INTRODUCTION — Mitral valve prolapse (MVP) is a common cause of mitral regurgitation (MR). Although most patients with MVP have mild, trivial, or no MR [1], MVP is the most common cause of surgical MR in developed countries [2]. Other potential complications include infective endocarditis and arrhythmias. The diagnosis of MVP is suspected on physical examination and confirmed by echocardiography.

The definition, classification, etiology, pathology, and diagnosis of MVP will be reviewed here. Other aspects of MVP and associated MR are discussed separately. (See "Nonarrhythmic complications of mitral valve prolapse" and "Arrhythmic complications of mitral valve prolapse" and "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet" and "Mitral valve prolapse syndrome".)

EPIDEMIOLOGY — The prevalence of mitral valve prolapse (MVP) in the general population varies among studies, mostly due to variable criteria used for diagnosis. Reports published early in the development of echocardiography suggested high MVP prevalence, 4 to 10 percent [3-5] and even close to 20 percent in selected populations. These early reports are now considered inaccurate because echocardiographic criteria for diagnosis were not yet fully developed and lacked specificity.

Using currently accepted definition of MVP, the Framingham Heart Study reported an overall prevalence of 2.4 percent [6]. Individuals with classic MVP (leaflet thickness ≥5 mm; 1.3 percent) and non-classic MVP (leaflet thickness <5mm; 1.1 percent) had similar age and sex distributions. In another population-based study (Cardia), the prevalence of MVP in 4136 young adults was only 0.6 percent [7]. In a Canadian study of 972 patients, MVP prevalence was similar in three ethnic groups (2.7 percent in South Asian, 3.1 percent in European, and 2.2 percent in Chinese) [8]. MVP patients were leaner and had a greater degree of mitral regurgitation than the general population [6,7]. It is unclear whether prevalence differences between studies are age-related and should be interpreted as demonstrating a link between aging and MVP prevalence.

MVP may be slightly more common in women than in men. In the Framingham study, there was a nonsignificant trend toward a female preponderance among those with MVP (59.5 versus 52.7 percent in those without MVP) [6]; in the larger Olmsted county study, 64 percent of individuals with MVP were women [9].

The majority of patients with MVP have mitral regurgitation (MR) (70 percent in one cross-sectional population-based study), but most patients with MVP (approximately 75 percent in the same study) have mild, trace, or no MR [1]. Severe MR is uncommon, identified in 4 percent of patients with MVP.

DEFINITION AND CLASSIFICATION — The diagnosis of mitral valve prolapse (MVP) was previously based upon a combination of clinical exam findings and echocardiographic criteria; the current definition relies on imaging alone.

The current imaging definition of MVP is billowing of any portion of the mitral leaflets ≥2 mm above the annular plane in a long axis view (parasternal or apical three-chamber) (image 1) [10]. Prolapse of the mitral valve is defined as an abnormal systolic displacement of one or both leaflets into the left atrium (systolic billowing) due to a disruption or elongation of leaflets, chordae, or papillary muscles. Simple override of the anterior leaflet (ie, the anterior leaflet passing behind the posterior leaflet in systole without crossing the annulus plane as commonly seen in ischemic mitral regurgitation, due to tethering of the posterior mitral leaflet) must be distinguished from MVP, as this has therapeutic implications. Indeed, percutaneous repair with the MitraClip system is an approved indication for primary MVP, but not for ischemic mitral regurgitation at this time.

This abnormal movement has been challenging to define given the saddle shape of the mitral annulus, which is accentuated in systole due to displacement of the annulus at the commissures towards the ventricular apex [11,12]. Thus, in the apical four chamber view, the leaflets may appear posterior to the annulus, even in a completely normal subject [13,14]. These observations published in the late 1980s led to a change in the accepted echocardiographic view for identification of MVP from “any view” to “a (three chamber) long-axis view”.  

