**5. Mitral regurgitation**

Mitral valve regurgitation is a complex entity that could be caused by either one of the following etiological factors such as; Marfan syndrome, acute rheumatic valve disease, degenerative [myxomatous], bacterial endocarditis, acute ischemia, papillary muscle rupture. However, mitral regurgitations are further categorized into two broad groups; acute and chronic [primary and secondary] mitral regurgitation and into two generally accepted classifications namely; Carpentier and Duran's classification. Although identifying patients at risk, symptomatic, asymptomatic and progressive stage of mitral valve regurgitation encountered in clinical settings have been made easier as compared to previous years with the most recent American Heart Association (AHA) and the American College of Cardiology (ACC) guidelines for patient management (see appendix A and B) [25].

Common clinical presentations encountered with LAM are either stenosis due to tumor prolapse into mitral orifice or regurgitation due to tumor induced valve trauma. Furthermore, Mitral valve regurgitation associated with LAM is caused by ventricular and annular dilatation, failure of leaflet coaptation and the direct damage of the leaflets and/or subvalvular apparatus due to the presence of the myxoma body itself as it transverses through the mitral valve during each systolic and diastolic phase coupled with the myxoma body adherence to nearby structures of the mitral valve. The myxoma prolapse from the left atrium toward the left ventricle during the entire cardiac cycle eventually leads to mitral valve regurgitations of varying degrees, cause volume overload propagating both left atrial and left ventricular dilatation, annular dilatation due to the continuous mechanical stretch of the prolapsing tumor on the mitral annulus during each systolic and diastolic phase. However, the extent of valvular obstruction varies with body position as the presence of the myxoma body itself affects transmitral blood flow and also tends to mask mild and moderate to severe mitral regurgitations due to the huge and floating myxoma body where large myxomas with long stalk produces a temporally complete obstruction of the mitral valve orifice resulting in syncope. The continuous pendulum like or "wrecking ball" effect of the myxoma during each cardiac circle against the entirety of the mitral valve apparatus gives raise to regurgitations and its severity is highly dependent on the resultant effect of the myxoma body itself on the mitral valve [26–35]. The grade and severity of the regurgitation is highly dependent on the myxomas body size, stalk length [small, large, prolapsing and non- prolapsing] and to some varying degree body position and the resultant changes of blood flow through the left heart [36].

#### **5.1. Carpentier classification**

**4. Pathology and physiopathology**

44 Structural Insufficiency Anomalies in Cardiac Valves

leading to regurgitation.

**5. Mitral regurgitation**

lines for patient management (see appendix A and B) [25].

The tendency of mitral valve regurgitation and the adjunct mitral valve prolapse development is inevitably high with the presence of left atrial myxoma either before or after any interventions been made. The development of mitral valve prolapse is due to the persistent rebound pendulum-like motion of the left atrial myxoma on the valve apparatus during each cardiac circle. Echocardiographically, mitral valve prolapse is defined as the upward displacement of the mitral leaflets above 2 mm in diastole [silent] which is usually the case in patients presenting with LAM and above 3 mm [massive] which increases the regurgitant jets seen during the echocardiographic studies. However, mid-systolic click to late systolic murmur is pathognomonic auscultatory findings with mitral valve prolapse and underling regurgitation as it varies from being benign to a gradual or sudden advance stage depending on the prolapse and regurgitation grade either before or after therapeutic interventions with a significant morbidity and mortality rate. Fortunately, apart from the massive prolapse, bacterial endocarditis, thromboembolism, atrial fibrillations, myxomatous degenerations [Barlow's disease] and rheumatic heart diseases play key roles in the resultant regurgitations caused by the left atrial myxoma. Histological features of mitral valve prolapse and regurgitation are marked spongiosa proliferation, mucopolysaccharide acid replacement of the leaflet collagen causing thickening and leaflet redundancy. As a result of the changes made such as fibrotic leaflets, thinning and/or elongation of the chordae tendineae, proper valve coaptation during systole is rendered impossible due to the redundant and elongated leaflets coupled with overshooting into the left atrium and the disrupted tendineae which eventually ruptures

