Mitral valve prolapse (MVP) is a

valvular heart disease Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These ...

characterized by the displacement of an abnormally thickened mitral valve leaflet into the

left atrium The atrium ( la, ātrium, , entry hall) is one of two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular valves. There are two ...

during systole. It is the primary form of myxomatous degeneration of the valve. There are various types of MVP, broadly classified as classic and nonclassic. In severe cases of classic MVP, complications include mitral regurgitation, infective endocarditis,

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, ...

, and, in rare circumstances,

cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...

. The diagnosis of MVP depends upon echocardiography, which uses

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...

to visualize the mitral valve. MVP is the most common valvular abnormality and is estimated to affect 2–3% of the population and 1 in 40 people might have it. The condition was first described by

John Brereton Barlow John Brereton Barlow (24 October 1924 – 10 December 2008) was a world-renowned South African cardiologist. He qualified as a doctor in 1951, gained experience as a registrar in Hammersmith Hospital and the Royal Postgraduate Medical School in Lo ...

in 1966. It was subsequently termed ''mitral valve prolapse'' by

J. Michael Criley John Michael Criley, MD, FACC, MACP, (born 1931) is Professor Emeritus at the David Geffen School of Medicine at University of California, Los Angeles (UCLA). Biography He has made a number of pioneering contributions to the field of cardiology ...

. Although mid-systolic click (sound of prolapsing mitral leaflet) and systolic murmur have been noticed earlier with stethoscope in 1887 by physicians M. Cuffer and M. Barbillon.

Signs and symptoms

Murmur

Upon auscultation of an individual with mitral valve prolapse, a mid-systolic click, followed by a late systolic murmur heard best at the apex, is common. The length of the murmur signifies the time period over which blood is leaking back into the left atrium, known as regurgitation. A murmur that lasts throughout the whole of systole is known as a holo-systolic murmur. A murmur that is mid to late systolic, although typically associated with less regurgitation, can still be associated with significant hemodynamic consequences. In contrast to most other heart murmurs, the murmur of mitral valve prolapse is accentuated by standing and Valsalva maneuver (earlier systolic click and longer murmur) and diminished with squatting (later systolic click and shorter murmur). The only other heart murmur that follows this pattern is the murmur of

hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...

. An MVP murmur can be distinguished from a hypertrophic cardiomyopathy murmur by the presence of a mid-systolic click which is virtually diagnostic of MVP. The

handgrip maneuver The handgrip maneuver is performed by clenching one's fist forcefully for a sustained time until fatigued. Variations include squeezing an item such as a rolled up washcloth. Physiological response The handgrip maneuver increases afterload by ...

diminishes the murmur of an MVP and the murmur of hypertrophic cardiomyopathy. The handgrip maneuver also diminishes the duration of the murmur and delays the timing of the mid-systolic click. Both Valsalva maneuver and standing decrease venous return to the heart thereby decreasing left ventricular diastolic filling ( preload) and causing more laxity on the chordae tendineae. This allows the mitral valve to prolapse earlier in systole, leading to an earlier systolic click (i.e. closer to S₁), and a longer murmur.

Mitral valve prolapse syndrome

Historically, the term mitral valve prolapse syndrome has been applied to MVP associated with palpitations, atypical

precordial pain In anatomy, the precordium or praecordium is the portion of the body over the heart and lower chest.dyspnea on exertion, low body mass index, and electrocardiogram abnormalities (

ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short perio ...

), syncope,

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

, headaches, lightheadedness, exercise intolerance,

gastrointestinal disturbances Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the liver, g ...

, cold extremities and other signs suggestive of autonomic nervous system dysfunction ( dysautonomia).

Mitral regurgitation

Mitral valve prolapse is frequently associated with mild mitral regurgitation, where blood aberrantly flows from the left ventricle into the left atrium during systole. In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., federal district, five ma ...

, MVP is the most common cause of severe, non-ischemic mitral regurgitation. This is occasionally due to rupture of the chordae tendineae that support the mitral valve. The degree of MVP regurgitation severeness is usually estimated in grading system: * 0 (none or trivial) * Grade 1 (mild) * Grade 2 (moderate) * Grade 3 (moderate to severe) * Grade 4 (severe)

Cardiac arrhythmia

People with mitral valve prolapse might have arrhythmic mitral valve prolapse which includes higher incidence of ventricular contraction disorders and tachycardia compared to the normal population, although the relationship between both phenomena is not entirely clear. Prolapse of both mitral leaflets and the presence of mitral regurgitation further increases the risk of severe ventricular arrhythmias during exertion, which may not be resolved with surgery. The most common rhythm disorder is ventricular extrasystole, followed by paroxysmal atrial tachycardia.