Historically, while a mid-systolic click and late-systolic murmur were described in the late 19^th century, their association with mitral regurgitation was first demonstrated by Barlow in 1963 [15]. The relationship between the late systolic click-murmur and abnormal mitral motion was further characterized in a larger series of 90 patients [16]. MVP was subsequently linked to numerous symptoms and clinical syndromes, but many studies finding associations with MVP used variable and insufficiently stringent diagnostic criteria. In addition, many names have been used for MVP in the literature (click-murmur syndrome, Barlow’s disease, myxomatous mitral valve disease, floppy mitral valve, etc), leading to further confusion. Diagnostic criteria for MVP have evolved from being based on physical examination (with auscultatory findings considered diagnostic even with a normal echocardiogram [17,18]) to including overbroad echocardiographic criteria (including findings on M-mode and in the four-chamber view) to the current criteria.

Since diagnostic criteria for MVP have evolved, the literature on MVP must be reviewed with care. Many studies of MVP have design flaws due to inadequate controls and/or insufficiently stringent criteria for MVP. In addition, patients previously misdiagnosed with MVP require appropriate evaluation and counseling.

There are multiple ways of classifying MVP, underscoring the heterogeneity of this disorder:

●Etiologically, MVP is classified as primary (degenerative disease in the absence of identifiable connective tissue disease, sporadic, or familial) versus secondary MVP (associated with an identifiable disorder such as Marfan syndrome) (table 1).

●Clinically, MVP can be classified as syndromic when extra-cardiac manifestations are present (eg, pectus excavatum) versus non-syndromic, isolated MVP. The etiologies and mechanisms of regurgitation in various forms of MVP are summarized in the table (table 1).

●MVP is also classified by severity of the abnormal movement of the valve. The leaflets are described as billowing when the tips of leaflets remain in the left ventricle (LV) versus flail when the tip(s) of one (or both) leaflets prolapses into the left atrium (LA).  

●Morphologically, MVP is classified as classic (also known as Barlow’s syndrome with markedly and diffusely thickened leaflets [≥5 mm] with bileaflet prolapse) versus non-classic (with limited or absent thickening [thickness <5mm] and segmental prolapse). (See 'Pathology' below and 'Primary MVP' below.)

●Doppler echocardiography can also distinguish MVP without mitral regurgitation (MR) from MVP with MR.

The 2014 American Heart Association/American College of Cardiology guidelines for the management of patients with valvular heart disease separate mitral regurgitation by mechanism into primary (disease of one or more valve components including leaflets, chordae tendineae, papillary muscles, or annulus) and secondary (disease of the left ventricle) [19]. In this classification, primary disease includes all causes of MR involving the components of the valve (including MVP, calcific degeneration, cleft mitral valve, and leaflet perforations).

PRIMARY MVP

Sporadic primary MVP — Mitral valve prolapse (MVP) is the most common cause of organic severe mitral regurgitation in the Western world [20] and is characterized by myxomatous degeneration of the mitral valve leaflet(s) in the absence of a recognizable connective tissue disorder. The degree of involvement of the mitral valve leaflets and chords is variable, and results in a continuous spectrum of disease varying from “classic” to “non-classic” disease as described below. (See 'Pathology' below.)

Primary MVP can be associated with other valvular abnormalities (tricuspid valve in up to 40 to 50 percent of patients, and aortic valve in 10 to 20 percent) [10,21,22], thoracic skeletal abnormalities [23,24], von Willebrand syndrome [25], and hypomastia [26]. The latter two associations suggest that MVP may be related to a linked mesenchymal dysplasia, although hypomastia may also be a simple reflection of patients’ lean body habitus.

Familial primary MVP — While most of the cases of primary MVP are sporadic, familial cases have been identified since at least 1966 [24,25]. The most common transmission pattern is autosomal dominant with incomplete penetrance [27]. The prevalence in first degree relatives is relatively high, ranging from 30 to 50 percent [28,29]. Three loci have been mapped to chromosomes 16, 11, and 13, but the underlying genetic defects are not currently known [27].

