Background
Mitral valve prolapse (MVP) is generally a benign condition, yet it is also an important contributing risk factor for arrhythmias, endocarditis, stroke, [1] mitral regurgitation (MR), mitral valve replacement (MVR) surgery, [2] and sudden death. [3, 4] Although now considered to be much less common in the general population than previously described, [5, 6] MVP is associated with a multitude of other medical conditions, especially connective tissue disorders, as well as migraine (especially migraine with aura), [7] autoimmune disease, [8] open-angle glaucoma, [9] straight back syndrome (shown in the image below), and idiopathic sudden sensorineural hearing loss. [10]
MVP likely progresses over time, beginning in some instances with "nondiagnostic MVP morphology" (NDM) on echocardiography, [11] and occasionally progressing to MR over decades. Many individuals are asymptomatic, although palpitations, fatigue, and orthostasis are not uncommon, especially when the patient is volume depleted. Symptoms of chest pain, dyspnea, anxiety, and panic [12] are probably no more common with MVP than in the general population.
Mitral valve prolapse. A patient with straight back syndrome.
Pathophysiology
A myxomatous degeneration from collagen dissolution leads to excess mucopolysaccharides in the middle spongiosa layer of the mitral valve leaflets, resulting in stretching of the leaflets and the chordae tendineae. Mitral valve prolapse (MVP) occurs when the left ventricular (LV) size is small in comparison to an enlarged mitral annulus, leaflets, or chordae tendineae, and it can be induced in healthy women with typical body habitus following dehydration that is reversed with rehydration. Mitral valve prolapse resolves during pregnancy and following weight gain in anorexic patients.
Studies have shown that abnormalities of elastic fibers found in floppy mitral valves are related to genetic variants in fibrillin, one of the components of the microfibrils, as well as elastin and collagen I and II. [13, 4] Mitral valve prolapse is associated with a variety of medical conditions involving connective tissues, such as joint hypermobility disorders, [14] and Ehlers Danlos and Marfan syndromes. Mitral valve prolapse is also associated with autoimmune disorders such as systemic lupus erythematosus and autoimmune thyroid disease; many patients with mitral valve prolapse have positive autoantibodies including ANA, rheumatoid factor, and anticardiolipin antibody. [8]
A constellation of abnormalities (eg, increased sensitivity to adrenergic stimuli, increased catecholamines, abnormal beta-receptors, increased atrial natriuretic factor, renin-aldosterone dysregulation, decreased intravascular volume, magnesium deficiency) [15] has been thought to lead to chest pain, dyspnea, fatigue, dizziness, near-syncope symptoms, and anxiety in a subset of patients with mitral valve prolapse. [16, 17]
Cardiac manifestations include supraventricular more so than ventricular arrhythmias, palpitations, mitral regurgitation, bacterial endocarditis, and sudden death. Chest pain may not be more common in patients with mitral valve prolapse than in the general population, and it may be attributed to myofascial syndromes, hyperventilation, coronary spasm, esophageal dysmotility, or gastroesophageal reflux. [18]
Mitral valve prolapse can result in cerebrovascular ischemia, which may be related to abnormal platelet activity or coagulation disorders (eg, anticardiolipin antibody, protein C or S deficiencies).
Etiology
Most cases of mitral valve prolapse (MVP) are primary, idiopathic in nature, and expressed as an autosomal dominant trait that exhibits both sex- and age-dependent penetrance. [19]
Connective tissue disorders
Connective tissue conditions that may lead to MVP include the following:
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Ehlers-Danlos syndrome (ie, types I, II, IV)
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Stickler syndrome
Muscle disorders
Duchenne muscular dystrophy, fragile X syndrome, mucopolysaccharidoses, and myotonic dystrophy may lead to the development of MVP.
Heart diseases
Congenital heart disease (eg, atrial septal defect [ASD], Ebstein anomaly, and acquired heart disease (eg, papillary muscle dysfunction [eg, ischemia, myocarditis], cardiac trauma, post mitral valve surgery, rheumatic endocarditis) can cause MVP.
Miscellaneous
Wolff-Parkinson-White syndrome and von Willebrand disease may also lead to MVP.
Epidemiology
United States data
Mitral valve prolapse (MVP) can be identified by echocardiography in an estimated 0.3% [6] to 3% of the general population, and it is identified in 7% of autopsies. [4, 20]
International data
The worldwide incidence of mitral valve prolapse is similar to that in the United States.
