eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Mitral Valve Prolapse

Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH, Consulting Staff, Department of Child Health, University Hospital of Hartlepool, UK

Updated: Oct 8, 2008

Introduction

Background

Mitral valve prolapse (MVP), the most common anomaly of the mitral valve apparatus, occurs when one or both mitral valve leaflets excessively billows into the left atrium toward the end of systole. Mitral regurgitation (MR) develops in some patients with mitral valve prolapse, particularly those with more significant prolapse, when the valve edges fail to coapt. An extreme form of prolapse could include chordal rupture, in which the prolapsed mitral valve is flail. Mitral valves excised from patients with severe MR secondary to mitral valve prolapse have large leaflets and various histologic alterations.

Besides the symptoms attributable to the MR, various neuroendocrine and autonomic disturbances occur in some patients with mitral valve prolapse. In these patients, prolapse may be an epiphenomenon of the underlying autonomic or neurohumoral illness. The term mitral valve prolapse syndrome is often used to refer to the collection of these manifestations. However, in a significant proportion of patients, the mitral valve prolapse is trivial, and no such associated manifestations are present. In these patients, mitral valve prolapse constitutes an essentially benign condition.

Mitral valve prolapse syndrome was recognized as early as 1916, when Sir James MacKenzie described the soldier's heart in spare, thin young men with great vasomotor instability, easy fatigability, breathlessness, and pain over the region of the heart. Kerley first described the syndrome in 1920, and Lincoln described the syndrome in 1928. In 1963, Barlow and colleagues made the first clinical diagnosis of the syndrome as it is known today. The advent of echocardiography led to further advances and formed the basis of current knowledge.

Idiopathic mitral valve prolapse may be congenital in some patients, but recognition may be delayed until adolescence or adulthood. Associated complicating issues include cardiac arrhythmia, heart failure secondary to severe MR (rare), and, occasionally, thromboembolic events. Familial cases are known and occur in an autosomal dominant pattern with variable penetrance and expression (familial mitral valve prolapse).

Pathophysiology

Mitral valve prolapse is a heterogeneous disorder and may originate from various underlying causes affecting one or more portions of the mitral valve leaflets, chordae tendineae, papillary muscle, and/or valve annulus. The syndrome may occur in isolation or in association with generalized connective tissue abnormalities, such as Marfan syndrome and Ehlers-Danlos syndrome, in which specific enzymatic defects are found. Mitral valve prolapse may occur in the context of inflammatory disease such as rheumatic fever or endocarditis.

Isolated mitral valve prolapse can be sporadic or familial, demonstrating autosomal dominant and X-linked inheritance. Three different loci on chromosomes 16, 11, and 13 are linked to mitral valve prolapse, but no specific gene has been described. Another locus on chromosome X has also been found to cosegregate with a rare form of mitral valve prolapse called X-linked myxomatous valvular dystrophy.¹

Isolated mitral valve prolapse has been independently associated with low body mass index; however, the reason for this association remains unexplained.²

Mitral valve prolapse may be secondary to rupture or dysfunction of the papillary muscles following myocardial infarction or ischemia, rupture of chordae tendineae due to infective endocarditis, or abnormal left ventricular wall motion in the setting of myocardial ischemia and/or primary myocardial disease. In these patients, the posterior leaflet in the floppy valve tends to have a significantly longer basal free-edge length and more frequent chordal rupture compared with patients with postinflammatory disease.

A connective tissue abnormality, possibly related to collagen metabolism, may underlie the idiopathic disorder. Abnormalities of collagen and elastic fibers have been documented in floppy mitral valves (FMV). Urokinase-plasminogen activator (PLAU), which is suggested in the pathogenesis of elastin and collagen degradation in arterial aneurysm, has also been implicated in mitral valve prolapse (PLAU T4065C TC genotype). A locus for autosomal dominant mitral valve prolapse has also been described on chromosome 11p15.4.

Electron microscopy of the affected valve leaflets shows a haphazard arrangement, disruption, and fragmentation of collagen fibrils. Myxomatous proliferation of the mitral valve, in which the middle spongiosa layer is predominantly involved, leads to the presence of unusually large amounts of myxomatous material and acid mucopolysaccharide. Degeneration of collagen within the central core of the chordae tendineae may lead to chordal rupture. Mitral valve prolapse can also follow rheumatic fever and myocardial infarction, in which case the prolapse is secondary to inflammatory or ischemic chordal rupture, respectively.

Metabolic and neuroendocrine abnormalities also occur in mitral valve prolapse and may separately result in prolapse unrelated to a connective tissue disorder. In such patients, increased norepinephrine and epinephrine may be found. Abnormalities in autonomic and neuroendocrine regulation have been demonstrated, including hyper-response to adrenergic stimulation, parasympathetic abnormalities (vagal withdrawal), altered baroreflex activity, renin-aldosterone regulation abnormalities, decreased intravascular volume, decreased left ventricular volume in upright posture, and atrial natriuretic factor secretion abnormalities.