An X-linked recessive form seems to be related to filamin A mutations, and results in a rare form of multivalvular myxomatous degeneration (X-linked myxomatous valvular dystrophy) [30,31]. In affected males, this disease is characterized by myxomatous degeneration of the mitral valve frequently associated with aortic valve degeneration. Female carriers can also exhibit valvular degeneration, but this is usually less severe.

Echocardiography is indicated for formal diagnosis in patients with a family history of MVP.

SECONDARY MVP

Secondary MVP associated with connective tissue disorders — Mitral valve prolapse (MVP) is more prevalent in patients with Marfan syndrome, MASS phenotype, Ehlers–Danlos syndrome, osteogenesis imperfecta, and pseudoxanthoma elasticum [27,32]. Among patients with Marfan syndrome, mitral valve prolapse occurs more frequently in patients with FBN1 mutations as compared to those with TGFBR2 mutations (eg, 45 and 21 percent [33]). (See "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders".)

Secondary MVP due to mechanisms other than myxomatous degeneration — A number of other diseases are associated with imbalance of the mitral valve complex, leading to prolapse and flail of the mitral valve. Infective endocarditis causes destructive lesions, and ruptured chordae may ensue, leading to flail mitral leaflet(s). Myocardial ischemia is not a cause of MVP, but myocardial infarction with papillary muscle rupture causes one or both leaflets to prolapse in the left atrium (LA), often with a muscle tip attached. Similarly, blunt chest trauma with rupture of chordae or papillary muscle can cause a flail mitral leaflet. Acute rheumatic fever may cause prolapse by true elongation of the valvular tissue, but subsequent tissue retraction makes the occurrence of a prolapse due to chronic rheumatic heart disease exceptional unless there is a ruptured chord.

Other diseases, such as hypertrophic cardiomyopathy, myxomas, or prominent mitral annular calcifications, may also cause ruptured chordae and thereby cause leaflet prolapse. While mitral regurgitation in these cases is technically due to leaflet prolapse, the diagnosis is usually obvious from the clinical presentation and echocardiographic findings, and not associated with myxomatous degeneration of the leaflets.

MVP has also been found in as many as 15 percent of patients with Ebstein's anomaly [34]. (See "Clinical manifestations and diagnosis of Ebstein anomaly".) This suggests a role for LV deformation in creating mitral imbalance and prolapse despite a structurally normal mitral valve.

PATHOLOGY — Anatomically, the mitral valve is formed by a long and narrow anterior leaflet and a shorter and wider posterior leaflet occupying a larger portion of the annular circumference (figure 1). Thus, when the mitral valve is closed, it appears from the atrial side as the “mitral smile” with two leaflets and two commissures (anterolateral and posteromedial). The leaflets’ bases are attached to the annulus and their tips to the chordae, which join the papillary muscles.

In primary and secondary mitral valve prolapse (MVP) associated with connective tissue disorders, the degenerative process may involve the entire mitral valvular complex (leaflets, chordae, mitral annulus). The hallmark macroscopic valvular lesion of MVP is excessive mitral leaflet tissue leading to folding and hooding. Depending on the extent of the myxomatous degeneration, one or more segments of one or both leaflets are affected [35,36]. The chordae are elongated, have reduced strength, and may rupture [37]. The annulus is typically dilated and frequently disjuncted from its normal myocardial support. In contrast, the papillary muscles are usually normal in structure. Physiologically, various combinations of the leaflet, chordal, and annular alterations yield insufficient apposition of the rough zones of the leaflets so they no longer support each other during systole and fall into the left atrium.

While there is great diversity of lesions, the macro-alterations of MVP are often grouped under two headings. At one end of the spectrum is “classic” (also known as Barlow’s disease or diffuse myxomatous) MVP, characterized by thickened and diffusely redundant myxomatous leaflet tissue with prolapse of most of the leaflet segments, severe mitral annular enlargement, and elongated (rarely ruptured) chords (figure 2 and movie 1A-B) [38]. Mitral annular disjunction is an abnormality of the mitral annulus fibrosus resulting in a systolic gap between the insertion of the posterior mitral leaflet and the basal inferolateral myocardium (movie 2). This disjunction commonly occurs in patients with advanced classic disease [39].

