Physiology and pathology

DR. MOHAMED ELAWADI

PROF. OF CARDIOTHORACIC SURGERY

Developments in magnetic resonance and ECHO imaging have increased our understanding of the dynamic physiology within the Functional Mitral Unit.

Detailed knowledge of the components contained within this intricate structure has allowed a more comprehensive insight into valvular function and dysfunction, as well as establishing the physiological consequences of surgical intervention on the mitral valve.

Opening and closure of the mitral valve leaflets, within the Functional Unit, are predominantly determined by pressure changes across the valve.

However, the Functional Unit facilitates valve opening and closure by alteration of annular dimensions, specific leaflet physiological properties, and subvalvar apparatus function.

These factors allow optimal performance, and when not present lead to dysfunction.

Mitral Valve Annular Dynamics

The annulus undergoes significant deformation during the cardiac cycle with up to a 40% reduction in circumference during systole.

The annular area is largest during late-diastole, immediately prior to atrial systole, and smallest in late-systole altering in size by 10–20%.

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Left atrial systole initiates the reduction in mitral annular size prior to ventricular systole.

Sixty-five percent of the reduction in annular circumference that occurs takes place prior to the onset of ventricular systole, preparing the Functional Unit for an increase in trans-mitral valve pressure gradient during ventricular systole.

In a similar fashion, the increase in annular size that occurs to maximize the mitral valve area during ventricular diastole, also occurs prior to the commencement of ventricular diastole.

This prepares the Functional Unit to facilitate

trans-mitral blood flow; both the annular circumference and area start to increase in late ventricular systole, and are maximal just prior to atrial systole.

In addition to changes in overall size, the annulus

rotates and moves apically during systole when the

ventricle shortens.

This leads to a more elliptical shape thereby reducing the anteroposterior dimension of the annulus and maximizing the layer of coaptation of the mitral valve leaflets.

The posterior mitral annular change is influenced by ventricular contraction.

The anterior mitral valve annulus undergoes a flexible change thus buffering the differential movement between the aortic root and the posterior annulus and maintaining the left ventricular outflow tract.

Mitral Valve Leaflet Physiology

Leaflet movement is also dynamic in nature, dependent on a number of physiological factors.

These factors add to the ability of the Functional Unit to Minimize leaflet stress and withstand increases in trans-mitral pressure gradient.

The dynamic nature of these leaflet changes is influenced by many components within the mitral valve Functional Unit.

Atrial contraction plays a crucial role in preparing

the leaflets for closure.

Atrial contraction increases the velocity of blood flow across the mitral valve, and this increased velocity flow thereby leads to a reduction in the lateral displacement force, as determined by the principle of Bernoulli, which states that a slow-moving fluid exerts more pressure than a fast-moving fluid.

One of the most dramatic everyday examples of

Bernoulli’s principle can be found in the airplane, in which lift occurs due to pressure differences on the surface of its wing

This reduction in displacement force during atrial contraction therefore allows the mitral valve leaflets to move centrally, thereby initiating the process of closure.

This activity, alongside the reduction in annular

size during atrial contraction, plays a huge role in optimizing mitral valve Functional Unit performance.

When atrial contraction is not present, as occurs in junctional rhythm or atrial fibrillation, pre-ventricular systolic leaflet movement and annular dimension reduction, do not occur, resulting in an increased tendency to early mitral valve regurgitation.

The left atrial muscle, therefore, has a huge bearing on the mitral valve Functional Unit in preparation for closure.

Leaflet innervation by the cholinergic and adrenergic

nervous systems, with both afferent and efferent

nerves present alongside smooth muscle cells within

the leaflet substrate, lead to leaflet stiffening during

periods of increased trans-mitral valve gradients.

This, therefore, reduces leaflet-deforming stresses during

ventricular systole, whilst maximizing leaflet compliance

during ventricular diastole, thereby maximizing

the mitral valve orifice area.

Finally, the mitral valve annulus also plays a crucial role in optimizing leaflet function.

Its hyperbolic paraboloid configuration allows a reduction of the stresses exerted on the valve leaflets during periods of increased trans-mitral valve pressure gradient.

The anterior mitral valve leaflet is more extensile in the radial rather than the circumferential direction,allowing increases in length of the leaflet with increased trans-mitral pressure gradients, thereby potentially increasing the zone of leaflet coaptation.

The posterior leaflet, which is hinged on two-thirds

of the mitral valve annulus, is more distensible in both

radial and circumferential directions, allowing both

increases in posterior leaflet length, and circumference,

as annular size reduces during ventricular systole.

