Mitral valve prolapse

Mitral valve prolapse

MITRAL VALVE PROLAPSE ABSTRACT.-Mitral valve prolapse is a common mitral valve disorder manifested clinically as a midsystolic click and/or a late ...

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MITRAL

VALVE

PROLAPSE

ABSTRACT.-Mitral valve prolapse is a common mitral valve disorder manifested clinically as a midsystolic click and/or a late systolic murmur (the click-murmur syndrome) and pathologically as billowing or prolapsing mitral leaflets (the floppy valve syndrome). Not only is it one of the two most common congenital heart diseases and the most common valve disorder diagnosed in the United States, but it is also prevalent throughout the world. Mitral valve prolapse may be associated with a variety of other conditions or diseases. Diagnosis of mitral valve prolapse should be made on clinical grounds and, if necessary, supported by echocardiography. The majority of patients with mitral valve prolapse suffer no serious sequelae. However, major complications such as disabling anghm-like chest pains, progressive mitral regurgitation, infective endocarditis, thromboembolism, serious arrhythmias, and sudden death may occur. Unless these serious complications occur, most of the patients with mitral valve prolapse need no treatment other than reassurance, inchul3ng those with atypical chest pain or palpitation unconfirmed by objective data. Therapy with a betablocker for disabling chest pain and/or arrhythmias and antiplatelet therapy for cerebral embolic events may be indicated. In occasional patients with significant mitral regurgitation surgery may be neces-rY-

IN BRIEF PREVALENCE Mitral valve prolapse is the most common valve disease in the United States. It is also a universal disease, described in nearly every country in the world. The prevalence has been reported to vary between 1% and 24%. PATHOLOGY

The essential pathological process in mitral valve prolapse is collagen dissolution with myxomatous degeneration in the principal support structure of the valve. Not only is the surface area of the myxomatous mitral valve much larger than normal, but the mitral 486

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annulus is also greatly dilated. The gross morphology of increased surface area, decreased density, and dilated annulus of the mitral valve explains the characteristic appearance of large, voluminous, and ballooning cusps in mitral valve prolapse. INHERITANCE

AND

GENETICS

There is strong evidence for autosomal dominant inheritance of mitral valve prolapse. Although mitral valve prolapse in virtually all instances is inherited and is the most common mendelian cardiovascular abnormality in humans, such demonstrations may not be consistent using the auscultatory and echocardiographic markers for phenotypic recognition. The latter may reflect differences in etiology of mitral valve prolapse or variability in expression of a single gene depending on interaction with environmental or other genetic factors. ASSOCIATED

CONDITIONS

AND

PATHOPHYSZOLOGY

Mitral valve prolapse may be primary or secondary. In spite of the multitude of seemingly unrelated diseases associated with mitral valve prolapse, it is possible to develop a unifying concept concerning the pathophysiology. The common denominator of the underlying mechanism for mitral valve prolapse is that the suspension apparatus of the mitral valve is too big for the size of the left ventricular cavity. CLZNZCAL FEATURES

Although most of the patients with mitral valve prolapse are asymptomatic or have vague complaints, occasional patients may have disabling symptoms of chest pain, easy fatigue, palpitation, dyspnea, dizziness, or syncope. The diagnosis should always be made on clinical grounds. The typical midsystolic click and/or late systolic murmur are characteristic, although one or both may not always be present at each examination. It is therefore important that auscultation be carried out in various body positions and in combination with various maneuvers, especially Valsalva’s and squatting, before one concludes that a late systolic murmur is not present. DIAGNOSTIC

ZNVESTZGATZONS

Among the various methods of diagnostic investigations, both noninvasive and invasive, echocardiography has been most useful. DM, September

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However, overuse or abuse should be avoided. Echocardiography should not be a substitute for careful clinical auscultation. A ‘negative’ echocardiogram does not exclude nor does a ‘positive’ echocardiogram clinch the diagnosis. Cardiac catheterization and angiography are seldom necessary for the diagnosis of mitral valve prolapse. However, on rare occasions when the patient’s chest pain is indistinguishable from angina due to coronary artery disease, the latter may require selective coronary arteriography for a definitive diagnosis. COMPLKATIONS Although the vast majority of patients with mitral valve prolapse suffer no serious consequences, several major complications may occur: Chest pain is the most common presenting symptom that brings the patient with mitral valve prolapse to the doctor. The possible mechanisms for chest pain include (1) mechanical stress on papillary muscle; (2) coronary artery spasm; (3) left ventricular dysfunction; (4) myocardial oxygen supply/demand imbalance; (5) coexistent coronary artery disease; (6) psychosomatic complaints; and (7) extracardiac causes such as chest wall syndrome and esophageal motility disorders. Mitral regurgitation, although usually mild, may progress in certain individuals. It is usually the result of infective endocarditis or ruptured chordae tendineae. With or without chordal rupture, mitral valve prolapse is the most common cause of pure mitral regurgitation in patients undergoing mitral valve replacement nowadays. Infective endocarditis is a rare but serious complication of mitral valve prolapse. Antibiotic prophylaxis should be advised for all patients with mitral valve prolapse at the time of any procedure that is associated with bacteremia, at least if the patient has a murmur of mitral regurgitation at any time. Thromboembolism is a recognized complication of mitral valve prolapse. Up to one third of patients under 45 years of age with transient cerebral ischemic attacks have mitral valve prolapse as compared to 7%-8% in the control population. Serious arrhythmias constitute one of the most frequent complications in mitral valve prolapse. They are the most probable mechanism for sudden death associated with mitral valve prolapse. TREATMENT Most of the patients with mitral valve prolapse need no treatment other than reassurance. Endocarditis prophylaxis is advisable in all patients with a systolic murmur suggestive of mitral regurgitation. 488

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Therapy with a beta-blocker is indicated in patients with disabling chest pains and/or cardiac arrhythmias. Antithrombotic and antiplatelet therapy should be considered in patients with cerebral embolic events. In occasional patients with significant mitral regurgitation who are not responsive to medical treatment, surgical intervention may have to be considered. Repair is preferred to replacement.