Frequency

United States

Mitral valve prolapse is the most prevalent cardiac valve disorder. Mitral valve prolapse is a common finding in otherwise healthy teenagers and young adults, particularly those patients who present with palpitations, chest pain, or dizziness. More than one third of cases in younger children are associated with other congenital heart defects. Reports vary, but 3-5% of pediatric patients likely have clinically significant mitral valve prolapse. However, a recent report from California places the prevalence at only 0.6%.³

International

Prevalence rates are 1-2% in children and 5-15% in adolescents and young adults. In a series of 278 surgically removed mitral valves with pure regurgitation, mitral valve prolapse was present in 43%.⁴

Mortality/Morbidity

When present, associated abnormalities dictate the risk. Presence of significant MR and prolonged QT interval on ECG may also influence outcome. QT prolongation is slightly more prevalent among patients with mitral valve prolapse and may be associated with repolarization abnormalities and arrhythmia vulnerability. When severe, MR can lead to heart failure.

Mortality is rare in children. Sudden death is also rare and occurs more often in young women with a history of recurrent syncope, sustained supraventricular tachycardia, or complex ventricular tachycardia. Family history of cardiac sudden death often is a risk-stratifying indicator.

Development of MR and the progression of mild or moderate MR to severe MR are important determinants to morbidity. One study showed that the prevalence of MR increased from 29% of patients to 43% of patients during 4.3 years of follow-up.⁵ Other possible complications include congestive cardiac failure, rupture of chordae tendineae, infective endocarditis (in 0.1-0.3 cases per 100 patient years), thromboembolic phenomena including cerebrovascular accidents, and sudden death. Cardiac arrhythmias such as ventricular tachycardia and ventricular fibrillation are more common in mitral valve prolapse.

Sex

Some studies show mitral valve prolapse is twice as frequent in females as in males.

Age

Although findings are more frequent in older children and adults, the defect is believed to be present at birth.

Clinical

Physical

Most patients are asymptomatic, and mitral valve prolapse (MVP) is an incidental auscultatory finding. Beta-blockers may markedly attenuate or abolish the symptoms, a fact that is important to remember while evaluating a patient who is receiving these agents. Findings are more marked when patients are examined in the outpatient department rather than in the inpatient setting, reflecting the contributory role of adrenergic state.

• Chest pain
  • Chest pain occurs in 10% of patients diagnosed with mitral valve prolapse.
  • Chest pain may be caused by any of the following factors:
    • Excessive stretching of the chordae tendineae, leading to traction on papillary muscles
    • Coronary microembolism from platelet aggregates and fibrin deposits in the angle between the left atrium and the posterior mitral leaflet
    • Inappropriate tachycardia and excessive postural changes and physical and emotional stresses
    • Hyperadrenergic state, which increases myocardial oxygen demand
    • Coronary artery spasm
• Palpitations
  • Palpitations are present in 7.4% of patients.
  • Occurrence may be related to cardiac arrhythmia, although this has not been conclusively proven.
• Fatigability and dyspnea
  • These often develop upon exertion.
  • The cause may be alterations in centrally modulated breathing cycle control.
• Neuropsychiatric
  • Panic attacks may occur.
  • Nervousness, presyncope, and syncope occur in 0.9% of patients.
  • Thromboembolism, arrhythmia, or vasodepressor-vasovagal problems may be involved.
• Pulse
  • Findings are usually normal.
  • Pulse is occasionally irregular in the presence of premature contractions.
  • Exaggerated tachycardia (high-volume in severe mitral regurgitation [MR]) following exertion is not unusual.
• Skeletal abnormalities
  • These are observed in two thirds of patients and do not fit into any of the recognized connective tissue disorders, although an occasional patient may have Marfan syndrome or other related syndromes.
  • Common findings are as follows:
    • Hypomastia
    • Thin children
    • Height-to-weight ratio greater than normal
    • Arm span greater than height (dolichostenomelia)
    • Arachnodactyly
    • Scoliosis
    • Narrow anteroposterior chest diameter (straight back)
    • Pectus excavatum or pectus carinatum
    • Cathedral palate
    • Crowding of teeth
    • Joint hypermobility
• Auscultation
  • Apical midsystolic nonejection click and late systolic murmur are the hallmarks, but either may occur alone.
  • Heart sounds are usually normal, but the first heart sound (S1) may be accentuated when prolapse occurs early in systole because of the summation of S1 and mitral click.
  • Multiple clicks occur when prolapse of different leaflets occurs at different times during the systole and may resemble pericardial friction rub.
  • In patients with redundant floppy mitral valves and significant MR, the murmur may be holosystolic and the click may be absent.
  • In cases in which the posterior mitral valve leaflet is prolapsing, the murmur may radiate along the left sternal border to the aortic area, thus mimicking left ventricular outflow tract murmur. If the anterior leaflet prolapses, the murmur radiates to the axilla and the spine.
• Dynamic auscultation
  • In the sitting or standing position in late systole, the click may appear earlier and the murmur may be more prominent. The systolic click moves toward S1 upon standing, often merging with S1 if marked postural tachycardia occurs, and new clicks may appear. If an exaggerated heart rate response occurs, the murmur becomes longer and often louder to holosystolic. Occasionally the murmur is present only in the upright posture.
  • When squatting from standing position, the click and murmur may move back to late systole. Continuous auscultation, while the patient is standing from squatting position, reveals the click and murmur moving back to early systole on a beat-to-beat basis as the heart rate accelerates.
  • A systolic precordial honk or whooping sound may occasionally be heard with the murmur. Often these are heard only in the sitting or standing position and may be limited to a few beats immediately after standing.
  • Dynamic auscultatory changes reflect alterations in the timing of the mitral valve prolapse, the timing and extent of the MR, the expected changes in left ventricular volume, myocardial contractility, and heart rate. In the upright posture, venous return decreases, as does the left ventricular volume. The reflex tachycardia that occurs in the upright position further reduces left ventricular volume. Timing and degree of the prolapse are determined by the position of the mitral leaflets at end diastole, which, in turn, is dependent on the distance from the mitral valve annulus to the attachment of the chordae to papillary muscles. Low left ventricular end-diastolic volume shortens the mitral annular papillary muscle distance, allowing the leaflets to prolapse earlier in systole.
  • Prompt squatting from standing position increases venous return and left ventricular volume; thus, the systolic click and murmur may become late systolic. Squatting, however, may also be associated with an increase in peripheral vascular resistance, which, in turn, increases the tension on the mitral valve apparatus, preferentially directing blood flow into the left atrium, rather than to the peripheral circulation. The late systolic click and murmur then become accentuated in the squatting position.
• Other maneuvers
  • Other maneuvers are possible but none is as practical as a systematically performed postural dynamic auscultation.
  • These maneuvers include the following:
    • Leg elevation
    • Isometric hand grip exercise
    • Valsalva maneuver
    • Application of tourniquets to the extremities
    • Lower body negative pressure or amyl nitrate inhalation

