into the LVOT for ejection. During this baffle function, the papillary muscles and chordal structures hold the leaflets in place. All of this occurs in the normal heart while preserving laminar flow and allowing for expenditure of minimal energy along the directional pathway of blood coursing through the left side of the heart.

The components of the mitral valve apparatus begin with the walls of the left atrium and end with the anchoring walls of the left ventricle. The left atrium can have an effect on the mitral valve by dilating to such a degree that it retracts or places tension, thus distorting the annulus area and everting the leaflets not allowing proper coaptation of the leaflets. In this situation, mitral regurgitation is already present and begets more mitral regurgitation. The mitral annulus can dilate, calcify, and become abscessed compromising the function of the mitral leaflets. The annulus can calcify to the point of altering the orifice and can result in resistance to flow across that area. One of the hallmarks of mitral valve prolapse is a dilated, enlarged, sometimes calcified mitral annulus that loses its saddle shape and becomes more flattened. Repair of such valves requires an annular ring to resize and reshape the mitral orifice as defined by the mitral annulus. The leaflets themselves can be involved by many processes that result in abnormal function to include infection, myxomatous processes, fibroelastic deficiency, trauma, rheumatic disease, radiation, and various other inflammatory processes. The processes that affect the leaflets can affect the chordal structures in a similar fashion. The papillary muscles can be affected by ischemia, scarring, as well as infection. The left ventricle can remodel, and the papillary muscles and chordal structures can be displaced and tether the leaflets altering coaptation and resulting in mitral regurgitation.

Classification of disorders of the mitral valve can be grouped into primary abnormalities such as degenerative, rheumatic, congenital, infective, marantic, annular calcification, trauma, valve tumors and others. Secondary abnormalities that alter the mitral valve apparatus are idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, and myocardial infiltrative diseases.¹,² Guidelines for quantitation have been updated and offer general concepts in addition to quantitative methods.³

Illustrations of these problems are demonstrated in the following displays.

CLASSIFICATION OF MITRAL VALVE DISORDERS

Primary Mitral Valve Disorders
- Degenerative
  - Myxomatous degeneration
  - Fibroelastic deficiency
- Rheumatic
- Endocarditis (infective and marantic)
- Congenital (cleft mitral valve)
- Mitral annular calcification
- Valvular tumors
Secondary Mitral Valve Disorders
- Functional
  - Dilated cardiomyopathy
  - Ischemic
  - Hypertrophic cardiomyopathy
  - Myocardial infiltrative diseases

SECTION 2 DEGENERATIVE MITRAL VALVE DISORDERS

The degenerative category of mitral valve diseases is a primary disorder of the mitral valve that results in mitral regurgitation. It is the most common of the disorders of the mitral valve encountered today. This category has been studied in detail, and knowledge of this process has led to the understanding of the natural history and to surgical repair. Surgeons such as Carpentier, the father of modern mitral valve repair, have made major contributions to our understandings of these processes. Carpentier emphasized the importance of defining the etiology of the disease, the lesion that resulted from the disease, and the dysfunction that was created by the disease. This is referred to as the “pathophysiologic triad” described by Carpentier in the early 1980s and remains useful today. The repair technique of Carpentier that follows this analysis of the pathophysiology and pathoanatomy is referred to as the “French Correction.”⁴,⁵

The subcategories of degenerative valves fall into two major types of abnormalities. The first category is myxomatous degeneration resulting in thickened, structurally weakened, redundant leaflets that prolapse toward the left atrium in systole. These valves have come to be known as “Barlow valves.” They are thickened, stretched, and redundant due to myxomatous infiltration and weakening of the fibrous structure of the leaflets and chords. Another category in the degenerative group is fibroelastic deficiency valves in which the leaflets are not so thickened but have weakened collagenous components resulting in more regional changes and regional areas of prolapse, usually in the P2 area. These individuals with fibroelastic changes may progress slowly but have the potential to develop severe acute mitral regurgitation when a chord ruptures. Some of these processes that have stretched redundant leaflets are seen in certain inherited connective tissue disorders such as Marfan syndrome and others (see next page). Further understanding of these processes in the future may lead to molecular alterations that could be beneficial from the clinical standpoint.²,⁶,⁷,⁸

These abnormalities will be illustrated in the sections that follow.