Mitral valve regurgitation is a complex entity that could be caused by either one of the following etiological factors such as; Marfan syndrome, acute rheumatic valve disease, degenerative [myxomatous], bacterial endocarditis, acute ischemia, papillary muscle rupture. However, mitral regurgitations are further categorized into two broad groups; acute and chronic [primary and secondary] mitral regurgitation and into two generally accepted classifications namely; Carpentier and Duran's classification. Although identifying patients at risk, symptomatic, asymptomatic and progressive stage of mitral valve regurgitation encountered in clinical settings have been made easier as compared to previous years with the most recent American Heart Association (AHA) and the American College of Cardiology (ACC) guide-

Common clinical presentations encountered with LAM are either stenosis due to tumor prolapse into mitral orifice or regurgitation due to tumor induced valve trauma. Furthermore, Mitral valve regurgitation associated with LAM is caused by ventricular and annular dilatation, failure of leaflet coaptation and the direct damage of the leaflets and/or subvalvular apparatus due to the presence of the myxoma body itself as it transverses through the mitral As widely used and proposed by Carpentier, the anterior leaflet is indicated as A1, A2, and A3 but lacks a clear distinction between A1 and A2 and also between A2 and A3 because of its smooth surface. However, the analogous segments of the posterior leaflets are also indicated as P1 [anterolateral], P2 [middle], and P3 [posteromedial] and highly distinctive from each other [37]. Regurgitations occur when there is an annular dilatation and/or the free edge of one or both leaflets overrides the entire valve orifice during systole, chordae tendineae destruction or rupture, a papillary muscle tear or detachment, architectural left ventricular destruction and acute ischemia as a result of embolization due to the myxoma friability (**Table 1**). Regurgitations caused by LAM express themselves differently according to grades, degree, and size of the myxoma, different loading conditions, body structure, position and other masked underlying pathology so therefore, for a successfully understanding of mitral regurgitation caused by LAM, a clear knowledge of the components and anatomy of the mitral valve apparatus, possible functional alterations, analysis of the leaflet motion, and a proper grading system is essential for a better prognosis after management or repair [1] (**Figure 2**).


**Table 1.** Carpentier's classification of regurgitation of the mitral valve.

• Type A is evident when there is annular dilatation only or in combination with leaflet perforation, as in endocarditis.

infarction precipitating severe left ventricular dysfunction and adverse remodeling which eventually causes papillary muscle detachment, tethering leaflets with associated annular

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Ischemic mitral regurgitation is defined as a moderate to severe mitral leak precipitated by acute myocardial infarction caused by partial or total complete obstruction of one or more coronary arteries on a different level due to the myxoma friability which gives rise to various degree of mitral regurgitation by changing the geometry of the ventricle [spherical shape], distorted wall motion, lateral and apical deracinated papillary muscles or its deformation due to ischemia [41].

This type of regurgitation is perpetuated as little pieces of embolus from the myxoma gets stocked at the edges of the leaflets forming small nodules which prevents complete valve closure

**Figure 3.** (A) Duran classification of a well-structured mitral valve leaflet, A: anterior; PM: posterior middle; P1: posterior lateral; P2: posterior medial. (B) Modified type A: anterior. P: posterior. PM: posterior middle [1: lateral. 2: Medial].

dilatation preventing proper coaptation [40].

**5.5. Ischemic heart disease**

**5.6. Degenerative heart disease**


#### **5.2. Duran classification**

Kumar et al. proposed their classifications based on the chordae tendineae insertion gotten from the two papillary muscle groups. Thus, the posterior leaflet scallops were designated as P1 [anterolateral] and P2 [posteromedial] and the larger middle scallop as posterior middle which was subdivided as PM1 and PM2 based on chordal origins while the anterior leaflets were divided into A1 with chordae crossing from the anterolateral papillary muscle and A2 with chordae from the posteromedial papillary muscle [38] (**Figure 3**).