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Tsung 0. Cheng, M.D., is a salutatorian graduate of the University of Pennsylvania School of Medicine at the St. John’s University, Shanghai, China. After receiving a Masof ter of Science (Medicine) degree from the University Pennsylvania in Philadelphia and completing a residency in internal medicine at the Northwestern University Division of Cook County Hospital in Chicago, he undertook fellowships in cardiology and cardiopulmonary physiology at the Harvard Medical School and The Johns Hopkins University School of Medicine. In 1956-1957 Dr. Cheng was an instructor in cardiology at the Massachusetts General Hospital in Boston under Dr. Paul D. White. He then joined the faculty of the State University of New York Downstate Medical Center in Brooklyn where he worked with Drs. Zsidore Snapper and William Dock. At present he is a Professor of Medicine at The George Washington University and Health Sciences in Washington, School of Medicine D.C. Dr. Cheng is board-certified in internal medicine and cardiovascular disease, and a Fellow of the American College of Physicians, American College of Cardiology AmeriHeart Associacan College of Chest Physicians, American tion Council on Clinical Cardiology, American College of AngioZogv, International College of Angiologv, and Society for Cardiac Angiography. Among his numerous honors are Honorary Professor at Shanghai Second Medical University, Shanghai, China; Visiting Professor at Peking Union Medical College, Beijing (Peking), China; and Advisor at Guangdong Provincial Cardiovascular Institute in Guangzhou (Canton), China. Dr. Cheng is an associate editor of Angiology and a senior editor of Vascular Medicine. He is the editor-in-chief of the recently published book entitled The International Textbook of Cardiology in which he coauthored a chapter on mitral valve billowing and prolapse with Dr. John B. Barlow. DM, September

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MITRAL

DEFINITION

VALVE

AND HISTORICAL

PROLAPSE

BACKGROUND

Mitral valve prolapse (MVP) is a common mitral valve disorder that manifests clinically as a midsystolic click and/or a late systolic murmur (the click-murmur syndrome) and pathologically as a billowing or prolapsing mitral leaflet(s) (the floppy valve syndrome). Although the entity was recognized relatively recently, it received only one sentence of mention in the latest edition of Friedberg’s Diseases of the Heart, published in 1966.’ The syndrome was probably not new but had been present since antiquity.’ Unfortunately, it remained buried under different names for a long time,’ and then was misinterpreted in the recent past as being extracardiac.s6 It was not until the early 1960s when Reid’ and Barlow et al.,8 from South Africa, called attention to the mitral origin of the mid- to late systolic click or murmur, or both, that the syndrome was recognized and correctly labeled. Barlow and Pocock, who described the clinical features in detail, called it “billowing” mitral leaflet syndrome,g and Criley and co-workers” introduced the term “prolapse,” now widely accepted, to describe the mitral valve abnormality * Since then numerous reports have appeared in the literature, making MVP one of two most common congenital heart diseases,” if not the commonest valve disease,13 in the United States. PREVALENCE MVP is not only the most frequently diagnosed valve disorder in the United States but it is a universal disease, having been described in nearly every country in the world. The reported prevalence has varied from 1% to 24% of the population (Table 1). It is as common in blacks as in whites,28,36,41 more common in women than men,‘8, 20,21,28,30,31,34,41 and more common in the young than in the old, especially in females.40 Young women in the Framingham study *The word “prolapse,” though quite descriptive from a medical standpoint, can sometimes sound frightening to the patient, who may interpret “prolapse” in both English and Chinese Wuochui) to have an ominous meaning.” DM, September

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TABLE 1. Prevalence of M V P Around the World CO”h!TRY

Australia’4 BraZili Britain’“* BritainI Britainl’t Canada” China (Hans in Sichuan?’ China (Kazaks in Xinjiang?’ China (schoolchildren in Guangdong?’ Denmarkz3 Francez4 German?* Polandz6 Turkefl Italy Italy (blacks?’ Italy (athlete#’ Japan (schoolchildre#’ Japan31 Japan”‘* Russia33 Spain% South Africa3’ South Africa (blacks)36 Sweden3’ USA3-’ USA (black@ USA (health SLIIV#

MALE

FEiWALti

(90)

(90)

4

4

OVERALL

I% 1

4

4 2 3.9

5.2

2.2 2.8

6.3 7.7

5 4.5 22 4.3 5.3 1.9 7 6

0.7

3.3

0.78 1x* 11

1.23 4x* 8

1x

2x

7 3 9

8 6.2-17 24 15.4

4 7.6 1.8 1.4 10 1 7.5 11 2.64 2~ 0.36 4.3 14.3 17.9 7.4 17

*Echocardiographic studies tAutopsy studies. *Expressed as a ratio.

from the United States constitute the largest epidemiologic study 17% of women in group of individuals in the general population: their 20s had MVP. The prevalence decreased to 1% of women in their 8Os, while men had a prevalence of 3% at all ages.4o Why MVP is more common in females than males is not entirely clear, although smaller left ventricular size3g’43 and lower body weightM in women may play a role. MVP is the most common (7%) cardiac abnormality observed echocardiographically in stable newborn girls.* The secondary fibrosis of the mitral leaflets and chordae tendineae, which has been observed in some pathologic series” and also suggested by the de492

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creasing magnitude of MVP on echocardiographic follow-up of patients over long periods of time,46 may explain the reduced frequency of Mvp diagnosed in older patients. ‘MVP is very prevalent in athletes1g’2g and soldiers.47848 The incidence in athletes from two echocardiographic studies was 10%” and 22% .I9 MVP is the main cause of sports-associated cardiologic morbidity in the British Army147 especially syncopeP8 It seems apparent that the widely differing prevalences reported from different parts of the world depend in part on whether the study was prospective or retrospective, whether it was a part of health survey4’ or a preselected population,1g’2s whether it was a surgical”’ or autopsy18’31 series, differences in age and sex,4o differences in races,‘l’ 28,36,41 and methods of diagnostic examinationauscultatory, echocardiographic,16, 2’S32 or angiographic .50,51 PATHOLOGY Patients with MVP have an anatomically “floppy” mitral valve (Fig 1). The mitral valve shows redundant leaflets with domes protruding toward the left atrial cavity (Fig 2). When the domes show a distinct overshoot, the condition produces an anatomic substrate for mitral insufficiency. However, not all floppy mitral valves diagnosed either by the pathologist in the autopsy room or by the surgeon in the operating room will necessarily have been insufficient during life. The essential pathologic process in MVP is collagen dissolution with myxomatous degeneration in the principal support structures of the valve-a continuous complex of chordae tendineae and pars fibrosa-the so-called dyscollagenosis.” Characteristically the affected leaflets are voluminous, redundant, and thickened. Not only is the surface area of anterior and posterior valve cusps of myxomatous mitral valves from patients with MVP, especially those with significant mitral regurgitation, much larger than in normal controls,52 but the mitral annulus is also greatly dilated?3 The gross morphology of increased surface area, decreased density, and dilated annulus of the mitral valve explains the characteristic appearance of large, voluminous and ballooning cusps seen on echocardiograms and angiocardiograms and in the operating or autopsy room. INHERITANCE

AND GENETICS

Since its first recognition in the early 196Os, the familial occurrence of MVP began to gain ready acceptance. After Barlow and Bosman54 in 1966 described a kindred in which six of 17 relatives studied were affected, several families of affected kindreds in two or three generations have been described,s”57 including some kindreds DM, September

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FIG 2. Prolapsing mitral valve viewed from left atrium during open heart operation (From Barlow JB, Cheng TO: Mitral valve billowing and prolapse, in Cheng TO: The lnternafional Textbook of Cardiology. New York, Pergamon Press, 1986, pp 497-524. Used by permission.)