BARLOW SYNDROME AND THE BARLOW VALVE

Interest in the mid systolic click and late systolic murmur from the clinical standpoint started with Barlow and Reid. They developed the concept that the origin of the click was from the mitral apparatus and not from what previously was thought to be from an extracardiac source. Their conceptual understanding of the origin of this sound still holds today. The sound of the mid to late systolic click comes from the process of the mitral leaflets shifting position in mid to late systole producing abrupt tension in the valve and chordal structures. These events result in the sound. This process is associated with valves that have myxomatous changes within their microscopic structure. Sometimes this process is advanced to the point of producing very redundant leaflets with various degrees of hooding, redundancy, chordal stretching, and even chordal rupture.⁹,¹⁰,¹¹

Interestingly, Dr. Barlow submitted his work initially for publication in Circulation, and it was rejected. Later he visited Dr. Victor McKusick at Johns Hopkins University where his work was discussed, and he was subsequently invited to publish his work in the Journal of Chronic Disease. At Hopkins he met a young resident Dr. Michael Criley who had termed the syndrome “mitral valve prolapse” when catheterization laboratory angiographic observations were made of the valve prolapsing up into the left atrium in systole. Barlow did not like the term prolapse and continued to refer to the valve as billowing. Dr. Tsung Cheng relates that Dr. Barlow often said that he thought that the syndrome should be referred to as the Barlow-Cheng syndrome since Cheng had described the late systolic murmur of papillary muscle dysfunction a few years later.¹²,¹³

The myxomatous mitral valve under the microscope shows infiltration of myxomatous material and weakening and disruption of the integrity of the supporting collagen tissue. The four-layered architecture of the valve (the atrialis, spongiosa, fibrosa, and ventricularis) is abnormal with loose collagen in the fibrous, expanded spongiosa containing excessive proteoglycans and disrupted elastin in the atrialis.¹⁴ This leads to elongation and nodular thickening of chords and hooding of leaflets and can lead to chordal rupture, severe mitral regurgitation, heart failure, and even sudden death. Endocarditis can become superimposed on these valves and hasten chordal rupture and even cause perforation.

Individuals who have this abnormality are identified earlier in life than are those with fibroelastic deficiency. As Barlow and Reid discovered, they have midsystolic clicks and late systolic murmurs. Clinicians make this discovery with the stethoscope and then confirm and quantitate the problem with echocardiography. It has many clinical variants and a variable prognosis. In addition, individuals with certain inherited connective tissue disorders are predisposed to these abnormalities earlier in life as part of their clinical syndrome.¹⁵,¹⁶,¹⁷

The Carpentier Classification

FIGURE 3.1 Carpentier defined the mitral valve as having eight regions. Three posterior leaflet regions separated by commissures and three anterior leaflet regions and two commissural regions. These are best identified by viewing the valve from the “surgeon’s view” or placing the mitral aortic curtain at 12 o’clock. (From Carpentier A, Adams DH, Filsoufi F. Carpentier’s Reconstructive Valve Surgery. From Valve Analysis to Valve Reconstruction. Philadelphia, PA: Elsevier; 2010.)

FIGURE 3.2 Degenerative mitral valve disease. Left: fibroelastic deficiency. Right: Barlow disease.