At the other end is “non-classic” disease known as fibroelastic deficiency first described by Carpentier [40], which can be seen in up to 40 percent of patients requiring mitral valve repair. It usually affects individuals over the age of 60 and is characterized by involvement of a single segment (most commonly P2 scallop), with thin and somewhat redundant leaflets, ruptured chords, and mild mitral annular enlargement (figure 2 and movie 3A-B). The flail segment is thickened and myxomatous in a very localized manner.

Forme fruste Barlow’s disease appears as an intermediate between classic and non-classic disease. It is important to make the distinction between various forms, as the complexity of surgical repair increases with the extent of mitral valve involvement by myxomatous degeneration.

Histologically, the characteristic myxomatous lesion is proliferation of the spongiosa of the mitral valve leaflets, with mucopolysaccharide deposits and excessive water content causing leaflet thickening and redundancy. The collagen composition is altered, with a marked increase in type III collagen [36]; elastin fibers appear fragmented [37]. Focal accumulation of activated valvular interstitial cells and increased expression of matrix metalloproteinases suggest that abnormal tissue remodeling is responsible for the disease [41].

Qualitative histological analysis cannot differentiate between Barlow’s disease and fibroelastic deficiency [42]. However, a more elaborate semiquantitative analysis shows different patterns, with more myxomatous infiltration, collagen proliferation, and elastic fiber lesions in Barlow’s disease and Marfan syndrome than in fibroelastic deficiency.

CLINICAL MANIFESTATIONS — Since symptoms do not reliably indicate mitral valve prolapse (MVP), the key clinical manifestations of MVP are auscultatory findings that lead to evaluation by echocardiography.

MVP syndrome — Numerous nonspecific symptoms and signs such as chest pain, palpitations, dyspnea, exercise intolerance, dizziness, anxiety disorders, and electrocardiographic abnormalities have been attributed to MVP. MVP syndrome has been defined as the combination of these symptoms and signs with mitral valve prolapse. However, the validity of MVP syndrome has been questioned since many reports of associations had flawed study designs (including inadequate control groups and use of insufficiently stringent diagnostic criteria for MVP). These issues are discussed in detail separately. (See "Mitral valve prolapse syndrome".)

Symptoms — As noted above, various nonspecific symptoms such as palpitations, dyspnea, exercise intolerance, and dizziness have been attributed to MVP. However, symptoms are not reliable indicators of MVP. Furthermore, symptoms frequently seen in individuals with MVP have not been conclusively determined to be more prevalent than in the general population. As an example, in a study of 147 patients referred for echocardiography for suspected MVP, the presence of symptoms was not associated with MVP on echocardiography (found in 22 percent) [43]. (See "Mitral valve prolapse syndrome".)

While MVP represents the main cause of severe organic mitral regurgitation (MR) in the developed countries, only a minority of patients with MVP ultimately develop severe MR due to profound leaflet prolapse and/or chordal rupture (see "Clinical manifestations and diagnosis of chronic mitral regurgitation" and "Acute mitral regurgitation in adults"):

●With chronic severe MR, most patients remain asymptomatic for years and the development of symptoms is generally insidious with time or at the onset of atrial fibrillation. The most common symptom of severe MR is dyspnea. Fatigue is a much less specific symptom and thus less likely to improve after surgery.

●A less common presentation is the chordal rupture syndrome whereby acute severe MR causes sudden dyspnea, chest pressure, and often rapidly progressive pulmonary edema. Hypotension and other signs of shock occur in rare cases.

●An area of active investigation is the arrhythmogenic potential of MVP, including a potential risk for sudden cardiac death. (See "Arrhythmic complications of mitral valve prolapse".)

●When acute MR progression is superimposed upon chronic MR, patients may present more subacutely with progressive dyspnea.