Causes

• Heritable disorders of connective tissue include the following:
  • Marfan syndrome
  • Ehlers-Danlos syndrome types I, II, IV
  • Stickler syndrome
  • Polycystic kidney disease, adult type
  • Osteogenesis imperfecta
  • Fragile X syndrome
  • Martin-Bell syndrome
  • Pseudoxanthoma elasticum
  • Periarteritis nodosa
• Skeletal abnormalities include the following:
  • Asthenic habitus
  • Straight back syndrome
  • Pectus excavatum
  • Pectus carinatum
  • Cardiac abnormalities
  • Atrial septal defect (ostium secundum), including atrial septal aneurysm, tricuspid valve prolapse, aortic valve prolapse, and Ebstein anomaly of tricuspid valve
  • Holt-Oram syndrome
  • Accessory atrioventricular pathways
  • Coronary artery anomalies
  • Hypertrophic cardiomyopathy
• Other diseases include the following:
  • Graves disease
  • Thyroiditis
  • Sickle cell disease
  • Muscular dystrophy
  • Myotonic dystrophy
  • Von Willebrand disease
• Several reports suggest magnesium deficiency underlies the disease in some patients.

Differential Diagnoses

Mitral Stenosis, Acquired
Mitral Stenosis, Congenital
Mitral Valve Insufficiency

Other Problems to Be Considered

Congenital mitral regurgitation
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Rheumatic mitral regurgitation
Tricuspid valve prolapse

Workup

Laboratory Studies

• In patients with mitral valve prolapse (MVP), perform blood and other laboratory tests as dictated by the condition of the patient.