in which everyone had MVP (the “all-in-the-family” phenomenon) .‘, ” An autosomal dominant mode of inheritance was first suggested in 1969 by Hunt and Sloman?’ who used mainly auscultation and occasionally angiography to diagnose MVP. Subsequently 40% to 50% of first-degree relatives were found to be affected in several echocardiographic studies.6043 Further evidence for autosomal dominant inheritance is the finding in three series60’62’64 that one parent was affected in each pair studied. Expression of the MVP gene appears to be affected by both sex and age. Females have a higher incidence of MVP in the cumulative findings of available population surveys.14’ 3883gJ40,65 Similarly, more first-degree female relatives (56%66 to 60%60) than male relatives (23%66 to ~7%~‘) are affected. There is also an age-dependent onset with a decline in signs of IvlVP with increasing age, especially in young first-degree relatives.61’ 63,” An increased frequency of HLA antigens in patients with MVP was found by two groups67, 68 but not by two others6’, 7o Studies of other genetic markers such as dermal arches7” 71 have been even less conelusive . Although M W is inherited in virtually all instances and is the commonest mendelian cardiovascular abnormality in humans, demonDM, September

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t

ASSOCL4nON

Primary MVP” Floppy valve syndmme7* Connective tissue disorders Marfan syndmme72 Ehlets-Danlos syndrome” Pseudoxanthoma elasticurnS Turner syndmme” Relapsing polychondritis” Joint hypermobility syndmme’3 Collagen diseases Rheumatic endocarditis” Mitral stenosis74 Lupus erythematosus” Hernia” Coronary artery disease’S79 Cardiomyopathy Hypertmphic”,” Congestive” Myocarditis” Mitral commissumtomy”

DEFlNITE

TABLE 2. Conditions Associated With MVP*

Congenital heart disease (atrial septal defect, ventricular septal defect, patent ductus arteriosus, aorticpulmonary window, complete absence of left pericardium, membranous subaortic stenosis, supravalvular aortic stenosis, Ebstein’s anomaly, corrected transposition, infundibular pulmonary stenosis, Uhl’s anomaly?’ Pulmonary hypertensions5’86 Tricuspid valve pmlapses7-9’ Aortic valve pmlapseSsO, ” Bicuspid aortic valveg3 Athletes’9,Z9 Noonan’s syndmme35 Congenital prolonged QT syndmme35 Keratoconusw Hyperthymidism3’

PROBABLE ASSOCIATION

ASSOCIATION

Von Willebrand syndrome kwggested’os) (denied”“) Agoraphobia (suggested”~“2) (denied”3,“4) Anorexia nervosa kmconfitmed”5) Cachexia ktnconfirmed”5) Addison’s disease ktnconfirmed”5)

DEBATABLE

ASSOCIATION

*Note:

Direct

references

are given

only

Trauma43 Left atrial myxoma” Left ventricular aneurysm” Muscular dystmphy7’ Woltf-Parkinson-White syndmme7’ Skeletal abnormalities Straight back syndromes0 Pectus excavatum” Scoliosis” Other anomalies” Pulmonary emphysema35 Osteogenesis imperfecta3’ Inherited disorders of metabolism [Hunter’s and Hurler’s syndromes, San Fillip0 syndrome, Fabry’s disease, Sandhoff’s disease?’ Orthostatic hypotension83’84

DEFINITE

for conditions

not

mentioned

in Barlow

and

DEBATABLE

Pocock.%“*

Rheumatoid arthritisg5 Sickle cell disease’” Hypomastia” Stickler’s syndmmeg8 Migraineg9 Coronary artery spasm”’ Absent hypoplastic circumflex43, “’ Variations in cornnary origins”’ Fragile X syndmme’03 Klinefelter syndmme’04 Hypomagnesemia35 Dysautonomia’05”06 Intracranial aneurysm’07 Neumectomesodermal histodysplasia35

PROBABLE ASSOClATlON

ASSOCIATION

stration of such may not be consistent using the auscultatory and echocardiographic markers for phenotypic recognition. The latter may reflect differences in etiology of MVP or variability in expression of a single gene depending on interaction with environmental or other genetic factors.66 ASSOCIATED

CONDITIONS

MVP may occur in patients with a variety of associated conditions or diseases that affect the mitral valve apparatus at different levelsthe annulus, the leaflets, the chordae, the papillary muscles, the left ventricular (LV) wall or cavity-or may be associated with other unexplained factors (Table 2). On the other hand, many people with MVP have none of these underlying conditions. Therefore it is useful to classify MVIJ into primary (idiopathic) and secondary. Such a classification serves to clarify our understanding of the pathogenesis of MVP. In spite of the multitude of seemingly unrelated disease processes causing the same phenomenon, it is possible to develop a unifying concept concerning its pathophysiology.43 In MVP the underlying mechanism has one common denominator: the suspension apparatus of the mitral valve is too big, either absolutely or relatively, for the LV cavity to contain (Fig 3). With the progressive reduction in LV volume as systole continues, the mitral valve would inevitably prolapse into the left atrium were it not checked by tensing of the chordae by the papillary muscles, which must contract at the same time. If there is either “too much” valve apparatus, such as in primary, familial or floppy valve syndrome, Marfan syndrome, rheumatic fever, coronary artery disease with papillary muscle dysfunction, or following injury, or “too little” cavity size, such as in idiopathic hypertrophic subaortic stenosis, atrial septal defect, straight back syndrome, pectus excavatum, the normal female heart, or athlete’s heart, systolic prolapse of the mitral valve ensues. Indeed, Markiewicz et a13’ found smaller LV end-diastolic dimensions and volumes by echocardiography among healthy females with MVP than among those without MVP. Similarly, the apparent decrease in frequency of MVP among older people may be due to a gradual increase in LV dimension which “corrects” the ventricular-valvular disproportion and thus minimizes or even eliminates prolapse.l15 As indicated in Table 2, MVP has also been found in association with many other extracardiac conditions. Although in some the relationship is probably coincidental, in many the relationship is causal. Embryologically, the mitral valve differentiates into its final form during the sixth week of fetal life, which is the time when the vertebral column and thoracic cage are beginning their chondrifica498

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I NORMAL

MITRAL

coronary artery disease Congenital absence of circumflex Post-valvotomy Trauma

TOO MUCH OF VALVE APPARATUS

TOO LITTLE OF CAVITY SIZE IHSS Amy1 nitrite Atrial septal defect Mid-systolic contraction Straight back Pact& excavatum Normal female Athlete’s heart

I

I

I

FIG 3. Pathophysiology of mitral valve prolapse. (From Barlow JB, Cheng TO: Mitral valve billowing and prolapse, in Cheng TO: The lnternafional Textbook of Cardiology. New York, Pergamon Press, 1986, pp 497-524. Used by permission.)

tion and ossification.116’ I17 Therefore, any interference with growth at this stage of development will affect both the mitral valve and the bony skeleton, which explains the high incidence of skeletal abnormalitiessSs2 in patients with MVP. Another explanation for the association is that MVP is a manifestation of a forme fruste of Marfan syndrome, with a basic connective tissue disorder affecting the skeleton, the connective tissue, and the mitral valve. Supporting the conclusion that there is widespread connective tissue and collagen abnormality are the findings of a high association between M W and various connective tissue and collagen diseases, a high frequency of herniorrhaphy in men with MVP reported from Manchester, England,17 and a high frequency of concomitant prolapse of the tricuspid valve87-g1and aortic valve88-goJ ” due to an underlying connective tissue abnormality of the fibrous support of the heart valves. It is of interest that the development of the mitral and tricuspid leaflets, chordae, annulus, and septum secundum, as well as the thoracic vertebrae, ribs, and sternum, proceeds simultaneously between days 42 and 49 of embryonic life.l18 This might account for the high association of MVP with secundum atrial septal defect,43, 119-124as well as the fact that chronic underloading of the LV through the left-toright interatrial shunt predisposes to MVF’,43 and that chronic overloading of the right ventricle further deforms the LV, causing the coaptation zone of the mitral valve to become distorted.“’ DM, September

