Pamela Jacquet-Davis, MD
Few disorders have evoked more interest and controversy over the last 3 decades than mitral valve prolapse. Mitral valve prolapse occurs more frequently in women than men, occurs at any age, and is the most common cardiac valvular abnormality. The diagnosis of mitral valve prolapse is generally made by detection of typical auscultatory or echocardiographic Jindings. However, many patients with mitral valve prolapse present to the physician with a variety of features that together constitute a mitral valve prolapse syndrome, thus a classi$cation of patients with mitral valve prolapse has been proposed: Anatomic mitral valve prolapse includes patients with a wide spectrum of mitral valve abnormalities from mild to severe. Symptoms and physical findings in these patients are directly related to mitral dysfunction and progressive mitral regurgitation. Mitral valve prolapse syndrome refers to the occurrence of symptoms such as palpitations, chest pain, fatigue, exercise intolerance, dyspnea, and syncope that cannot be explained on the basis of the mitral valve abnormality alone in patients with mitral valve prolapse. The pathogenesis of these symptoms is thought to be related to metabolic neuroendocrine dysfunction. Themostimportant therapeutic approach in patients with mitral valve prolapse relates to the identijication of those patients at risk for complications and reassurance of those patients with benign disease. (Prim Care Update Ob/Gyns 19%; 2:1-5) From the University cine, Tucson, Arizona.
The integrity and normal function of the mitral valve depends on several factors, the most important of which are the shape and size of the valve leaflets and annulus, the length and integrity of the chordae tendineae, and the normal contractile function of both the papillary muscles and the left ventricular muscle with which the chordae tendineae join. With its function dependent on so many delicately balanced factors it is not surprising that the mitral valve mechanism may often malfunction. The most common cause of such malfunction is prolapse of part or all of one or both cusps of the mitral valve into the left atrium during systole. Several mechanisms are responsible for prolapse of the leaflets, including papillary muscle rupture in myocardial infarction, ruptured chordae tendineae in bacterial endocarditis, or abnormal left ventricular wall motion in the setting of myocardial ischemia. These mechanisms are classified as secondary mitral valve prolapse. In the majority of cases, mitral valve prolapse is due to an inherited, autosomal dominant abnormality of the mitral leaflets and supportive chordae tendineae and is classified as primary mitral valve prolapse. Mitral valve prolapse may be seen as a feature of several syndromes in which a widespread defect in collagen is present as in Marfan and Ehlers-Danlos syndr0mes.l Furthermore, patients with primary mitral valve prolapse may have systemic features similar to those of patients with inheritable connective tissue disorders such as deformity of the anterior chest, large arm span compared with height, and joint hypermobility. Mitral Elsevier
valve prolapse can also be associated with atria1 septal defect, atria1 aneurysm, and noncardiac disorders such as Graves disease, sickle cell disease, or muscular dystroPhYa2
Prevalence Mitral valve prolapse is common and is probably the single most frequent cause of abnormal auscultatory findings in the heart. The lack of uniform criteria for diagnosis of mitral valve prolapse, the use of different study designs, and the different populations in which mitral valve prolapse has been studied make it difficult to reconcile discrepant conclusions about the significance of a finding that may occur in as many as 5 million people in the United States. As a result, the exact prevalence of mitral valve prolapse is unknown. An additional feature that contributes to variance between studies of mitral valve prolapse is ascertainment bias. Referral series in which patients undergo echocardiography as a result of symptoms or clinical features are more likely to indicate a high prevalence of mitral valve prolapse. Selection bias can also play a role in studies of recruited volunteers who, by virtue of troubling symptoms or a murmur dating back to childhood, may be more likely to respond to an advertisement soliciting study participants. Population-based studies are least subject to these difficulties and typically report lower prevalence estimates of mitral valve prolapse. A reasonable conclusion from published surveys is an incidence of 6% in adult women, who make up two-thirds of subjects, and 1