Imaging Studies

• Radiography
  • Chest radiography findings are normal. Cardiac size and pulmonary venous congestion appear when mitral regurgitation (MR) is severe.
  • Skeletal surveys reveal any abnormalities.
• Echo-Doppler studies
  • This is an essential tool to identify the presence and magnitude of mitral valve prolapse, the thickness of mitral valve leaflets, mitral annulus size, chordae tendineae length, and left ventricular and left atrial size and function. The test also reveals any associated heart diseases.⁶
  • Multiple views of the mitral valve annulus are essential, and the echo-Doppler findings have to be correlated with clinical data.
  • Two-dimensional, real-time echocardiographic pictures from parasternal long-axis window reveal the mitral valve leaflets coming together in systole and billowing into the left atrium beyond the atrioventricular junction. The medial aspect of the anterior leaflet and middle scallop of the posterior leaflet are visualized from this view. The lateral scallop of posterior leaflet can be seen only from the apical 4-chamber window, and, at times, mitral valve prolapse can be focal. The echocardiographic description of the mitral valve prolapse should include structural changes, such as leaflet thickening, redundancy, annular dilatation, and chordal elongation. A varying degree of noncoaptation of the leaflets is present, and MR can be identified by Doppler-color, pulse wave, and continuous wave. The MR jet can be defined, and its magnitude and direction estimated. The size of the left atrium and left ventricle are increased in the presence of moderate-to-severe MR.
  • Three-dimensional echocardiography is reportedly very helpful in delineating the prolapse and associated regurgitation. Segmental analysis of the mitral valve leaflets has been as successful with this technique as with transesophageal echocardiography.^7,8 It has also been reported to provide information that helps in surgical repair.
  • Transesophageal echocardiography has also improved the identification of leaflet morphology, assisting surgical repair.
  • M-mode echocardiography reveals a characteristic posterior movement of the posterior mitral leaflet during mid or late systole or pansystolic prolapse of both anterior and posterior mitral leaflets toward the left atrium. With the availability of 2-dimensional and Doppler studies, mitral valve prolapse should no longer be diagnosed solely on M-mode pictures.
  • These studies, particularly transesophageal echocardiography, also help identify potential embolic sources in patients with focal neurologic symptoms or signs.
  • Findings are always interpreted in the context of the clinical evaluation by dynamic auscultation. The diagnostic accuracy improves by use of a constellation of findings, which include structural and functional changes. Patients with echocardiographic criteria for mitral valve prolapse, without evidence of thickened redundant leaflets or significant MR, require careful review before mitral valve prolapse is diagnosed. Mere sagging of anterior leaflet in the 4-chamber view does not indicate mitral valve prolapse. Patients with typical auscultatory findings may be diagnosed even with questionable echocardiographic findings.
  • Rarely, patients with mitral valve prolapse may have typical echocardiographic findings but no abnormality on auscultation. Patients with suggestive symptoms and no auscultatory findings, who have nonspecific echocardiographic changes, present a real challenge and may require periodic reevaluation before a firm diagnosis can be made. Family history could be of help in some of these patients.
• Stress scintigraphy: Myocardial perfusion scintigraphy (eg, using thallium-201) during exercise may help identify the rare patient with mitral valve prolapse and myocardial ischemia.

Other Tests

• Electrocardiography
  • Results are usually normal; however, in about one half of children and adolescents, the findings may reveal inverted or biphasic T waves, especially in leads II, III, aVF, and/or V5-6. The T-wave abnormalities may vary at different times in the same patient and may improve with exercise or with beta-blocker therapy.
  • Arrhythmias described at rest or during exercise include premature atrial (23.6%) or ventricular (27.3%) contractions, supraventricular tachycardia, and conduction abnormalities. Patients with mitral valve prolapse demonstrate a higher frequency of left-sided accessory pathways. More serious findings include ventricular tachycardia and fibrillation.
  • A higher incidence of arrhythmia may be due to a prolonged QT interval. Diastolic depolarization of muscle fibers in the anterior mitral leaflet in response to stretch may also have a role.
  • Slow response action potentials originating in the atrial-like muscle fibers in the mitral valve leaflets can lead to sustained rhythmic action that penetrates the cardiac chambers.
• Phonocardiography: This was previously used as an adjunct to confirm the auscultatory findings.

Procedures

• Ambulatory 24-hour electrocardiography
  • A Holter monitor may help identify the nature and frequency of arrhythmic activity.
  • Premature ventricular beats (38%), multiform couplets, and tachyarrhythmias (8%) are usual findings.
• Exercise testing
  • This is useful in patients with palpitations and exercise-related symptoms.
  • Premature ventricular beats (16%), ventricular tachycardia (4%), and supraventricular ectopy are common findings. Ventricular fibrillation is a rare finding.
• Cardiac catheterization and angiography
  • These tests are generally restricted to patients with mitral valve prolapse and severe MR who may require valve repair or replacement.
  • Associated coronary artery disease can also be confirmed or excluded.
  • A left ventricular angiogram, obtained in the right anterior oblique view, best shows the posterior leaflet. A left anterior oblique projection reveals the anterior leaflet.
  • Other abnormalities that may be revealed include dilatation, decreased systolic contraction, calcification of the mitral annulus, and poor contraction of the basal portion of the left ventricle.
• Electrophysiology
  • Indications for electrophysiology (EPS) are similar to those in general clinical practice.
  • EPS is useful in the presence of supraventricular tachycardia because accessory atrioventricular pathways are common in patients with mitral valve prolapse. In this subset of patients, EPS is important because radiofrequency ablation can be performed during the same procedure, with a very high curative success rate.
• Tilt test: Upright tilt studies with blood pressure and cardiac rhythm monitoring may be valuable in patients with light-headedness or syncope when vasodepressor-vasovagal reaction is suspected and confirmation of clinical symptoms is desired.

Histologic Findings

• Mitral valves excised from patients with severe MR secondary to mitral valve prolapse have large leaflets and show various alterations.
• The most specific, fundamental, and characteristic histologic changes are (1) collagen dissolution and disruption in the pars fibrosa of the mitral valve leaflet and (2) replacement of the dense collagenous fibrosa by loose myxomatous connective tissue with high acid mucopolysaccharide content. Similar histologic abnormalities are observed in chordae tendineae.
• Scanning electron photomicrographs demonstrate surface folds and focal loss of endothelial cells on mitral valve leaflets obtained from patients with severe mitral valve prolapse and significant MR. These surface abnormalities may predispose to thromboembolic complications and/or infectious endocarditis.
• Continuous pressure and stress on the leaflets and chordae tendineae during left ventricular systole contribute to gradual progression of these histologic changes.