This results in greater mechanical stability of the

mitral valve with an increased ability for the posterior

leaflet to withstand increases in stress during periods

of high trans-mitral valve gradients.

These factors are important when considering surgical

intervention, and understanding the impact of

disease processes on the Functional Unit.

The normal layer of coaptation between the two leaflets, within the region of the rough zone, is 6–8 mm along the length of the leaflets, and is maximal between the A2/P2 scallops of the valve.

The excess tissue found in the leaflets is almost double the area of the annulus and restoring a sufficient zone of coaptation is the primary aim of all mitral repair techniques.

Mitral Valve Papillary Muscles

Counterintuitively, papillary muscles elongate during

early systole, when the left ventricular mass is contracting,

and shortening.

This delayed contraction, and consequent elongation, facilitates early closure of the mitral valve leaflets, ensuring early contact of the leaflets at the line of coaptation, and maximizing the zone of coaptation during early ventricular systole.

During later ventricular systole, papillary muscles shorten,

thereby resisting the increasing trans-mitral valve gradient

and preventing leaflet prolapse.

During early ventricular diastole, the papillary

muscles remain shortened, whilst the remaining ventricular muscle relaxes.

This delayed relaxation facilitates leaflet opening by retracting the leaflets within the ventricle away from each other during early ventricular diastole, as the trans-mitral valve gradient opens the Functional Unit.

Once the mitral valve is opened, papillary muscle relaxation occurs in preparation for the subsequent cardiac cycle.

Left Ventricular Muscle

The large posterior fascicle of the Bundle of His courses around the base of the posterior left ventricle and activates it in early systole before passing more distally.

This posterior bundle activates more myocardium than the right bundle and left anterior fascicle combined and thereby provides a crucial role in coordinating the phased, activation of the ventricles.

By activating the posterobasal region of the left ventricle early during this phased sequence, posterior annular changes in dimension occur early in systole.

This posterior annular shortening, associated with anterior displacement, facilitates early leaflet coaptation.

A loss of this early activation, as occurs with left bundle branch block, and with right ventricular pacing, potentially reduces the zone of coaptation, and increases the tendency to mitral valve regurgitation.

Summary of the Impact of Mitral ValvePhysiology

Ultimately, all changes in the mitral valve Functional

Unit leading up to its closure have the common aim of facilitating adequate leaflet coaptation to prevent regurgitation.

The early closure of the mitral valve thereby allows isovolumetric contraction to occur, optimizing

ventricular filling during this crucial phase of the cardiac cycle.

Starling’s Law determines that left ventricular

contractility is dependent upon left ventricular filling,and mitral valve function, therefore, potentially plays a fundamental role in optimizing left ventricular contractility.

This underlines the importance of ensuring early competence of the Functional Unit, and explains the complex interrelationship between the mitral valve functional Unit and overall cardiac performance.

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It gives off a variable number of obtuse marginal branches, the first of which demarcates the proximal from the distal circumflex.

In the majority of cases, the left circumflex coronary artery crosses underneath the coronary sinus at a variable distance along the course of the coronary sinus.

The coronary sinus passes within the posterior AV groove, but its course is more distant to the annulus than the circumflex coronary artery.

It is buried in the posterior left atrial wall above the annulus. Laterally, the coronary sinus is farthest away from the annulus, but it does course closer to the annulus posteroinferiorly.

FROM THE “BABEL SYNDROME” TO��THE “PATHOPHYSIOLOGICAL TRIAD

A sterling example of this is found in the multiple terminologies used to describe mitral valve pathology.

Terms such as prolapse, flail, partial flail redundant, overshooting, stretching, elongation, floppy, billowing, ballooning, Barlow, dysplasia, myxoid, and myxomatous,

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Other synonyms are Barlow, billowing, ballooning,

myxomatous valve, and mitral valve prolapse.

Another source of confusion comes from the fact that for

some specialists a given term such as “prolapse” means a

dysfunction (leaflet prolapse) while for others it refers to

a disease (mitral valve prolapse).

The same chaotic situation applies to the term “floppy valve,” which is used to define either a valve morphology, or a dysfunction, or a disease.

A classification can be obtained by using a pathophysiological triad with a sound distinction between the terms describing Valve Etiology (i.e., the cause of the disease),

Valve Lesions resulting from the disease, and Valve Dysfunction resulting from the lesions.

Pathophysiological Triad�

Classifying terms into these three groups permits selection of one single term among several synonyms.

Taking as an example the case of degenerative mitral valve diseases, Table outlines our selection based on historical, scientific, and semantic considerations.