Race-, sex-, and age-related demographics
The prevalence of MVP is similar among different ethnic groups. [21]
The female-to-male ratio is approximately 3:1. However, men have a higher risk than women of endocarditis, posterior prolapse, leaflet thickening, severe regurgitation, and men are more likely to undergo mitral valve surgery. [22]
The age of MVP onset is 10-16 years. MVP is uncommon before the adolescent growth spurt occurs, thus, it usually is detected in young adulthood. Although MVP is considered congenital, echocardiographic findings typically are absent in newborns.
Prognosis
Morbidity/mortality
In general, mitral valve prolapse (MVP) is initially a benign disorder, and in most situations, the prognosis is excellent. However, MVP may account for the majority of isolated cases of mitral regurgitation (MR), 90% of cases of ruptured chordae tendineae, 40% of strokes in young patients, and 10-15% of cases of endocarditis. [23]
MR is the most significant risk factor for other complications (eg, sudden death, stroke, endocarditis, atrial and ventricular arrhythmia [24, 25] ). Patients whose echocardiograms shows abnormal valve anatomy, men, and those older than 45 years are at an increased risk of developing MR.
Those with structural abnormalities (ie, thickened, deformed, or redundant mitral valve leaflets) are more likely to suffer complications (eg, progressive MR, endocarditis, sudden death), although a longitudinal study of 285 residents in Olmsted County, MN, suggests that progression of MR occurs in nearly 40% of MVP cases, regardless of age, gender, leaflet thickening, or initial grade of MR. [26]
Left ventricular (LV) remodeling, with elevated LV end-systolic volume index and LV end-systolic dimension, occurs even with isolated late systolic MR murmur similar to that seen with pan-systolic MR murmur. [27]
Patients who are older, lack social support, have higher anxiety, and fail to exercise regularly are at risk for more symptoms.
Cardiovascular mortality is predicted the most by moderate-to-severe MR and ejection fraction less than 50%, and less so by left atrial size greater than 40 mm, flail leaflet, atrial fibrillation, and age older than 50 years. [28, 29]
Cases of MVP with a murmur and not just an isolated click have a general mortality rate that is increased by 15-20%.
Complications
For the following complications, the absolute risk (ie, annual incidence) and the odds ratios (OR), comparing patients with MVP to the general population, are as follows:
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Sudden cardiac death - 0.06% annual incidence among patients with MVP and severe MR; OR of 50-100 with hemodynamically significant MR and depressed left ventricular function
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Rupture of chordae tendineae (the most frequent serious complication of MVP)
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Progressive MR - 0.06% annual incidence of requiring surgery; lifetime risk of surgery is 1.5% for women and 4-6% for men; OR of 30-40; increased risk in males, older than 75 years, elevated body weight, and high blood pressure.
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Stroke - 0.02% annual incidence versus less than 0.02% in uncomplicated MVP; OR of 4-6
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Infective endocarditis - 0.02% annual incidence; OR of 3-8; 1 in 1400 patients per year with MVP and murmur; increased risk in males older than 45 years
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Atrial fibrillation can be persistent in 15% or paroxysmal in 13% when MR is severe enough to require mitral valve replacement (MVR) surgery. These rates are lower than seen with mitral stenosis requiring MVR. [30]
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Individuals with idiopathic sudden sensorineural hearing loss (ISSNHL) have a higher incidence of MVP, mitral leaflet thickening, and MR, suggesting that MVP may be involved in the etiology of this sudden hearing loss. [10]
Patient Education
Patients with a murmur, patients who have echo evidence of nontrivial MR, or men older than 45 years who have valve thickening should inform their dentist and surgeon, although antibiotic prophylaxis prior to dental, respiratory, or infected skin or musculoskeletal tissue procedures would only be indicated if there was a history of infective endocarditis. [31]
Patients with palpitations should avoid caffeine, alcohol, stimulants, and smoking.
Symptoms of the classic mitral valve prolapse (MVP) syndrome may improve with exercise, meditation, and biofeedback.
For patient education resources, see& Heart Health Center, as well as Mitral Valve Prolapse, Chest Pain, and Palpitations.
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Mitral valve prolapse. A patient with straight back syndrome.