Sudden cardiac death

Severe mitral valve prolapse and moderate-to-severe mitral regurgitation and reduced left ventricular

ejection fraction An ejection fraction (EF) is the volumetric fraction (mathematics), fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or cardiac cycle, heartbeat). It can refer to the card ...

is associated with arrhythmias and atrial fibrillation that can progress to cardiac arrest and sudden cardiac death (SCD). Because there is no evidence that prolapse has contributed to these arrhythmias, these complications may be due to mitral regurgitation or congestive heart failure. The incidence of life threatening arrhythmias in the general population with MVP remain low. Sudden cardiac death results in 0.2% to 0.4% patients per year.

Risk factors

MVP may occur with greater frequency in individuals with Ehlers-Danlos syndrome,

Marfan syndrome Marfan syndrome (MFS) is a multi-systemic genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with long arms, legs, fingers, and toes. They also typically have exceptionally flexible joints a ...

or polycystic kidney disease. Other risk factors include Graves disease and chest wall deformities such as pectus excavatum. For unknown reasons, MVP patients tend to have a low body mass index (BMI) and are typically leaner than individuals without MVP. Also women tend to have joint hypermobility.

Rheumatic fever Rheumatic fever (RF) is an inflammation#Disorders, inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a Streptococcal pharyngitis, streptococcal throat infection. Sign ...

is common worldwide and responsible for many cases of damaged heart valves. Chronic

rheumatic heart disease Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful ...

is characterized by repeated inflammation with fibrinous resolution. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. The recurrence of rheumatic fever is relatively common in the absence of maintenance of low dose antibiotics, especially during the first three to five years after the first episode. Heart complications may be long-term and severe, particularly if valves are involved. Rheumatic fever, since the advent of routine penicillin administration for Strep throat, has become less common in developed countries. In the older generation and in much of the less-developed world, valvular disease (including mitral valve prolapse, reinfection in the form of valvular endocarditis, and valve rupture) from undertreated rheumatic fever continues to be a problem. In an Indian hospital between 2004 and 2005, 4 of 24 endocarditis patients failed to demonstrate classic vegetations. All had rheumatic heart disease (RHD) and presented with prolonged fever. All had severe eccentric mitral regurgitation (MR). (One had severe aortic regurgitation (AR) also.) One had flail posterior mitral leaflet (PML). The mitral valve, so named because of its resemblance to a

bishop A bishop is an ordained clergy member who is entrusted with a position of authority and oversight in a religious institution. In Christianity, bishops are normally responsible for the governance of dioceses. The role or office of bishop is ...

mitre The mitre (Commonwealth English) (; Greek: μίτρα, "headband" or "turban") or miter (American English; see spelling differences), is a type of headgear now known as the traditional, ceremonial headdress of bishops and certain abbots in t ...

, is the heart valve that prevents the backflow of blood from the

left ventricle A ventricle is one of two large chambers toward the bottom of the heart that collect and expel blood towards the peripheral beds within the body and lungs. The blood pumped by a ventricle is supplied by an atrium, an adjacent chamber in the upper ...

into the

of the heart. It is composed of two leaflets, one anterior and one posterior, that close when the left ventricle contracts. Each leaflet is composed of three layers of tissue: the ''atrialis'', ''fibrosa'', and ''spongiosa''. Patients with classic mitral valve prolapse have excess

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tissue ...

that thickens the spongiosa and separates collagen bundles in the fibrosa. This is due to an excess of dermatan sulfate, a glycosaminoglycan. This weakens the leaflets and adjacent tissue, resulting in increased leaflet area and elongation of the chordae tendineae. Elongation of the chordae tendineae often causes rupture, commonly to the chordae attached to the posterior leaflet. Advanced lesions—also commonly involving the posterior leaflet—lead to leaflet folding, inversion, and displacement toward the left atrium.

In diagnostics

Common risk factors in diagnostics for severe, arrhythmic mitral valve prolapse include: * Electrocardiography - Inferior T wave inversions in II, III, aVF leads, ST-segment depression, QT dispersion, QT prolongation, complex ventricular ectopy (PVCs), PVC-triggered ventricular fibrillation * Echocardiography - ≥ moderate mitral regurgitation, leaflet thickening, bi-leaflet MVP with redundancy, spiked systolic high-velocity signal (

pickelhaube The ( pl. ; from german: Pickel, lit=point' or 'pickaxe, and , , a general word for "headgear"), also , is a spiked helmet that was worn in the 19th and 20th centuries by Prussian and German military officers, firefighters and police. Although ...

spike) when ≥ 16 cm/s in mitral annular tissue Doppler imaging (TDI),

mitral annular disjunction Mitral annular disjunction (MAD) is a structural abnormality of the heart in the Mitral valve#Annulus, mitral annulus ring. It is generally defined as an abnormal displacement of the location of where the posterior mitral valve leaflet inserts onto ...