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Most patients with MVP are asymptomatic, and the discovery of one or more midsystolic clicks with or without a late systolic murmur at the apex is usually incidental or accidental. The typical patient is a young woman of tall stature, long arm span, and lean build, with a narrow anteroposterior chest diameter.lz5 Should they present complaints, they are often rather vague. Occasionally patients may have disabling symptoms of chest pain, easy fatigue, palpitation, dyspnea, dizziness, or syncope. Rarely, patients may present with other complications of MVP: arrhythmias, infective endocarditis, severe mitral valve regurgitation, congestive heart failure, and transient ischemic attacks. The characteristic physical findings of MVP are found on cardiac auscultation. The nonejection click is midsystolic or late systolic and may be single or multiple (Fig 4). When it is accompanied by a murmur, the latter is usually late systolic in timing and crescendo in character (see Fig 4). When the late systolic click is loud, it may sometimes be mistaken for the second heart sound and the late systolic murmur may consequently be mistaken for an early diastolic murmur (Fig 5). Rarely, the click may occur in early systole*3’126 or in early diastole (Fig 6).127-12sThe murmur may be pansystolic, with or without late systolic accentuation, in 8.6% of patients.13’ At times the murmur may assume a loud musical quality, simulating the honk of a goose131S132or the whoop of pertussis.132 Occasionally the murmurs may be audible to the patients themselves133’134 or across the room.134’*35 Osler first reported such an instance in 1880 in a 12year-old girl whose “remarkable whistling sound was distinctly audible at a distance of three feet two inches by measurement.“‘35 Osler also noted that there were times when the murmur completely disappeared. Because of the changing intensity and/or timing of either the click or the murmur, or both, with different body positions, it is important that auscultation be carried out with the patient in at least five positions-supine, left decubitus, sitting, standing, and squatting-to avoid missing the diagnosis.136 Dynamic auscultation with or without additional maneuvers, especially the Valsalva maneuver, should be employed not only to bring about the midsystolic click and/or late systolic murmur but also to differentiate primary MVP from other causes of late systolic murmurs such as rheumatic mitral regurgitation, idiopathic hypertrophic subaortic stenosis, aortic valvular stenosis, and papillary muscle dysfunction due to coronary artery disease (Table 3). Valsalva maneuver, amyl nitrite inhalation, and squatting are the three most helpful procedures that can easily be applied at the bedside. The murmur of MVP usually becomes longer and usually but 500

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TABLE

3.

Differential

Diagnosis of Late Svstolic Murmurs* MVP

Systolic

click

First sound Diastolic sound Post PVC

Mid-late -t Early click 1

Inspiration Valsalva

#

Handgrip Squatting Standing Amy1 nitrite

I

Rim3

IHSS

AS

PM0

0 J s3 t)

Rare S4

Early tf s4

Transient t s3 + s4

I

I i

9

; t

‘Abbreviations: MVP, mitral valve prolapse; RMR, rheumatic mitral regurgitation; IHSS, idiopathic hypertrophic subaortic stenosis; AS, aortic-valvular stenosis; PMD, papillary muscle dysfunction; post PVC, beat following a premature ventricular contraction; S,, diastolic gallop; S,, presystolic gallop; S, + S,, both diastolic and presystolic gallops. 0 indicates absent, c* indicates no change, 1 indicates decrease, T indicates increase, # indicates variable. tExcept in early-onset MVP, where first sound may be accentuated.‘37

not necessarily louder following the Valsalva maneuver, which almost always increases the murmur of idiopathic hypertrophic subaortic stenosis and decreases the murmur of aortic valvular stenosis. Amy1 nitrite inhalation may either increase or decrease the murmur of MSP, but it always softens the murmur of rheumatic mitral regurgitation. On prompt squatting the murmur decreases in MVP and idiopathic hypertrophic subaortic stenosis but increases in rheumatic mitral regurgitation. The effect of all these maneuvers is to influence the relationship between the telesystolic position of the mitral valve, on one hand, and LV volume, pressure, and contractiliv, on the other.43 With a smaller LV end-diatolic volume, the mitral leaflets tend to be closer to a position of prolapse which is attained sooner after the onset of systole; the converse is true with a larger end-diastolic volume. A change in LV contractility is another factor responsible for the variablity in timing of the murmur; an increase in the velocity of fiber shortening in the preprolapse period results in earlier timing and a decrease has the opposite effect. It should be emphasized that with certain maneuvers there may be different effects on the murmur, depending on which effects predominate or exert opposing influences. For example, increasing the peripheral vascular resistance and LV systolic pressure may increase the murmur of MM? because of the increased LV to left atrium gradient, or possibly the murmur may decrease in intensity if the LV end-diastolic volume becomes large enough to exceed the “critical” systolic prolapse volume. This is most probably the mechanism by which MVP may decrease or even disappear during pregnancy.138 Similarly, isometric handgrip 504

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exercise, which increases LV volume by increasing the impedance to LV emptying, causes the murmur of MVP to move toward the second sound. However, the increases in heart rate and contractility associated with handgrip would have the opposite effect.13’ Another example is amyl nitrite inhalation, following which the reduced LV size results in an earlier click and longer murmur but the lower LV systolic pressure tends to decrease the degree of mitral regurgitation and thus the intensity of the murmur.76 Not everything associated with a mid- or late systolic click is MVP. For the nonejection clicks to be specific for MVP, they must be mobile .140Some mid- to late systolic clicks may be caused by conditions other than MVP (Table 4); in each of these conditions the nonejection click is nonmobile. Dynamic auscultation is thus of paramount importance in the diagnosis of Mvp. A diastolic click may also be heard in MVP,74~127~*2s~ 153 the incidence varying between 15%ls3 and 5% to S%.12g The diastolic click may simulate an opening snap, especially since MVP may coexist with mitral valve stenosis,74 but simultaneous echocardiographic and phonocardiographic recordings are helpful in the differential diagnosis. The diastolic click in MVP represents a continued reverse ballooning of the prolapsed mitral leaflet which returns during early LV relaxation.74’ lzg It should not be confused with either the physiologic third heart sound frequently heard in normal young persons, especially those with a narrow anteroposterior thoracic diameter, or the pathologic diastolic gallop accompanying significant mitral valve regurgitation. On rare occasions an early diastolic decrescendo murmur may be heard.“’ It represents either a reduction in the mitral valve orifice size due to posterior prolapse at the onset of LV filling TABLE

4.