FIGURE 3.3 The triad of types of valve abnormalities falls into three categories according to leaflet motion. Type I is seen in abnormalities such as perforations from endocarditis or long-standing atrial fibrillation and a dilated annulus. Type II is seen with abnormalities such as degenerative valves that have myxomatous changes or fibroelastic deficiency where leaflet motion is excessive. Type IIIA includes mitral stenosis and carcinoid syndrome. Type IIIB includes tethered valves as seen with dilated cardiomyopathy or alterations associated with hypertrophic cardiomyopathy. Carpentier’s classification of valve abnormalities according to leaflet motion has stood the test of time and is used frequently when considering mitral valve abnormalities. Carpentier used his techniques to repair valves that have fibroelastic deficiency and P2 segment prolapse, classified as Type II abnormalities. This is the most common type of valve dysfunction that lends itself to valve repair. (Modified from Carpentier A. Cardiac valve surgery—the “French correction”. J Thorac Cardiovasc Surg 1983;86(3):323-337; Carpentier AF, Lessana A, Relland JY, et al. The “physio-ring” an advanced concept in mitral valve annuloplasty. Ann Thorac Surg. 1995;60:1177-1185.)

MYXOMATOUS DISEASE OF THE MITRAL VALVE, MITRAL VALVE PROLAPSE AND FLAIL LEAFLET

FIGURE 3.4 A: Redundant “hooded” valve often called a “Barlow valve.” B: Thickened, nodular chords infiltrated by myxomatous material in another “Barlow valve.”

FIGURE 3.4 (continued) C: Ruptured chords to the tip of anterior mitral leaflet. (From Rodriguez L, Thomas JD, Monterroso V, et al. Validation of the proximal flow convergence method. Calculation of orifice area in patients with mitral stenosis. Circulation. 1993;88:1157-1165.)

The typical gross appearance of a “Barlow valve” is illustrated in (A). The leaflets are thickened from myxomatous infiltration and have a stretched, “hooded” appearance. Some chords are thick and some thin as seen in (B). Hooding increases the surface area of the leaflets and the tension on chords. This effect begets more of the same over time. The microscopic appearance of these valves shows abnormal architecture of loose collagen in the fibrous, expanded spongiosa containing proteoglycans and disrupted elastin fibers.¹⁷ Other terms have been used to describe these valves including billowing, “floppy,” prolapsed, and flail. Billowing valve implies that part of the leaflet itself extends up above the mitral valve annulus. Barlow preferred the term billowing to prolapse. Floppy valve implies leaflet thickness >5 mm due to redundant tissue. The so-called formefruste Marfan valve is sometimes described as “floppy.” Prolapse was first defined on M-mode echo as a coaptation point that was above the line between the closure point and the hinge point of the mitral valve.¹⁸ A flail leaflet due to ruptured chords implies that the free edge of the valve is untethered and points up into the atrium in systole (C).

INHERITED CONNECTIVE TISSUE DISORDERS ASSOCIATED WITH MITRAL VALVE LEAFLET THICKENING AND PROLAPSE17

Marfan syndrome
Ehlers-Danlos syndrome
Osteogenesis imperfecta
Pseudoxanthoma elasticum
Turner syndrome

ECHOCARDIOGRAPHIC FEATURES OF DEGENERATIVE MITRAL VALVE DISEASE, BARLOW SYNDROME, AND FIBROELASTIC DEFICIENCY

From studies at the bedside of individuals with a click and murmur by Barlow and Reid, our understanding of these entities has come far. It was a landmark clarification when the issue of the etiology of a midsystolic click was investigated. Previously, it was thought to have originated somewhere in the chest wall or pericardium. The variability of the timing of the midsystolic click and the duration of the late systolic murmur with maneuvers such as standing as documented on phonocardiogram put the entity of mitral valve prolapse on the radar screen.¹⁰,¹¹

From the initial echocardiographic M-mode studies, mitral valve prolapse was probably overdiagnosed. Our understanding of the saddle shape of the mitral annulus and 2D and 3D studies have further clarified the anatomy and physiology of this entity and have increased the accuracy of the diagnosis. Interest in surgical repair and analyses at the operating table allowed further understanding of mitral valve abnormalities. Three-dimensional echocardiography with parametric imaging has further defined coaptation points, leaflet billowing, gaps in coaptation, and their relationships to the normal or distorted mitral valve annulus. Surgeons have been involved in this process, and correlations of the imaging findings and those in the operating room have confirmed the accuracy of these techniques.¹⁵

Examples of these imaging techniques are illustrated on the following pages.