(MAD) * Cardiac MRI - myocardial/ papillary scars (

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permane ...

), myocardial stretch, systolic curling

Genetics

Mitral valve prolapse is a genetically heterogeneous

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and ...

trait, which can be passed down from one parent to child, who will have a 50% chance to inherit the mutated gene. An association with primary cilia defects has been reported. The

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...

s were found in the Zinc finger protein

DZIP1 Zinc finger protein DZIP1 is a protein that in humans is encoded by the ''DZIP1'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' o ...

gene which regulates ciliogenesis; the same problem was found in mice who also developed MVP with this gene. It was found that primary cilia loss during development results in progressive myxomatous degeneration and profound mitral valve pathology. Myxomatous degeneration of mitral valve is a genetic abnormality mapped to gene Xq28. Other genes associated with MVP are: * 13.q31.3-q32.1 * 16p12.1-p11.2 * Ch16p11.2-p12.1 * 11p15.4 * DCHS1

Diagnosis

Echocardiography is the most useful method of diagnosing a prolapsed mitral valve. Two- and three-dimensional echocardiography is particularly valuable as they allow visualization of the mitral leaflets relative to the mitral annulus. This allows measurement of the leaflet thickness and their displacement relative to the annulus. Thickening of the mitral leaflets >5 mm and leaflet displacement >2 mm above the annular plane in parasternal long-axis view indicates classic mitral valve prolapse. Prolapsed mitral valves are classified into several subtypes, based on leaflet thickness, type of connection to the mitral annulus, and concavity. Subtypes can be described as classic, nonclassic, symmetric, asymmetric, flail, or non-flail. All measurements below refer to adult patients; applying them to children may be misleading.

Classic versus nonclassic

Prolapse occurs when the mitral valve leaflets are displaced more than 2 mm above the

mitral annulus The mitral valve (), also known as the bicuspid valve or left atrioventricular valve, is one of the four heart valves. It has two cusps or flaps and lies between the left atrium and the left ventricle of the heart. The heart valves are all ...

high points. The condition can be further divided into classic and nonclassic subtypes based on the thickness of the mitral valve leaflets: up to 5 mm is considered nonclassic, while anything beyond 5 mm is considered classic MVP.

Symmetric versus asymmetric

Classical prolapse may be subdivided into symmetric and asymmetric, referring to the point at which leaflet tips join the mitral annulus. In symmetric coaptation, leaflet tips meet at a common point on the annulus. Asymmetric coaptation is marked by one leaflet displaced toward the atrium with respect to the other. Patients with asymmetric prolapse are susceptible to severe deterioration of the mitral valve, with the possible rupture of the chordae tendineae and the development of a flail leaflet.

Flail versus non-flail

Asymmetric prolapse is further subdivided into flail and non-flail. Flail prolapse occurs when a leaflet tip turns outward, becoming concave toward the left atrium, causing the deterioration of the mitral valve. The severity of flail leaflet varies, ranging from tip eversion to chordal rupture. Dissociation of leaflet and chordae tendineae provides for unrestricted motion of the leaflet (hence "flail leaflet"). Thus patients with flail leaflets have a higher prevalence of mitral regurgitation than those with the non-flail subtype.

Treatment

Individuals with mitral valve prolapse, particularly those without symptoms, often require no treatment. Those with mitral valve prolapse and symptoms of dysautonomia (palpitations, chest pain) may benefit from beta-blockers (e.g., propranolol, metoprolol, bisoprolol). People with prior stroke or atrial fibrillation may require

blood thinners Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where t ...

, such as

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat in ...

or warfarin. In rare instances when mitral valve prolapse is associated with severe mitral regurgitation, surgical repair or replacement of the mitral valve may be necessary. Mitral valve repair is generally considered preferable to replacement. Current ACC/

AHA AHA, Aha, or aha may refer to: Arts, entertainment and media * ''Aha!'' (TV program), an information and education TV program in the Philippines * a-ha, a Norwegian pop music band * ''Aha!'' (film), a 2007 Bangladeshi film * Aha (streaming se ...

guidelines promote repair of mitral valve in people before symptoms of heart failure develop. Symptomatic people, those with evidence of diminished left ventricular function, or those with left ventricular dilatation need urgent attention.