an overall incidence of 4% in the adult population.3 In general, there is a female to male predominance of about 2:1. Varying incidences depending on the sex and age of patients studied have been reported. The Framingham Study demonstrated a marked predominance among women: 18% in those aged 20 to 29 years, 13% in those aged 30 to 49 years, and 5% to 7% in those aged 50 to 70 years. Women over the age of 80 years who were studied had an incidence of 1.4%.4 In adolescence, the prevalence of mitral valve prolapse is at its greatest at about 15%. In contrast, age appears to show little relation to the prevalence of mitral valve prolapse in men, with relatively low rates of approximately 3% noted throughout adult life.5 Several factors may help explain the decline in mitral valve prolapse prevalence with age in women. It is most likely that mild posterior leaflet displacement in systole represents a normal pattern of mitral motion common in young, thin persons. In a study by Meyers et al,” strong evidence of the association of body weight and the prevalence of mitral valve prolapse was found. Nine of 28 patients with anorexia nervosa had mitral valve prolapse, and seven of the nine patients regained weight such that they reached 80% of expected body weight. All seven lost echocardiographic evidence of mitral valve prolapse when reevaluated after weight gain. Two of the patients lost weight again so that they were below 80% of their expected body weight. Evidence of echocardiographic mitral valve prolapse again appeared in these two patients. The disappearance of mitral valve prolapse with weight gain could explain the striking decline in the prevalence of this disorder in women with increasing age (because the increase in age is generally accompanied by an increase in weight). Alternatively, scarring and 2
tethering of chordae tendineae or leaflet fibrosis occurring with age may also cause loss of characteristic prolapse.
Diagnosis The diagnosis of mitral valve prolapse should be based on history, physical examination, echocardiography, and phonocardiography. Most patients are asymptomatic. The condition is often discovered incidentally during a physical examination for employment or school. A detailed history is important because mitral valve prolapse may be inherited and family members may have phenotypic features of disorders such as Klinefelter, Marfan or Ehlers-Danlos syndromes7 Auscultatory findings in patients with mitral valve prolapse depend on the degree of mitral valve dysfunction. Typical findings include an apical nonejection systolic click with or without a mid- to late-systolic murmur that shifts in timing with posture. The auscultatory change with posture is the key to the diagnosis of mitral valve prolapse and distinguishes it from almost all other cardiac diagnoses. Systolic clicks vary considerably from patient to patient and even within the same patient from time to time. They may appear or disappear as the patient changes posture and make different types of sounds in different patients. In the upright or standing position, the systolic click moves toward the first heart sound and the systolic murmur becomes longer and often louder. In some patients, the auscultatory findings may not be appreciated until the patient stands. Prompt squatting moves the click and murmur later in systole similar to supine auscultatory findings (Figure 1). The posture induced auscultatory changes are particularly dramatic when the listener does the stand-squat-stand maneuver with the patient, listen-
Figure 1. Schematic presentation of dynamic auscultation in the standing position (A) and schematic presentation in the squatting position (B). (S,, first heart sound; C, click; S,, second heart sound; jagged lines, murmur.)
ing the entire time.’ This is the most valuable maneuver in making the auscultatory diagnosis in mitral valve prolapse. Some patients, particularly older patients or patients who have restricted mobility, may not be able to perform the standsquat-stand maneuver quickly and easily enough to be helpful. In such cases, the Valsalva maneuver is a useful alternative, with the straining phase being equivalent to standing and the post-release phase similar to squatting. If the listener has similar limitations, he or she may sit in a chair while the patient, facing the listener, performs the standsquat-stand maneuver. The postural auscultatory changes occurring in mitral valve prolapse are primarily related to changes in left ventricular volume. Left ventricular volume is significantly less with the patient in the upright position compared with the supine position. Any maneuver that reduces ventricular volume exaggerates the prolapse and the auscultatory findings, and any maneuver that augments ventricular volume minimizes prolapse and auscultatory findings. Other techniques and Prim
Table 1. Auscultatory
Maneuver Left lateral position Sitting Standing Squatting Hand grip Leg raising Anxiety Exercise Valsalva-strain Valsalva-release + S,, movement not change.