Physical examination

Cardiac examination — The most common auscultatory features of mitral valve prolapse are the non-ejection click (single or multiple) and the murmur of mitral regurgitation. The click is thought to be caused by snapping of the mitral chordae during systole when the valve bows into the atrium. The click is mobile, meaning its timing varies with maneuvers that change the left ventricular volume, occurring earlier in systole with sitting, standing, or other interventions that reduce ventricular size, or later with those interventions that increase chamber size such as squatting (movie 4 and movie 5) [44]. An MVP click should be differentiated from the aortic or pulmonary ejection clicks (occurring early in systole, at the foot of the carotid upstroke) and from other cardiac sounds (split first or second heart sounds, pericardial sounds, atrial septal aneurysm clicks). (See "Auscultation of heart sounds".)

As noted above, most adults with MVP have mitral regurgitation (MR), but the majority of patients with MVP have mild, trace, or no MR, and severe MR is uncommon. (See 'Epidemiology' above.) The murmur of mitral regurgitation with MVP is late-systolic early in the course of the disease, and its point of maximal intensity and radiation pattern varies with the direction of the jet (anteriorly-directed jets can be heard over the entire precordial area, while posteriorly directed jets are typically best heard at the apex and radiate towards the axilla and the back). Once a flail or severe prolapse occurs, the murmur becomes holosystolic and is indistinguishable in tone from other causes of mitral regurgitation, but often will remain maximum at mid-late systole. With long-standing severe mitral regurgitation, apical impulse is displaced laterally, and clinical findings of left ventricular (LV) dysfunction (gallop sounds) and pulmonary hypertension (loud P2 component) can be found. (See "Auscultation of cardiac murmurs in adults" and "Physiologic and pharmacologic maneuvers in the differential diagnosis of heart murmurs and sounds".)

With acute severe MR (as may result from chordal rupture), the cardiac impulse is hyperdynamic but normal in location unless there has been preceding chronic MR. The murmur of acute MR may be early systolic, midsystolic, or holosystolic and is generally soft and low pitched, ending before A2. (See "Auscultation of cardiac murmurs in adults".)

Limited data are available on the diagnostic accuracy of auscultation for MVP, particularly when limited to studies using current echocardiographic diagnostic criteria. Identification of a mobile systolic click by an expert observer may be a highly sensitive finding (88 and 100 percent) with fair specificity (66 and 73 percent) [45,46]. In contrast, in a study of 147 patients referred for echocardiography for suspected MVP, identification of a systolic click by a referring physician had a sensitivity of 52 percent and specificity of 68 percent for MVP [43]. Of note, auscultatory manifestations are highly variable [44]. This, together with inconsistent clinical examination skills among physicians and variable auscultatory and echocardiographic criteria used to diagnose MVP, probably explains the conflicting observations on the accuracy of auscultatory findings in MVP.

Other physical examination findings — Observation of the general appearance and body habitus is usually the first step in the physical examination. Skeletal abnormalities found in patients with MVP include narrow anteroposterior chest diameter, scoliosis and loss of kyphosis of the thoracic spine, and pectus excavatum deformity, although the data on the frequency of MVP in patients with these abnormalities are limited [23,24,47]. Patients with MVP tend to have a lower BMI index than controls [6,7].

ECHOCARDIOGRAPHY

M-mode — M-mode echocardiography should no longer be used in making a positive diagnosis of mitral valve prolapse (MVP). Previously used M-mode criteria for MVP are not reliable because the normal motion of the base of the heart can either mask or mimic true prolapse.

2D echocardiography — Leaflet displacement ≥2 mm above the plane of the mitral annulus in long axis views (parasternal or apical three-chamber) is the accepted criterion for a positive diagnosis of MVP (image 1) [10]. Other 2D features associated with MVP are abnormalities in leaflet length, annular diameter (enlarged), and chordal length (elongated).