Prevention of infective endocarditis

Individuals with MVP are at higher risk of bacterial infection of the heart, called infective endocarditis. This risk is approximately three-to eightfold the risk of infective endocarditis in the general population. Until 2007, the

American Heart Association The American Heart Association (AHA) is a nonprofit organization in the United States that funds cardiovascular medical research, educates consumers on healthy living and fosters appropriate cardiac care in an effort to reduce disability and death ...

recommended prescribing

antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

before invasive procedures, including those in dental surgery. Thereafter, they concluded that "prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis." Many organisms responsible for endocarditis are slow-growing and may not be easily identified on routine blood cultures (these fastidious organisms require special culture media to grow). These include the

HACEK The HACEK organisms are a group of fastidious Gram-negative bacteria that are an unusual cause of infective endocarditis, which is an inflammation of the heart due to bacterial infection. HACEK is an abbreviation of the initials of the genera o ...

organisms, which are part of the normal oropharyngeal flora and are responsible for perhaps 5 to 10% of infective endocarditis affecting native valves. It is important when considering endocarditis to keep these organisms in mind.

Prognosis

Generally, MVP is benign. However, MVP patients with a murmur, not just an isolated click, have an increased mortality rate of 15-20%. The major predictors of mortality are the severity of mitral regurgitation and reduction in

Prophylaxis

The consensus is that mitral valve prolapse is a non-preventable condition, although some of its complications may occur. Because symptoms rarely appear, the productivity of the patient's life is not affected. The worsening of the disorder can be delayed by avoiding smoking, the use of contraceptives (because they have the risk of clotting) and regulating the amount and type of exercise and nutrition under the supervision of a health professional. The risk of infective endocarditis is considered high in patients with prosthetic heart valves, moderate in those with mitral prolapse concomitant with mitral regurgitation and low in patients with mitral prolapse without other valve disease.

Antibiotic prophylaxis

Those with mitral prolapse are at increased risk of infective endocarditis, a bacterial infection of the heart tissue, as a result of certain routine non-sterile procedures, such as brushing the teeth. However, in April 2007, a study by the

had determined that the risks of prescribing antibiotics outweigh the prophylactic antibiotics before invasive surgery, such as dental surgery or biopsy by colonoscopy or bronchoscopy.

Epidemiology

Prior to the strict criteria for the diagnosis of mitral valve prolapse, as described above, the incidence of mitral valve prolapse in the general population varied greatly. Some studies estimated the incidence of mitral valve prolapse at 5 to 15 percent or even higher. One 1985 study suggested MVP in up to 35% of healthy teenagers. Recent elucidation of mitral valve anatomy and the development of three-dimensional echocardiography have resulted in improved diagnostic criteria, and the true prevalence of MVP based on these criteria is estimated at 2-3%. As a part of the Framingham Heart Study, for example, the prevalence of mitral valve prolapse in

Framingham, MA Framingham () is a city in the Commonwealth of Massachusetts in the United States. Incorporated in 1700, it is located in Middlesex County and the MetroWest subregion of the Greater Boston metropolitan area. The city proper covers with a popul ...

was estimated at 2.4%. There was a near-even split between classic and nonclassic MVP, with no significant age or sex discrimination. MVP is observed in 7% of autopsies in the United States. In a

Taiwan Taiwan, officially the Republic of China (ROC), is a country in East Asia, at the junction of the East and South China Seas in the northwestern Pacific Ocean, with the People's Republic of China (PRC) to the northwest, Japan to the northe ...

ese CHIEF heart study of Asian adult military personnel, it was estimated that out of 2442 people in Hualien aged 18 to 39, mitral valve prolapse occurred in 3.36%. People with MVP had lower body mass index, somatic symptoms related to exercise (chest pain, dyspnea, palpitations during exercise) and systolic click in auscultation. 7 out of 82 participants with MVP had mild pectus excavatum.

Research

In a human and mice study of MVP, a relationship was found between MVP and progressive fibrosis effects on left ventricular structure, which suggests the cause of molecular and cellular changes are a response of papillary and inferobasal myocardium to increased chordal tension from prolapsing mitral valve leaflets.

In animals

In 2019 an experimental adeno-associated virus (AAV)-based

gene therapy Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human D ...

method developed by Rejuvenate Bio which was successfully and effectively used on mice that reversed multiple age-related diseases: heart failure, kidney failure,

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinati ...

and obesity. Mice experienced a 58% increase in heart function and 75% reduction in kidney degeneration. Rejuvenate Bio in collaboration with

Tufts University Tufts University is a private research university on the border of Medford and Somerville, Massachusetts. It was founded in 1852 as Tufts College by Christian universalists who sought to provide a nonsectarian institution of higher learnin ...

later used the same method on Cavalier King Charles spaniel to stop the progression of mitral valve disease by stopping the accumulation of scar tissue in the heart.

History

The term ''mitral valve prolapse'' was coined by

in 1966 and gained acceptance over the other descriptor of "billowing" of the mitral valve, as described by

References

External links

* {{Circulatory system pathology Valvular heart disease Syndromes