Mitral Valve Prolapse

US Pharm. 2008;33(2):28-33

Mitral valve prolapse (MVP) is a condition that affects nearly 15 million Americans.¹ It is the most common cause of severe, nonischemic mitral regurgitation in the United States. Its cause is unknown, but in some patients it appears to be a genetically determined collagen tissue disorder. Mitral valve prolapse encompasses a broad spectrum of severity. Some patients with this condition are asymptomatic, while others experience an array of symptoms that can be life altering. The prognosis of this condition is excellent, but a small subset of patients will develop serious complications.² Pharmacists can play a role in managing patients with MVP by providing needed reassurance of the benign prognosis for asymptomatic patients as well as by offering proper medication counseling to those patients who require medication treatment.

BACKGROUND
Understanding the mitral valve itself is important in managing MVP and can help lead to effective treatment. The mitral valve of the heart is a complicated apparatus and is located between the left atrium and the left ventricle. The mitral valve has two flaps. In some people, one or both of the mitral valve flaps are enlarged and do not close properly. When the left ventricle contracts, the valve's flaps bulge (prolapse) backward into the left atrium. This heart abnormality is called MVP. Mitral valve prolapse is a common source of valve repair and replacement for patients with isolated mitral regurgitation in the U.S. It is important to note that MVP is the most common form of valvular heart disease.¹

The term mitral valve prolapse describes a defect in the mitral valve of the heart. A different term, mitral valve prolapse syndrome, is commonly used to indicate the presence of MVP and an assemblage of other physical abnormalities such as autonomic dysfunction, palpitations, and pectus excavatum. These other physical abnormalities can result in a variety of unrelated symptoms. It is estimated that MVP syndrome affects between 3% to 6% of adults in the U.S. ¹ This syndrome can often be debilitating to patients and extremely frustrating for physicians to properly manage.

SIGNS AND SYMPTOMS

Mitral Valve Prolapse
Mitral valve prolapse is typically diagnosed during a routine physical exam with a stethoscope. Most patients with MVP are female. It affects individuals of differing ages but most commonly those patients between the ages of 14 and 30. Patients with MVP share a hallmark physical finding of a midsystolic click and a late systolic murmur.³ Interestingly, many patients with MVP appear to be part of a connective tissue phenotypic spectrum. Often, these patients have "tall, thin habitus, thoracic cage deformity and joint hypermobility as well as low blood pressure."^4,5 Most patients with MVP do not have symptoms, do not have problems, and will not need treatment. Those patients who do complain of symptoms report chest discomfort, anxiety, fatigue, and dyspnea. It is inconclusive if these symptoms are actually due to the prolapse of the mitral valve or if they are coincidental occurrences.¹ For symptomatic patients, the most common reason for symptoms is the leakage of blood backward through the valve. This is known as regurgitation. Patients who experience regurgitation often have symptoms of a racing or irregular heartbeat, dizziness, lightheadedness, fatigue, chest pain, and shortness of breath.³

Mitral Valve Prolapse Syndrome
Many patients who present with MVP also exhibit symptoms that appear to be unrelated. As mentioned earlier, these patients are often diagnosed with a condition known as MVP syndrome. Mitral valve prolapse syndrome is usually diagnosed after a patient has seen a multitude of specialists. Patients present with an array of symptoms that are often cause for misdiagnosis. These patients appear to have an autonomic or neuroendocrine system imbalance. This condition is often referred to as dysautonomia (malfunction of the autonomic nervous system). The autonomic nervous system is complex and controls necessary functions such as respiration, heartbeat, blood pressure, vision, and digestion. When the autonomic system is out of balance, it can cause a multitude of symptoms, including panic attacks, anxiety, fatigue, palpitations, migraines, hypotension, and irritable bowel syndrome. It has been hypothesized that there is a potential role of the renin angiotensin system in the pathogenesis of MVP syndrome. Investigations are being conducted to examine the possible relation between the A-C polymorphism of the AT ₁ gene and MVP syndrome. One study has found a link.⁴

Diagnosis of MVP syndrome is determined by physical examination, a careful medical history, and, in most cases, an echocardiogram. Symptoms of MVP syndrome do not typically present before the age of 14.^4,5 It is important to note that patients without MVP often present with similar dysautonomic symptoms. It is unclear if this condition is related solely to a valvular abnormality or if there is a genetic link involved.²

LABORATORY EXAMINATION
Electrocardiogram
Although the electrocardiogram may provide some valuable information in patients with MVP, patients typically present with a normal ECG. If there is an abnormality, it will present as ST-Tñwave depression or T-wave inversion in the inferior leads (II, III, and VF). Occasionally, the ECG will show supraventricular or ventricular premature contractions. Electrocardiograms may be useful for documenting arrhythmias in patients who experience palpitations.³

