Mitral valve prolapse (MVP) is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium 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, and, in rare circumstances, cardiac arrest.
The diagnosis of MVP primarily relies on echocardiography, which uses ultrasound 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 in 1966. It was subsequently termed mitral valve prolapse by J. Michael Criley. Although mid-systolic click (the sound produced by the prolapsing mitral leaflet) and systolic murmur associated with MVP were observed as early as 1887 by physicians M. Cuffer and M. Barbillon using a stethoscope.
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. 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 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, dyspnea on exertion, low body mass index, and electrocardiogram abnormalities (ventricular tachycardia), syncope, low blood pressure, headaches, lightheadedness, exercise intolerance, gastrointestinal disturbances, 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, 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 severity of regurgitation in MVP is typically estimated using a 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 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 can be non-syndromic, isolated, familial and syndromic. The syndromic variant may occur with greater frequency in individuals with Ehlers-Danlos syndrome, Marfan syndrome, Loeys–Dietz syndrome, Williams–Beuren syndrome 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 is common worldwide and responsible for many cases of damaged heart valves. Chronic rheumatic heart disease 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's mitre, is the heart valve that prevents the backflow of blood from the left ventricle into the left atrium 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 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 spike) when ≥ 16 cm/s in mitral annular tissue Doppler imaging (TDI), mitral annular disjunction (MAD) Cardiac MRI – myocardial/papillary scars (fibrosis), myocardial stretch, systolic curling
Histopathology MVP is understood histologically, as a form of myxomatous degeneration, which is a type of connective tissue changes.
In MVP, the spongiosa layer of the mitral valve leaflets undergoes proliferation, and the cells in this layer multiply and expand. This proliferation is associated with the accumulation of deposits of mucopolysaccharide, which have a high water content, which leads to an increase in the thickness and redundancy (excess tissue) of the leaflets of the mitral valve.
Also in people with MVP, there is an increase in the content of type III collagen, a protein that provides structure and strength to tissues. At the same time, the elastin fibers, which provide elasticity to the tissues, become fragmented. This combination of changes contributes to the overall structural alterations observed in MVP.
Causes
Genetics Mitral valve prolapse is a genetically heterogeneous autosomal dominant trait, which can be passed down from one parent to child, who will have a 50% chance to inherit the mutated gene.
Research has shown an association between MVP and primary cilia defects. Studies have identified mutations in the Zinc finger protein DZIP1 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 the mitral valve is a genetic abnormality that is mapped to the Xq28 gene. And additionally to FLNA.
To date, only one of the genes that have been associated with MVP is a direct regulator of connective tissue maintenance and extracellular matrix composition: TLL1, in a gain-of-function mechanism.
Other genes that have been associated with MVP include:
13.q31.3-q32.1 16p12.1-p11.2 Ch16p11.2-p12.1 11p15.4 DCHS1 Genetic and chromosome defect causes of MVP are complex and currently not fully understood. Further research is needed to fully identify all of the genes and genetic mechanisms involved in the development of MVP.
Other Recent studies have suggested an association between MVP and the upregulation of 5HTR2B expression. This upregulation is associated with increased serotonin (5HT) receptor signaling which is involved in the remodeling of the mitral valve prolapse. The researchers also found that blocking 5HTR2B can reduce mitral valve interstitial cells (MVIC) activation in vitro and MV remodeling in vivo. Suggesting that 5HT receptor signaling plays a role in the pathological remodeling of MVP.
Withdrawn drug such as benfluorex stimulated serotonergic pathways, which lead to valve degeneration with increased valve interstitial cell proliferation resulting in increased rate of valvular pathologies in people taking the drug.
In a 2023 study a potential link between the use of SSRIs and the development of mitral valve regurgitation was found. Findings suggest that SSRIs may accelerate degenerative mitral valve regurgitation (DMR), particularly in people with a specific 5-HTTLPR genotype ('long-long'). The researchers recommend genotyping DMR patients to assess serotonin transporter (SERT) activity and advocate for caution in prescribing SSRIs to those with a family history of DMR.
Diagnosis