Treatment

Medical Care

In childhood, mitral valve prolapse (MVP) is not progressive, and specific therapy is not indicated for the vast majority of patients. Asymptomatic patients with isolated mitral systolic clicks need only counseling and reassurance.

Avoid excessive use of caffeine, cigarettes, alcohol, and prescription or over-the-counter drugs that contain stimulants such as epinephrine or ephedrine to minimize catecholamine and cyclic adenosine monophosphate (AMP) stimulation. Prevention of volume depletion before, during, and immediately after exercise may help. Subacute bacterial endocarditis antibiotic prophylaxis coverage for at-risk procedures is indicated in patients with mitral valve prolapse and mitral regurgitation (MR). See Antibiotic Prophylactic Regimens for Endocarditis.⁹

Additional dental care recommended for patients at risk for infective endocarditis includes the following:

• Regular toothbrushing after eating
• No cookies, sweets, or sweet drinks between meals
• Regular dental checks every 6 months
• Fluoride supplements in locations where the fluoride in drinking water is less than 0.3 ppm for children younger than 2 years or less than 0.7 ppm for children younger than 2 years
• Dental treatments (more than 2) scheduled at an interval of 14 days or longer

Surgical Care

Recent advances have made reconstructive mitral valve surgery feasible in patients with congestive heart failure, severe MR secondary to mitral valve prolapse, or both.¹⁰ For details of surgical intervention, results, postoperative care, and complications of MR, see Mitral Regurgitation.

Consultations

A multidisciplinary approach is preferable, including the following:

• Pediatrician
• Pediatric cardiologist
• Radiologist
• Geneticist
• Cardiothoracic specialist
• Physiotherapist
• Family medicine specialist
• Orthopedist

Activity

A gradual return to exercise may be tolerated. In the absence of studies on the effect of exercise on the progression of mitral valve prolapse, the best approach at present is based on common sense and good clinical judgment.

Patients with symptoms of syncope, presyncope, or palpitations upon exertion should undergo thorough evaluations and avoid competitive sports for at least 6 months after the last significant episode. In the presence of significant MR, limitations apply as for any other cause of MR.

Coexisting aortic root dilatation and aortic regurgitation can further limit activity.

Patients with cardiac arrhythmia should have periodic exercise tests performed and ambulatory ECG recordings obtained while doing the type of exercise they are likely to undertake.

Sudden death is extremely uncommon in mitral valve prolapse.

Medication

Medical strategies for mitral valve prolapse (MVP) include the following:

• Anticongestive heart failure therapy
• Antibiotic prophylaxis during surgery, dental, and genitourinary procedures - Only necessary if associated MR is present (See Antibiotic Prophylactic Regimens for Endocarditis.)⁹
• Antiarrhythmic therapy - May be indicated in patients with documented and/or symptomatic arrhythmia, depending on findings of noninvasive and/or invasive electrophysiologic testing
• Beta-blockers - May be beneficial for symptom prevention, reduction in ectopy, treatment of vasodepressor syncope, panic attacks, or antiarrhythmic therapy¹¹
• Antiplatelet therapy - Used in patients with thromboembolic episodes
• ACE inhibitors - Used in patients with significant MR
• Low-dose aspirin and/or anticoagulant therapy - Considered in patients with thromboembolic episodes

Beta-adrenergic blocking agents

These agents block the beta-adrenergic receptor and are modulators of the autonomic system. They inhibit chronotropic, inotropic and vasodilatory responses to beta-adrenergic stimulation.

Propranolol (Inderal)

Inhibits beta1-adrenergic and beta2-adrenergic receptors. Class II antiarrhythmic, nonselective, beta-adrenergic receptor blocker with membrane-stabilizing activity that decreases automaticity of contractions.

Dosing

Adult

30-160 mg/d PO divided tid/qid

Pediatric

1-4 mg/kg/d PO divided bid/qid

Interactions

Enhances hypotensive action of ACE inhibitors, alcohol, anesthetics, corticosteroids, and diuretics; increases negative inotropic action of calcium channel blockers

Contraindications

Documented hypersensitivity; bronchial asthma, bradycardia, hypotension, second-degree and third-degree heart block, or severe peripheral arterial disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; slowly withdraw drug and closely monitor; reduce dose in liver or renal failure and myasthenia gravis; adverse effects include bradycardia, hypotension, bronchospasm, GI upset, fatigue, and rash; taper over 1-2 wk when discontinuing

Antiplatelet agents

These drugs are used for secondary prevention of thrombotic cerebrovascular or cardiac disease.