Nonejection

Clicks Due to Causes Other Than MVP

FXTRACARDIAC

INTRXARDlAC

Left-sided pneumothorz? Mediastinal emphysema’41

Pacemaker sound’42 Atrial myxoma Right’43-‘45 Left“+’ Complete heart block’46 AV dissociationz4’ Ventricular aneurysm Subvalvular“” Free wall“” Septal”” Cardiomyopathy Hypertmphir? Restrictive141 Aortic insufficiency’51~‘52

Pleumpericardial adhesions”‘4’ PericarditiG 14’ Splenic flexure syndmme14’

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or a continuation of mitral regurgitation after aortic valve closure during isometric relaxation when the pressure gradient between LV and left atrium persists.12s ELECTROCARDIOGRAPI-IY

AND VECTORCARDIOGRAFWY

The scalar electrocardiogram (ECG) in MVP is usually normal, whether or not the subject is symptomatic. However, nonspecific STT wave changes and inverted T waves are seen frequently in the inferior, and sometimes also lateral, leads-thus the terms “electrocardiographic-auscultation syndrome”‘54 and “auscultatory-electrocardiographic syndrome.“54 Q waves simulating myocardial infarction have been reported.54’ 155-157Although the exact mechanism of these changes is unknown, the following hypotheses have been proposed: (1) secondary myocardial ischemia resulting from increased tension on the papillary muscles and/or the underlying myocardium following the sudden tensing of the billowing mitral leaflet,g (2) associated coronary artery compression54 or spasm,100’157,15’ (3) autonomic imbalance, as normalization of the ST-T wave changes has been reported to follow propranolol administration,l” (4) concomicardiomyopatant coronary artery disease,76’77 and (5) underlying thy. 118,160Prolongation of the QT interval has been observed in MVP and, when present, may be important because of its association with ventricular arrhythmias.lfil Cardiac arrhythmias are common in MVP. All types of arrhythmias, including atrial and ventricular premature beats, supraventricular and ventricular tachyarrhythmias, accelerated atrioventricular conduction, sinoatrial arrhythmias, bradyarrhythmias due to sick sinus syndrome, and atrioventricular block of varying degrees, have been both described clinicallyX6” I62 and documented by electrophysiologic testing.163’164 The mechanisms of these arrhythmias are not clear, although the same hypotheses advanced for the genesis of abnormal ECG changes in MVP could also apply here, especially the abnormal stretch of the prolapsing mitral leaflet.‘65’166 The latter theory is particularly attractive, since mitral leaflets have been demonstrated to contain atrial-specific muscle fibers in direct continuity with left atrial myocardium, and spontaneous phase 4 depolarization of these muscle fibers in the anterior mitral leaflet in response to stretch, as has been demonstrated experimentally, may generate slow-response action potentials and sustained rhythmic action that propagates to the left atrial ~all.‘~~, 16’These properties may set the stage for left-sided bypass tracts and for re-entrant supraventricular tachyarrhythmia, the most common sustained tachyarrhythmia in M.vP.‘6g Finally, progressive left atrial and LV dilation from mitral regurgitation secondary to MVP further enhances the incidence of atria1 and ventricular arrhythmias.17” 171The Framingham study in506

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dicates a high prevalence of complex or frequent ventricular dysrhythmias during U-hour ambulatory ECG monitoring in subjects with MVP: more than 50% of the subjects with echocardiographically detected MVP had complex or frequent ventricular premature beats (Lawn grade 2 or higher) and 28% of such subjects had supraventricular tachycardias during such monitoring.172 However, these dysrhythmias were so common in subjects without MVP in the Framingham study that the excess of dysrhythmias in those with MVP did not reach statistical significance.“’ The relation of these dysrhythmias to sudden death will be discussed later. Exercise ECG, which is commonly used in evaluating patients with chest pain associated with MVP, may often be falsely positive in the absence of coronary disease. The prevalence of an abnormal exercise ECG varies from 10% to 60%, the overall prevalence being 33%173 to 40% .174The specificity of exercise ECG, however, can be greatly enhanced by prior administration of beta-blockers; in 86% of patients with MVP and positive exercise ECGs, the test became negative 1 hour after oral administration of 40 to 60 mg of propranolol.‘74 Exercise testing has also demonstrated arrhythmias in as many as 75% useful for detecting of tested subjects with MVP175; it is particularly dangerous arrhythmias that require medication to avoid sudden death.176 Vectorcardiographic abnormalities have been reported in 72% 177to 99%‘78 of patients with MVP. The reported abnormalities are in (1) the direction of the maximal QRS vector, especially in the horizontal plane, (2) the magnitude of the maximal QRS vector, (3) the maximal righward force and the maximal anterior force of the QRSs”e loop, (4) the morphology and contour of the QRSs^e loop, (5) the direction of the maximal T vector, (6) the morphology of the Ts^e loop, (7) the rotation and inscription speed of the Ts^e loop, and (8) the QRS-T angle .17’Vectorcardiographic analysis of atrial activation showed a decrease of total atrial activation time, about 13% less than normal, consistent with the hypothesis that MVP is secondary to widespread pathologic changes or is a consequence of neurovegetative imbalance.17’ ECHOCARDIOGRAPHY The development of echocardiography was one of the milestones in clinical detection of MVP. Presently, MVP is the most common abnormality found in patients referred for echocardiographic examination. The diagnostic features on M-mode echocardiography are: (1) posterior excursion of the leaflet(s) during late systole, (2) holosystolic hammocking of one or both mitral leaflets, (3) systolic anterior motion, followed by notching in midsystole and late systolic posterior motion,180’181 and (4) sudden posterior collapse of the anDM, September

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terior mitral leatlet in early systole as it attempts to contact the prolapsing posterior leatlet.13’ The first two are the most frequent and specific signs of MVP. A recent M-mode study’82 concluded that these two major echocardiographic signs of MVP, namely, late systolic posterior motion and holosystolic hammocking of the mitral leaflets, when combined as a single criterion, had a sensitivity of 85% and a specificity of 99%. Other signs, including systolic echoes in the mid-left atrium, systolic anterior motion, early diastolic anterior motion of the posterior mitral leaflet, and shaggy or heavy cascading linear diastolic echoes posterior to the mitral valve, although highly specific, are less common and occur always in combination with late systolic posterior motion or holosystolic hammocking. The finding of late systolic prolapse or holosystolic hammocking of the mitral valve has withstood the test of time and has proved quite specific with rare exceptions. Occasionally apparent posterior displacement of the mitral valve in patients with pericardial effusion due to systolic posterior swinging of the heart183 or in patients with dilated congestive cardiomyopathy’H’185 may superficially resemble, but should not be confused with, MVP. Echocardiographic MVP has also been reported during premature ventricular contractions in apparently normal subjects, but not with sinus beats.ls6 Although M-mode echocardiography has been a boon in the diagnosis of MVP, especially in its worldwide application in epidemiologic surveys, it has also created some confusion and controversies. The confusion arises from the observation that it is possible to produce “echocardiographic MVP” by an abnormal inferiorly directed orientation of the transducer187 and that minor degrees of late systolic posterior motion of the body of the leaflet are common in normal subjects.“’ Controversies result from the arbitrarily proposed criteria of 2 mm, 3 mm, or 5 mm of systolic posterior motion of the mitral valve below a line connecting the closure point of leaflets with the point of opening of the leaflets in diastole.*3”8581ss Because of the confusion and controversies introduced by the Mmode echocardiogram which visualizes only part, an “icepick” view, of the mitral valve, it is not surprising that the advent of two-dimensional echocardiography (2DE) with its spatial orientation was hailed with great enthusiasm for the diagnosis of MVP, for which purpose it has been considered by some16, 1go,1g1to be superior to M-mode echocardiography. Superior arching of the mitral leaflets above the plane of the atrioventricular ring, as represented by a line extending from the base of the aortic valve to the atrioventricular junction, is the most reliable indication of MLVP. When both the long-axis and four-chamber views are utilized (Fig 71, diagnostic accuracy is increased. Our experience with both types of echocardiography in the diagnosis of MSP has been somewhat at variance with that reported in others. We are seldom able to demonstrate MVP on echocardiog50s