FIGURE 3.5 Degenerative mitral valve disease. Top: Barlow disease; Bottom: fibroelastic deficiency. (Adapted from Carpentier A, Adams DH, Filsoufi F. Carpentier’s Reconstructive Valve Surgery. From Valve Analysis to Valve Reconstruction. Philadelphia, PA: Elsevier; 2010.)

PRIMARY MITRAL VALVE DISORDERS WITH MYXOMATOUS DEGENERATION, “BARLOW DISEASE,” OR “BARLOW VALVE”

FIGURE 3.6 Examples of various degrees of involvement. (Adapted from Carpentier A, Adams DH, Filsoufi F. Carpentier’s Reconstructive Valve Surgery. From Valve Analysis to Valve Reconstruction. Philadelphia, PA: Elsevier; 2010.)

CASE PRESENTATION

Severe Myxomatous Degeneration of the Mitral Valve With Only Mild Mitral Regurgitation

A 23-year-old man who is said to have a variant of Marfan syndrome, perhaps forme fruste. He had normal exercise tolerance but did have a history of brief episodes of atrial fibrillation. He had been followed in the pediatric cardiology clinic for mitral valve prolapse.

FIGURE 3.7 Severe mitral valve prolapse with very redundant AMVL and less so of the PMVL—the very redundant AMVL overshoots the PMVL and prolapses to and beyond the mitral annulus. The surface area of the anterior leaflet is much increased and places extra tension on the subvalvular apparatus. This tension generated by the expanding leaflets “tugging” on the papillary muscle areas can sometimes generate serious ventricular arrhythmias. TTE, PLX view.

PRIMARY MITRAL VALVE DISEASE WITH MYXOMATOUS CHANGES INVOLVING BOTH LEAFLETS, RUPTURED CHORDS TO THE ANTERIOR MITRAL VALVE LEAFLET, AND SEVERE MITRAL REGURGITATION

2D and 3D Images

FIGURE 3.8 Ruptured chords to the mid portion of the AMVL resulting in severe mitral regurgitation with a posterior radiating jet. The direction of the radiation of the jet is an index to the most involved segment of the leaflets. TTE, PLA view.

FIGURE 3.9 Flail segment of the AMVL prolapsing above the plane of the MV annulus (black arrow) and resulting in severe MR. 3D TEE, 145° view (the “surgeon’s view”).

PRIMARY MITRAL VALVE DISORDER DUE TO FIBROELASTIC DEFICIENCY AND MITRAL REGURGITATION

FIGURE 3.10 Fibroelastic deficiency. (Adapted from Carpentier A, Adams DH, Filsoufi F. Carpentier’s Reconstructive Valve Surgery. From Valve Analysis to Valve Reconstruction. Philadelphia, PA: Elsevier; 2010.)

Individuals who have primary mitral valve disease due to fibroelastic deficiency commonly do not have extensive myxomatous changes in the valve leaflets. They do have degenerative changes in the fibrous integrity of the leaflets, and this most commonly involves the posterior leaflet. As this leaflet stretches and loses its usual anatomic shape, additional tension is placed on this segment and the corresponding supporting chords can lead to chordal rupture. The regionality of this problem lends itself to surgical resection, repair, and reconstruction of the annulus with a ring. The most common area to be involved is the P2 region of the posterior leaflet where flail or severe prolapsed valve segments are present and lend themselves to repair. The anterior mitral can be involved, and repair can be more difficult or not possible. The Barlow valve with myxomatous degeneration and billowing and hooding of both valve leaflets represents the most difficult valve to repair and requires special surgical talents.⁶

Three-dimensional echocardiography with parametric imaging can demonstrate the billowing segments of the valve, coaptation points, and annular shape. Two-dimensional echocardiographic images along with 3D imaging offer a road map for surgical considerations.

The following sections illustrate these issues.