Louder + Sl -+ Sl -+ s2 Louder, + s2 + s, + Sl -+ Sl -+ s2
the first heart sound:
that manipulate left ventricular volume and can be used in the diagrmsis of mitral valve prolapse are elevating the legs, isometric hand grip, and the Valsalva maneuver [Table 1). To confirm the diagnosis of mitral valve prolapse, two dimensional and motion mode echocardiography is used. Besides confirming the diagnosis, echocardiography is also helpful in assessing mitral leaflet thickness and mitral annulus dilatation in diagnosing chordae rupture, and in assessing left ventricular and left atria1 size. Doppler ultrasound is helpful in assessing the presence and severity of mitral regurgitation and regurgitation in other valves. Electrocardiogram and chest x-ray may reveal nonspecific abnormalities but are not diagnostic of mitral valve prolapse.
Classification and Management MITRAL
This classification includes the term “floppy mitral valve” referring to the surgical and pathologic findings of expanded valve leaflet area with elongated or abnormal chordae tendineae, a dilated mitral annulus, and characteristic structural changes in the valve leaflets (Table 2). Symptoms and physical findings of patients in this classification are Volume
Murmur Louder Louder, longer Louder, longer Later Louder, C later Later Louder, longer Louder, longer Softer, longer Louder, later
? + S,
+ Sz, movement
the second heart sound:
directly related to mitral valve dysfunction and complications associated with progressive mitral regurgitation.g The slow progression of mitral regurgitation that can occur in patients with mitral valve prolapse results in a pansystolic murmur and loss of the click. Such a sequence of events represents progressive stretching and distortion of a myxomatous valve until it becomes the true floppy valve well known to the surgeon. Left atria1 and left ventricular morphologic changes can occur due to enlargement from volume overload and result in the development of ventricular pump failure. The damaged surface of the mitral valve and endocardium can contribute to the development of bacterial thrombotic endocardial lesions with embolic and infection potential. Cardiac arrhythmias may occur due to the stretching of the atria1 conductive system, papillary muscle stretch, tension, or fibrosis. Risk factors for the development of complications in patients with mitral valve prolapse include, thick, redundant mitral leaflets, sex (male > Table 2. Prolause
Click syndrome Click murmur syndrome Barlow syndrome Floppy valve syndrome Billowina nosterior leaflet svndrome Ballooning of the mitral valve leaflets
female), age (>50 years), and a mitral systolic murmur. Asymptomatic patients with isolated clicks usually have mitral valve prolapse of limited clinical significance and are unlikely to show disease progression. In general, patients with a systolic murmur should receive antibiotic prophylaxis for diagnostic and therapeutic procedures that may create bacteremia. The prevention of endocarditis is the major consideration in these patients. They should also be encouraged to maintain the best possible oral hygiene, because poor dental hygiene, periodontal infections, or oral mucosal ulcers caused by ill-fitting dentures can cause bacteremia without dental procedures. Recommendations for prophylaxis, have been published by numerous authoritative groups.“” Patients with clicks, mid- to latesystolic murmurs, and increased mitral valve surface area and annulus size have mitral valve prolapse with mild to moderate mitral regurgitation, with a greater potential for progression. Therapeutic considerations in these patients include preventing endocarditis and recognizing progressive mitral regurgitation. Progressive mitral regurgitation with the development of significant or refractory congestive failure is usually associated with left atria1 enlargement progressing to left atria1 failure and the development of chronic atria1 fibrillation. Young women who develop clinical manifestations of retinal, cerebral, or peripheral emboli should discontinue oral contraceptive use, abstain from tobacco use, and be placed on antiplatelet therapy, as well as be considered for anticoagulation therapy. If medical therapy directed at atria1 fibrillation (control of ventricular rate) and treatment of the congestive failure associated with mitral regurgitation (vasodilators and diuretic therapy) are of limited benefit, then surgery should be consid3
ered. Ventricular arrhythmias require individual assessment and identification of precipitating factors. Caffeine or other stimulants such as alcohol, tobacco, and sympathomimetric drugs should be avoided in mitral valve prolapse patients especially those with tachyarrhythmias. Supraventricular tachycardia can be suppressed with digitalis, calcium channel blockers, or P-blockers singly or in combination. When recurrent arrhythmias are refractory to medical management or the patient is intolerant to therapy, pacemaker devices may be helpful.