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FIG 7. Long-axis (A) and four-chamber (6) two-dimensional echocardiograms showing prolapse of both mitral leaflets, especially the posterior (arrowhead). LV, left ventricle; LA, left atrium; RV, right ventricle; Ao, aorta. (From Barlow JB, Cheng TO: Mitral valve billowing and prolapse, in Cheng TO: The lnfernational Textbook of Cardiology. New York, Pergamon Press, 1986, pp 497-524. Used by permission.)

raphy in patients with isolated nonejection systolic click, but we agree that MVP can usually be confirmed in the presence of a constant, as opposed to a transient, late systolic murmur. Patients with holosystolic murmurs have relatively marked MVP, and this can invariably be shown on both M-mode echocardiography and 2DE.35 The role of Doppler in the diagnosis of MVP awaits further study.lgl Our attitude at present is that echocardiography is not a substitute for careful clinical auscultation, and that a “normal” echocardiogram does not exclude MVP, nor does an “abnormal” echocardiogram clinch the diagnosis. DM, September

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Among the other valuable contributions of MVP, three deserve special mention:

by 2DE in the diagnosis

1. Identification of hIVP as the most frequent cause (30%), rather than rheumatic mitral valve disease (28%), of clinical mitral regurgitation,‘s2 a finding supported by a more recent surgical pathologic study which reported even a higher incidence, 62% and 3%) respectively.4s 2. Discovery of associated prolapse of the tricuspid valve in up to 50% and of the aortic valve in up to 20% of patients with -,87-92,193,194 and of the much more rarely encountered association of pulmonary and mitral valve prolapse.l”, lg6 3. Diagnosis of ruptured chordae and vegetations in infective endocarditis, which will be discussed in the section on Complications . PHONOCARDIOGRAPHY, APEXCARDIOGRAPHY, SYSTOLIC TIME INTERVALS

AND

Phonocardiography, which has now been replaced by echocardiography in the diagnosis of MVP in most institutions, remains the most useful, simple, noninvasive tool in the diagnostic evaluation of patients with suspected or confirmed MVP. Not only is it simple and inexpensive to perform, it is accurate in timing the nonejection click and the late systolic murmur. Phonocardiography is particularly useful in following and documenting the responses of the nonejection click and the late systolic murmur to the various maneuvers discussed earlier. The apexcardiogram may show a sharp midsystolic dip or retraction coincident with the midsystolic click (see Figs 4 and 5) which results from tugging of chordae on papillary muscles at the time of peak prolapse of the mitral leaflets.s’1s7’1g8 The systolic dip and systolic click move directionally together as an effect of standing or amyl nitrite inhalation.ls7’ ls8 It should be noted that the doublepeaked apical systolic impulse is also found in hypertrophic cardiomyopathy. measured systolic time intervals at supine Kraus and Naughton”’ rest before and immediately after multistage treadmill exercise in 12 subjects with MVP. In 9 subjects, an increase of 1 to 49 msec was observed in LV ejection time following exercise. They concluded that exercise elicited or evoked evidence of LV dysfunction, which, to them, is a concomitant of h4VP.

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Because the presence of LV contraction abnormalities in patients with MVP has suggested a myocardiopathic mechanism, and because symptoms and both resting and postexercise ECG abnormalities associated with MVP may not be easily distinguishable from those of coronary artery disease, the role of radionuclide scintigraphy with either thallium perfusion scan2oo-2o3 or technetium-99m gated blood pool scan204’205has been assessed as a possible adjunct in the noninvasive evaluation of patients with MVP. When the results are negative, i.e., when there are no exercise-induced perfusion defects on thallium scan and no wall motion abnormalities or inappropriate response of ejection fraction following exercise on gated blood pool scan, the diagnosis of primary MVP unassociated with coronary artery disease or cardiomyopathy seems to be certain.201-205 The converse, however, is less certain, since false positive results have been reported with both thaBium206208 and gated blood poo12o582ogscans in patients with MVP and normal coronary arteriograms. CARDIAC

CATHETERIZATION

The majority of patients with uncomplicated MVP and no or mild mitral regurgitation have normal hemodynamic measurements at cardiac catheterization,210 including LV end-diastolic pressure, cardiac index, ejection fraction, contractility index (stroke work per end-diastolic volume), and preejection period&V ejection time index.‘l’ However, elevated LV end-diastolic pressure has been reported in some series even in the absence of significant mitral regurgitation,16” 211perhaps a reflection of the myocardial dysfunction associated with MVP in these patients. The presence of significant mitral regurgitation may be indicated by a prominent V wave in the left atrial or pulmonary artery wedge pressure tracings, elevated LV end-diastolic pressure, and reduced effective cardiac index. Myocardial lactate abnormalities (lactate production or less than 10% lactate extraction) have been described in MVP both at rest and during atrial pacing.21S215 ANGIOGRAPHY Left ventricular for the diagnosis one or both mitral regurgitation (Fig inordinately high

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cineangiography has been the reference standard of MVP. Typically there is end-systolic prolapse of leaflets with or without varying degrees of mitral 8). However, more recent studies51J216 indicate an incidence of angiographic evidence of MVP, espe-

511

FIG 8. Typical doughnut-shaped appearance of prolapsing triscalloped posterior leaflet and anterior leaflet of the mitral valve demonstrated on left ventriculography in right anterior oblique projection.

cially of the posterior mitral leaflet, in a variety of cardiac disorders, yielding a large discrepancy among clinical, echocardiographic, and angiographic findings suggestive of MVP. Particular attention to the mitral fulcrum and fornix is important in differentiating pseudoprolapse from true MVP. The mitral fulcrum is the point of attachment of the mitral leaflets to the annulus, and the fornix is that part of the LV between the fulcrum and papillary muscles. The mitral fulcrum is identifiable angiographicatly in the right anterior oblique projection by contrast media trapped in the recess between the leaflet and the adjacent endocardium (Fig 9).‘17 The diagnosis of MVP is made when there is posterior and inferior para-annular displacement of the mitral leaflet beyond the level of the mitral fulcrum during systhe importance, tole. More recent report~~~~-~~~ further underscored which was first reported in 1966 by Barlow and Bosman,54 of the disappearance in diastole of these protrusions in true MVP, whereas the contrast-filled contour remains unchanged in this normal fulcrum during the following diastole in pseudoprolapse (see Fig 9). An even better technique to demonstrate MVP is by negative contrastenhanced left atriography, which circumvents altogether the issue of the LV fulcrum (Fig 10). 512

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FIG 9. Pseudoprolapse simulated by the posterior mitral fulcrum (F/, which is present during both systole (A) and diastole (B), adjacent to a concave fornix (arrow).