When surgical intervention is contemplated, knowledge of the detailed mitral valve anatomy is needed to effectively communicate the necessary information to the surgical team. The anatomical description of the mitral valve proposed by Carpentier (figure 1) divides the posterior leaflet into anterolateral (P1), middle (P2), and postero-medial (P3) scallops. While the anterior leaflet does not have obvious anatomical divisions, corresponding segments are labeled similarly A1 to A3. Expert examination of the mitral valve at transthoracic echocardiography (TTE) enables determination of the location and extent of disease for pre-operative planning in up to 98 percent of the patients [48], although 2D and 3D transesophageal echocardiography (TEE) provide superior delineation of the anatomy [49]. Intra-operative TEE is recommended for mitral valve cases; image quality is superior to TTE and allows detecting finer anatomic details (ruptured chords, more precise location of origin of mitral regurgitant jet). Information about the location, extent of disease, and origin(s) of the mitral regurgitant jet needs to be communicated to the surgical team for adequate planning. Surgical intervention for classic MVP is likely to involve a significantly more complex approach than needed for localized fibroelastic deficiency seen with non-classic MVP.

3D echocardiography — The development of 3D technology, especially real time 3D-TEE, provides excellent rendering of the mitral valve complex. Live 3D-TEE has become routine in pre/intraoperative imaging of the mitral valve and in percutaneous mitral valve interventions. 3D-TEE efficiently identifies correct location of prolapse and flail segments, and by reconstruction of the 3D image from the left atrial view (surgical view), information is easily communicated to the surgical team (figure 1 and movie 1B, 3B). In a study comparing 2D TEE with 3D-TEE, both expert and less experienced echocardiographers more accurately described the mitral valve pathology using 3D-TEE (with surgical pathology as the reference), with less experienced interpreters gaining a significantly greater advantage from using 3D-TEE [50]. 3D-TEE is the key imaging modality for guidance of percutaneous mitral valve repair with the MitraClip system. (See "Transcatheter mitral valve repair".)

With increased use of 3D-TEE, cleft-like indentations of the posterior mitral leaflet are more frequently recognized, and may be present in up to one-third of patients with myxomatous MVP (movie 6) [51]. Appropriate recognition of cleft-like indentation is important when planning surgical or percutaneous mitral valve repair. However, it must be emphasized that not all cleft-like indentations apparent on 3D reconstruction are associated with mitral regurgitation (ie, many are "non-functional" clefts, being visible only during diastole, which do not require repair). The best approach to determine the significance of cleft-like indentation is to examine the mitral valve anatomy from the left ventricular en-face view, in both 3D and 3D color.

3D-TEE also allows insights into the dynamic mitral annulus function, with early-systolic area contraction and saddle-shape deepening contributing to mitral competency. The mitral annulus in MVP is also dynamic but considerably different from normal patients, with loss of early-systolic area contraction and diminished saddle-shape deepening despite similar magnitude of ventricular contraction, suggestive of ventricular-annular decoupling [11]. With the rapid development of percutaneous interventions for mitral regurgitation, accurate assessment of the mitral valve anatomy (annulus area and perimeter, inter-commissural and septal-lateral diameters) becomes increasingly important. These can be reliably measured by both 3D echocardiography and computed tomography (CT).

Doppler imaging — While 2D and 3D imaging techniques allow identification of anatomical substrate, Doppler echocardiographic techniques are key to estimating severity of MR. The criteria used to diagnose severe MR are discussed separately. (See "Echocardiographic evaluation of the mitral valve" and "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Identifying the severity of MR'.)

MR severity should be quantitated in all patients with a visual appearance of greater than mild MR on Color Doppler. Formal quantification of mitral valve severity not only minimizes errors intrinsic to Color Doppler visual quantification of severity, but also provides essential information about a patient’s individual risk. Quantitative measures of MR (regurgitant volume and orifice) are essential predictors of outcome [52] as confirmed in two independent prospective studies totaling more than 1000 patients followed long-term [53,54]. (See "Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet".)

OTHER IMAGING

Cardiovascular magnetic resonance — Cardiovascular magnetic resonance (CMR) imaging is an emerging tool in assessment of valvular heart disease. Small studies have shown that mitral valve prolapse (MVP) can be diagnosed by CMR and focal late gadolinium enhancement of mitral valve leaflets and papillary muscles has been observed [55]. The clinical utility of this approach has not been evaluated. CMR also enables quantification of mitral regurgitation (MR) as discussed separately. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Regurgitant valve disease'.)