#### **5.3. Acute mitral regurgitation**

Acute mitral regurgitation occurs due to annular prolapse and the disruption of other different structures of the mitral valve. The papillary muscle rupture or the detachment of the chordae tendineae from the papillary muscles caused by the resultant myxoma pendulum-like movement during each cardiac circle causing disrupted valve motion and a rise in volume overload in combination with the high friable tendencies of LAM leading to embolization of the coronary arteries which eventually ends in myocardial infarction. The acute volume overload on the left ventricle combined with the regurgitant flow of blood into the left atrium during systole results in acute pulmonary congestion, dyspnea, and poor cardiac output [39].

#### **5.4.** *Chronic mitral regurgitation*

When categorizing chronic mitral regurgitation caused by left atrial myxoma, it is important that the physician gives a proper distinction between chronic primary [degenerative] and chronic secondary [functional] mitral regurgitation as it clearly helps in identifying the underlying pathology in relation to the resultant effect caused by the myxoma itself.


infarction precipitating severe left ventricular dysfunction and adverse remodeling which eventually causes papillary muscle detachment, tethering leaflets with associated annular dilatation preventing proper coaptation [40].

#### **5.5. Ischemic heart disease**

• Type A is evident when there is annular dilatation only or in combination with leaflet per-

• Type B is caused by elongated chordae tendineae, as constantly seen in degenerative dis-

• Type C occurs when there is leaflet perforation or chordal rupture, as found in rheumatic

• Type D there is chordal rupture [rheumatic] or in combination with papillary muscle de-

Kumar et al. proposed their classifications based on the chordae tendineae insertion gotten from the two papillary muscle groups. Thus, the posterior leaflet scallops were designated as P1 [anterolateral] and P2 [posteromedial] and the larger middle scallop as posterior middle which was subdivided as PM1 and PM2 based on chordal origins while the anterior leaflets were divided into A1 with chordae crossing from the anterolateral papillary muscle and A2

Acute mitral regurgitation occurs due to annular prolapse and the disruption of other different structures of the mitral valve. The papillary muscle rupture or the detachment of the chordae tendineae from the papillary muscles caused by the resultant myxoma pendulum-like movement during each cardiac circle causing disrupted valve motion and a rise in volume overload in combination with the high friable tendencies of LAM leading to embolization of the coronary arteries which eventually ends in myocardial infarction. The acute volume overload on the left ventricle combined with the regurgitant flow of blood into the left atrium during systole results in acute pulmonary congestion, dyspnea, and poor cardiac output [39].

When categorizing chronic mitral regurgitation caused by left atrial myxoma, it is important that the physician gives a proper distinction between chronic primary [degenerative] and chronic secondary [functional] mitral regurgitation as it clearly helps in identifying the

• *Chronic primary mitral regurgitation:* This regurgitation is as a result of the myxomas destruction of a single valve component either in its function or architecture such as annular dilatation with regurgitant jets from the left ventricle to the left atrium. However, the prolonged and severe volume overload produced eventually causes irreversible myocardial

• *Chronic secondary mitral regurgitation:* In this type of regurgitation, the entire valve apparatus is somewhat normal but the regurgitant jets are caused by embolization of the coronary arteries on different levels from the fragments of the myxoma giving rise to myocardial

underlying pathology in relation to the resultant effect caused by the myxoma itself.

damage, episodic periods of heart failure and finally sudden death

ease, or thinning of the papillary muscle, found in ischemic heart disease.

with chordae from the posteromedial papillary muscle [38] (**Figure 3**).

foration, as in endocarditis.

46 Structural Insufficiency Anomalies in Cardiac Valves

tachment or displacement [ischemic].

diseases.

**5.2. Duran classification**

**5.3. Acute mitral regurgitation**

**5.4.** *Chronic mitral regurgitation*

Ischemic mitral regurgitation is defined as a moderate to severe mitral leak precipitated by acute myocardial infarction caused by partial or total complete obstruction of one or more coronary arteries on a different level due to the myxoma friability which gives rise to various degree of mitral regurgitation by changing the geometry of the ventricle [spherical shape], distorted wall motion, lateral and apical deracinated papillary muscles or its deformation due to ischemia [41].