Application of the Pathophysiological Triad in�Degenerative Mitral Valve Diseases�

A comprehensive understanding of valvular

pathology implies clear distinction between etiology, lesions, and dysfunctions. This triad can be applied to all cardiac valves

The pathophysiological triad facilitates communication

between cardiologists, echocardiographers, and

surgeons and greatly clarifies clinical investigations.

In addition, it has significant clinical relevance for the

individual patient because “long-term prognosis depends

upon etiology, repair strategy depends upon dysfunction,and surgical techniques depend upon lesions

ETIOLOGY

Primary valve diseases involve the valvular tissue.

Secondary valve diseases affect the supporting

structures of the valves—that is, the ventricles for the

mitral and tricuspid valves and the aorta and pulmonary

artery for the aortic and pulmonary valves, respectively.

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The determination of the etiology of valvular disease is

important because it helps to establish the medical treatment, which should precede or follow valve reconstruction.

In addition, it is the single most important predictor

of long-term prognosis.

Etiology of Valvular Diseases�Primary Valve Diseases�

Secondary Valve Diseases

Mechanism of functional mitral regurgitation. A, normal mitral valve. B, ischemic mitral valve with pronounced posterior restriction in P3 after an episode�of ventricular ischemia. LV, left ventricle.

LESIONS

previously listed diseases can cause lesions

affecting one or several components of the heart valves:

the annulus, the leaflets, and the supporting structures

These lesions may be complex, multiple, and associated, making a comprehensive description by echocardiography difficult.

This difficulty is overcome by a “functional approach,” which focuses attention on the dysfunctions resulting from lesions rather than on the lesions themselves.

VALVE DYSFUNCTION: THE�“FUNCTIONAL CLASSIFICATION

In the late 1970s, as the techniques of valve reconstruction

developed, it became clear that it was no longer sufficient to classify the valvular pathologies in the classical three groups: valve stenosis, valve regurgitation, and combined stenosis and regurgitation.

The attempts to more precisely describe valve pathology by an exhaustive anatomical description of the lesions proved to be too complex to be practical.

This “anatomical approach” was progressively abandoned and more attention was placed on the valve dysfunction resulting from these lesions.

This led to the development of a functional classification.

The functional classification, introduced before echocardiography became available in the operating room, resulted in significant simplification of a complex field and proved to be particularly important for the reconstructive surgeon whose primary aim was to restore normal function rather than normal anatomy of the valve.

The “functional approach” of valvular disease is based

on analysis of the motion of the leaflets by echocardiography

and direct inspection by the surgeon.

Three functional types are described depending upon whether the

motion of the leaflets is normal (type I), increased (type II), or restricted (type III).

Restricted leaflet motion may occur mainly during the opening of the valve (type IIIa) or during valve closure (type IIIb) .

Types I and II valve dysfunctions result in valve regurgitation whereas type III may result in valve regurgitation, stenosis, or both.

Carpentier’s “Functional �Classification”2�

Assessing the type of dysfunction in valvular disease is

important because it helps surgeons identify the lesions

causing the dysfunction .

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Type I: Valve dysfunction with normal leaflet motion

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In type I valve dysfunction, the course of the leaflets

between systole and diastole has normal amplitude.

The valve is regurgitant because of either leaflet perforation or lack of leaflet coaptation, a consequence

of annular dilatation.

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Type II: Valve dysfunction with excess leaflet motion�(leaflet prolapse).

In type II dysfunction, the motion of one or more leaflets is increased and the free edge of one or several leaflets overrides the plane of the orifice during valve closure.

The hemodynamic consequence is a regurgitation. A leaflet prolapse of the mitral or tricuspid valve may be due either to chordae rupture or elongation or to papillary muscle rupture or elongation.

Leaflet prolapse of the aortic or pulmonary valves may result from leaflet rupture, edge distension,

or commissure detachment.

Type III: Valve dysfunction with restricted leaflet motion

In type III dysfunction, the motion of one

or more leaflets is limited, either during valve

opening and closure (type IIIa), leading to various degrees of valve stenosis and regurgitation, or during valve closure (type IIIb), leading to valve regurgitation.

B

A

The “functional classification” of valvular diseases

allows the Echocardiographery to assess and localize valvular dysfunctions.

It provides valuable information to the surgeon, who can then proceed to a full inventory of the lesions in the areas where a dysfunction has been

identified.

The complexity of valvular lesions contrasts with the simplicity of the resulting valvular dysfunctions

The functional classification is the foundation of

valve analysis. It serves as a guideline to achieve a successful valve reconstruction.

The functional classification complements the classical assessment of the hemodynamic consequences of valvular lesions, helping to define the indications for surgery, particularly as it relates to valve reparability.