Left ventricular angiography — Angiography is not used to diagnose MVP. However, in some patients referred for cardiac catheterization, MVP may be incidentally found on left ventricular angiography, showing the displacement of the mitral valve leaflets into the left atrium with late systolic MR. These patients should be further evaluated by echocardiography. In addition, hemodynamic catheterization and LV angiography are used for assessment of MR severity in patients with discordant clinical and echocardiographic findings.

DIAGNOSIS — Clinical examination remains the key step in making a diagnosis of mitral valve prolapse (MVP). The auscultatory findings of non-ejection clicks and systolic murmur are the initial observations leading to a diagnosis by echocardiography. On two-dimensional echocardiography, leaflet displacement ≥2 mm above the plane of the mitral annulus in long axis views (parasternal or apical three-chamber) is the accepted criterion for a positive diagnosis of MVP (image 1) [10]. Echocardiography provides information not only about the presence (or absence) of mitral leaflet prolapse, but also allows a comprehensive evaluation of the subvalvular structures, assessment of mitral regurgitation, and of hemodynamic consequences.  

As noted in the 2014 American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, all patients with known or suspected valvular heart disease should undergo careful history, physical examination, and transthoracic echocardiogram [19]. Echocardiography is also indicated for formal diagnosis in patients with a family history of MVP.

The guidelines provide guidance on the frequency of repeat routine imaging according to disease stages: every three to five years for stage B (progressive disease) with mild regurgitation, every one to two years for stage B with moderate regurgitation, and every 6 to 12 months for stage C1 (asymptomatic severe mitral regurgitation without evidence of left ventricular dysfunction) [19]. In addition, patients with a change in symptoms should undergo repeat evaluation. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Serial monitoring'.)

Differential diagnosis — In patients presenting with mitral regurgitation, MVP should be distinguished from other causes of mitral regurgitation (MR), which are discussed separately. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation", section on 'Etiology'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topic (see "Patient education: Mitral valve prolapse (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Mitral valve prolapse (MVP) is a complex entity, with significant confusion in the literature related to use of variable denominations, definitions, and diagnostic criteria. (See 'Definition and classification' above.)

●The prevalence of MVP in the United States is estimated at 0.6 to 2.4 percent, which is significantly lower than previously reported. This estimate is lower due to the current use of a more stringent definition of MVP. (See 'Epidemiology' above.)

●MVP is classified as primary (sporadic or familial forms; no other identifiable disease) or secondary (associated with identifiable connective tissue disorder or associated with other non-myxomatous mitral valve disease). (See 'Definition and classification' above.)

●Morphologically, MVP is classified as classic (with markedly and diffusely thickened leaflets [≥5 mm] with bileaflet prolapse) versus non-classic (with limited or absent leaflet thickening [thickness <5mm] and segmental prolapse). (See 'Definition and classification' above and 'Pathology' above.)

●Clinical examination remains the first step in diagnosis of MVP. The non-ejection click is mobile, meaning that the timing varies with maneuvers that alter left ventricular volume. The mitral regurgitant murmur can be late systolic (early in the disease) or holosystolic (severe prolapse or flail). (See 'Physical examination' above.)

●Echocardiography is the key imaging study in the diagnosis of MVP. Prolapse is defined as systolic mitral leaflet displacement ≥2 mm above the annular plane in the parasternal or apical long axis views. (See 'Definition and classification' above and '2D echocardiography' above.)

●Echocardiography is indicated for formal diagnosis in patients with clinical examination suggestive of MVP or those with a family history of MVP. (See 'Echocardiography' above.)

●Transesophageal echocardiography (TEE), especially 3D-TEE and color Doppler 3D-TEE, provide excellent diagnostic accuracy and helps planning for surgical and percutaneous repair. (See '3D echocardiography' above.)

●Formal quantification of mitral regurgitation (MR) severity is indicated in all patients with more than mild MR, as it provides reliable prognostic information in patients with MVP. (See 'Doppler imaging' above.)