MITRAL VALVE PROLAPSE SYNDROME The term mitral valve prolapse syndrome refers to patients with mitral valve prolapse and the coexistence of symptoms that cannot be explained on the basis of valvular dysfunction alone. The symptoms include palpitations, orthostatic rhythm disturbances with syncope and presyncope, chest pain, fatigue, poor exercise tolerance, dyspnea, and neuropsychiatric symptoms.8Tg The presenting symptom complex of patients with mitral valve prolapse syndrome suggests the existence of a hyperadrenergic state, autonomic dysfunction, metabolic disturbance, or combinations of these factors. Increased adrenergic activity, abnormal catecholamine regulation, and adrenergic hyperresponsiveness observed in some patients with mitral valve prolapse syndrome suggests that some symptoms may be catecholamine related or mediated. In other patients with the syndrome, altered vagal tone, adrenergic receptor activity or baroreceptor activity may play a role in the pathogenesis of symptoms. Patients with mitral valve prolapse syndrome have low intravascular volume and have been observed to have a subnormal increase
Table 3. Principles
of Management for Mitral Valve Prolapse Syndrome
Explain and reassure Avoid volume depletion and the use of diuretics Avoid catecholamines or other cyclic adenosine monophosphate stimulants Avoid drugs that may increase adrenergic receptor sensitivity (eg, thyroxine) Avoid long-term therapy Initiate an exercise program
in renin and aldosterone in response to volume depletion.‘,ll These findings may help explain why certain mitral valve prolapse syndrome patients are more susceptible to volume depletion (eg, acute illness, diuretic use, dehydration, and surgical or traumatic blood loss). The cyclic volume changes in menstruating women and the protracted volume changes in pregnancy may modify their sense of well being or alter symptoms that are related to volume regulatory mechanisms. Thus in mitral valve prolapse syndrome, there may exist alterations in the heart, the kidneys, the adrenals, and the autonomic nervous system that coexist and interact, creating a neuroendocrine cardiovascular process that may account for symptoms unexplained on the basis of the valvular abnormality alone.ll The basic principles of managing patients with mitral valve prolapse syndrome are shown in Table 3. A concerned approach by the physician is important because patients will have fear, uncertainty, and a confusion about alterations in body function as the motivating factors in seeking medical attention. The most important steps in their management are to take a detailed medical history and perform a thorough physical examination. Symptoms may occur against the backdrop of physical or emotional stresses in life, quite often with a precipitating event such as trauma, surgery, marital separation, stressful job, or impending job change or loss. Suggestions for stress modification and reestablishment of order in the patient’s life, provided by the physi-
cian, may be of enormous value in diminishing the patient’s symptoms. The removal of catecholamines and cyclic adenosine monophosphate stimulation by abstaining from cigarettes, alcohol, caffeine, and over the counter drugs containing epinephrine and ephedrine is important in decreasing the arrythmias. If there are no serious exercise induced arrythmias, enrollment in a graduated aerobic exercise program may be accompanied by gratifying psychological and physiological benefits. Although the mechanism for the beneficial effect of exercise is unknown, it has been suggested that the catecholamine receptor system may play a role because catecholamine levels are altered during exercise. Low dose p-blockers administered over a short time during stressful periods may be beneficial if there are no contraindications for use. A careful explanation of the physician’s findings, an explanation of what is known about the mechanism of symptoms, and the best possible answers to the anxious patient’s list of questions constitute the cornerstone of long-term management. This classification is clinically useful; it stratifies symptomatic patients with mitral valve prolapse who have symptoms related to autonomic dysfunction from patients whose symptoms are related to progressive mitral valve dysfunction, it identifies a group of patients with mitral valve dysfunction and autonomic dysfunction who require consideration for antibiotic prophylaxis for endocarditis in addition to other forms of treatment, and it Prim
MITRAL VALVE PROLAPSE Table 4. Classification
of Mitral Valve Prolapse Anatomic
Mitral Valve Prolapse
Common mitral valve abnormality with a spectrum of structural and functional changes, mild to severe The basis for: Systolic click; mid-late systolic murmur Mild or progressive mitral valve dysfunction Progressive mitral regurgitation, atria1 fibrillation, congestive heart failure Infectious endocarditis Embolic phenomena Characterized by long natural history May be heritable, or associated with heritable disorders of connective tissue Conduction system involvement, possibly leading to arrhythmias and conduction defects
defines a group of symptomatic patients who need reassurance from physicians about the benign course of their disease (Table 4).