Aspirin (Anacin, Bayer, Empirin)

Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

Dosing

Adult

75-100 mg/d PO

Pediatric

5-10 mg/kg/d PO; not to exceed 100 mg/d

Interactions

Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose lowering effect of sulfonylurea drugs; enhanced absorption with metoclopramide; increases levels of methotrexate and acetazolamide

Contraindications

Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, asthma; due to association of aspirin with Reye syndrome, not for use in children (<16 y) with flu

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants; use in pregnancy may cause increased risk of bleeding during delivery; high doses may cause premature closure of ductus arteriosus with complications; enhances risk of kernicterus in babies if given to mother toward term; adverse effects include bronchospasm, GI hemorrhage, and other hemorrhages

Dipyridamole (Persantine)

Acts by decreasing platelet aggregation. Inhibits thrombus formation in the arterial side of circulation.

Dosing

Adult

300-600 mg/d PO divided tid/qid

Pediatric

2.5 mg/kg PO bid

Interactions

Theophylline may decrease hypotensive effects; antiplatelet activity may increase heparin toxicity; enhances and prolongs action of adenosine

Contraindications

Documented hypersensitivity; peptic ulcer disease; hereditary coagulopathies

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in hypotension; medication has peripheral vasodilating effects; exacerbates heart failure, asthma, angina, and MI; adverse effects include GI upset, dizziness, headache, hot flushes, tachycardia, and bleeding tendency

Diuretics

These drugs are used to release retained fluid and lower preload.

Furosemide (Lasix)

Inhibits reabsorption of fluid from ascending limb of the Henle loop in renal tubule. Administered IV. Has venodilation action; thus, also lowers preload even before diuresis effect. Useful in acute heart failure and exacerbations of chronic heart failure.

Dosing

Adult

40 mg PO bid; or 20-50 mg IV, repeat q6-8h

Pediatric

1-4 mg/kg PO qd or bid; or 1-4 mg/kg IV q8h

Interactions

Enhanced hypotension with ACE inhibitors; enhanced risk of nephrotoxicity with nonsteroidal antiinflammatory drugs; coadministration with amiodarone causes flecainide-enhanced toxicity because of the risk of hypokalemia; possible enhanced ototoxicity with aminoglycosides; enhanced hypotension and risk of cardiac arrhythmia with sotalol

Contraindications

Documented hypersensitivity; hepatic coma, anuria, and state of severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte (monitor for hypokalemia and hyponatremia), CO₂, glucose, creatinine, uric acid, calcium, and BUN level determinations during first few months of therapy and periodically thereafter; aggravates diabetes mellitus, porphyria, and liver failure; caution in pregnancy and breastfeeding

Spironolactone (Aldactone)

Potassium-sparing diuretic. Acts on the distal convoluted tubule of the kidney as an aldosterone antagonist. Has synergistic action with furosemide.

Dosing

Adult

100-200 mg/d PO

Pediatric

0.5-1.5 mg/kg PO bid

Interactions

Risk of hyperkalemia with ACE inhibitors, cyclosporin, or potassium supplements

Contraindications

Documented hypersensitivity; hyperkalemia, hyponatremia, severe renal impairment, Addison disease

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal and hepatic impairment; may cause GI upset, hyponatremia, hyperkalemia, lethargy, confusion, impotence, gynecomastia, and is carcinogenic in rodents

Amiloride (Midamor)

Pyrazine-carbonyl-guanidine unrelated chemically to other known antikaliuretic or diuretic agents. Potassium-conserving (antikaliuretic) drug that, compared with thiazide diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity. Acts directly on the distal renal tubule, usually used along with a potassium-losing diuretic.

Dosing

Adult

5-10 mg PO bid

Pediatric

<20 kg: 0.2 mg/kg PO bid; not to exceed 10 mg/d
>20 kg: Administer as in adults

Interactions

Risk of hyperkalemia with ACE inhibitors, cyclosporine, or potassium supplements; decreased effect with NSAIDs

Contraindications

Documented hypersensitivity; elevated serum potassium levels, >5.5 mEq/L; impaired renal function, acute or chronic renal insufficiency, and evidence of diabetic nephropathy; closely monitor electrolytes if evidence of renal functional impairment, BUN level >30 mg/100 mL, or serum creatinine levels >1.5 mg/100 mL

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Potassium retention associated with use of an antikaliuretic agent accentuated in presence of renal impairment and may result in rapid development of hyperkalemia; monitor serum potassium level, mild hyperkalemia usually not associated with abnormal ECG; GI upset, dry mouth, skin rash, confusion, and postural hypotension may develop

ACE inhibitors

These agents reduce afterload and decrease myocardial remodeling, which worsens chronic heart failure.

Captopril (Capoten)

Accepted as essential part of heart failure therapy. Not only gives symptomatic improvement but also prolongs survival.