Echocardiogram
A two-dimensional and Doppler echocardiography is the most useful, noninvasive test for diagnosing MVP. It is effective in identifying the abnormal position and prolapse of the mitral valve leaflets.⁵ MVP can be diagnosed when one or both mitral leaflets demonstrate at least 2 mm of systolic displacement superior to a line connecting the annular hinge points in a long-axis view. ² The diagnosis of MVP is even more certain when the echocardiography shows a leaflet thickness greater than 5 mm. Echocardiograms are helpful in detecting left atrial size, left ventricle size, and function. The echocardiogram is also helpful in determining the extent of mitral leaflet redundancy for patients at risk for developing complications.⁵

Although the echocardiogram is a confirmatory test for diagnosing MVP, it may not always be abnormal. It is recommended that all patients with MVP have an initial echocardiogram to assess left atrial and left ventricle size, left ventricle function, and mitral leaflet movement and thickness.¹ Sequential echocardiograms are not usually deemed necessary in asymptomatic patients with MVP unless such patients present with clinical indications that their condition is worsening. ⁵ Using echocardiography as a screening tool for MVP is not recommended for patients who do not have a systolic click or murmur on several auscultatory examinations, regardless of whether the patient is symptomatic. ¹

COMPLICATIONS

Regurgitation

The most frequent and important complication of MVP is a condition known as mitral regurgitation (MR). In this condition the mitral valve is particularly leaky and allows excessive blood to leak backwards into the left atrium.⁶ Physical examination is not always reliable in diagnosing MR and, in fact, cannot accurately measure the severity of MR.⁷ The gradual progression of MR in patients with MVP may result in increasing dilation and dysfunction of the left atrium and left ventricle. MR that becomes severe can lead to cardiac arrhythmias, congestive heart failure, and an increased risk of sudden death.⁷ Patients who suffer from severe MR are also at an increased risk of developing infective endocarditis, which can be fatal.^8,1

Although MVP appears to be prevalent more among women, males who are older than 50 years do present with MVP. These men have a threefold higher risk than women of ultimately needing surgery for severe MR. Patients with hypertension and a high body-mass index are at higher risks for developing severe MR.³ Age is also of importance when considering who is at greater risk for developing severe MR. The prevalence of severe MR is infrequent before the fifth decade of life. ² Echocardiography is used to diagnose severe MR. Patients whose echocardiogram reveals thickened leaflets, posterior leaflet prolapse, and increased left ventricular dimensions are at greater risk for development of severe MR. Contrastingly, patients with thin leaflets have a lower risk of developing severe MR.

Patients with MR may be asymptomatic for years. The average interval from diagnosis to the onset of symptoms is 16 years.⁷ Most available data focus on patients with severe regurgitation. There are few data on the rate of progression of disease with mild to moderate regurgitation. The progression may be slow and insidious or it may be abrupt. Abrupt progression is indicative of a chordal rupture, which leads to flail leaflet. Patients with severe symptomatic MR have a poor clinical outcome. Survival rates are 33% at 8 years in the absence of surgical intervention. Most deaths are related to heart failure, but there is significant incidence of sudden death.⁷

Endocarditis
Endocarditis is inflammation of the endocardium or lining layer of the heart, and the most common heart structures involved are the valves. Endocarditis is either infective or noninfective depending on the source of the problem. Patients who develop infective endocarditis are typically infected with staphylococci or streptococci.⁹ Individuals with suspected endocarditis often require echocardiographic evaluation to detect and characterize the hemodynamic and pathologic consequences of type of endocarditis. Patients developing endocarditis typically exhibit major cardiac complications. One complication includes damaged cardiac valves, including the mitral valve. The functional and structural integrity of these valves may be completely destroyed by the invading infectious organism. Patients who develop endocarditis require antimicrobial therapy, and in some instances surgical management is warranted.⁹

Patients with MVP who experience regurgitation are at a three- to eightfold increased risk for developing infective endocarditis. Predictors of increased risk for developing infective endocarditis include males older than 45 years, the presence of a systolic murmur, and leaflet thickening and redundancy.² Because endocarditis is associated with substantial morbidity and mortality, patients with MVP regurgitation are encouraged to take antibiotics prior to dental procedures and certain types of surgery. By taking prophylactic antibiotic therapy, patients are less likely to develop infective endocarditis.³ In a patient with MVP and the absence of regurgitation, the incidence of infective endocarditis is similar to that of the general population, and therefore antibiotic prophylaxis is not warranted.²

TREATMENT AND FOLLOW-UP
Asymptomatic Patients
Most patients with MVP are asymptomatic and are not at high risk for serious complications. Practitioners should manage these patients by providing reassurance of their benign prognosis. Patients should be encouraged to live a healthy lifestyle and exercise regularly.¹

Asymptomatic patients with mild or no regurgitation can be clinically evaluated every 3 to 5 years. Sequential echocardiograms are not deemed necessary unless cardiovascular symptoms develop or if progression of MR is suspected.¹