Conclusion Mitral valve prolapse is being diagnosed with increasing frequency although the exact prevalence is unknown. Currently, a classification of mitral valve prolapse is suggested based on anatomic characteristics and a symptom complex. Those patients classified as having anatomic mitral valve prolapse usually demonstrate a connective tissue disorder involving the mitral valve size, annulus, and chordae tendineae. In most of these patients a systolic murmur is present and prophylactic antibiotics are given for procedures that are likely to cause bacteremia. These patients are likely to demonstrate mitral regurgitation symptomatology. Patients who are classified as having mitral valve prolapse syndrome, however, may present with a constellation of symptoms such as chest pain, fa-
Patients with mitral valve prolapse Symptom complex: chest pain, fatigue, palpitation, arrhythmia, dyspnea, exercise intolerance, neuropsych symptoms Neuroendocrine or autonomic dysfunction may provide explanation for symptoms Mitral valve prolapse-a possible marker for autonomic dysfunction
tigue, dyspnea, and neuropsychiatric disorders with mild valvular
dysfunction. These patients do not progress to develop mitral regurgitation. It is important to educate and reassure mitral valve prolapse patients concerning the relatively benign disease course most of them will have.
References 1. Glesby MJ, Pyeritz RE. Association of mitral valve prolapse and systemic abnormalities of connective tissue. JAMA 1989;262:523-8. 2. Boudoulas H, Wooley CF (eds) Mitral valve prolapse and the mitral valve prolapse syndrome. Mount Kisco (NY): Futura Publishing, Inc., 1988. 3. Jeresaty RM. Mitral valve prolapse. New York: Raven Press, 1979. 4. Savage DD, Garrison RJ, Devereux RB, Castelli WP, Anderson SJ, Levy D. Mitral valve prolapse in the general population. 1. Epidemiologic features: the Framingham Study. Am Heart J 1983;106:571. 5. Devereux RB, Kramer-Fox R, Kligfield P. Mitral valve prolapse: causes, clinical manifestations and management. Ann Intern Med 1989; 11:305-7. 6. Meyers DC. Mitral valve prolapse in
Valve Prolapse Syndrome
anorexia nervosa. In: Meyers D (ed). Selected papers and recommendations of the Second International Conference on Eating Disorders. Sydney (Australia): Ashwood House Publishers, 1987. Pyeritz RE, Wappel MA. Mitral valve dysfunction in the Marfan syndrome. Am J Med 1983;74:797807. Singh RG, Capucci R, Roman MJ, Borer J, Hochreiter C, Devereux R. Mitral valve prolapse and risk factors for severe mitral regurgitation [abstract]. J Am Co11 Cardiol 1993; 21:242A. Braunwald E. The mitral valve prolapse syndrome. In: Braunwald E (ed). Heart disease. Philadelphia: WB Saunders, 1992:1935. Dajani AS, Bisno AL, Chung KJ. Prevention of bacterial endocarditis: recommendation by the American Heart Association, JAMA 1990; 264:2919. Boudoulas H. Mitral valve prolapse: etiology, clinical presentation, and neuroendocrine function. J Heart Valve Dis 1992;1:175-88.
Address correspondence and reprint requests to Pamela Jacquet-Davis, MD, University of Arizona, College of Medicine, 1501 N. Campbell Ave., Tucson, AZ 85724.