Dosing

Adult

6.25-25 mg PO tid

Pediatric

0.1-1 mg/kg PO tid; initiate at lower dosage range and titrate upward

Interactions

NSAIDs may reduce hypotensive effects of captopril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases levels; probenecid may increase levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics;
enhanced hypotensive effect with coadministration of anesthetic agents; cyclosporine enhances risk of hyperkalemia; potassium-sparing diuretics or potassium supplements enhance risk of hyperkalemia

Contraindications

Documented hypersensitivity; renal artery stenosis, left ventricular outflow obstruction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Category D in second and third trimesters; caution in renal impairment, valvular stenosis, or severe congestive heart failure; adverse effects include hypotension, tachycardia, and renal failure; therapy must be commenced while blood pressure is adequate and state of hydration satisfactory; small doses are started while in hospital and blood pressure is monitored; persistent dry cough has been reported in 5-20% of children and may require change to another agent in the group or to an angiotensin receptor blocker; other adverse effects include angioedema, rash, serum sickness, GI upset, pancreatitis, hepatitis, cholestatic jaundice, blood dyscrasias, bronchospasm, headache, dizziness, and fatigue

Cardiac glycoside

These agents provide symptomatic improvement in heart failure.

Digoxin (Lanoxin)

Improves myocardial contractility, reduces heart rate, and lowers sympathetic stimulation in chronic heart failure.

Dosing

Adult

Maintenance: 125-250 mcg/d PO

Pediatric

Maintenance dose:
Preterm infant: 5-7.5 mcg/kg/d PO
Term infant: 6-10 mcg/kg/d PO
1 month to 2 years: 10-15 mcg/kg/d PO
2-5 years: 7.5-10 mcg/kg/d PO
5-10 years: 5-10 mcg/kg/d PO
>10 years: 2.5-5 mcg/kg/d PO
Daily dose typically divided bid if age <10 y

Interactions

Medications that may increase digoxin levels include alprazolam, benzodiazepines, bepridil, captopril, cyclosporine, propafenone, propantheline, quinidine, diltiazem, aminoglycosides, amiodarone, anticholinergics, diphenoxylate, erythromycin, felodipine, flecainide, furosemide, hydroxychloroquine, itraconazole, nifedipine, omeprazole, quinine, ibuprofen, indomethacin, esmolol, tetracycline, tolbutamide, and verapamil; medications that may decrease serum digoxin levels include aminoglutethimide, antihistamines, cholestyramine, neomycin, penicillamine, aminoglycosides, PO colestipol, hydantoins, hypoglycemic agents, antineoplastic treatment combinations (including carmustine, bleomycin, methotrexate, cytarabine, doxorubicin, cyclophosphamide, vincristine, procarbazine), aluminum or magnesium antacids, rifampin, sucralfate, sulfasalazine, barbiturates, kaolin/pectin, and aminosalicylic acid

Contraindications

Documented hypersensitivity; beriberi heart disease, idiopathic hypertrophic subaortic stenosis, constrictive pericarditis, and Wolff-Parkinson-White syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Reduce dose in renal impairment; avoid hypokalemia; avoid IV use except when absolutely essential; avoid in sick sinus syndrome and thyroid disease; monitor blood level in suspected toxicity and in high-risk situations; major noncardiac adverse effects include vomiting, nausea, abdominal pain, visual disturbances, headache, and fatigue; cardiac adverse effects include arrhythmia (paroxysmal atrial tachycardia with block) and heart block

Follow-up

Further Inpatient Care

• Admission of patients with mitral valve prolapse (MVP) is seldom required, except in the case of complications or for consideration of surgical intervention.

Further Outpatient Care

• Patients require continued follow-up care and evaluation into adult life.
• Repeat evaluations every 3-5 years to identify any progression.
• Infective endocarditis prophylaxis is indicated in patients with mitral valve prolapse and mitral regurgitation (MR) while undergoing at-risk procedures. For more information, see Antibiotic Prophylaxis Regimens for Endocarditis.
• Patients with accessory pathways should have detailed electrophysiology studies and radiofrequency ablation of the accessory pathway.
• Coronary artery anomalies should be excluded in patients with chest pain before they participate in sports.
• Mild prolapse on echocardiography, in the absence of clinical findings (15-20% of patients), does not indicate true mitral valve prolapse syndrome. Parents and patients need to be reassured.

Inpatient & Outpatient Medications

• Anti–heart failure medications
• Propranolol
• Aspirin
• Dipyridamole
• Warfarin
• Antibiotics for endocarditis prophylaxis

Complications

• MR: Progression or appearance of MR is one of the main complications. Over 4.3 years, approximately 14% of patients developed MR.
• Congestive cardiac failure
• Rupture of chordae tendineae
• Infective endocarditis, in 0.1-0.3 cases per 100 patient years
• Thromboembolic phenomena including cerebrovascular accidents and sudden death
• Cardiac arrhythmia
• Ventricular tachycardia and fibrillation

Prognosis

• The condition is not progressive in childhood, and specific therapy is not indicated for the vast majority of patients.
• Progression to significant MR or sudden death is rare.
• Asymptomatic patients with isolated mitral systolic clicks need only counseling and reassurance.