Symptomatic Patients
MVP patients who demonstrate palpitations associated with tachycardia, increased adrenergic symptoms, chest pain, anxiety, or fatigue often respond well to therapy with low-dose, beta-blocking agents. Symptoms related to orthostatic changes, such as postural hypotension, can be treated with increased fluid and salt intake. If patients experience severe orthostatic symptoms, mineralocorticoid therapy may be warranted.¹

According to the guidelines of the American College of Cardiology/American Heart Association, symptomatic MVP patients with histories of transient ischemic attacks may benefit by being placed on aspirin therapy (80-325 mg/day). Symptomatic MVP patients with histories of stroke and recurrent transient ischemic attacks while on aspirin therapy are advised to take long-term anticoagulation therapy such as warfarin. ¹

Patients with MVP syndrome are often encouraged to take measures to correct their autonomic dysfunction. Certain measures would include proper diet, limiting caffeine intake, and increasing exercise. It has been suggested that heavily symptomatic MVP patients have low serum magnesium levels. These patients also often present with hyperadrenergic activity. Studies have demonstrated that when this is the case, magnesium supplementation may lead to improvement of symptoms. Magnesium supplementation may also decrease catecholamine excretion and reduce overall weakness, chest pain, dyspnea, palpitations, and anxiety.¹⁰ Symptomatic patients may find symptom improvement by taking 200 to about 800 mg of magnesium a day. One common side effect of magnesium is diarrhea. If a patient experiences diarrhea, he or she should decrease the daily amount of magnesium. In general, magnesium is considered a safe mineral, but people with heart problems or kidney problems should be cautious of taking too much.

Surgery Options
Symptomatic patients with severe MR should be evaluated for mitral valve repair, and replacement is sometimes indicated. Valvular surgery is recommended for patients with severe MR accompanied by atrial fibrillation or pulmonary hypertension. There are different types of surgery options for patients. Mitral valve repair and mitral valve replacement are two options. There is a consensus in the medical literature that mitral valve repair is preferred over mitral valve replacement.

Mitral valve repair is a surgical procedure that preserves the patient's mitral valve. The surgeon attempts to modify the original mitral valve. This is called valvuloplasty, which eliminates backward blood flow. Surgeons also sometimes repair the valve by tightening or replacing the ring around the valve. This is called annuloplasty. Mitral valve repair has many advantages over valvular replacement. Patients undergoing mitral valve repair have lower operative mortality, better long-term survival, and lower risks of thromboembolic events. ²

Mitral valve replacement is performed when mitral valve repair is not possible. In this procedure, the surgeon removes the damaged mitral valve and replaces it with a prosthetic valve. There are two types of prosthetic valves used, mechanical valves and tissue valves. Mechanical valves are made of metal. Patients who choose this route will be required to take an anticoagulant medication for the remainder of their lives. Tissue valves are made from biological tissue such as pig's heart valves, and patients are not required to take an anticoagulant medication. Typically, mechanical valves last longer than tissue valves.

CONCLUSIONS
Mitral valve prolapse is not a preventable disorder. Patients with MVP can lead normal, productive, symptom-free lives. The prognosis for someone with uncomplicated MVP (without regurgitation) is excellent. Patients who present with MVP often differ in disease severity. Some patients are asymptomatic, while others experience more extreme symptoms that may be life altering. One major part of managing patients with MVP is providing reassurance, because most patients are asymptomatic and not at high risk for complications. Health care providers should reassure patients with mild or no symptoms of the benign prognosis. All patients with MVP are encouraged to lead a normal lifestyle that includes a regular exercise plan. Patients who have evidence of disease complications, such as regurgitation, are at increased risk for mortality and morbidity. ¹¹

References

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3. Mayo Clinic Web site. Available at: www.mayoclinic.com. Accessed November 5, 2007.

4. Szombathy T, et al. Angiotensin II type 1 receptor gene polymorphism and mitral valve prolapse syndrome. Am Heart J. 2000;139:101-105.

5. Maron B, et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis and Marfan syndrome. J Am Coll Cardiol. 2005:40:1340-1345.

6. American Heart Association Web site. Available at americanheartheart.org. Accessed November 6, 2007.

7. Otto C. Evaluation and management of chronic mitral regurgitation. N Engl J Med. 2001;345:740-746.

8. Jonkaitiene R, Benetis R, Ablonskyte-Dudoniene R, Jurkevicius R. Mitral valve prolapse: diagnosis, treatment and natural course. 2005;41:325-334.

9. Lester S, Wilansky S. Endocarditis and associated complications. Crit Care Med. 2007:35:384-391.

10. Lichodziejewska B, et al. Clinical symptoms of mitral valve prolapse are related to hypomagnesemia and attenuated by magnesium supplementation. Am J Cardiol. 1997:79:768-772.

11. St John Sutton M, Weyman A. Mitral valve prolapse prevalence
and complications: an ongoing dialogue. Circulation. 2002;106:1305-1307.