Of the two leaflets, the posterior leaflet, which is a triscalloped structure (see Fig 81, is the most commonly involved in MVP on both anatomic and angiographic studies.220S221Pathologic studies indicate that combined leaflet prolapse is the commonest presentation of MVP and that isolated anterior leaflet prolapse is uncommon.z22 Although the optimal angiographic projection for visualization of posterior leaflet prolapse is the conventional 30’ right anterior oblique view, prolapse of the anterior leaflet is more difficult to see in this view because of overlapping and superposition of the opacified aortic valve. The left anterior oblique projection is more useful for idenDM, September

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FIG 10 A, left sItrial (LA) injection through a transseptal catheter in the right anterior oblique projection. Prolapsed mitral valve (arrow) appears as an area of negative contrast. 6, subsequeni t left ventricular (LV) injection in the same projection. Same prolapsed mitral )Jalve (arrow) appears as an area of positive contrast, accompanied by marked mitral reg lurgitation 01utlining the entire left atrium (LA). (From Barlow JB, Cheng TO: Mitral valve b illowing and prolapse, in Cheng TO: The International Textbook of Cardiology. New York, Pergamon Press, 1986, pp 497-524. Used by permission.)

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tification of prolapse of the anterior leaflet because the two mitral leaflets do not overlap in this view; the prolapsing anterior leaflet is seen as a convexity lying in close proximity to the aortic root, protruding into the left atrium and occupying the anterior-superior segment of the mitral annulus (Fig 11). Other abnormalities noted on LV cineangiography include segmental contractile abnormalities, located predominantly in the basal, mid, and anterolateral segments,118’223~224an elevated mean rate of LV circumferential fiber shortening,223 dilated mitral annu1us,225and mitral regurgitation of various degrees. These contraction abnormalities have been proposed as evidence that a primary cardiomyopathy causes MW, but more likely they are secondary to MVP, as evidenced by normalization of these LV contraction abnormalities in some patients following surgical replacement of the prolapsed mitral valve.226 Because of the known high prevalence and frequent association of both coronary artery disease and hWP in the general population, because patients with MVP often present with chest pain that sometimes is indistinguishable from angina due to coronary artery disease, and because coronary artery disease and MVP have different

FIG 11. Left ventriculogram (LV) in left anterior oblique projection of the same patient as in Figure 10, showing anterior mitral valve prolapse as a convexity with regurgitation (ventrical arrow) into the left atrium (LA) in close proximity to the root of the aorta (Ao), and also prolapse of the posterior mitral leaflet as another convexity with regurgitation (oblique arrow). (From Barlow JB, Cheng TO: Mitral valve billowing and prolapse, in Cheng TO: The lnternafional Textbook of Cardiology. New York, Pergamon Press, 1986, pp 497-524. Used by permission.) IIM, September

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prognostic implications, selective coronary arteriography is usually indicated in patients over the age of 40 who are studied angiographically for evaluation of h&P. In patients with primary h4VP, coronary arteriograms have invariably been normal. However, in most of the patients-over go%-it is possible to distinguish primary MVP from MVP secondary to coronary artery disease merely from the ventriculographic appearance alone of the prolapsed mitral valve.z27 A prolapsed mitral valve in primary MVP looks like the beak of a bird, whereas in coronary artery disease it usually looks like a nipple.“’ This difference in angiographic appearance of the prolapsed mitral valve, which has been confirmed228’22g since its original description, is explained by the fact that the chordae tendineae are uniformly elongated in primary MVP but are unevenly tethered in papillary mucle dysfunction secondary to coronary artery disease. Another use of angiography in the diagnostic evaluation of patients with MVP is the detection of associated prolapse of other cardiac valves. Tricuspid valve prolapse has been detected by right ventriculography in 46% to 54% of patients with MVP.230 Although angiographic diagnosis of tricuspid valve prolapse is fraught with considerable difficulty because of possible distortion of the tricuspid valve by the transvalvular placement of the angiographic catheter and the known variability of the angiographic appearance of the normal tricuspid valve and annulus, such a high association is supported by both echocardiographic87-89’ ‘I3 lg3,lg4 and pathologic17B “’ studies. Associated aortic valve prolapse is not as common; it is detected even less frequently angiographicall~” 232 than echocardiographicallp 8g,g2 or pathological1y.l” 222 COMPLICATIONS The vast majority of patients with MSP have no serious complications. However, there are six major complications that may accompany IvIVP: chest pain, progressive mitral regurgitation, infective endocarditis, thromboembolism, serious arrhythmias, and sudden death. CHEST PAtN The most common presenting symptom that brings the patients with MVP to the doctor is disabling chest pain, which may be indistinguishable from angina. Although the exact mechanism is unknown, there are eight possible explanations, as described below. 1. Chest Wall Syndrome.Since patients with MVP often are thinchested, the chest pain in some, which is usually sticking in quality 616

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and frequently localized at the point of maximal impulse, where it by pressure, is obviously chest wall in origin. is often reproducible 2. Mechanical Stress on Papillary Muscle.-The chest pain in patients with MVP may be related to the increased myocardial tension associated with traction on the papillary muscles and the contiguous myocardium. The latter has been demonstrated both apexcardiographically1g7,1s8 and angiocardiographically.118J226 Such contraction abnormalities can indeed result from the prolapsing mitral valve. Surgical replacement of the valve results in their disappearance .226 3. Coronary Artery Spasm.-That patients with MVP are more prone to develop coronary artery spasm is now well established. 1oo~157~158~228~233~236 In some instances it has been postulate& 157,237,238 that arrhythmia, sudden death, and acute myocardial infarction may result from spasm of a normal coronary artery in reflex response to billowing of the posterior mitral leaflet. Although ergonovine testing for symptomatic coronary artery spasm in patients with MVP has generally yielded disappointing results,233, 235J 23g this mechanism is probably responsible for chest pain in some patients with MW. The possibility that coronary artery spasm is the underlying etiology of chest pain in some patients with MVP raises a theoretical argument against g-blocker therapy and for calcium channel blocker therapy in these patients. is mounting evidence of significant LV 4. LV Dysfunction.-There dysfunction in patients with MVP from studies by systolic time intervals,lss angiography,“‘, 16’S240 and myocardial biopsy.241, 242 Some investigators characterize it as a form of cardiomyopathy,160’242-244 as one of the manifestations of cardiomyopathy is chest pain.245