FIBROELASTIC DEFICIENCY OF THE MITRAL LEAFLETS

Ruptured Chords to the P1 Segment of the Posterior Mitral Leaflet

FIGURE 3.11 Ruptured chords to the P1 region of the PMVL—this leaflet prolapses above the plane of the mitral annulus and has its origin in the annulus close to the left atrial appendage and therefore is in the P1 region of the PMVL (yellow arrow). TEE, 92° view, 2C view.

FIGURE 3.12 The same patient from a similar view with color Doppler demonstrating the jet coursing across the mitral orifice away from the left atrial appendage and toward the inter atrial septum. TEE, 65° view.

EVALUATION OF THE SEVERITY OF CHRONIC MITRAL REGURGITATION BY ECHOCARDIOGRAPHY

The 2017 guidelines for evaluation for grading the severity of mitral regurgitation are available for reference.³ They include an assessment of the structure of the mitral valve, the size of the left atrium, and qualitative, semiquantitative, and quantitative recommendations for grading of severity. For example, a flail leaflet or a very dilated left ventricle with severe tenting would be associated with severe mitral regurgitation. A color flow jet area that is large, eccentric, or coursing around the left atrium or into the pulmonary veins is an eyeball clue to severe mitral regurgitation. A grossly large flow convergence (proximal isovelocity surface area [PISA]) throughout systole or a holosystolic dense CW jet profile suggests that severe mitral regurgitation is present (see table on the following page).

Semiquantitative methods including measurement of the vena contracta width and assessment of the pulmonary vein flow pattern offer quick estimates of severity of mitral regurgitation.

Quantitative methods include effective regurgitant orifice area (EROA) by the PISA method, regurgitant volume, and regurgitant fraction. The 2017 guidelines changed the EROA limits for severe functional mitral regurgitation to >0.40 cm² recognizing that sometimes lower numbers are associated with elliptical regurgitant areas in this entity. Regurgitant volume and regurgitant fraction also are quantitative methods. Table 3.1 summarizes the criteria for evaluation of the severity of mitral regurgitation on echocardiography.

TABLE 3.1 CRITERIA FOR EVALUATION OF THE SEVERITY OF MITRAL REGURGITATION

Structural	Flail leaflet or severe tenting Dilated left atrium
Qualitative	Large jet Large flow convergence Holosystolic dense jet that is triangular
Semiqualitative	Wide vena contracta Systolic flow reversal Dominant E-wave
Quantitative	Large EROA > 0.4 cm² Large regurgitant volume > 60 mL Regurgitant fraction > 50%

Grading of Chronic Mitral Regurgitation, the 2017 Guidelines³

FIGURE 3.13 These 2017 guideiines offer parameters for determining the severity of chronic mitral regurgitation. Source: Zohgbi WA, Adams D, Ronow RO, et al. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation. A report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr. 2017;30(4):303-371.

Imaging and Calculations Obtained From the Principle of the Proximal Isovelocity Surface Area

An apical view should be chosen that identifies the PISA as a hemisphere and is in an axis that is as parallel as possible to the Doppler beam. This is most accurately done when there is one jet.
The scale should be turned down in the direction of flow such that the PISA radius is as well defined as possible (usually in the 20-30 cm/s range).
The PISA radius should be measured from the base of the hemisphere to the outer aliased limit. One can sometimes measure the vena contracta when these settings are made.
Next, the CW Doppler should be used to find the complete envelope of the MR jet, and this should be traced to obtain the maximum velocity and the velocity time integral (VTI) of the velocity profile.
The surface area of a sphere is 4θr² and that of a hemisphere is 2θr². The continuity equation can be rearranged such that the effective orifice area (ERO) equals 2θr² × the ratio of the aliasing velocity to the maximum MR velocity (not the VTI).
In order to calculate the regurgitant fraction, one has to measure the velocitytime integral of the LVOT using pulsed wave Doppler, the LVOT diameter, and from these calculate the volume per beat. The MR volume is equal to the ERO × the VTI of the MR velocity profile. The regurgitant fraction (%) is the MR volume divided by the stroke volume × 100.