Patient Education

• Careful explanation of the clinical findings and the nature of mitral valve prolapse help to reassure the anxious patient.
• Normal activity can be allowed if MR is not severe
• Antibiotic prophylaxis during surgery and dental procedures is only necessary if associated MR is present.
• The vast majority of patients with MVP remain asymptomatic for their entire lives and require observation every few years for reassurance.
• Patients with orthostatic syncope secondary to dehydration should take extra salt and water during and following sport activities and competition.
• Pregnancy requires infective endocarditis prophylaxis during delivery. Other implications are based on the severity of MR.
• For excellent patient education resources, visit eMedicine's Heart Center. Also, see eMedicine's patient education article Mitral Valve Prolapse.

Miscellaneous

Medicolegal Pitfalls

• Failure to make the diagnosis
• Failure to fully investigate patients who are symptomatic
• Failure to restrict exercise in patients who are symptomatic
• Failure to recognize the higher risk of arrhythmia during anesthesia and the perioperative period
• Failure to properly interpret findings: Patients with mitral valve prolapse (MVP) syndrome require a careful history and thorough physical examination because of the possibility of misinterpreting history, physical findings, borderline laboratory test results, and nonspecific ECG or echocardiography changes.
• Overtreatment
• Overdiagnosis
• Failure to investigate unexplained symptoms: Any unexplained symptoms should be viewed with due concern and investigated.

Special Concerns

• Diagnosis should include the type of prolapse (late systolic, holosystolic, anterior, or posterior leaflet), thickness of mitral valve leaflets, size of mitral annulus, and the left ventricular and left atrial size and function. The diagnosis should also include presence, severity, and timing of mitral regurgitation (MR); define jet direction and magnitude; and clearly list associated abnormalities.
• Patients with orthostatic syncope secondary to dehydration should take excess salt and water during and following sport activities and competition.
• Patients are more sensitive to volume depletion; hence chronic diuretic therapy should be avoided.

Multimedia

Media file 1: Chest radiograph of 5-year-old girl with mitral valve prolapse (MVP) and mild mitral regurgitation. The radiograph shows cardiomegaly and normal pulmonary vasculature.

Media file 2: Two-lead electrocardiogram of a child with mitral valve prolapse (MVP) showing T-Wave inversion in leads III and aVF.

Media file 3: Two-dimensional echocardiographic picture taken from the parasternal long-axis view showing prolapse of both anterior and posterior mitral valve leaflets into the left atrium at systole.

Media file 4: Color-Doppler echocardiography of a child with mitral valve prolapse showing jet of mitral regurgitation.

Media file 5: M-mode echocardiographic picture of mitral valve prolapse showing pansystolic prolapse of both anterior and posterior mitral leaflets toward left atrium.

Media file 6: Plain radiograph of the left hand of a 10-year-old boy with marfanoid syndrome and mitral valve prolapse (MVP) showing the long thin metacarpals. The metacarpal index is longer than normal.

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Keywords

mitral valve prolapse, Barlow syndrome, billowing mitral valve syndrome, Da Costa syndrome, effort syndrome, familial MVP, floppy mitral valve syndrome, irritable heart syndrome, myxomatous mitral valve, neuro-circulatory asthenia, redundant cusp syndrome, soldier heart syndrome, systolic click-murmur syndrome, mitral regurgitation, heart failure, Marfan syndrome, Ehlers-Danlos syndrome, rheumatic fever, endocarditis, myocardial infarction, ischemia, syncope supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, cardiac arrhythmia, panic attacks, presyncope, Stickler syndrome

polycystic kidney disease, osteogenesis imperfecta, fragile X syndrome, Martin-Bell syndrome, pseudoxanthoma elasticum, periarteritis nodosa, asthenic habitus, straight back syndrome, pectus excavatum, pectus carinatum, atrial septal defect ostium secundum, tricuspid valve prolapse, aortic valve prolapse, Ebstein anomaly, Holt-Oram syndrome, hypertrophic cardiomyopathy, Graves disease, thyroiditis, sickle cell disease, muscular dystrophy, myotonic dystrophy, Von Willebrand disease, magnesium deficiency

Contributor Information and Disclosures

Author

Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH, Consulting Staff, Department of Child Health, University Hospital of Hartlepool, UK
Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH is a member of the following medical societies: British Cardiac Society, Royal College of Paediatrics and Child Health, and Royal College of Physicians and Surgeons of Glasgow
Disclosure: Nothing to disclose.

Medical Editor

Charles I Berul, MD, Associate Professor of Pediatrics, Harvard Medical School; Senior Associate, Department of Cardiology, Children's Hospital of Boston
Charles I Berul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, Heart Rhythm Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Julian M Stewart, MD, PhD, Associate Chairman of Pediatrics, Director, Center for Hypotension, Westchester Medical Center; Professor of Pediatrics and Physiology, New York Medical College
Julian M Stewart, MD, PhD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

CME Editor

Gilbert Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College
Gilbert Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Stuart Berger, MD, Professor of Pediatrics, Division of Cardiology, Medical College of Wisconsin; Chief of Pediatric Cardiology, Medical Director of Pediatric Heart Transplant Program, Medical Director of The Heart Center, Children's Hospital of Wisconsin
Stuart Berger, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American College of Chest Physicians, American Heart Association, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

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