#### **5.6. Degenerative heart disease**

This type of regurgitation is perpetuated as little pieces of embolus from the myxoma gets stocked at the edges of the leaflets forming small nodules which prevents complete valve closure

**Figure 3.** (A) Duran classification of a well-structured mitral valve leaflet, A: anterior; PM: posterior middle; P1: posterior lateral; P2: posterior medial. (B) Modified type A: anterior. P: posterior. PM: posterior middle [1: lateral. 2: Medial].

leading to regurgitant backflow of blood into the left atrium during the course of each cardiac circle which over time leads to an enlarged left atrium and ventricle causing heart failure.

involved with a well-planned follow-up regimen as regurgitations in some cases might not be detected immediately after the intraoperative Transesophageal echocardiography is used to check if the myxoma was totally resected and the surgery satisfactory as it could be termed by the physician as a physiological residual regurgitation seen after such kind of surgery which could be detrimental in the long term. However, current clinical features and echocardiographic criteria's are not sufficient enough to detect mitral regurgitations and probable underlying pathological conditions early to achieve an effective medical management and/

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The most challenging problem both surgeons and interventionist face is the doubtful nature surrounding possible resultant masked regurgitations with LAM as this could be residual following myxomas resection coupled with the underlying pathological factors aligned with this neoplasm as it propagates the destruction, perforation, elongation, thinning, tethering, thickening, retraction, displacement and ischemic changes seen in mitral valve regurgitation and/ or prolapse. Bearing this in mind, at the slightest suspicion of hemodynamic and architectural change in mitral valve apparatus and ventricular geometry [remodeling] during medical management or surgical intervention, a thorough assessment of the mitral valve apparatus should be made using Transthoracic echocardiography [outpatient settings] and Transesophageal echocardiography [inpatient settings] in combination with the surgeons direct vision assessment if surgery was the treatment of choice irrespective of the known diagnosis [myxoma] in order to rule out any possible concomitant pathology such as coronary embolization to achieve favorable long-term prognosis. Finally, future directions and approaches made by the various scientific communities should be directed toward identifying the key dynamic concepts behind LAM biological, physiological and pathological components, clinical features and the echocardiographic criteria's to be used in an early detection of mitral valve regurgitation and the possible underlying pathological processes and/or complications that could precipitate silent mitral valve insufficiencies after medical management or surgical interventions

as this will be an important achievement and a novel contribution to the field.

We the authors appreciate the contributions Iroegbu Phoebe Chioma and Adeghe Peace

**ICD**: Concept and design, a major contributor to the interpretation and writing of the

**ZZ, ZH & JL**: Critically revised and analyzed the manuscript for scientific logic and reasoning.

or surgical therapy.

**Conflict of interest**

**Author's contributions**

Eseose made to the manuscript.

manuscript.

The authors declare no conflict of interest.

#### **5.7. Rheumatic heart disease**

Myxoma [Latin Greek word "muxa" for mucus] means a myxoid tumor of primitive connective tissue, a primary tumor affecting adult hearts commonly in the left atrium but can, however, be found in other locations. LAM inflammatory process gives rise to a rapid sequence of chordal thickening and retraction, commissural fusion and finally thickened leaflets [incomplete opening and closure of the leaflets] with an enlarged annulus which eventually leads to regurgitation. Though an uncommon relation to the underlying processes involved with LAM throughout its development until therapy, pathologist has confirmed postoperatively the pathological component of LAM to be a spindle tumor with mucus production histologically made up of fusiform, stellate, and or polygonal cells [42–45] and histologically associated with interleukin-6 [46].

#### **5.8. Endocarditis**

This type of regurgitation caused by LAM is rear as compared to other underlying resultant pathological cause and may even be described by some physicians, surgeons, and interventionist as idiopathic due to its ambiguity. The vegetations formed involves series of the pathological process which is activated as a result of incomplete resection of the LAM in combination with natural human oral streptococcal inhabitants [Streptococcus sanguinis and/ or dysgalactiae] which gets into the bloodstream when opportunities present themselves such as during surgeries and colonize the heart valves especially the mitral valve. The result at first is noninfective, but as the collection of platelets, fibrin, microcolonies of microorganisms, and the scant inflammatory cells increases, it shifts to a subacute stage and finally to full-blown endocarditis due to bacterial accumulations as they lodge and aggregate at the site of the incomplete LAM resection [1, 47].