5. Myocardial Supply/Demand Imbalance.-One study found that increasing afterload with phenylephrine infusion reliably evoked chest pain in symptomatic MVP patients but did not elicit symptoms in those without chest pain. Thus a myocardial oxygen supply and demand imbalance could be responsible for chest pain in some of these patients. Rapid right atrial or coronary sinus pacing produced abnormal coronary sinus lactate productionZ138214 and/or chest painz14 in about one third of the patients, again suggestive of myocardial hypoxia and ischemia. 6. Coexisting Coronary Artery Disease.-Since both coronary artery disease and MS@ are prevalent in the population at large, they certainly can coexist in the same patient. On the other hand, abundant evidence indicates that MVP can result from coronary artery disease,43’ 50.7.%79,247-250 That the mechanism is ischemic papillary mus-

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cle dysfunction has been well documented clinically,‘5’ 76J250 surgiAlthough at times it may be difficult cally,m7 and experimentally.z5* to distinguish chest pain in MYP from true angina secondary to coronary artery disease, it is usually possible to distinguish the two on physical examination,76 by angiography? and, in most cases, by radionuclide scintigraphy.201-205 7. Psychosomatic Complaint.-There seems to be a higher prevalence of panic disorders, one symptom of which is chest pain, in patients with MVP.““-‘lz 8. Esophageal Dysfunction.--In certain patients with MVP, esophageal motility disorders have been found to account for their chest pains ?52 MITRAL

REGURGITATION

Although patients with MVP often have some degree of mitral regurgitation, as evidenced by the presence of a late systolic murmur or as assessed by Doppler echocardiography, even without an audible murmur‘,253 it is usually minimal or mild. In the majority of patients there is little or no increase in the degree of mitral regurgitation. However, 3% to 9% of patients with MVP followed up over 10 to 40 years254-258 will develop progressive mitral regurgitation. It is usually the result of development of atrial fibrillation, infective endocarditis, or ruptured chordae tendineaeF5’ However, although 11% of patients with MSP have echocardiographic evidence of ruptured chordae, most (75% 1 do not have symptomatic deterioration.260 On the other hand, clinically unsuspected rupture of chordae was found in most of the patients with MVP who underwent operation for severe mitral regurgitation.232’255 With or without chordal rupture, floppy mitral valve is certainly the commonest cause of pure mitral regurgitation in patients undergoing mitral valve replacement.z”‘-2”3 INFECTIVE

ENDOCARDITIS

The risk of infective endocarditis for patients with MVP is eight times that for patients without underlying heart disease.264 In one series of patients with infective endocarditis affecting the mitral valve, MVP was the basis for about one third of the cases associated with isolated mitral regurgitation.265 Although the prophylactic management of patients with MVP remains controversial~66268 prophylaxis should be recommended for patients with MVP at the time of any procedure that is associated with bacteremia, at least if the patient has a murmur of mitral regurgitation at any time.26s It is unnecessary to prescribe prophylaxis in subjects with “silent” MVP de518

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tected only by echocardiography. In view of the frequent variability of auscultatory findings in h4VP, the absence of a murmur on a single examination should not be used to exclude the risk of infective endocarditis. THROMBOEMBOLISM Bland emboli are a recognized but rare complication of MVP. They may result from fissuring and thrombus formation on the valve,27o or from the formation of aggregates of platelets and fibrin in the angle between the posterior mitral leaflet and the left atrial wallz7’ Up to one third of patients under 45 years of age with cerebral ischemia were found to have MVP, compared to 7% to 8% of control populations,z72’273whereas the incidence was the same in both patients and controls over age 45.“’ Similar findings have been reported in the European274, 275and South Africanzzg literature. Abnormal platelet coagulant activities,276 shortened platelet survival time,277 and plasma platelet hyperactiviv73 have been postulated as mechanisms relating to emboli from the prolapsing mitral valve. Systemic embolization can occur into the coronary circulationz33 as well as into the cerebral circulation. SERIOUS ARRHYTHMlAS

AND SUDDEN DEATH

One of the most frequent complications seen in MVP is arrhythmias, mostly ventricular and atrial ectopy.72 These arrhythmias do not always correlate with the symptoms of palpitation or prolongation of the Q-T interva12” The most serious and most feared arrhythmic complication is sudden death, which is fortunately rare. To date there are 42 documented instances.‘76 It is highly probable that an arrhythmia, generally ventricular fibrillation, is responsible, although bradycardia and asystole have been reported.278 In an autopsy study of 14 cases of sudden death attributable to dysrhythmias associated with MVP,27’ five patients had a thrombotic lesion in the angle between the posterior mitral leaflet and the left atrial wall that contained fibrin and platelets, which may be important in the pathogenesis of the ventricular dysrhythmias. Three patients had minimal prolapse, which casts some doubt on the hypothesis that traction on the papillary muscler? or “diastolic dumping” of the voluminous leatlets27g may produce endocardial irritability and dysrhythmias. Rarely, acute rupture of chordae may result in sudden LV decompensation and cardiac arrest.280 A most important clinical problem is to identify those few patients with MVP who are at the greatest risk of sudden death. On present evidence we suggest that patients with ventricular ectopy or a conDM, September

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vincing history of syncope be subjected to 24-hour ambulatory monitoring or, if such facilities are not available, to a strenuous stress test. Those who exhibit dangerous arrhythmias should be maintained on antiarrhythmic drugs with regular monitoring to ensure that control is adequate. Large prospective long-term studies are needed to determine the overall risk of sudden death in MVP. In the meantime the risk of sudden death should not be mentioned to every patient with MVP or to his or her family, to avoid causing undue anxiety and neurosis. TREATMENT Most patients with MVP need no treatment other than reassurance, including those with atypical chest pain or palpitation unconfirmed by objective data. Endocarditis prophylaxis is advisable in all patients with systolic murmurs. Therapy with a B-adrenergic blocker is indicated in patients with disabling chest pains and/or arrhythmias. Sotalol, which has class III antiarrhythmic activity, has been found to be quite effective in the treatment of supraventricular and ventricular arrhythmias associated with MVP.281 Because of the possible association with coronary artery spasm, in which B-blockade may not only be ineffective but may exacerbate spasm, calcium channel blockers may be tried. Unless there is coexisting coronary artery disease, nitrates should be used with caution in the treatment of chest pains, since the reduction of LV cavity size after their administration may aggravate the mitral prolapse.43 Antithrombotic and antiplatelet therapy such as aspirin and dipyridamole should be considered in patients with cerebral embolic events~82’283 and the overall prognosis after the diagnosis of MVP-associated ischemia is good with respect to recurrent ischemic eventsFW In occasional patients with significant mitral regurgitation and reduced cardiac reserve who do not respond to medical management, mitral valve surgery may have to be considered. Repair is preferred to replacement,z85>286 including patients with ruptured chordae tendineaezs7; preservation of the chordae tendineae enhances LV contractile function,28~2g0 and repair is associated with lower operative mortalip and longer survival with fewer thrombotic and endocarditic complications than is replacement.2g2’ 2g3 REFERENCES

1. Friedberg CK: Diseases of the Heart, ed 3. Philadelphia, WB Saunders Co, 1966, p 1095. 2. Wooley CF: From irritable heart to mitral valve prolapse: The Osler connection. Am J cardiol 1984; 53:870-874. 3. Gallavardin L: Pseudo-dedoublement du deuxieme bruit du coeur simulant 520

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